1,568 results on '"Samuels A"'
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2. Antidotes for Science Phobia.
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Samuels, Linda S.
- Abstract
Discusses the need for science courses to be rigorous, promote student success, and enhance self-esteem in order to address students' phobia of science. Discusses the philosophy of science education and techniques and strategies to reach the goals that arise from this philosophy. Presents models that work with advanced biology students and middle school students. (JRH)
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- 1996
3. Life Science Learning Center, Los Angeles Valley College.
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Samuels, Edward
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A description is provided of Los Angeles Valley College's Life Science Learning Center (LSLC), which provides: (1) a resource center addressed to the individualized learning needs of students served by the Biology Department; (2) a learning environment enabling students to proceed in self-paced, activity-centered, concept-oriented experiences in an open-entry/open-exit mode; (3) an environment in which learning requirements can be diagnosed and individual needs provided for in the areas of remediation, reinforcement of regular classwork, and enrichment experiences; and (4) the opportunity for an enhanced degree of interdisciplinary interaction. After outlining the LSLC's objectives, the paper provides information on the operation and organization of the facility, including hours of operation; the LSLC's biotutorial and independent study annex; instructional and staffing considerations such as the physical presence of certificated staff, the use of staff to develop learning activities and programs, the role of student laboratory assistants, and the LSLC's classified staff. Finally, the LSLC's major accomplishments are discussed. A list of CAI programs developed and used at the center is appended. (LAL)
- Published
- 1984
4. Conclusion
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Samuels, Robert, Sloan, Tod, Series editor, and Samuels, Robert
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- 2016
- Full Text
- View/download PDF
5. Engineering Monolignol p -Coumarate Conjugates into Poplar and Arabidopsis Lignins
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Smith, Rebecca A., Gonzales-Vigil, Eliana, Karlen, Steven D., Park, Ji-Young, Lu, Fachuang, Wilkerson, Curtis G., Samuels, Lacey, Ralph, John, and Mansfield, Shawn D.
- Published
- 2015
6. A million persons, a million dreams: a vision for a national center of radiation epidemiology and biology
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Armin Ansari, John E. Till, Isaf Al-Nabulsi, Joey Y. Zhou, Emily A. Caffrey, Steve R. Blattnig, Sarah S. Cohen, Michael T. Mumma, Derek W. Jokisch, Richard W. Leggett, Caleigh Samuels, Kathryn D. Held, Lawrence T. Dauer, Sergei Y. Tolmachev, Paul K Blake, R. Craig Yoder, John D. Boice, Brian T. Quinn, and Ashley P. Golden
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Male ,Nuclear Weapons ,medicine.medical_specialty ,Government ,Radiological and Ultrasound Technology ,Chronic radiation syndrome ,MEDLINE ,Disease ,Radiation Exposure ,Nuclear weapon ,medicine.disease ,Nuclear Power Plants ,Environmental health ,Acute exposure ,Epidemiology ,medicine ,Humans ,Dementia ,Female ,Radiology, Nuclear Medicine and imaging ,Radiometry ,Biology - Abstract
Background Epidemiologic studies of radiation-exposed populations form the basis for human safety standards. They also help shape public health policy and evidence-based health practices by identifying and quantifying health risks of exposure in defined populations. For more than a century, epidemiologists have studied the consequences of radiation exposures, yet the health effects of low levels delivered at a low-dose rate remain equivocal. Materials and methods The Million Person Study (MPS) of U.S. Radiation Workers and Veterans was designed to examine health effects following chronic exposures in contrast with brief exposures as experienced by the Japanese atomic bomb survivors. Radiation associations for rare cancers, intakes of radionuclides, and differences between men and women are being evaluated, as well as noncancers such as cardiovascular disease and conditions such as dementia and cognitive function. The first international symposium, held November 6, 2020, provided a broad overview of the MPS. Representatives from four U.S. government agencies addressed the importance of this research for their respective missions: U.S. Department of Energy (DOE), the Centers for Disease Control and Prevention (CDC), the U.S. Department of Defense (DOD), and the National Aeronautical Space Agency (NASA). The major components of the MPS were discussed and recent findings summarized. The importance of radiation dosimetry, an essential feature of each MPS investigation, was emphasized. Results The seven components of the MPS are DOE workers, nuclear weapons test participants, nuclear power plant workers, industrial radiographers, medical radiation workers, nuclear submariners, other U.S. Navy personnel, and radium dial painters. The MPS cohorts include tens of thousands of workers with elevated intakes of alpha particle emitters for which organ-specific doses are determined. Findings to date for chronic radiation exposure suggest that leukemia risk is lower than after acute exposure; lung cancer risk is much lower and there is little difference in risks between men and women; an increase in ischemic heart disease is yet to be seen; esophageal cancer is frequently elevated but not myelodysplastic syndrome; and Parkinson's disease may be associated with radiation exposure. Conclusions The MPS has provided provocative insights into the possible range of health effects following low-level chronic radiation exposure. When the 34 MPS cohorts are completed and combined, a powerful evaluation of radiation-effects will be possible. This final article in the MPS special issue summarizes the findings to date and the possibilities for the future. A National Center for Radiation Epidemiology and Biology is envisioned.
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- 2021
7. Nutritional quality of Calobota sericea fodders. A preliminary assessment
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Francuois L Müller, Clement Cupido, and M. Igshaan Samuels
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Ecology ,Agronomy ,biology ,Perennial plant ,Calobota ,Animal Science and Zoology ,Forage ,Nutritional quality ,Rangeland ,biology.organism_classification ,Legume - Abstract
This study aimed to provide preliminary information regarding the nutritional quality of Calobota sericea, a preferred perennial legume forage species from the water-limited rangelands of South Afr...
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- 2021
8. Effects of the substitution of fishmeal with mealworm meal on enzymes, haemolymph and intestinal microbiota of the Pacific white shrimp
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Richard Ian Samuels, Cristina Rios, Felipe do Nascimento Vieira, J. De Dea Lindner, Débora Machado Fracalossi, Roseane L. Panini, Carlos P. Silva, and L.A. Acordi Menezes
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Mealworm ,0303 health sciences ,animal structures ,business.industry ,fungi ,Litopenaeus ,04 agricultural and veterinary sciences ,Biology ,Gut flora ,biology.organism_classification ,Shrimp ,Shrimp farming ,03 medical and health sciences ,Fish meal ,Aquaculture ,Insect Science ,040102 fisheries ,0401 agriculture, forestry, and fisheries ,Food science ,Digestion ,business ,030304 developmental biology ,Food Science - Abstract
Shrimp farming is one profitable sector of aquaculture and the Pacific white shrimp (Litopenaeus vannamei) is the most cultivated species worldwide. Nutrition is considered as one of the greatest challenges in shrimp farming due to its dependence on fishmeal (FM) as an ingredient in the feed. The main goal of the present work was to analyse if the substitution of FM by yellow mealworm (Tenebrio molitor) meal (TM) influences digestive enzyme expression, haemolymph parameters or the intestinal microbiota of shrimp juveniles. Shrimps (average initial weight 4.42±0.02 g) were fed five experimental diets where FM protein was gradually substituted by TM protein (0, 25, 50, 75, and 100%). The shrimps were fed four times per day with an amount equivalent to approximately 6% of their biomass for 42 days. The total haemocyte count, protein concentration and prophenoloxidase activity in the haemolymph were not significantly altered (P>0.05) when FM was substituted by TM. However, the agglutinating activity of shrimp serum determined against dog erythrocytes was higher in the shrimp group fed 25% TM. The absolute and specific activities of trypsin, chymotrypsin, lipase, α-amylase and the patterns of proteolytic activities were not affected by the dietary treatments. The shrimp gut bacterial microbiota profile was similar with the genera Pseudoalteromonas, Rubritalea, Ruegeria, Tenacibaculum, and Vibrio detected. These results show that TM is viable alternative for the replacement of FM, without any deleterious effects on expression of key digestive enzymes, gut microbiota or the immune system of the Pacific white shrimp.
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- 2021
9. Safety, immunogenicity and efficacy of PfSPZ Vaccine against malaria in infants in western Kenya: a double-blind, randomized, placebo-controlled phase 2 trial
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Ginnie Abarbanell, Allan Dungani, Elizabeth L Nzuu, Robert A. Seder, Thomas L. Richie, David Styers, Salim Abdulla, Ryan E. Wiegand, Eric R. James, Winnie Chebore, Peter F. Billingsley, Dennis K. Bii, Simon Kariuki, Tony Sang, B. Kim Lee Sim, Maxmillian Mpina, Kephas Otieno, Paul Ndaya Oloo, Aaron M. Samuels, Martina Oneko, Gail E Potter, Dorcas Akach, Said Jongo, Natasha Kc, Laura C. Steinhardt, Phillip A. Swanson, Reuben Yego, Stephen L. Hoffman, Julie Gutman, and Claudia Daubenberger
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medicine.medical_specialty ,biology ,business.industry ,Plasmodium falciparum ,General Medicine ,medicine.disease ,biology.organism_classification ,Vaccine efficacy ,General Biochemistry, Genetics and Molecular Biology ,PfSPZ vaccine ,Vaccination ,Tolerability ,Immunity ,Internal medicine ,parasitic diseases ,medicine ,business ,Adverse effect ,Malaria - Abstract
The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) vaccine provides protection against P. falciparum infection in malaria-naive adults. Preclinical studies show that T cell-mediated immunity is required for protection and is readily induced in humans after vaccination. However, previous malaria exposure can limit immune responses and vaccine efficacy (VE) in adults. We hypothesized that infants with less previous exposure to malaria would have improved immunity and protection. We conducted a multi-arm, randomized, double-blind, placebo-controlled trial in 336 infants aged 5–12 months to determine the safety, tolerability, immunogenicity and efficacy of the PfSPZ Vaccine in infants in a high-transmission malaria setting in western Kenya ( NCT02687373 ). Groups of 84 infants each received 4.5 × 105, 9.0 × 105 or 1.8 × 106 PfSPZ Vaccine or saline three times at 8-week intervals. The vaccine was well tolerated; 52 (20.6%) children in the vaccine groups and 20 (23.8%) in the placebo group experienced related solicited adverse events (AEs) within 28 d postvaccination and most were mild. There was 1 grade 3-related solicited AE in the vaccine group (0.4%) and 2 in the placebo group (2.4%). Seizures were more common in the highest-dose group (14.3%) compared to 6.0% of controls, with most being attributed to malaria. There was no significant protection against P. falciparum infection in any dose group at 6 months (VE in the 9.0 × 105 dose group = −6.5%, P = 0.598, the primary statistical end point of the study). VE against clinical malaria 3 months after the last dose in the highest-dose group was 45.8% (P = 0.027), an exploratory end point. There was a dose-dependent increase in antibody responses that correlated with VE at 6 months in the lowest- and highest-dose groups. T cell responses were undetectable across all dose groups. Detection of Vδ2+Vγ9+ T cells, which have been correlated with induction of PfSPZ Vaccine T cell immunity and protection in adults, were infrequent. These data suggest that PfSPZ Vaccine-induced T cell immunity is age-dependent and may be influenced by Vδ2+Vγ9+ T cell frequency. Since there was no significant VE at 6 months in these infants, these vaccine regimens will likely not be pursued further in this age group. The PfSPZ Vaccine does not protect infants from infection with Plasmodium falciparum, the major cause of malaria.
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- 2021
10. Influence of Fc Modifications and IgG Subclass on Biodistribution of Humanized Antibodies Targeting L1CAM
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Maya Suzuki, Zachary Samuels, Brandon Nemieboka, Hong-fen Guo, Kimberly J. Edwards, Nai-Kong V. Cheung, Hong Xu, Sai Kiran Sharma, Alessandra Piersigilli, Jason S. Lewis, and Joshua A. Korsen
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Biodistribution ,biology ,L1 ,Chemistry ,medicine.drug_class ,Fc receptor ,Mice, Nude ,Neural Cell Adhesion Molecule L1 ,Antibodies, Monoclonal, Humanized ,Immunoglobulin light chain ,Monoclonal antibody ,Molecular biology ,Subclass ,Immunoglobulin Fab Fragments ,Mice ,In vivo ,Immunoglobulin G ,biology.protein ,medicine ,Animals ,Tissue Distribution ,Radiology, Nuclear Medicine and imaging ,Antibody - Abstract
Immuno-positron emission tomography (immuno-PET) is a powerful tool to noninvasively characterize the in vivo biodistribution of engineered antibodies (Abs). Methods L1 cell adhesion molecule (L1CAM)-targeting HuE71 immunoglobulin G1 (IgG1) and immunoglobulin G4 (IgG4) Abs bearing identical variable heavy and light chain sequences but different fragment crystallizable (Fc) portions were radiolabeled with Zirconium-89 (89Zr) and the in vivo biodistribution was studied in SKOV3 ovarian cancer xenografted nude mice. Results In addition to showing uptake in L1CAM-expressing SKOV3 tumors like its parental counterpart HuE71 IgG1, the afucosylated variant having enhanced Fc-receptor (FcR) affinity showed high nonspecific uptake in lymph nodes. On the other hand, aglycosylated HuE71 IgG1 with abrogated FcR binding did not show lymphoid uptake. The use of IgG4 subclass showed high nonspecific uptake in the kidneys, which was prevented by mutating serine at position 228 to proline (S228P) in the hinge region of the IgG4 Ab to mitigate in vivo fragment antigen-binding (Fab) arm exchange. Conclusion Our findings highlight the influence of Fc-modifications and the choice of IgG subclass on the in vivo biodistribution of Abs and the potential outcomes thereof.
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- 2021
11. Morphological and physiological responses of Calobota sericea plants subjected to water limitation and subsequent rewatering
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J. Stephen Boatwright, Clement Cupido, Lincoln Raitt, Francuois L Müller, Samson B. M. Chimphango, M. Igshaan Samuels, and Lilburne Cyster
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Drought stress ,Stomatal conductance ,geography ,geography.geographical_feature_category ,Ecology ,biology ,Drought resistance ,Calobota ,biology.organism_classification ,Pasture ,Physiological responses ,Agronomy ,Animal Science and Zoology ,Rangeland ,Legume - Abstract
Calobota sericea is a native legume of South Africa, confined to the water-limited rangelands, and it has recently been prioritised for additional characterisation regarding its pasture potential. ...
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- 2021
12. Evaluation of SARS-CoV-2 IgG antibody reactivity in patients with systemic lupus erythematosus: analysis of a multi-racial and multi-ethnic cohort
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Amit Saxena, Katerina Svigos, Brian Jaros, Janine Sullivan, Alexis J Engel, Pamela Rosenthal, Alexa Steuer, H. Michael Belmont, Miao Chang, Euna Lee, Trevor Young, Yamen Homsi, Andres Piatti, Susan Katz, Mala Masson, Julie Nusbaum, Natalie Azar, Mayce Haj-Ali, Brian D. Golden, Kavini Mehta, Michael Golpanian, Jordan E. Axelrad, Robin Lipschitz, Bruce Garner, Vaish Sekar, Rochelle Castillo, Joshua Novack, Michael Colin, Nazia Hussain, Andrew Porges, Jonathan Samuels, Keshav Mangalick, Lauren Rangel, Ruth Fernandez-Ruiz, Stephen Smiles, Connor Peterson, Stelios Viennas, Paula Rackoff, Steven Carsons, Rebecca H. Haberman, Anang Modi, Soumya M. Reddy, Fardina Malik, Mimi Y. Kim, Jill P. Buyon, Robert Lesser, Kaitlyn Yin, Avani Kolla, Samrachana Adhikari, Sicy Lee, Avram Goldberg, Simon Hong, Shannon Chang, Ashira D Blazer, Andrea L. Neimann, Bruce Solitar, Philip M. Carlucci, Allison Guttmann, Lauren Fried, Jessica Hoey, Di Yan, David Hudesman, Andrea B. Troxel, Gary Zagon, Gary Solomon, Craig Smuda, Alan Chen, Lindsey Quintana, Jose U. Scher, Konstantin Brodetskiy, Benjamin Plotz, Shruti Shankar, Deborah Ramirez, Rebecca B Blank, Peter M. Izmirly, Kimberly Robins, Lenore Brancato, Kristina K Deonaraine, Lily Cao, Lauren Wong, Harry Shen, Sabina Sandigursky, Eileen Lydon, and Jennifer Stein
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medicine.medical_specialty ,Systemic lupus erythematosus ,biology ,business.industry ,Immunology ,Ethnic group ,Arthritis ,Articles ,medicine.disease ,Serology ,Immune system ,Rheumatology ,Internal medicine ,Humoral immunity ,Cohort ,biology.protein ,Immunology and Allergy ,Medicine ,Antibody ,skin and connective tissue diseases ,business - Abstract
Summary Background Patients with systemic lupus erythematosus (SLE) are at risk of developing COVID-19 due to underlying immune abnormalities and regular use of immunosuppressant medications. We aimed to evaluate the presence of SARS-CoV-2 IgG antibodies in patients with SLE with or without previous COVID-19-related symptoms or RT-PCR-confirmed SARS-CoV-2 infection. Methods For this analysis, we included patients with SLE from two cohorts based in New York City: the Web-based Assessment of Autoimmune, Immune-Mediated and Rheumatic Patients during the COVID-19 pandemic (WARCOV) study; and the NYU Lupus Cohort (a prospective registry of patients at NYU Langone Health and NYC Health + Hospitals/Bellevue). Patients in both cohorts were tested for SARS-CoV-2 IgG antibodies via commercially available immunoassays, processed through hospital or outpatient laboratories. Patients recruited from the NYU Lupus Cohort, referred from affiliated providers, or admitted to hospital with COVID-19 were tested for SARS-CoV-2 IgG antibodies as part of routine surveillance during follow-up clinical visits. Findings 329 patients with SLE were included in this analysis, 146 from the WARCOV study and 183 from the NYU Lupus Cohort, and were tested for SARS-CoV-2 antibodies between April 29, 2020, and Feb 9, 2021. 309 (94%) were women and 91 (28%) were of Hispanic ethnicity. 51 (16%) of 329 patients had a positive SARS-CoV-2 IgG antibody test. Seropositive patients were more likely than seronegative patients to be Hispanic (24 [47%] of 51 vsz 67 [24%] of 278). Other demographic variables, SLE-specific factors, and immunosuppressant use were not associated with SARS-CoV-2 positivity. Of the 29 patients with COVID-19 previously confirmed by RT-PCR, 18 (62%) were on immunosuppressants; 24 (83%) of 29 patients tested positive for SARS-CoV-2 IgG antibodies. Of 17 patients who had symptoms of COVID-19 but negative concurrent RT-PCR testing, one (6%) developed an antibody response. Of 26 patients who had COVID-19-related symptoms but did not undergo RT-PCR testing, six (23%) developed an antibody response. Of 83 patients who had no symptoms of COVID-19 and no RT-PCR testing, four (5%) developed an antibody response. Among 36 patients who were initially SARS-CoV-2 IgG positive, the majority maintained reactivity serially (88% up to 10 weeks, 83% up to 20 weeks, and 80% up to 30 weeks). Seven (70%) of ten patients with confirmed COVID-19 had antibody positivity beyond 30 weeks from disease onset. Interpretation Most patients with SLE and confirmed COVID-19 were able to produce and maintain a serological response despite the use of a variety of immunosuppressants, providing reassurance about the efficacy and durability of humoral immunity and possible protection against re-infection with SARS-CoV-2. Funding National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, and Bloomberg Philanthropies COVID-19 Response Initiative Grant.
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- 2021
13. Temperature memory and non-structural carbohydrates mediate legacies of a hot drought in trees across the southwestern USA
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Michael Bangs, Drew M. P. Peltier, Yao Liu, David Auty, William R. L. Anderegg, Marcy E. Litvak, John D. Shaw, Jessica S. Guo, Kimberly E. Samuels-Crow, Larissa L. Yocom, Michael Fell, Phiyen Nguyen, Michelle Wilson, Christopher R. Schwalm, Kiona Ogle, and George W. Koch
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biology ,Physiology ,Ecology ,Climate Change ,Carbohydrates ,Temperature ,Climate change ,Plant Science ,Pinus edulis ,biology.organism_classification ,food.food ,Droughts ,Trees ,Recovery period ,food ,Juniperus osteosperma ,Dendrochronology - Abstract
Trees are long-lived organisms that integrate climate conditions across years or decades to produce secondary growth. This integration process is sometimes referred to as ‘climatic memory.’ While widely perceived, the physiological processes underlying this temporal integration, such as the storage and remobilization of non-structural carbohydrates (NSC), are rarely explicitly studied. This is perhaps most apparent when considering drought legacies (perturbed post-drought growth responses to climate), and the physiological mechanisms underlying these lagged responses to climatic extremes. Yet, drought legacies are likely to become more common if warming climate brings more frequent drought. To quantify the linkages between drought legacies, climate memory and NSC, we measured tree growth (via tree ring widths) and NSC concentrations in three dominant species across the southwestern USA. We analyzed these data with a hierarchical mixed effects model to evaluate the time-scales of influence of past climate (memory) on tree growth. We then evaluated the role of climate memory and the degree to which variation in NSC concentrations were related to forward-predicted growth during the hot 2011–2012 drought and subsequent 4-year recovery period. Populus tremuloides exhibited longer climatic memory compared to either Pinus edulis or Juniperus osteosperma, but following the 2011–2012 drought, P. tremuloides trees with relatively longer memory of temperature conditions showed larger (more negative) drought legacies. Conversely, Pinus edulis trees with longer temperature memory had smaller (less negative) drought legacies. For both species, higher NSC concentrations followed more negative (larger) drought legacies, though the relevant NSC fraction differed between P. tremuloides and P. edulis. Our results suggest that differences in tree NSC are also imprinted upon tree growth responses to climate across long time scales, which also underlie tree resilience to increasingly frequent drought events under climate change.
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- 2021
14. Association of Pepsin With Inflammatory Signaling and Effusion Viscosity in Pediatric Otitis Media
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Joseph E. Kerschner, Pawjai Khampang, Robert H. Chun, Ke Yan, Michael E. McCormick, Nikki Johnston, Tina L. Samuels, Mana Espahbodi, and Caroline A. McCormick
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Gastroenterology ,Pepsin ,Internal medicine ,medicine ,Humans ,Interleukin 8 ,Child ,biology ,Otitis Media with Effusion ,Viscosity ,business.industry ,Mucin ,Infant ,Interleukin ,Pepsin A ,Cross-Sectional Studies ,Otitis ,Cytokine ,Otorhinolaryngology ,Effusion ,Child, Preschool ,Neutrophil elastase ,biology.protein ,Female ,medicine.symptom ,business - Abstract
OBJECTIVE Otitis media (OM) is a common inflammatory disease spectrum. Cytokine signaling, neutrophil activity, and mucin hypersecretion during recurrent and chronic OM contribute to persistent, viscous middle ear (ME) effusions, hearing loss, and potential for developmental delay. Extraesophageal reflux (EER), specifically pepsin, triggers inflammatory signaling in respiratory mucosa and is associated with OM. The objective of this study was to investigate the association of pepsin with ME inflammatory signaling and the outcomes and examine causality in vitro. STUDY DESIGN Cross-sectional study. METHODS ME fluid (MEF) and preoperative audiometric data were collected from 30 pediatric subjects undergoing tympanostomy tube placement for recurrent OM or OM with effusion. MEF viscosity was characterized by the surgeon. Pepsin, inflammatory molecules, and mucin were assayed by enzyme-linked immunosorbent assay (ELISA). ME epithelial primary culture was exposed to 0.1 to 1 mg/ml pepsin at pH 5, 6, and 7 for 30 minutes, and cytokine expression was assayed via qPCR. RESULTS Pepsin was observed in the MEF of 77% of patients (range 71-2,734 ng/ml). Pepsin correlated with effusion viscosity, interleukins -6 and -8, neutrophil elastase, and mucin 5B (P
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- 2021
15. INFLUENCE OF WATER EXCESS OR DEFICIENCY ON LEAF NUTRIENT CONTENT AND PLANT GROWTH IN SUGARCANE AND OTHER CROPS
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George Samuels
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Plant growth ,Agronomy ,fungi ,food and beverages ,Animal Science and Zoology ,Biology ,Agronomy and Crop Science ,Nutrient content - Abstract
INFLUENCE OF WATER EXCESS OR DEFICIENCY ON LEAF NUTRIENT CONTENT AND PLANT GROWTH IN SUGARCANE AND OTHER CROPS
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- 2021
16. Forage legumes from the Mediterranean Fynbos biome of South Africa with potential for domestication: slope aspect affects tissue fibre and mineral composition
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A. Muthama Muasya, John Howieson, James S. Boatwright, Samson B. M. Chimphango, M. Igshaan Samuels, Odette E Curtis-Scott, Luke H. Gallant, and Clement Cupido
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Mediterranean climate ,geography ,geography.geographical_feature_category ,Ecology ,Biome ,Forage ,Vegetation ,Biology ,Pasture ,Agronomy ,Animal Science and Zoology ,Species richness ,Rangeland ,Domestication - Abstract
Fabaceae plants contribute greatly to a high quality of pasture in rangelands, because of high levels of protein in their tissues. Despite this established importance, only a few southern African legumes have been evaluated for nutritional value and domestication. The Overberg renosterveld vegetation of the Fynbos biome occupies undulating landscapes that have multiple slope aspects, creating variable microclimatic conditions affecting nutrient dynamics, species richness and plant chemical compositions. We assessed the effect of slope aspect on fiber and mineral composition of forage species present to provide information on the importance of slope for species characterization and nutritional value for domestication. Tissue samples from six replicates of the same species occurring on opposing aspects were collected for nutritional assessment. Results on the data showed that fibre and mineral composition differed in species occurring on different slopes, albeit with few exceptions. The concentrations of P, K and Mg in some species were significantly higher on the cooler and wetter south facing slopes relative to north facing slopes. Nutrient elements in soil samples collected from each site varied with slope aspects and elements. It is recommended that topography should be considered when studying forage nutritional assessments as part of future domestication programs.
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- 2021
17. Subcellular coordination of plant cell wall synthesis
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Samuel King, Heather E. McFarlane, Natalie Hoffmann, and A. Lacey Samuels
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Cell type ,Golgi Apparatus ,Biology ,Endoplasmic Reticulum ,General Biochemistry, Genetics and Molecular Biology ,Extracellular matrix ,Cell wall ,Cell membrane ,03 medical and health sciences ,symbols.namesake ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Wall ,Polysaccharides ,Plant Cells ,Organelle ,medicine ,Homeostasis ,Secretion ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Cell Membrane ,Cell Biology ,Golgi apparatus ,Endocytosis ,Cell biology ,Xyloglucan ,medicine.anatomical_structure ,chemistry ,Glucosyltransferases ,symbols ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Organelles of the plant cell cooperate to synthesize and secrete a strong yet flexible polysaccharide-based extracellular matrix: the cell wall. Cell wall composition varies among plant species, across cell types within a plant, within different regions of a single cell wall, and in response to intrinsic or extrinsic signals. This diversity in cell wall makeup is underpinned by common cellular mechanisms for cell wall production. Cellulose synthase complexes function at the plasma membrane and deposit their product into the cell wall. Matrix polysaccharides are synthesized by a multitude of glycosyltransferases in hundreds of mobile Golgi stacks, and an extensive set of vesicle trafficking proteins govern secretion to the cell wall. In this review, we discuss the different subcellular locations at which cell wall synthesis occurs, review the molecular mechanisms that control cell wall biosynthesis, and examine how these are regulated in response to different perturbations to maintain cell wall homeostasis.
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- 2021
18. The Effects of Turnip Mosaic Virus Infections on the Deposition of Secondary Cell Walls and Developmental Defects in Arabidopsis Plants Are Virus-Strain Specific
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Silvia López-González, Fernando Ponz, Mathias Schuetz, A. Lacey Samuels, Flora Sánchez, Concepción Gómez-Mena, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Ministerio de Ciencia e Innovación (España), Gómez-Mena, Concepción, Schuetz, Mathias, Samuels, A Lacey, and Ponz, Fernando
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biology ,Viral protein ,Plant culture ,Plant Science ,Turnip mosaic virus ,biology.organism_classification ,medicine.disease_cause ,Virus ,SB1-1110 ,Microbiology ,Viral chimeras ,Transcriptome ,Secondary cell wall ,Arabidopsis ,medicine ,Arabidopsis thaliana ,Viral strains ,Gene ,Developmental alterations - Abstract
12 Pág. Centro de Biotecnología y Genómica de Plantas., Two isolates of Turnip mosaic virus (UK 1 and JPN 1), representative of two different viral strains, induced differential alterations on secondary cell wall (SCW) development in Arabidopsis thaliana, suggesting cell-type specific effects of these viral infections. These potential effects were analyzed in inflorescence stems and flowers of infected plants, together with other possible cellular effects of the infections. Results obtained from macroscopic and histochemical analyses showed that infection with either virus significantly narrowed stem area, but defects in SCW were only found in JPN 1 infections. In flowers, reduced endothecium lignification was also found for JPN 1, while UK 1 infections induced severe floral cell and organ development alterations. A transcriptomic analysis focused on genes controlling and regulating SCW formation also showed notable differences between both viral isolates. UK 1 infections induced a general transcriptional decrease of most regulatory genes, whereas a more complex pattern of alterations was found in JPN 1 infections. The role of the previously identified viral determinant of most developmental alterations, the P3 protein, was also studied through the use of viral chimeras. No SCW alterations or creeping habit growth were found in infections by the chimeras, indicating that if the P3 viral protein is involved in the determination of these symptoms, it is not the only determinant. Finally, considerations as to the possibility of a taxonomical reappraisal of these TuMV viral strains are provided., The work at the CBGP was funded by several INIA grants. During the course of the work SL-G was funded by a predoctoral FPI-INIA fellowship/contract. We thank the Spanish Ministry of Science for the Severo Ochoa Excellence Accreditations to the CBGP (SEV-2016-0672).
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- 2021
19. Fate or coincidence: do COPD and major depression share genetic risk factors?
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Lea K. Davis, Digna R. Velez Edwards, Bradley W. Richmond, Nancy J. Cox, Victoria L. Martucci, Timothy S. Blackwell, David C. Samuels, and Melinda C. Aldrich
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Adult ,Male ,Oncology ,Multifactorial Inheritance ,Linkage disequilibrium ,medicine.medical_specialty ,Genome-wide association study ,Comorbidity ,Biology ,Polymorphism, Single Nucleotide ,behavioral disciplines and activities ,Linkage Disequilibrium ,Pulmonary function testing ,Pulmonary Disease, Chronic Obstructive ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,mental disorders ,Genetics ,medicine ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,Association Studies Article ,Molecular Biology ,Genetics (clinical) ,Aged ,030304 developmental biology ,Depressive Disorder, Major ,0303 health sciences ,COPD ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Tennessee ,respiratory tract diseases ,Phenotype ,030228 respiratory system ,Major depressive disorder ,Female ,Genome-Wide Association Study - Abstract
Major depressive disorder (MDD) is a common comorbidity in chronic obstructive pulmonary disease (COPD), affecting up to 57% of patients with COPD. Although the comorbidity of COPD and MDD is well established, the causal relationship between these two diseases is unclear. A large-scale electronic health record clinical biobank and genome-wide association study summary statistics for MDD and lung function traits were used to investigate potential shared underlying genetic susceptibility between COPD and MDD. Linkage disequilibrium score regression was used to estimate genetic correlation between phenotypes. Polygenic risk scores (PRS) for MDD and lung function traits were developed and used to perform a phenome-wide association study (PheWAS). Multi-trait-based conditional and joint analysis identified single-nucleotide polymorphisms (SNPs) influencing both lung function and MDD. We found genetic correlations between MDD and all lung function traits were small and not statistically significant. A PRS–MDD was significantly associated with an increased risk of COPD in a PheWAS [odds ratio (OR) = 1.12, 95% confidence interval (CI): 1.09–1.16] when adjusting for age, sex and genetic ancestry, but this relationship became attenuated when controlling for smoking history (OR = 1.08, 95% CI: 1.04–1.13). No significant associations were found between the lung function PRS and MDD. Multi-trait-based conditional and joint analysis identified three SNPs that may contribute to both traits, two of which were previously associated with mood disorders and COPD. Our findings suggest that the observed relationship between COPD and MDD may not be driven by a strong shared genetic architecture.
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- 2021
20. Longitudinal optical coherence tomography to visualize the in vivo response of middle ear biofilms to antibiotic therapy
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Pawjai Khampang, Jungeun Won, Darold R. Spillman, Ke Yan, Wenzhou Hong, Ryan G. Porter, Michael A. Novak, Stephen A. Boppart, Joseph E. Kerschner, and Samuels Marshall
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Chinchilla ,Tympanic Membrane ,Antibiotics ,01 natural sciences ,0302 clinical medicine ,030223 otorhinolaryngology ,Multidisciplinary ,biology ,medicine.diagnostic_test ,Ceftriaxone ,Imaging and sensing ,Anti-Bacterial Agents ,medicine.anatomical_structure ,Middle ear ,Medicine ,medicine.symptom ,Biomedical engineering ,Tomography, Optical Coherence ,medicine.drug ,medicine.medical_specialty ,medicine.drug_class ,Science ,Ear, Middle ,Article ,010309 optics ,03 medical and health sciences ,Optical coherence tomography ,stomatognathic system ,In vivo ,Ophthalmology ,biology.animal ,0103 physical sciences ,medicine ,Animals ,Humans ,Otitis Media with Effusion ,business.industry ,Biofilm ,Paediatrics ,Disease Models, Animal ,Otitis Media ,stomatognathic diseases ,Otitis ,Biofilms ,sense organs ,Bacterial infection ,business - Abstract
Studying the impact of antibiotic treatment on otitis media (OM), the leading cause of primary care office visits during childhood, is critical to develop appropriate treatment strategies. Tracking dynamic middle ear conditions during antibiotic treatment is not readily applicable in patients, due to the limited diagnostic techniques available to detect the smaller amount and variation of middle ear effusion (MEE) and middle ear bacterial biofilm, responsible for chronic and recurrent OM. To overcome these challenges, a handheld optical coherence tomography (OCT) system has been developed to monitor in vivo response of biofilms and MEEs in the OM-induced chinchilla model, the standard model for human OM. As a result, the formation of MEE as well as biofilm adherent to the tympanic membrane (TM) was longitudinally assessed as OM developed. Various types of MEEs and biofilms in the chinchilla model were identified, which showed comparable features as those in humans. Furthermore, the effect of antibiotics on the biofilm as well as the amount and type of MEEs was investigated with low-dose and high-dose treatment (ceftriaxone). The capability of OCT to non-invasively track and examine middle ear conditions is highly beneficial for therapeutic OM studies and will lead to improved management of OM in patients.
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- 2021
21. Targeted RNAseq assay incorporating unique molecular identifiers for improved quantification of gene expression signatures and transcribed mutation fraction in fixed tumor samples
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Jiaxin Qu, Chunxiao Fu, Rebekah Gould, Todd Pappas, Lili Du, W. Fraser Symmans, Christos Hatzis, Lajos Pusztai, Michal Marczyk, Rosanna Lau, Michael Samuels, Bruno Valentin Sinn, and Alexander J. Trevarton
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0301 basic medicine ,Targeted RNAseq ,Cancer Research ,Tissue Fixation ,lcsh:RC254-282 ,law.invention ,Specimen Handling ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,law ,Complementary DNA ,Formaldehyde ,Neoplasms ,Gene expression ,Genetics ,Biomarkers, Tumor ,Humans ,Gene ,Polymerase chain reaction ,Polymerase ,Messenger RNA ,Paraffin Embedding ,biology ,Chemistry ,Sequence Analysis, RNA ,Gene Expression Profiling ,Assay development ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Molecular biology ,Reverse transcriptase ,030104 developmental biology ,Concordance correlation coefficient ,Oncology ,Technical Advance ,030220 oncology & carcinogenesis ,Mutation ,biology.protein ,Transcriptome ,Unique molecular identifiers - Abstract
Background Our objective was to assess whether modifications to a customized targeted RNA sequencing (RNAseq) assay to include unique molecular identifiers (UMIs) that collapse read counts to their source mRNA counts would improve quantification of transcripts from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples. The assay (SET4) includes signatures that measure hormone receptor and PI3-kinase related transcriptional activity (SETER/PR and PI3Kges), and measures expression of selected activating point mutations and key breast cancer genes. Methods Modifications included steps to introduce eight nucleotides-long UMIs during reverse transcription (RT) in bulk solution, followed by polymerase chain reaction (PCR) of labeled cDNA in droplets, with optimization of the polymerase enzyme and reaction conditions. We used Lin’s concordance correlation coefficient (CCC) to measure concordance, including precision (Rho) and accuracy (Bias), and nonparametric tests (Wilcoxon, Levene’s) to compare the modified (NEW) SET4 assay to the original (OLD) SET4 assay and to whole transcriptome RNAseq using RNA from matched fresh frozen (FF) and FFPE samples from 12 primary breast cancers. Results The modified (NEW) SET4 assay measured single transcripts (pER/PR (p=0.002) more reproducibly in technical replicates from FFPE samples. The modified SET4 assay was more precise for measuring single transcripts (Rho 0.966 vs 0.888, pER/PR (Rho 0.985 vs 0.968) or PI3Kges (Rho 0.985 vs 0.946) in FFPE, compared to FF samples. It was also more precise than wtRNAseq of FFPE for measuring transcripts (Rho 0.986 vs 0.934, pER/PR (Rho 0.993 vs 0.915, p=0.004), but not PI3Kges (Rho 0.988 vs 0.945, p=0.051). Accuracy (Bias) was comparable between protocols. Two samples carried a PIK3CA mutation, and measurements of transcribed mutant allele fraction was similar in FF and FFPE samples and appeared more precise with the modified SET4 assay. Amplification efficiency (reads per UMI) was consistent in FF and FFPE samples, and close to the theoretically expected value, when the library size exceeded 400,000 aligned reads. Conclusions Modifications to the targeted RNAseq protocol for SET4 assay significantly increased the precision of UMI-based and reads-based measurements of individual transcripts, multi-gene signatures, and mutant transcript fraction, particularly with FFPE samples.
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- 2021
22. Biological performance and oviposition preference of tomato pinworm Tuta absoluta when offered a range of Solanaceous host plants
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Nilson Rodrigues-Silva, Marcelo Coutinho Picanço, Mayara Cristina Lopes, Lucas de Paulo Arcanjo, Tamíris Alves de Araújo, Gerson Adriano Silva, Tarcisio S. V. Galdino, Richard Ian Samuels, and Elenir Aparecida Queiroz
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Male ,0106 biological sciences ,Integrated pest management ,Oviposition ,Science ,medicine.disease_cause ,01 natural sciences ,Article ,Solanum lycopersicum ,Infestation ,Pepper ,medicine ,Animals ,Wild tomato ,Solanaceae ,Plant Diseases ,Multidisciplinary ,Invasive species ,biology ,Host (biology) ,fungi ,food and beverages ,biology.organism_classification ,Lepidoptera ,010602 entomology ,Horticulture ,Fertility ,Medicine ,Female ,Tuta absoluta ,PEST analysis ,Introduced Species ,Agroecology ,010606 plant biology & botany - Abstract
The tomato pinworm Tuta absoluta (Lepidoptera: Gelechuidae) is native to South America and has now become the main tomato pest in Europe, Africa and Asia. The wide range of host plants attacked by this pest has been reported as one of the main reasons for the success of this important insect species. However, the information currently available on the biological performance of T. absoluta on Solanaceae has been obtained from a limited number of host species. The Solanaceae family is composed of thousands of species, many of which are potential hosts for T. absoluta. Our results showed that the highest oviposition rates occurred on cultivated tomato plants, potato and wild tomato. The lowest rates occurred on “gilo”, “jurubeba”, green pepper and pepper. The highest survival rates of the immature stages occurred on potato and the lowest on pepper, green pepper and “jurubeba”. Female fertility, following infestation of the different plant species, was highest for insects that developed on tomato or potato and the lowest rates were seen on American black nightshade. The net reproductive rate and the intrinsic growth rate were highest on potato and tomato. Cluster analysis grouped tomato and potato as highly susceptible to attack, American black nightshade, juá, eggplant, gilo and wild tomato as moderately susceptible, whilst pepper, green pepper and jurubeba were categorized as resistant to T. absoluta. These results clearly demonstrate that the choice of solanaceous host plant species has a direct impact on the fitness parameters of the tomato pinworm as well as survival potential, dispersion and establishment at new sites. These results are important for the planning of integrated pest management strategies.
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- 2021
23. The Biology of Szelenyiopria talitae (Hymenoptera: Diapriidae): Larval Parasitoid of the Leaf-Cutting Ant Acromyrmex subterraneus (Hymenoptera: Formicidae)
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Veronica de Morais, Milton Erthal, Rita de Kássia Guarnier da Silva, Thais Berçot Pontes Teodoro, Richard Ian Samuels, Denise Delores Oliveira Moreira, Claudio Luiz Moreira de Souza, Carlos P. Silva, and Thalles Cardoso Mattoso
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Larva ,biology ,Host (biology) ,media_common.quotation_subject ,Zoology ,Parasitism ,General Medicine ,Hymenoptera ,biology.organism_classification ,Competition (biology) ,Diapriidae ,Parasitoid ,PEST analysis ,media_common - Abstract
The biology of a koinobiont parasitoid of leaf-cutting ant larvae, Szelenyiopria talitae (Hymenoptera: Diapriidae), was studied from naturally infested Acromyrmex subterraneus (Hymenoptera: Formicidae) nests. Nests were collected in the field from the Atlantic rainforest biome in the state of Rio de Janeiro. A total of fifty-three nests were collected from 2015 to 2018. Parasitized nests were only found during the months of September and October. Approximately 22% of the nests collected over a four-year period were found to have been parasitized by S. talitae. The mean within-nest parasitism rate was 66.3%. This diapriid displayed both solitary (14%) and gregarious parasitism (86%), with up to a maximum of 12 parasitoids developing within a single host. Gregarious parasitism with two (29%) or three (21%) S. talitae per host was most frequently observed. There was a positive correlation between the number of parasitoids per host and host size (dry weight), indicating that S. talitae females oviposited a higher number of eggs in larger hosts. There was also a negative correlation between S. talitae pharate adult size and the number of parasitoids per host, which could have been caused by sibling competition for limited host resources. The high levels of parasitism seen here had a debilitating effect on the colonies. Acromyrmex subterraneus is a serious pest in Brazil, and these studies lay the foundation for understanding the impact of S. talitae on ant populations.
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- 2021
24. Temporal controls on crown nonstructural carbohydrates in southwestern US tree species
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Drew M. P. Peltier, Michael Fell, Christopher R. Schwalm, Linnea Gear, Marcy E. Litvak, Yao Liu, Kiona Ogle, Kimberly E. Samuels-Crow, George W. Koch, Michelle Wilson, Jessica S. Guo, Larissa L. Yocom, Stacy Jefferys, William R. L. Anderegg, Phiyen Nguyen, Michael Bangs, and David Auty
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Physiology ,Carbohydrates ,Plant Science ,Pinus edulis ,Trees ,food ,Botany ,medicine ,Ecosystem ,Sugar ,reproductive and urinary physiology ,biology ,δ13C ,Moisture stress ,Seasonality ,Pinus ,biology.organism_classification ,medicine.disease ,Carbon ,food.food ,nervous system diseases ,Plant Leaves ,nervous system ,Juniperus osteosperma ,Osmoregulation ,Carbohydrate Metabolism ,biological phenomena, cell phenomena, and immunity - Abstract
In trees, large uncertainties remain in how nonstructural carbohydrates (NSCs) respond to variation in water availability in natural, intact ecosystems. Variation in NSC pools reflects temporal fluctuations in supply and demand, as well as physiological coordination across tree organs in ways that differ across species and NSC fractions (e.g., soluble sugars vs starch). Using landscape-scale crown (leaves and twigs) NSC concentration measurements in three foundation tree species (Populus tremuloides, Pinus edulis, Juniperus osteosperma), we evaluated in situ, seasonal variation in NSC responses to moisture stress on three timescales: short-term (via predawn water potential), seasonal (via leaf δ13C) and annual (via current year’s ring width index). Crown NSC responses to moisture stress appeared to depend on hydraulic strategy, where J. osteosperma appears to regulate osmotic potentials (via higher sugar concentrations), P. edulis NSC responses suggest respiratory depletion and P. tremuloides responses were consistent with direct sink limitations. We also show that overly simplistic models can mask seasonal and tissue variation in NSC responses, as well as strong interactions among moisture stress at different timescales. In general, our results suggest large seasonal variation in crown NSC concentrations reflecting the multiple cofunctions of NSCs in plant tissues, including storage, growth and osmotic regulation of hydraulically vulnerable leaves. We emphasize that crown NSC pool size cannot be viewed as a simple physiological metric of stress; in situ NSC dynamics are complex, varying temporally, across species, among NSC fractions and among tissue types.
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- 2020
25. Pepsin in gastroesophageal and extraesophageal reflux: molecular pathophysiology and diagnostic utility
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Tina L. Samuels and Nikki Johnston
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biology ,business.industry ,Bioinformatics ,Pathogenicity ,Extraesophageal reflux ,Pathophysiology ,03 medical and health sciences ,Biomarker ,fluids and secretions ,0302 clinical medicine ,Otorhinolaryngology ,Pepsin ,030220 oncology & carcinogenesis ,Ph testing ,biology.protein ,Non acid reflux ,Medicine ,Surgery ,Sample collection ,030223 otorhinolaryngology ,business - Abstract
Purpose of review Gastroesophageal and extraesophageal reflux are prevalent and costly diseases. Recognition of the pathogenicity of nonacid reflux has stimulated interest in alternatives to acid-targeting diagnostics and therapeutics. Pepsin is the most deleterious enzyme in refluxate, eliciting inflammatory and carcinogenic effects irrespective of acid. Its presence in all refluxate and detection in saliva have situated pepsin as the most widely researched biomarker for reflux today. This review summarizes emerging findings regarding pepsin-mediated damage during reflux and developments in pepsin-targeting diagnostics. Recent findings New evidence supports a role for pepsin in epithelial--mesenchymal transition, an important process in carcinogenesis and fibrosis. The first global transcriptomic analysis of pepsin-exposed laryngeal cells was described, yielding evidence of a putative airway pepsin receptor. Evaluation of pepsin diagnostics highlighted the need for rigorous validation in which pepsin concentrations are corroborated by a secondary quantitative assay, and reflux is confirmed or excluded by multichannel intraluminal impedance pH testing. Standards for sample collection and storage, and normative and pathological values are lacking. Summary Progress continues to be made in our understanding of pepsin-mediated damage with implications for novel therapeutic strategies. Salivary pepsin diagnostics continue to garner interest; however, further work appears necessary to improve their accuracy and reproducibility.
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- 2020
26. Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis
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Michelle E. Roh, Billy Ngasala, Alassane Dicko, Alfred B. Tiono, Dominic Mosha, Patrick Sawa, Ingrid Chen, Aaron M. Samuels, Richard Mwaiswelo, Andreas Mårtensson, Amanda Maestre, Elaine Craig, Teun Bousema, Menno R. Smit, Joseph Okebe, Umberto D'Alessandro, Philippe J Guerin, Badria B. El-Sayed, Roly Gosling, Will Stone, Chris Drakeley, Anders Björkman, Karen I. Barnes, Georgina S Humphreys, Salah-Eldin G El-zaki, Joelle Brown, Alice C Eziefula, Maria I Arroyo-Arroyo, Jaishree Raman, Titus K. Kwambai, Kasia Stepniewska, Ric N. Price, Guido J. H. Bastiaens, Simon Kariuki, Bronner P. Gonçalves, Pediatrics, General Paediatrics, and APH - Global Health
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0301 basic medicine ,Primaquine ,Combination therapy ,Plasmodium falciparum ,030231 tropical medicine ,Pharmacology ,Persistence (computer science) ,Antimalarials ,qv_258 ,gametocytemia ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,0302 clinical medicine ,Gametocytaemia ,single low-dose primaquine ,qv_256 ,medicine ,Gametocyte ,Animals ,Humans ,Immunology and Allergy ,Malaria, Falciparum ,Artemisinin ,Single low dose primaquine ,biology ,business.industry ,Artemether, Lumefantrine Drug Combination ,Public Health, Global Health, Social Medicine and Epidemiology ,Odds ratio ,biology.organism_classification ,Artemisinins ,wc_750 ,Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,030104 developmental biology ,Infectious Diseases ,Carriage ,qx_135 ,Artemether ,business ,medicine.drug - Abstract
Background Since the World Health Organization recommended single low-dose (0.25 mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant Plasmodium falciparum, several single-site studies have been conducted to assess efficacy. Methods An individual patient meta-analysis to assess gametocytocidal and transmission-blocking efficacy of PQ in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (1) gametocyte carriage in the first 2 weeks post treatment; and (2) the probability of infecting at least 1 mosquito or of a mosquito becoming infected. Results In 2574 participants from 14 studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytemia on day 0 (odds ratio [OR], 0.22; 95% confidence interval [CI], .17–.28 and OR, 0.12; 95% CI, .08–.16, respectively). Rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (P = .010 for day 7). Addition of 0.25 mg/kg PQ was associated with near complete prevention of transmission to mosquitoes. Conclusions Transmission blocking is achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.
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- 2020
27. Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya
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Ya Ping Shi, Winnie Chebore, Simon Kariuki, Venkatachalam Udhayakumar, Benard Guyah, Kelsey Anne Rondini, Samaly S. Svigel, Sheila Sergent, Kephas Otieno, Aaron M. Samuels, Eric S. Halsey, Nelli Westercamp, and Zhiyong Zhou
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lcsh:Arctic medicine. Tropical medicine ,Combination therapy ,lcsh:RC955-962 ,030231 tropical medicine ,Genes, Protozoan ,Plasmodium falciparum ,Drug Resistance ,Protozoan Proteins ,Drug resistance ,Biology ,Pfk13 ,Parasitemia ,law.invention ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Antimalarials ,0302 clinical medicine ,Pfpm2 ,law ,parasitic diseases ,medicine ,Prevalence ,Anti-malarial drug resistance ,Humans ,lcsh:RC109-216 ,030212 general & internal medicine ,Copy-number variation ,Artemisinin ,Malaria, Falciparum ,Polymerase chain reaction ,Pfmdr1 ,Pfcrt ,Research ,Infant ,biology.organism_classification ,Virology ,Kenya ,Multiple drug resistance ,Infectious Diseases ,Parasitology ,Child, Preschool ,Biomarkers ,medicine.drug - Abstract
BackgroundAnti-malarial drug resistance remains a major threat to global malaria control efforts. In Africa,Plasmodium falciparumremains susceptible to artemisinin-based combination therapy (ACT), but the emergence of resistant parasites in multiple countries in Southeast Asia and concerns over emergence and/or spread of resistant parasites in Africa warrants continuous monitoring. The World Health Organization recommends that surveillance for molecular markers of resistance be included within therapeutic efficacy studies (TES). The current study assessed molecular markers associated with resistance to Artemether−lumefantrine (AL) and Dihydroartemisinin−piperaquine (DP) from samples collected from children aged 6–59 months enrolled in a TES conducted in Siaya County, western Kenya from 2016 to 2017.MethodsThree hundred and twenty-three samples collected pre-treatment (day-0) and 110 samples collected at the day of recurrent parasitaemia (up to day 42) were tested for the presence of drug resistance markers in thePfk13propeller domain, and thePfmdr1andPfcrtgenes by Sanger sequencing. Additionally, thePfpm2gene copy number was assessed by real-time polymerase chain reaction.ResultsNo mutations previously associated with artemisinin resistance were detected in thePfk13propeller region. However, other non-synonymous mutations in thePfk13propeller region were detected. The most common mutation found on day-0 and at day of recurrence in thePfmdr1multidrug resistance marker was at codon 184F. Very few mutations were found in thePfcrtmarker (Pfpm2gene copy number had a single gene copy. None of the associations between observed mutations and treatment outcomes were statistically significant.ConclusionThe results indicate absence ofPfk13mutations associated with parasite resistance to artemisinin in this area and a very high proportion of wild-type parasites forPfcrt. Although the frequency ofPfmdr1184Fmutations was high in these samples, the association with treatment failure did not reach statistical significance. As the spread of artemisinin-resistant parasites remains a possibility, continued monitoring for molecular markers of ACT resistance is needed to complement clinical data to inform treatment policy in Kenya and other malaria-endemic regions.
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- 2020
28. A new species of Ceratogaulus from Nebraska and the evolution of nasal horns in Mylagaulidae (Mammalia, Rodentia, Aplodontioidea)
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Jonathan J. M. Calede and Joshua X. Samuels
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0106 biological sciences ,010506 paleontology ,biology ,Paleontology ,social sciences ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,humanities ,Mylagaulus ,Mylagaulidae ,Extant taxon ,Evolutionary biology ,Feature (computer vision) ,Allometry ,0105 earth and related environmental sciences - Abstract
Members of the Mylagaulidae have been known for over a century to bear nasal horns; the only rodents, extinct or extant, ever to have done so. This striking feature is known from five of the over 3...
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- 2020
29. Endophytic colonization of tomato plants by the entomopathogenic fungus Beauveria bassiana for controlling the South American tomato pinworm, Tuta absoluta
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Gerson Adriano Silva, Ana Carolina Loreti Silva, Aline Teixeira Carolino, Pedro Henrique Nogueira Abib, and Richard Ian Samuels
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0106 biological sciences ,0301 basic medicine ,Cultural Studies ,Agriculture (General) ,Biological pest control ,Beauveria bassiana ,Pest ,Bassiana ,01 natural sciences ,Endophyte ,Conidium ,S1-972 ,03 medical and health sciences ,Crop damage ,Fungus ,biology ,Inoculation ,Pathogen ,fungi ,Religious studies ,food and beverages ,biology.organism_classification ,010602 entomology ,Horticulture ,030104 developmental biology ,Biological control ,Entomopathogenic fungus ,Tuta absoluta ,Insect - Abstract
Background The deployment of entomopathogenic fungi (EPF) for the control of crop pests is an important alternative to synthetic pesticides. Despite recent advances in EPF formulations and application techniques, their efficacy is still limited by abiotic and biotic factors. Entomopathogenic fungi naturally colonize plant tissues or they can be artificially inoculated, protecting the plants from insect attack. Beauveria bassiana is the most widely used fungal biological control agent and has potential as an endophyte to protect a range of crops. Although B. bassiana is known to be pathogenic to the South American tomato pinworm, Tuta absoluta (Meyrick), this fungus could be more efficient when deployed as an endophyte to protect tomato plants from attack. Methods Three B. bassiana isolates were screened for virulence against T. absoluta larvae by application of conidia to leaf surfaces. Following confirmation of virulence, tomato plants were then exposed to conidial suspensions using a forced uptake technique. Only one isolate, LPP139, colonized the leaves. Seedlings were then inoculated with LPP139 and the presence of the fungus in different plant tissues was monitored over 30 days. Possible effects of B. bassiana endophytic colonization on plant development were also evaluated. Following confirmation of endophytic colonization of leaf tissues, T. absoluta 2nd or 3rd instar larvae were offered leaves and survival was monitored over a 7-day period. Results All three B. bassiana isolates were virulent to T. absoluta, with approximately 90% mortality over 10 days when conidia had been applied to leaf surfaces. Various plant inoculation techniques were tested but only seedling inoculation was successful. LPP139 successfully colonized all of the plant tissues. High percentages of colonization were observed in roots, stems and leaves up to 30 days after inoculation, with no negative effects on plant growth. When T. absoluta larvae were exposed to B. bassiana colonized leaves, survival was reduced to zero over a 7-day period. Conclusions The endophytic colonization of tomato plants with EPF is a promising method of controlling the South American tomato pinworm. The fungus was detectable for up to 30 days, longer than has been previously observed for tomato plants. Seedling inoculation could be a viable commercial option for marketing pre-colonized tomato plants.
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- 2020
30. Feasibility of direct venous inoculation of the radiation-attenuated Plasmodium falciparum whole sporozoite vaccine in children and infants in Siaya, western Kenya
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Julie Gutman, Peter F. Billingsley, E.M. Nyang'au, B. K. L. Sim, Y. Abebe, Elizabeth L Nzuu, Y.R. Cherop, Simon Kariuki, Robert A. Seder, Thomas L. Richie, A.D. Odila, Aaron M. Samuels, Eric R. James, Martina Oneko, Tony Sang, Laura C. Steinhardt, Wathsala Wijayalath, Ryan E. Wiegand, Stephen L. Hoffman, Dorcas Akach, and Mary J. Hamel
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Pediatrics ,medicine.medical_specialty ,Adolescent ,Plasmodium falciparum ,030231 tropical medicine ,Vaccines, Attenuated ,Article ,03 medical and health sciences ,0302 clinical medicine ,Malaria Vaccines ,medicine ,Animals ,Humans ,030212 general & internal medicine ,Malaria, Falciparum ,Child ,Vein ,General Veterinary ,General Immunology and Microbiology ,biology ,Malaria vaccine ,business.industry ,Vaccination ,Public Health, Environmental and Occupational Health ,Infant ,Vaccine efficacy ,medicine.disease ,biology.organism_classification ,Kenya ,PfSPZ vaccine ,Infectious Diseases ,medicine.anatomical_structure ,Tolerability ,Sporozoites ,Child, Preschool ,Feasibility Studies ,Molecular Medicine ,business ,Malaria - Abstract
PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, is administered by direct venous inoculation (DVI) for maximal efficacy against malaria. A critical issue for advancing vaccines that are administered intravenously is the ability to efficiently administer them across multiple age groups. As part of a pediatric safety, immunogenicity, and efficacy trial in western Kenya, we evaluated the feasibility and tolerability of DVI, including ease of venous access, injection time, and crying during the procedure across age groups. Part 1 was an age de-escalation, dose escalation trial in children aged 13 months-5 years and infants aged 5-12 months; part 2 was a vaccine efficacy trial including only infants, using the most skilled injectors from part 1. Injectors could use a vein viewer, if needed. A total of 1222 injections (target 0.5 mL) were initiated by DVI in 511 participants (36 were 5-9-year-olds, 65 were 13-59-month-olds, and 410 infants). The complete volume was injected in 1185/1222 (97.0%) vaccinations, 1083/1185 (91.4%) achieved with the first DVI. 474/511 (92.8%) participants received only complete injections, 27/511 (5.3%) received at least one partial injection (
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- 2020
31. Screening of Fungi Isolated from the Brazilian Restinga for Insecticidal Activity
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Vicente Mussi-Dias, Richard Ian Samuels, Maria das Graças Machado Freire, Aline Teixeira Carolino, Adão Valmir Dos Santos, and Denise Dolores Oliveira Moreira
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Traditional medicine ,fungi ,Geography, Planning and Development ,Biological pest control ,Biodiversity ,food and beverages ,Development ,Biology - Abstract
Research on microorganisms for the control of pests and pathogens is increasing. Such organisms display antagonistic effects on pests and pathogens, at the same time, they do not interfere with the sustainable development processes and are environmentally safe for human populations. Thus, bioprospection of fungi from restinga ecosystems is of interest as a novel source of microorganism and a yet unexplored source of chemical structures. This study selected endophytic fungi and fungi from the restinga soil samples to investigate their biological activity against insects. Fifty-three fungal isolates were used in screening bioassays against Atta sexdens rubropilosa leaf-cutting ant workers via direct contact of the insects with sporulating fungi cultures. This assay indicated that Trichoderma caused the highest mortality. Extracts from Trichoderma were then assessed for biological activity via ingestion, contact or exposure to fungal volatiles. Results showed that one Trichoderma sp. isolate (TR1) caused 50% mortality in 2, 1.5 and 4 days when ingested, sprayed onto the ants or by exposing ants to volatiles, respectively. Although this fungus is not known to be entomopathogenic, it could have potential use as an additional tool for pest control as it produces metabolites with antagonistic effects.
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- 2020
32. Establishment of an in vitro RNA polymerase transcription system: a new tool to study transcriptional activation in Borrelia burgdorferi
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Travis J. Bourret, Laura S. Hall, Anthony A. Armstrong, William K. Boyle, Frank C. Gherardini, Daniel P. Dulebohn, and D. Scott Samuels
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0301 basic medicine ,Transcriptional Activation ,030106 microbiology ,lcsh:Medicine ,Sigma Factor ,Biology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Bacterial Proteins ,Transcription (biology) ,Sigma factor ,RNA polymerase ,Gene expression ,Enzyme Stability ,Transcriptional regulation ,Bacterial transcription ,Borrelia burgdorferi ,Promoter Regions, Genetic ,lcsh:Science ,RNA polymerase II holoenzyme ,Enzyme Assays ,Multidisciplinary ,lcsh:R ,Promoter ,DNA-Directed RNA Polymerases ,Gene Expression Regulation, Bacterial ,Hydrogen-Ion Concentration ,biology.organism_classification ,bacterial infections and mycoses ,Cell biology ,030104 developmental biology ,chemistry ,lcsh:Q ,Holoenzymes - Abstract
The Lyme disease spirochete Borrelia burgdorferi exhibits dramatic changes in gene expression as it transits between its tick vector and vertebrate host. A major hurdle to understanding the mechanisms underlying gene regulation in B. burgdorferi has been the lack of a functional assay to test how gene regulatory proteins and sigma factors interact with RNA polymerase to direct transcription. To gain mechanistic insight into transcriptional control in B. burgdorferi, and address sigma factor function and specificity, we developed an in vitro transcription assay using the B. burgdorferi RNA polymerase holoenzyme. We established reaction conditions for maximal RNA polymerase activity by optimizing pH, temperature, and the requirement for divalent metals. Using this assay system, we analyzed the promoter specificity of the housekeeping sigma factor RpoD to promoters encoding previously identified RpoD consensus sequences in B. burgdorferi. Collectively, this study established an in vitro transcription assay that revealed RpoD-dependent promoter selectivity by RNA polymerase and the requirement of specific metal cofactors for maximal RNA polymerase activity. The establishment of this functional assay will facilitate molecular and biochemical studies on how gene regulatory proteins and sigma factors exert control of gene expression in B. burgdorferi required for the completion of its enzootic cycle.
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- 2020
33. Actin is associated with tissue injury in trauma patients and produces a hypercoagulable profile in vitro
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Mitchell J. Cohen, Jason M. Samuels, Kirk C. Hansen, Ernest E. Moore, Grant W. Hennig, Julia R. Coleman, Nicholas D Grubinger, and Kalev Freeman
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Adult ,Male ,Proteomics ,medicine.medical_specialty ,Plasmin ,medicine.medical_treatment ,macromolecular substances ,In Vitro Techniques ,Critical Care and Intensive Care Medicine ,Fibrinogen ,Tissue plasminogen activator ,Mass Spectrometry ,Article ,Fibrin ,03 medical and health sciences ,Injury Severity Score ,0302 clinical medicine ,Trauma Centers ,Internal medicine ,Myosin ,Fibrinolysis ,medicine ,Humans ,Cytoskeleton ,Gelsolin ,Microscopy, Confocal ,biology ,business.industry ,030208 emergency & critical care medicine ,Actins ,Thrombelastography ,Endocrinology ,biology.protein ,Wounds and Injuries ,Female ,Surgery ,business ,Chromatography, Liquid ,medicine.drug - Abstract
BACKGROUND: While tissue injury provokes fibrinolysis shutdown in trauma, the mechanism remains elusive. Cellular death causes release of structural proteins, including actin and myosin, which may interact with clot formation and structure. We hypothesized that tissue injury is associated with high circulating actin and that actin produces a hypercoagulable profile with decreased fibrinolysis in vitro. METHODS: Blood was collected from trauma activation patients at a single Level I trauma center for thrombelastography and proteomics. Proteomic analyses were performed through targeted liquid chromatography coupled with mass spectrometry using isotope-labeled standards for quantification of actin and its endogenous inhibitor gelsolin. Based on the results, we added physiologic concentrations of cytoskeletal G-actin to whole blood from healthy volunteers and analyzed changes in thrombelastography, as well as to plasma and examined clot architecture using confocal microscopy of fluorescently labeled fibrinogen. RESULTS: Overall, 108 trauma patients were included: majority (71%) men, median age of 32.7 years, 66% blunt mechanism, median New Injury Severity Score (NISS) of 41. Compared with patients without severe tissue injury (NISS < 15, n = 10), patients with severe tissue injury (NISS > 15, n = 98) had higher levels of circulating actin (0.0428 vs. 0.0301, p = 0.02). Further, there was a trend toward lower gelsolin levels in patients with fibrinolysis shutdown (0.1844 vs. 0.2052, p = 0.17) and tissue plasminogen activator resistance (0.1676 vs. 0.2188, p = 0.06).Ten healthy volunteers were included in the in vitro experiments (50% male; median age, 31.3 years). Actin significantly increased angle (40.0° to 52.9°, p = 0.002) and decreased fibrinolysis (percent clot lysis 30 minutes after reaching maximum amplitude, 4.0% to 1.6%; p = 0.002), provoking fibrinolytic shutdown in three patients. The addition of actin to control plasma decreased fiber resolvability of fibrin clots, monitored by microscopy, and decreased plasmin-mediated fibrinolysis. CONCLUSION: Actin increases clot propagation and provokes fibrinolysis shutdown in vitro, through a mechanism of plasmin inhibition. High circulating levels of actin are present in trauma patients with severe tissue injury, suggesting actin contributes to fibrinolysis shutdown in the setting of tissue injury.
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- 2020
34. H+/K+ATPase Expression in the Larynx of Laryngopharyngeal Reflux and Laryngeal Cancer Patients
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Ke Yan, Joel H. Blumin, Kenneth W. Altman, Tina L. Samuels, Talia S. Frolkis, Nikki Johnston, Clive Wells, Michele A. Battle, Jonathan M. Bock, and Caroline A. McCormick
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0301 basic medicine ,Larynx ,ATPase ,Cell ,H(+)-K(+)-Exchanging ATPase ,03 medical and health sciences ,Laryngopharyngeal reflux ,0302 clinical medicine ,Gene expression ,Laryngopharyngeal Reflux ,Tumor Cells, Cultured ,medicine ,Humans ,Laryngeal Neoplasms ,Cells, Cultured ,biology ,business.industry ,Cancer ,medicine.disease ,Proton pump ,Hypopharynx ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Tumor necrosis factor alpha ,business - Abstract
OBJECTIVES The gastric H+/K+ ATPase proton pump has previously been shown to be expressed in the human larynx, however its contribution to laryngopharyngeal reflux (LPR) signs, symptoms and associated diseases such as laryngeal cancer is unknown. Proton pump expression in the larynx of patients with LPR and laryngeal cancer was investigated herein. A human hypopharyngeal cell line expressing the proton pump was generated to investigate its effects. STUDY DESIGN In-vitro translational. METHODS Laryngeal biopsies were obtained from three LPR and eight LSCC patients. ATP4A, ATP4B and HRPT1 were assayed via qPCR. Human hypopharyngeal FaDu cell lines stably expressing proton pump were created using lentiviral transduction and examined via transmission electron microscopy and qPCR for genes associated with inflammation or laryngeal cancer. RESULTS Expression of ATP4A and ATP4B was detected in 3/3 LPR, 4/8 LSCC-tumor and 3/8 LSCC-adjacent specimens. Expression of ATP4A and ATP4B in FaDu elicited mitochondrial damage and expression of IL1B, PTGS2, and TNFA (P
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- 2020
35. RNA Sequencing Reveals Cancer‐Associated Changes in Laryngeal Cells Exposed to Non‐Acid Pepsin
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Atefeh Zeighami, Joel H. Blumin, Michael T. Zimmermann, Nikki Johnston, Tina L. Samuels, Jessica E. Southwood, Wendy Demos, and Jonathan M. Bock
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Inflammation ,medicine.disease_cause ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Pepsin ,medicine ,Humans ,030223 otorhinolaryngology ,Laryngeal Neoplasms ,Cells, Cultured ,biology ,Sequence Analysis, RNA ,business.industry ,Cancer ,RNA ,Epithelial Cells ,medicine.disease ,LRP1 ,Pepsin A ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Adenocarcinoma ,Larynx ,medicine.symptom ,Carcinogenesis ,business - Abstract
OBJECTIVE Laryngopharyngeal reflux (LPR) is a common affliction that contributes to laryngeal inflammation, symptoms that impact quality of life, and life-threatening illnesses such as cancer. Effective treatment strategies for LPR are lacking. Pepsin is a proinflammatory and carcinogenic element of refluxate. Investigation of molecular pathways involved in pepsin-mediated damage may lead to identification of novel biomarkers and therapeutic targets for LPR. In this study, RNA sequencing was used to examine changes in human laryngeal epithelial cells following brief pepsin insult. Cells were immortalized to generate a model to aid future study of laryngeal injury and therapeutics. STUDY DESIGN In vitro translational. METHODS Laryngeal epithelial cells were cultured from a patient without signs or symptoms of LPR or laryngeal cancer. Cells were treated with 0.1 mg/ml pepsin for 1 hour or normal growth media (control) prior to RNA sequencing. Cells were immortalized via HPV E6/7 and characterized by microscopy, immunohistochemistry, G-banding, and soft agar assay. RESULTS Three hundred ninety-seven genes exhibited differences in expression with pepsin treatment (P
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- 2020
36. Rare earth elements induce cytoskeleton-dependent and PI4P-associated rearrangement of SYT1/SYT5 endoplasmic reticulum–plasma membrane contact site complexes in Arabidopsis
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Erica Corsi, Miguel A. Botella, EunKyoung Lee, Elizabeth Samuels, Abel Rosado, Jessica Pérez-Sancho, Francisco Benitez-Fuente, Alberto P. Macho, Aristéa Alves Azevedo, Brenda Vila Nova Santana, Jiří Friml, and Steffen Vanneste
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0106 biological sciences ,0301 basic medicine ,Calmodulin ,Physiology ,media_common.quotation_subject ,Arabidopsis ,rare earth elements ,Gadolinium ,Plant Science ,Endoplasmic Reticulum ,01 natural sciences ,synaptotagmins ,Synaptotagmins ,03 medical and health sciences ,Lanthanum ,Internalization ,Cytoskeleton ,media_common ,calcium ,plasma membrane (PM) ,Cortical endoplasmic reticulum ,biology ,AcademicSubjects/SCI01210 ,Arabidopsis Proteins ,Chemistry ,Endoplasmic reticulum ,Cell Membrane ,cytoskeleton ,PI4P ,Cell Biology ,phosphoinositides ,Research Papers ,Membrane contact site ,endoplasmic reticulum (ER) ,stress adaptation ,Cytosol ,030104 developmental biology ,ER–PM membrane contact sites ,Synaptotagmin I ,Biophysics ,biology.protein ,SYT1/SYT5 ,010606 plant biology & botany - Abstract
Rare earth elements induce ER membrane remodeling and increase ER–PM connectivity in a process that involves phosphoinositide-associated reorganization of synaptotagmin-tethering complexes., In plant cells, environmental stressors promote changes in connectivity between the cortical endoplasmic reticulum (ER) and the plasma membrane (PM). Although this process is tightly regulated in space and time, the molecular signals and structural components mediating these changes in interorganelle communication are only starting to be characterized. In this report, we confirm the presence of a putative tethering complex containing the synaptotagmins 1 and 5 (SYT1 and SYT5) and the Ca2+- and lipid-binding protein 1 (CLB1/SYT7). This complex is enriched at ER–PM contact sites (EPCSs), has slow responses to changes in extracellular Ca2+, and displays severe cytoskeleton-dependent rearrangements in response to the trivalent lanthanum (La3+) and gadolinium (Gd3+) rare earth elements (REEs). Although REEs are generally used as non-selective cation channel blockers at the PM, here we show that the slow internalization of REEs into the cytosol underlies the activation of the Ca2+/calmodulin intracellular signaling, the accumulation of phosphatidylinositol-4-phosphate (PI4P) at the PM, and the cytoskeleton-dependent rearrangement of the SYT1/SYT5 EPCS complexes. We propose that the observed EPCS rearrangements act as a slow adaptive response to sustained stress conditions, and that this process involves the accumulation of stress-specific phosphoinositide species at the PM.
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- 2020
37. Casamino acids slow motility and stimulate surface growth in an extreme oligotroph
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Toby Samuels, Charles S. Cockell, and David Pybus
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Autotrophic Processes ,Geologic Sediments ,0303 health sciences ,biology ,030306 microbiology ,Chemistry ,Microorganism ,nutritional and metabolic diseases ,Motility ,biology.organism_classification ,Agricultural and Biological Sciences (miscellaneous) ,Microbiology ,Comamonadaceae ,03 medical and health sciences ,Variovorax paradoxus ,Colonization ,Amino Acids ,Adaptation ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology - Abstract
Environmental cues that regulate motility are poorly understood, but specific carbon and nitrogen sources, such as casamino acids (CAA), are known to stimulate motility in model organisms. However, natural environments are commonly more nutrient-limited than laboratory growth media, and the effect of energy-rich CAA on the motility of oligotrophic microorganisms is unknown. In this study, an extreme oligocarbotroph, Variovorax paradoxus YC1, was isolated from weathered shale rock within a disused mine level in North Yorkshire, UK. The addition of 0.1% CAA to minimal media significantly reduced the motility of YC1 after 72 h and inhibited swimming motility resulting in enhanced surface growth. We propose this response to CAA is a physiological adaptation to oligotrophy, facilitating the colonization of nutrient-rich environments.
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- 2019
38. Interleukin 1 receptor antagonist (IL1RN) gene variants predict radiographic severity of knee osteoarthritis and risk of incident disease
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Svetlana Krasnokutsky, Michael Doherty, Mukundan Attur, Steven B. Abramson, Marc C. Hochberg, Jose U. Scher, Anthony G. Wilson, Joanne M. Jordan, Hua Zhou, Jenny T. Bencardino, Virginia B. Kraus, Michelle S. Yau, Braxton D. Mitchell, and Johathan Samuels
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0301 basic medicine ,rheumatoid arthritis ,Male ,medicine.medical_specialty ,Knee Joint ,Immunology ,Single-nucleotide polymorphism ,Osteoarthritis ,Gastroenterology ,Polymorphism, Single Nucleotide ,Risk Assessment ,Severity of Illness Index ,General Biochemistry, Genetics and Molecular Biology ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Risk Factors ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,genetics ,Interleukin 6 ,Aged ,030203 arthritis & rheumatology ,biology ,business.industry ,Haplotype ,Middle Aged ,Osteoarthritis, Knee ,medicine.disease ,Radiography ,Interleukin 1 Receptor Antagonist Protein ,030104 developmental biology ,Interleukin 1 receptor antagonist ,interleukins ,Haplotypes ,inflammation ,Rheumatoid arthritis ,Case-Control Studies ,Cohort ,biology.protein ,Female ,business - Abstract
ObjectiveIn these studies, we examined the association of single nucleotide polymorphisms (SNPs) of the IL1RN gene with radiographic severity of symptomatic knee osteoarthritis (SKOA) and the risk of incident OA. We also explored these genetic polymorphisms in patients with new onset rheumatoid arthritis (RA).MethodsOver 1000 subjects who met American College of Rheumatology criteria for tibiofemoral OA were selected from three independent, National Institute of Health (NIH)-funded cohorts. CTA and TTG haplotypes formed from three SNPs of the IL1RN gene (rs419598, rs315952, rs9005) were assessed for association with radiographic severity, and risk for incident radiographic OA (rOA) in a nested case–control cohort. These IL1RN haplotypes were also assessed for association with disease activity (DAS28) and plasma inflammatory markers in patients with RA.ResultsCarriage of the IL1RN TTG haplotype was associated with increased odds of more severe rOA compared with age-matched, sex-matched and body mass index-matched individuals. Examination of the osteoarthritis initiative Incidence Subcohort demonstrated that carriage of the TTG haplotype was associated with 4.1-fold (p=0.001) increased odds of incident rOA. Plasma IL-1Ra levels were lower in TTG carriers, while chondrocytes from TTG carriers exhibited decreased secretion of IL-1Ra. In patients with RA, the TTG haplotype was associated with increased DAS28, decreased plasma IL-1Ra and elevations of plasma inflammatory markers (hsCRP, interleukin 6 (IL-6)).ConclusionCarriage of the IL1RN TTG haplotype is associated with more severe rOA, increased risk for incident OA, and increased evidence of inflammation in RA. These data suggest that the IL1RN TTG risk haplotype, associated with decreased IL-1Ra plasma levels, impairs endogenous ‘anti-inflammatory’ mechanisms.
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- 2019
39. Human Direct Skin Feeding Versus Membrane Feeding to Assess the Mosquitocidal Efficacy of High-Dose Ivermectin (IVERMAL Trial)
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Titus K. Kwambai, Menno R. Smit, Penelope A. Phillips-Howard, Duolao Wang, John E. Gimnig, Feiko O. ter Kuile, Simon Kariuki, Eric Ochomo, David Waterhouse, Teun Bousema, Ghaith Aljayyoussi, Stephen A. Ward, Nabie Bayoh, Aaron M. Samuels, Meghna Desai, Bernard O. Abong'o, General Paediatrics, APH - Global Health, and Pediatric surgery
- Subjects
0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,Insecticides ,Mosquito Control ,Anopheles gambiae ,030231 tropical medicine ,malaria ,Physiology ,Placebo ,Uncomplicated malaria ,03 medical and health sciences ,Young Adult ,All institutes and research themes of the Radboud University Medical Center ,0302 clinical medicine ,Ivermectin ,parasitic diseases ,Anopheles ,medicine ,Animals ,Humans ,direct skin feeding ,Articles and Commentaries ,biology ,Antiparasitic Agents ,business.industry ,membrane feeding ,Venous blood ,Feeding Behavior ,medicine.disease ,biology.organism_classification ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,030104 developmental biology ,Infectious Diseases ,Culicidae ,Membrane feeding ,Female ,business ,Malaria ,medicine.drug - Abstract
Background Ivermectin is being considered for mass drug administration for malaria, due to its ability to kill mosquitoes feeding on recently treated individuals. In a recent trial, 3-day courses of 300 and 600 mcg/kg/day were shown to kill Anopheles mosquitoes for at least 28 days post-treatment when fed patients’ venous blood using membrane feeding assays. Direct skin feeding on humans may lead to higher mosquito mortality, as ivermectin capillary concentrations are higher. We compared mosquito mortality following direct skin and membrane feeding. Methods We conducted a mosquito feeding study, nested within a randomized, double-blind, placebo-controlled trial of 141 adults with uncomplicated malaria in Kenya, comparing 3 days of ivermectin 300 mcg/kg/day, ivermectin 600 mcg/kg/day, or placebo, all co-administered with 3 days of dihydroartemisinin-piperaquine. On post-treatment day 7, direct skin and membrane feeding assays were conducted using laboratory-reared Anopheles gambiae sensu stricto. Mosquito survival was assessed daily for 28 days post-feeding. Results Between July 20, 2015, and May 7, 2016, 69 of 141 patients participated in both direct skin and membrane feeding (placebo, n = 23; 300 mcg/kg/day, n = 24; 600 mcg/kg/day, n = 22). The 14-day post-feeding mortality for mosquitoes fed 7 days post-treatment on blood from pooled patients in both ivermectin arms was similar with direct skin feeding (mosquitoes observed, n = 2941) versus membrane feeding (mosquitoes observed, n = 7380): cumulative mortality (risk ratio 0.99, 95% confidence interval [CI] 0.95–1.03, P = .69) and survival time (hazard ratio 0.96, 95% CI 0.91–1.02, P = .19). Results were consistent by sex, by body mass index, and across the range of ivermectin capillary concentrations studied (0.72–73.9 ng/mL). Conclusions Direct skin feeding and membrane feeding on day 7 resulted in similar mosquitocidal effects of ivermectin across a wide range of drug concentrations, suggesting that the mosquitocidal effects seen with membrane feeding accurately reflect those of natural biting. Membrane feeding, which is more patient friendly and ethically acceptable, can likely reliably be used to assess ivermectin’s mosquitocidal efficacy. Clinical Trials Registration NCT02511353., Ivermectin is being considered for mass drug administration for malaria, due to its ability to kill mosquitoes feeding on recently-treated individuals. Membrane feeding, which is more patient friendly, likely reflects the effects of direct-skin feeding in assessing ivermectin’s mosquitocidal efficacy.
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- 2019
40. Cross-Reactive Antibodies to SARS-CoV-2 and MERS-CoV in Pre-COVID-19 Blood Samples from Sierra Leoneans
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Augustine Goba, John Demby Sandi, Luis M. Branco, Megan L. Heinrich, Sophia A. Koval, Mambu Momoh, Karissa Chao, Patricia Snarski, Duane J. Bush, Andrew R. Hoffmann, Alexandra Melton, Nell G. Bond, Antoinette R. Bell-Kareem, Irina Aimukanova, Robert J. Samuels, Matthew L. Boisen, Rodrigo Borrega, Jaikin E Harrell, Lansana Kanneh, Anatoliy P. Koval, Megan M. Rowland, Whitney N. Phinney, Zoe L. Branco, Robert F. Garry, Pardis C. Sabeti, Debra Elliott, Diana K. S. Nelson, Kristian G. Andersen, Dahlene N. Fusco, James E. Robinson, Kaylynn J. Genemaras, Lilia I. Melnik, Raju Lathigra, Jeffrey G. Shaffer, Michael Gbakie, Julie A. Rouelle, Ashley A. Smira, Allison R. Smither, John S. Schieffelin, Gilberto Sabino-Santos, Don Grant, and Arnaud Drouin
- Subjects
Male ,sub-Saharan Africa ,Cross Protection ,viruses ,COVID-19 caseloads and deaths ,Blood Donors ,severe acute respiratory syndrome coronavirus-2 ,medicine.disease_cause ,Antibodies, Viral ,Serology ,Epitopes ,Pandemic ,Medicine ,Lassa fever ,Antigens, Viral ,Coronavirus ,education.field_of_study ,biology ,Alphacoronavirus ,virus diseases ,recombinant antigens ,pre-existing immunity to coronaviruses ,enzyme-linked immunosorbent assays ,pseudovirus neutralizing antibodies ,Middle Eastern respiratory syndrome coronavirus ,QR1-502 ,Infectious Diseases ,Middle East Respiratory Syndrome Coronavirus ,Female ,Antibody ,Population ,Cross Reactions ,Microbiology ,Article ,Sierra leone ,Sierra Leone ,Betacoronavirus ,Age Distribution ,Immunity ,Virology ,Coronavirus Nucleocapsid Proteins ,Humans ,Viral Pseudotyping ,education ,business.industry ,SARS-CoV-2 ,COVID-19 ,medicine.disease ,Phosphoproteins ,Antibodies, Neutralizing ,United States ,biology.protein ,business - Abstract
Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing immunity to coronaviruses is another potential factor. Blood samples from Sierra Leonean Lassa fever and Ebola survivors and their contacts collected before the first reported COVID-19 cases were assessed using enzyme-linked immunosorbent assays for the presence of antibodies binding to proteins of coronaviruses that infect humans. Results were compared to COVID-19 subjects and healthy blood donors from the United States. Prior to the pandemic, Sierra Leoneans had more frequent exposures than Americans to coronaviruses with epitopes that cross-react with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The percentage of Sierra Leoneans with antibodies reacting to seasonal coronaviruses was also higher than for American blood donors. Serological responses to coronaviruses by Sierra Leoneans did not differ by age or sex. Approximately a quarter of Sierra Leonian pre-pandemic blood samples had neutralizing antibodies against SARS-CoV-2 pseudovirus, while about a third neutralized MERS-CoV pseudovirus. Prior exposures to coronaviruses that induce cross-protective immunity may contribute to reduced COVID-19 cases and deaths in Sierra Leone.
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- 2021
41. Impacts of travel distance and travel direction on back-to-back games in the National Basketball Association
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Doug Lawson, Célyne H. Bastien, Charles Samuels, Michael A. Grandner, and Jonathan Charest
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Travel ,Basketball ,biology ,business.industry ,Athletes ,food and beverages ,Athletic Performance ,biology.organism_classification ,Scientific Investigations ,Physical medicine and rehabilitation ,Neurology ,Medicine ,Humans ,Neurology (clinical) ,Circadian rhythm ,Seasons ,business ,Association (psychology) ,Sleep ,human activities ,health care economics and organizations ,Probability - Abstract
STUDY OBJECTIVES: Travel fatigue and circadian disruptions are known factors that can hinder performance in professional athletes. The present study focused on travel distance and direction on back-to-back games over the 2013–2020 seasons in the National Basketball Association (NBA). METHODS: The outcomes were based on winning percentage with additional covariates including the direction of travel (eastward or westward), the distance traveled (0–500 km; 501–1,000 km; 1,001–1,500 km; 1,501 km and more), team quality, and season. If a team played both games of a back-to-back sequence on the road, they were considered Away-Away; if a team played the first game of a back-to-back sequence at home they were considered Home-Away; if a team played the first game of a back-to-back sequence on the road they were considered Away-Home. RESULTS: The sequence Away-Home significantly increases the likelihood of winning compared with the Away-Away and Home-Away sequences: 54.4% (95% confidence interval [CI], 54.4%–54.5%), 39.2% (95% CI, 37.2%–41.2%), and 36.8% (95% CI, 36.7%–36.8%), respectively. When teams travel back home, every additional 500 km reduces the likelihood of winning by approximately 4% (P = .038). Finally, after withdrawing the Away-Home sequence, traveling eastward significantly increases the chance of winning (P = .024) compared with westward travel but has no significant impact on the probability of winning compared with neutral time zone travel (P = .091). CONCLUSIONS: The accumulation of travel fatigue and the chronic circadian desynchronization that occurs over the NBA season can acutely disturb sleep and recovery. It appears that tailored sleep and recovery strategies need to be dynamically developed throughout the season to overcome the different challenges of the NBA schedule. CITATION: Charest J, Samuels CH, Bastien CH, Lawson D, Grandner MA. Impacts of travel distance and travel direction on back-to-back games in the National Basketball Association. J Clin Sleep Med. 2021;17(11):2269–2274.
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- 2021
42. Metarhizium anisopliae blastospores are highly virulent to adult Aedes aegypti, an important arbovirus vector
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Adriano Rodrigues de Paula, Leila Eid Imad da Silva, Tariq M. Butt, Richard Ian Samuels, Anderson Ribeiro, Gerson Adriano Silva, and Carlos P. Silva
- Subjects
Metarhizium ,Mosquito Control ,Biological pest control ,Metarhizium anisopliae ,Virulence ,Mosquito Vectors ,Infectious and parasitic diseases ,RC109-216 ,Aedes aegypti ,Fungus ,Conidium ,Microbiology ,Conidia ,Dengue ,Aedes ,parasitic diseases ,Blastospore ,Animals ,Pest Control, Biological ,Arbovirus ,biology ,Pathogen ,Research ,fungi ,Blastospores ,Spores, Fungal ,biology.organism_classification ,Spore ,Infectious Diseases ,Larva ,Biological control ,Female ,Parasitology ,Arboviruses - Abstract
Background The use of entomopathogenic fungi (EPF) for the control of adult mosquitoes is a promising alternative to synthetic insecticides. Previous studies have only evaluated conidiospores against adult mosquitoes. However, blastospores, which are highly virulent against mosquito larvae and pupae, could also be effective against adults. Methods Metarhizium anisopliae (ESALQ 818 and LEF 2000) blastospores and conidia were first tested against adult Aedes aegypti by spraying insects with spore suspensions. Blastospores were then tested using an indirect contact bioassay, exposing mosquitoes to fungus-impregnated cloths. Virulence when using blastospores suspended in 20% sunflower oil was also investigated. Results Female mosquitoes sprayed with blastospores or conidia at a concentration of 108 propagules ml−1 were highly susceptible to both types of spores, resulting in 100% mortality within 7 days. However, significant differences in virulence of the isolates and propagules became apparent at 107 spores ml−1, with ESALQ 818 blastospores being more virulent than LEF 2000 blastospores. ESALQ 818 blastospores were highly virulent when mosquitoes were exposed to black cotton cloths impregnated with blastospores shortly after preparing the suspensions, but virulence declined rapidly 12 h post-application. The addition of vegetable oil to blastospores helped maintain virulence for up to 48 h. Conclusion The results showed that blastospores were more virulent to adult female Ae. aegypti than conidia when sprayed onto the insects or applied to black cloths. Vegetable oil helped maintain blastospore virulence. The results show that blastospores have potential for use in integrated vector management, although new formulations and drying techniques need to be investigated. Graphical abstract
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- 2021
43. Immune landscape in vulvar cancer-draining lymph nodes indicates distinct immune escape mechanisms in support of metastatic spread and growth
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Koen Van de Vijver, Anne Marijne Heeren, Sanne Samuels, Maaike C. G. Bleeker, Tanja D. de Gruijl, Jossie Rotman, Gemma G. Kenter, Guus Fons, H. J. M. A. A. Zijlmans, Ekaterina J Jordanova, Medical oncology laboratory, Obstetrics and gynaecology, Pathology, AII - Cancer immunology, CCA - Cancer biology and immunology, Amsterdam Reproduction & Development (AR&D), Neurology, and Obstetrics and Gynaecology
- Subjects
Cancer Research ,Chemokine ,Priming (immunology) ,MICROENVIRONMENT ,Plasmacytoid dendritic cell ,PHENOTYPE ,Dendritic cells ,ACTIVATION ,Medicine and Health Sciences ,Immunology and Allergy ,Cytotoxic T cell ,Neoplasm Metastasis ,INDOLEAMINE 2 ,RC254-282 ,T-lymphocytes ,Vulvar Neoplasms ,biology ,suppressor cells ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Middle Aged ,Oncology ,Tumor microenvironment ,Lymphatic Metastasis ,SURVIVAL ,VACCINATION ,Molecular Medicine ,Cytokines ,Female ,SQUAMOUS-CELL CARCINOMA ,Adult ,Immunology ,Immune system ,myeloid-derived ,tumor microenvironment ,Humans ,REGULATORY T-CELLS ,dendritic cells ,Aged ,Pharmacology ,PLASMACYTOID DENDRITIC ,3-DIOXYGENASE ,Basic Tumor Immunology ,cytokines ,PD-L1 EXPRESSION ,Myeloid-derived suppressor cells ,CELLS ,Cancer research ,biology.protein ,Myeloid-derived Suppressor Cell ,Lymph Nodes ,CD8 - Abstract
BackgroundTherapeutic immune intervention is highly dependent on the T-cell priming and boosting capacity of tumor-draining lymph nodes (TDLN). In vulvar cancer, in-depth studies on the immune status of (pre)metastatic TDLN is lacking.MethodsWe have phenotyped and enumerated various T-cell and myeloid subsets in tumor-free (LN−, n=27) and metastatic TDLN (LN+, n=11) using flow cytometry. Additionally, we studied chemokine and cytokine release profiles and assessed expression of indoleamine 2,3-dioxygenase (IDO) in relation to plasmacytoid dendritic cell (pDC) or myeloid subsets.ResultsMetastatic involvement of TDLN was accompanied by an inflamed microenvironment with immune suppressive features, marked by hampered activation of migratory DC, increased cytokine/chemokine release, and closely correlated elevations of pDC and LN-resident conventional DC (LNR-cDC) activation state and frequencies, as well as of terminal CD8+ effector-memory T-cell (TemRA) differentiation, regulatory T-cell (Treg) rates, T-cell activation, and expression of cytotoxic T-lymphocyte protein-4 (CTLA-4) and programmed cell death protein-1 (PD-1) immune checkpoints. In addition, high indoleamine 2,3-dioxygenase (IDO) expression and increased frequencies of monocytic myeloid-derived suppressor cells (mMDSC) were observed. Correlation analyses with primary and metastatic tumor burden suggested respective roles for Tregs and suppression of inducible T cell costimulator (ICOS)+ T helper cells in early metastatic niche formation and for CD14+ LNR-cDC and terminal T-cell differentiation in later stages of metastatic growth.ConclusionsMetastatic spread in vulvar TDLN is marked by an inflamed microenvironment with activated effector T cells, which are likely kept in check by an interplay of suppressive feedback mechanisms. Our data support (neoadjuvant) TDLN-targeted therapeutic interventions based on CTLA-4 and PD-1 blockade, to reinvigorate memory T cells and curb early metastatic spread and growth.
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- 2021
44. Durability of antibody responses and frequency of clinical and subclinical SARS-CoV-2 infection six months after BNT162b2 COVID-19 vaccination in healthcare workers
- Author
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Alyssa R. Lindrose, Spencer L. Sterling, Julian Davies, Monique Hollis-Perry, Mimi A Wong, Yolanda Alcorta, Simon Pollett, Allison M. W. Malloy, Wei Wang, Cara H. Olsen, Eric D Laing, Emily C Samuels, Marana A Tso, Carol D. Weiss, Russell Vassell, Timothy Burgess, Richard Wang, Kathleen F Ramsey, Christopher C. Broder, David R. Tribble, Belinda M. Jackson-Thompson, Anatalio E Reyes, Luca Illinik, Si'Ana A Coggins, Emilie Goguet, Edward Mitre, Orlando Ortega, Tonia Conner, Christopher A. Duplessis, Edward Parmelee, Santina Maiolatesi, and Gregory Wang
- Subjects
medicine.medical_specialty ,biology ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Serological evidence ,Vaccination ,Titer ,Antibody response ,Internal medicine ,biology.protein ,Medicine ,Antibody ,business ,Subclinical infection - Abstract
Antibodies against SARS-CoV-2 decay but persist six months post-vaccination, with lower levels of neutralizing titers against Delta than wild-type. Only 2 of 227 vaccinated healthcare workers experienced outpatient symptomatic breakthrough infections despite 59 of 227 exhibiting serological evidence of exposure to SARS-CoV-2 as defined by development of anti-nucleocapsid protein antibodies.
- Published
- 2021
45. Higher CSF Ferritin Heavy-Chain (Fth1) and Transferrin Predict Better Neurocognitive Performance in People with HIV
- Author
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James R. Connor, William S. Bush, Robert K. Heaton, Stephanie M. Patton, David C. Samuels, Todd Hulgan, Donald Franklin, Harpreet Kaur, Scott Letendre, Asha R. Kallianpur, and Ronald J. Ellis
- Subjects
0301 basic medicine ,Oncology ,Male ,Neurology ,AIDS Dementia Complex ,HIV Infections ,Neurodegenerative ,Neurocognitive performance ,Myelination ,0302 clinical medicine ,Cerebrospinal fluid ,Medicine ,Psychology ,Longitudinal Studies ,Prospective Studies ,Prospective cohort study ,chemistry.chemical_classification ,biology ,Transferrin ,Middle Aged ,Mental Status and Dementia Tests ,Iron metabolism ,Mental Health ,Myelin maintenance ,Female ,Cognitive Sciences ,Oxidoreductases ,Adult ,medicine.medical_specialty ,Neuroscience (miscellaneous) ,Viremia ,CSF ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Predictive Value of Tests ,Clinical Research ,Internal medicine ,Acquired Cognitive Impairment ,Humans ,Prospective study ,Neurology & Neurosurgery ,business.industry ,Neurosciences ,HIV ,medicine.disease ,Brain Disorders ,Ferritin ,030104 developmental biology ,chemistry ,Ferritins ,biology.protein ,business ,Neurocognitive ,030217 neurology & neurosurgery ,Biomarkers - Abstract
HIV-associated neurocognitive disorder (HAND) remains prevalent despite antiretroviral therapy and involves white matter damage in the brain. Although iron is essential for myelination and myelin maintenance/repair, its role in HAND is largely unexplored. We tested the hypotheses that cerebrospinal fluid (CSF) heavy-chain ferritin (Fth1) and transferrin, proteins integral to iron delivery and myelination, are associated with neurocognitive performance in people with HIV (PWH). Fth1, transferrin, and the pro-inflammatory cytokines TNF-α and IL-6 were quantified in CSF at baseline (entry) in 403 PWH from a prospective observational study who underwent serial, comprehensive neurocognitive assessments. Associations of Fth1 and transferrin with Global Deficit Score (GDS)-defined neurocognitive performance at baseline and 30-42 months of follow-up were evaluated by multivariable regression. While not associated with neurocognitive performance at baseline, higher baseline CSF Fth1 predicted significantly better neurocognitive performance over 30 months in all PWH (p < 0.05), in PWH aged < 50 at 30, 36, and 42 months (all p < 0.05), and in virally suppressed PWH at all three visit time-points (all p < 0.01). Higher CSF transferrin was associated with superior neurocognitive performance at all visits, primarily in viremic individuals (all p < 0.05). All associations persisted after adjustment for neuro-inflammation. In summary, higher CSF Fth1 is neuroprotective over prolonged follow-up in all and virally suppressed PWH, while higher CSF transferrin may be most neuroprotective during viremia. We speculate that higher CSF levels of these critical iron-delivery proteins support improved myelination and consequently, neurocognitive performance in PWH, providing a rationale for investigating their role in interventions to prevent and/or treat HAND.
- Published
- 2021
46. Single-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress response
- Author
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Rahul Maurya, Hoon Kim, Sunit Das, Amit D. Gujar, Philip C. De Witt Hamer, Elise T. Courtois, Chew Yee Ngan, Kevin J. Anderson, Floris P. Barthel, Niels Verburg, Kevin C. Johnson, Dacheng Zhao, Ketan R. Bulsara, Martine Seignon, Paul Robson, Frederick S. Varn, Eun Hee Yi, Nicholas Navin, Marcos R. Estecio, Diane Luo, Roel G.W. Verhaak, Michael Samuels, Ming Tang, Neurosurgery, Amsterdam Neuroscience - Systems & Network Neuroscience, and CCA - Cancer biology and immunology
- Subjects
Regulation of gene expression ,Mutation ,Genetic heterogeneity ,Genomics ,Biology ,medicine.disease_cause ,medicine.disease ,Transcriptome ,Glioma ,DNA methylation ,Genetics ,medicine ,Cancer research ,Epigenetics - Abstract
Glioma intratumoral heterogeneity enables adaptation to challenging microenvironments and contributes to therapeutic resistance. We integrated 914 single-cell DNA methylomes, 55,284 single-cell transcriptomes and bulk multi-omic profiles across 11 adult IDH mutant or IDH wild-type gliomas to delineate sources of intratumoral heterogeneity. We showed that local DNA methylation disorder is associated with cell–cell DNA methylation differences, is elevated in more aggressive tumors, links with transcriptional disruption and is altered during the environmental stress response. Glioma cells under in vitro hypoxic and irradiation stress increased local DNA methylation disorder and shifted cell states. We identified a positive association between genetic and epigenetic instability that was supported in bulk longitudinally collected DNA methylation data. Increased DNA methylation disorder associated with accelerated disease progression and recurrently selected DNA methylation changes were enriched for environmental stress response pathways. Our work identified an epigenetically facilitated adaptive stress response process and highlights the importance of epigenetic heterogeneity in shaping therapeutic outcomes.
- Published
- 2021
47. The multifaceted role of lemur tyrosine kinase 3 in health and disease
- Author
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Georgios Giamas, Viviana Vella, Christos Tolias, Teresa Gagliano, Mark Samuels, and Angeliki Ditsiou
- Subjects
QH301-705.5 ,Carcinogenesis ,Immunology ,Breast Neoplasms ,Disease ,Review ,Biology ,Protein Serine-Threonine Kinases ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Breast cancer ,LMTK3 ,medicine ,Humans ,cancer ,Lemur tyrosine kinase 3 ,Biology (General) ,Protein kinase A ,Review Articles ,General Neuroscience ,Cancer ,Membrane Proteins ,small molecule kinase inhibitor ,protein kinase ,medicine.disease ,Gene Expression Regulation, Neoplastic ,CNS ,Identification (biology) ,Female ,Neuroscience ,Signalling pathways ,Signal Transduction - Abstract
In the last decade, LMTK3 (lemur tyrosine kinase 3) has emerged as an important player in breast cancer, contributing to the advancement of disease and the acquisition of resistance to therapy through a strikingly complex set of mechanisms. Although the knowledge of its physiological function is largely limited to receptor trafficking in neurons, there is mounting evidence that LMTK3 promotes oncogenesis in a wide variety of cancers. Recent studies have broadened our understanding of LMTK3 and demonstrated its importance in numerous signalling pathways, culminating in the identification of a potent and selective LMTK3 inhibitor. Here, we review the roles of LMTK3 in health and disease and discuss how this research may be used to develop novel therapeutics to advance cancer treatment.
- Published
- 2021
48. The vitamin A transporter STRA6 adjusts the stoichiometry of chromophore and opsins in visual pigment synthesis and recycling
- Author
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Srinivasagan Ramkumar, Ivy S. Samuels, Nathan A. Berger, Beata Jastrzebska, Vipul M. Parmar, and Johannes von Lintig
- Subjects
Retinal degeneration ,Opsin ,genetic structures ,medicine.drug_class ,Biology ,chemistry.chemical_compound ,Mice ,Genetics ,medicine ,Animals ,Retinoid ,Vitamin A ,Molecular Biology ,Genetics (clinical) ,Retina ,Retinal pigment epithelium ,Opsins ,Rod Opsins ,Membrane Proteins ,Retinal ,General Medicine ,Chromophore ,medicine.disease ,Cone Opsins ,eye diseases ,Cell biology ,Retinol binding protein ,medicine.anatomical_structure ,chemistry ,Retinal Cone Photoreceptor Cells ,Retinaldehyde ,Original Article ,sense organs ,Retinal Pigments - Abstract
The retinal pigment epithelium of the vertebrate eyes acquires vitamin A from circulating retinol binding protein for chromophore biosynthesis. The chromophore covalently links with an opsin protein in the adjacent photoreceptors of the retina to form the bipartite visual pigment complexes. We here analyzed visual pigment biosynthesis in mice deficient for the retinol-binding protein receptor STRA6. We observed that chromophore content was decreased throughout the life cycle of these animals, indicating that lipoprotein-dependent delivery pathways for the vitamin cannot substitute for STRA6. Changes in the expression of photoreceptor marker genes, including a downregulation of the genes encoding rod and cone opsins, paralleled the decrease in ocular retinoid concentration in STRA6-deficient mice. Despite this adaptation, cone photoreceptors displayed absent or mislocalized opsins at all ages examined. Rod photoreceptors entrapped the available chromophore but exhibited significant amounts of chromophore-free opsins in the dark-adapted stage. Treatment of mice with pharmacological doses of vitamin A ameliorated the rod phenotype but did not restore visual pigment synthesis in cone photoreceptors of STRA6-deficient mice. The imbalance between chromophore and opsin concentrations of rod and cone photoreceptors was associated with an unfavorable retinal physiology, including diminished electrical responses of photoreceptors to light, and retinal degeneration during aging. Together, our study demonstrates that STRA6 is critical to adjust the stoichiometry of chromophore and opsins in rod and cone photoreceptors and to prevent pathologies associated with ocular vitamin A deprivation.
- Published
- 2021
49. Functional characterization of a cellulose synthase, CtCESA1, from the marine red alga Calliarthron tuberculosum (Corallinales)
- Author
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A. Lacey Samuels, Filip Van Petegem, Jan Xue, Jochen Zimmer, Justin F. Acheson, Pallinti Purushotham, Ciaran McFarlane, Ruoya Ho, and Patrick T. Martone
- Subjects
0106 biological sciences ,Physiology ,Mutant ,Protein domain ,Plant Science ,Red algae ,01 natural sciences ,Cell wall ,03 medical and health sciences ,Cell Wall ,Arabidopsis ,Arabidopsis thaliana ,Phylogeny ,030304 developmental biology ,0303 health sciences ,biology ,Chemistry ,fungi ,food and beverages ,biology.organism_classification ,Research Papers ,Complementation ,Biochemistry ,Glucosyltransferases ,Rhodophyta ,Secondary cell wall ,010606 plant biology & botany - Abstract
In land plants and algae, cellulose is important for strengthening cell walls and preventing breakage due to physical forces. Though our understanding of cellulose production by cellulose synthases (CESAs) has seen significant advances for several land plant and bacterial species, functional characterization of this fundamental protein is absent in red algae. Here we identify CESA gene candidates in the calcifying red alga Calliarthron tuberculosum using sequence similarity-based approaches, and elucidate their phylogenetic relationship with other CESAs from diverse taxa. One gene candidate, CtCESA1, was closely related to other putative red algal CESA genes. To test if CtCESA1 encoded a true cellulose synthase, CtCESA1 protein was expressed and purified from insect and yeast expression systems. CtCESA1 showed glucan synthase activity in glucose tracer assays. CtCESA1 activity was relatively low when compared with plant and bacterial CESA activity. In an in vitro assay, a predicted N-terminal starch-binding domain from CtCESA1 bound red algal floridean starch extracts, representing a unique domain in red algal CESAs not present in CESAs from other lineages. When the CtCESA1 gene was introduced into Arabidopsis thaliana cesa mutants, the red algal CtCESA1 partially rescued the growth defects of the primary cell wall cesa6 mutant, but not cesa3 or secondary cell wall cesa7 mutants. A fluorescently tagged CtCESA1 localized to the plasma membrane in the Arabidopsis cesa6 mutant background. This study presents functional evidence validating the sequence annotation of red algal CESAs. The relatively low activity of CtCESA1, partial complementation in Arabidopsis, and presence of unique protein domains suggest that there are probably functional differences between the algal and land plant CESAs.
- Published
- 2021
50. The first records of Sinclairella (Apatemyidae) from the Pacific Northwest, USA
- Author
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Joshua X. Samuels
- Subjects
geography ,geography.geographical_feature_category ,Apatemyidae ,biology ,Insectivore ,Woodland ,biology.organism_classification ,Archaeology ,law.invention ,law ,Genus ,Mammal ,Turtle (robot) ,Cove ,Paleogene - Abstract
Author(s): Samuels, Joshua X. | Abstract: Apatemyidae are a rare and enigmatic group of small insectivorous mammals that lived in North America and Europe in the Paleogene. The last known apatemyids in North America are two species in the genus Sinclairella, known from sites in the Great Plains and Florida. Here, I formally describe an upper second molar and lower incisor of the apatemyid, Sinclairella dakotensis, from the incredibly well-studied Turtle Cove Member of the John Day Formation in Oregon. These early Arikareean age specimens represent the first records of the family west of the Rocky Mountains. Sinclairella dakotensis filled a ‘woodpecking’ niche unlike any other mammal known from the region, and its co-occurrence with a number of forest-adapted mammal species is consistent with previous interpretations of environments at the time having been dominated by woodlands.
- Published
- 2021
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