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1. Preclinical evidence for the effective use of TL-895, a highly selective and potent second-generation BTK inhibitor, for the treatment of B-cell malignancies

Author

Samantha M. Goodstal, Jing Lin, Timothy Crandall, Lindsey Crowley, Andrew T. Bender, Albertina Pereira, Maria Soloviev, John S. Wesolowski, Riham Iadevaia, Sven-Eric Schelhorn, Edith Ross, Federica Morandi, Jianguo Ma, and Anderson Clark

Subjects
Medicine, Science
Abstract

Abstract TL-895 (formerly known as M7583) is a potent, highly selective, adenosine triphosphate (ATP)-competitive, second-generation, irreversible inhibitor of Bruton’s tyrosine kinase (BTK). We characterized its biochemical and cellular effects in in vitro and in vivo models. TL-895 was evaluated preclinically for potency against BTK using IC50 concentration–response curves; selectivity using a 270-kinase panel; BTK phosphorylation in Ramos Burkitt’s lymphoma cells by ProteinSimple Wes analysis of one study; anti-proliferative effects in primary chronic lymphocytic leukemia (CLL) blasts; cell viability effects in diffuse large B-cell lymphoma (DLBCL) and mantle-cell lymphoma (MCL) cell lines; effects on antibody-dependent cell-mediated cytotoxicity (ADCC) from Daudi cells and chromium-51 release from human tumor cell lines; and efficacy in vivo using four MCL xenograft model and 21 DLBCL patient-derived xenograft (PDX) models (subtypes: 9 ABC, 11 GCB, 1 Unclassified). TL-895 was active against recombinant BTK (average IC50 1.5 nM) and inhibited only three additional kinases with IC50 within tenfold of BTK activity. TL-895 inhibited BTK auto-phosphorylation at the Y223 phosphorylation site (IC50 1–10 nM). TL-895 inhibited the proliferation of primary CLL blasts in vitro and inhibited growth in a subset of activated DLBCL and MCL cell lines. TL-895 inhibited the ADCC mechanism of therapeutic antibodies only at supra-clinical exposure levels. TL-895 significantly inhibited tumor growth in the Mino MCL xenograft model and in 5/21 DLBCL PDX models relative to vehicle controls. These findings demonstrate the potency of TL-895 for BTK and its efficacy in models of B-cell lymphoma despite its refined selectivity.

Published
2023
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2. p70S6K/Akt dual inhibitor DIACC3010 is efficacious in preclinical models of gastric cancer alone and in combination with trastuzumab

Author

Shota Fukuoka, Yoshikatsu Koga, Mayumi Yamauchi, Shigehiro Koganemaru, Masahiro Yasunaga, Kohei Shitara, Toshihiko Doi, Takayuki Yoshino, Toshio Kuronita, Brian Elenbaas, Pamela Wahra, Hong Zhang, Lindsey Crowley, Molly H. Jenkins, Anderson Clark, and Takashi Kojima

Subjects
Medicine, Science
Abstract

Abstract The PI3K-Akt-mTOR (PAM) pathway is implicated in tumor progression in many tumor types, including metastatic gastric cancer (GC). The initial promise of PAM inhibitors has been unrealized in the clinic, presumably due, in part, to the up-regulation of Akt signaling that occurs when the pathway is inhibited. Here we present that DIACC3010 (formerly M2698), an inhibitor of two nodes in the PAM pathway, p70S6K and Akt 1/3, blocks the pathway in in vitro and in vivo preclinical models of GC while providing a mechanism that inhibits signaling from subsequent Akt up-regulation. Utilizing GC cell lines and xenograft models, we identified potential markers of DIACC3010-sensitivity in Her2-negative tumors, i.e., PIK3CA mutations, low basal pERK, and a group of differentially expressed genes (DEGs). The combination of DIACC3010 and trastuzumab was evaluated in Her2-positive cell lines and models. Potential biomarkers for the synergistic efficacy of the combination of DIACC3010 + trastuzumab also included DEGs as well as a lack of up-regulation of pERK. Of 27 GC patient-derived xenograft (PDX) models tested in BALB/c nu/nu mice, 59% were sensitive to DIACC3010 + trastuzumab. Of the 21 HER2-negative PDX models, DIACC3010 significantly inhibited the growth of 38%. Altogether, these results provide a path forward to validate the potential biomarkers of DIACC3010 sensitivity in GC and support clinical evaluation of DIACC3010 monotherapy and combination with trastuzumab in patients with HER2- negative and positive advanced GCs, respectively.

Published
2023
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4. Effects of the Brief Simha Kriya Breathing Practice for Health Care Workers During the COVID-19 Pandemic.

Author

Wagner, Richard W., Mallaiah, Smitha, Anderson, Clark R., Engle, Rosalinda, Vasu, Varsha, Bruera, Eduardo, Subramaniam, Balachundar, Cohen, Lorenzo, and Narayanan, Santhosshi

Subjects
CANCER treatment, SCALE analysis (Psychology), SELF-evaluation, MEDICAL personnel, STRESS management, T-test (Statistics), CLINICAL trials, QUESTIONNAIRES, UNCERTAINTY, DESCRIPTIVE statistics, YOGA, BREATHING exercises, MIND & body therapies, LONGITUDINAL method, SURVEYS, ANALYSIS of variance, HEALTH behavior, DATA analysis software, PSYCHOSOCIAL factors, COVID-19 pandemic, SPECIALTY hospitals, TIME
Abstract

Introduction: During the COVID-19 pandemic, health care workers (HCWs) experienced increased anxiety, depression, loneliness, and other mental health issues. HCWs need additional resources to cope with the mental health impact of their work. Yoga techniques could be helpful strategies to manage different stressors during times of uncertainty. Methods: This prospective, single-arm, trial examined the effects of a brief pranayama yoga practice on the wellbeing of HCWs during the height of COVID-19. HCWs were recruited through announcements and institutional websites at a large major cancer center in the southern United States. A short, prerecorded, 5-min breathwork video intervention called "Simha Kriya" was provided to participants, and they were encouraged to practice one to two times daily for 4 weeks. Participants completed self-report instruments at baseline and weeks 1 and 4, including: (1) Perceived Stress Scale (PSS); (2) Brief Resilient Coping Scale (BRCS); and (3) a questionnaire assessing the experience of COVID-19 among HCWs that had five subscales. HCWs also conducted a measure of breath holding time. Paired sample t-tests and mixed-effects analysis of variance models examined changes over time. Results: One hundred participants consented to the study, with 88 female, 60 white, 39 worked remotely, and 27 were clinical staff. Sixty-nine participants provided data at week 1 and 56 at week 4. Participants' adherence to the breathing exercises between weeks 1 and 4 was similar, with a mean of six times per week. At week 4, there were significant decreases in the COVID-19 Distress score (p < 0.0001) and COVID-19 Disruption (p = 0.013), yet no changes in the PSS. There were also significant increases in COVID-19 Stress Management (p = 0.0001) and BRCS scores (p = 0.012), but no changes in Perceived Benefits of COVID-19 and no changes in breath holding time. Discussion: Brief yoga-based breathing practices helped reduce pandemic-specific stress, improved resilience, and stress management skills in HCWs. Trial Registration Number: NCT04482647. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Final-Year Results from the i3 Scale-Up of Reading Recovery

Author

Society for Research on Educational Effectiveness (SREE), May, Henry, Sirinides, Philip, Gray, Abby, Davila, Heather Goldsworthy, Sam, Cecile, Blalock, Toscha, Blackman, Horatio, Anderson-Clark, Helen, and Schiera, Andrew J.

Abstract

As part of the 2010 economic stimulus, a $55 million "Investing in Innovation" (i3) grant from the US Department of Education was awarded to scale up Reading Recovery across the nation. This paper presents the final round of results from the large-scale, mixed methods randomized evaluation of the implementation and impacts of Reading Recovery under this i3 Scale-Up. Over 10,000 low performing first-grade students from more than 1,000 schools participated in this study from 2010-2015. The evaluation design for the i3 scale-up of Reading Recovery includes a rigorous experimental research design (i.e., a multi-site randomized controlled trial) that supports strong causal inferences about program impacts, coupled with mixed methods descriptions of program implementation and contextual factors. Short-term impacts on students' reading performance are estimated by comparing mid-year reading achievement of students randomly assigned to participate in reading recovery at the beginning of first grade to students randomly assigned to the control condition. The consistently large positive impacts of Reading Recovery under the i3 scale-up suggest that this relatively large investment has led to substantial improvements in the reading performance of many thousands of students across the nation. In addition, results from the mixed-methods implementation evaluation revealed numerous programmatic and contextual factors that can support or hinder implementation of Reading Recovery by individual schools and may explain variation in impacts across sites.

Published
2015

6. Evaluation of the i3 Scale-Up of Reading Recovery: Year Two Report, 2012-13. CPRE Research Reports

Author

University of Pennsylvania, Consortium for Policy Research in Education (CPRE), University of Delaware (UD), Center for Research in Education and Social Policy (CRESP), May, Henry, Goldsworthy, Heather, Armijo, Michael, Gray, Abigail, Sirinides, Philip, Blalock, Toscha J., Anderson-Clark, Helen, Schiera, Andrew J., Blackman, Horatio, Gillespie, Jessica, and Sam, Cecile

Abstract

Reading Recovery is a short-term early intervention designed to help the lowest-achieving readers in first grade reach average levels of classroom performance in literacy. Students identified to receive Reading Recovery meet individually with a specially trained Reading Recovery teacher every school day for 30-minute lessons over a period of 12 to 20 weeks. The purpose of these lessons is to support rapid acceleration of each child's literacy learning. In 2010, The Ohio State University received a Scaling Up What Works grant from the U.S. Department of Education Investing in Innovation (i3) Fund to expand the use of Reading Recovery across the country. The award was intended to fund the training of 3,675 new Reading Recovery teachers in U.S. schools, thereby expanding service to an additional 88,200 students. The Consortium for Policy Research in Education (CPRE) was contracted to conduct an independent evaluation of the i3 scale-up of Reading Recovery over the course of five years. The evaluation includes parallel rigorous experimental and quasi-experimental designs for estimating program impacts, coupled with a large-scale mixed-methods study of program implementation. This report presents the findings of the second year of the evaluation. The primary goals of this evaluation are: (1) to provide experimental evidence of the impacts of Reading Recovery on student learning under this scale-up effort; (2) to assess the success of the scale-up in meeting the i3 grant's expansion goals; and (3) to document the implementation of the scale-up and fidelity to program standards. This document is the second in a series of three reports based on the external evaluation of the Reading Recovery i3 Scale-Up. The report represents results from the impact and implementation studies conducted over the 2012-2013 school year--the third year of the scale-up effort and the second full year of the evaluation. [This document is a reissue of the December 2014 CPRE Research Report RR-79 under the same title. For the Year One Report, see ED547669.]

Published
2014

8. The Development and Implementation of a Developmentally Appropriate Curriculum that Meets the Expectations of African American Parents.

Author

Anderson-Clark, Janet

Abstract

In response to parent complaints about the curriculum at an urban child care center, a procedure was developed to provide parents and teachers with an understanding of developmentally appropriate practices for young children. A curriculum that was developmentally and culturally relevant to the children at the school was also developed. The entire population served by the center was African American, although many clients had a Caribbean or Bahamian background. The preschool department was licensed to serve 55 children. Parents had complained that the children spent too much time playing, and that academic learning was not taking place. The workshops held as part of the parent and faculty education procedure increased parents' awareness of developmentally appropriate practices and the importance of play, but this increased awareness did not change the expectations of parents regarding academic competence in preschoolers, and their academic expectations remained higher than was appropriate for preschool children. The social studies curriculum that was implemented addressed the cultural awareness of the students in a developmentally appropriate way. Parents and staff members endorsed the program's strategies. The 17 appendixes include sample surveys and discussions of developmentally appropriate behavior and practice. (Contains 16 references.) (SLD)

Published
1996

17. Accelerated transferrin degradation in HFE-deficient mice is associated with increased transferrin saturation

Author

Chaudhury, Chaity, Kim, Jonghan, Mehnaz, Samina, Wani, Manzoor A., Oberyszyn, Tatiana M., Bronson, C.L., Mohanty, Sudhasri, Hayton, William L., Robinson, John M., and Anderson, Clark L.

Subjects
Rats as laboratory animals -- Research, Rats as laboratory animals -- Physiological aspects, Transferrin -- Research, Food/cooking/nutrition
Abstract

HFE, a major histocompatibility complex class I-related protein, is implicated in the iron overload disease, hereditary hemochromatosis. Whereas patients with hereditary hemochromatosis have low serum transferrin levels, little is known about transferrin turnover in HFE deficiency states. We injected mice intravenously with radioiodinated transferrin and compared plasma transferrin decay and steady-state endogenous transferrin concentration in the plasma between HFE-deficient and wild-type C57BL/6 mouse strains. HFE-deficient mice degraded transferrin faster than normal (P < 0.001) and had lower plasma transferrin concentrations (P < 0.001). Both HFE-deficient and wild-type mice were then fed diets with 3 different iron concentrations that we designated deficient (2-5 mg/kg of iron), control (0.2 g/kg), and overload (20 g/kg) for 6 wk immediately after weaning to create a range of serum iron concentrations and resultant transferrin saturations ranging from 16 to 78%. We found an inverse correlation between transferrin saturation and transferrin half-life (P< 0.0001, r = -0.839) for both HFE-deficient and wild-type mice, which suggests that HFE does not have a direct effect on transferrin catabolism; rather, HFE may influence transferrin half-life indirectly through its effect on transferring saturation, which in turn enhances transferrin decay in HFE-deficient mice.

Published
2006

18. Albumin binding to FcRn: Distinct from the FcRn- IgG interaction

Author

Chaudhury, Chaity, Brooks, Charles L., Carter, Daniel C., Robinson, John M., and Anderson, Clark L.

Subjects
Albumin -- Chemical properties, Protein binding -- Analysis, Immunoglobulin G -- Chemical properties, Decomposition (Chemistry) -- Analysis, Biological sciences, Chemistry
Abstract

MHC-related Fc receptor for IgG (FcRn) protects albumin and IgG from degradation by binding both proteins with high affinity at low pH in the acid endosome and diverting both from a lysosomal pathway, returning them to the extracellular compartment. Results suggest that the FcRn-albumin interaction has unique features distinct from FcRn- IgG binding despite the overall similarity in the pH- dependent binding mechanism by which both ligands are protected from degradation.

Published
2006

19. Familial hypercatabolic hypoproteinemia caused by deficiency of the neonatal Fc receptor, FcRn, due to a mutant [[beta].sub.2]-microglobulin gene

Author

Wani, Manzoor A., Haynes, Lynn D., Kim, Jonghan, Bronson, C.L., Chaudhury, Chaity, Mohanty, Sudhasri, Waldmann, Thomas A., Robinson, John M., and Anderson, Clark L.

Subjects
Protein metabolism disorders -- Research, Science and technology
Abstract

Two siblings, products of a consanguineous marriage, were markedly deficient in both albumin and IgG because of rapid degradation of these proteins, suggesting a lack of the neonatal Fc receptor, FcRn. FcRn is a heterodimeric receptor composed of a nonclassical MHC class I [alpha]-chain and [[beta].sub.2]-microglobulin ([[beta].sub.2]m) that binds two ligands, IgG and albumin, and extends the catabolic half-lives of both. Eight relatives of the siblings were moderately IgG-deficient. From sera archived for 35 years, we sequenced the two siblings' genes for the heterodimeric FcRn. We found that, although the [alpha]-chain gene sequences of the siblings were normal, the [[beta].sub.2]m genes contained a single nucleotide transversion that would mutate a conserved alanine to proline at the midpoint of the signal sequence. Concentrations of soluble [[beta].sub.2]m and HLA in the siblings' sera were albumin | IgG | MHC class I | hypoalbuminemia | hypogammaglobulinemia

Published
2006

20. Albumin turnover: FcRn-mediated recycling saves as much albumin from degradation as the liver produces

Author

Kim, Jonghan, Bronson, C.L., Hayton, William L., Radmacher, Michael D., Roopenian, Derry C., Robinson, John M., and Anderson, Clark L.

Subjects
Albumin -- Chemical properties, Chemical bonds -- Research, Fc receptors -- Research, Biological sciences
Abstract

It is now understood that the nonclassical major histocompatibility complex-I molecule FcRn binds albumin and retrieves it from an intracellular degradative fate. Whether FcRn in the liver modulates albumin turnover through effects on biosynthesis and production is not known. Thus we quantified the appearance of biosynthetically labeled albumin in plasma after an intravenous bolus injection of [[sup.3]H]leucine in FcRn-deficient mice. The production rates for both albumin (FcRn substrate) and transferrin (nonsubstrate) are increased by ~20% in FcRn-deficient mice compared with normal mice, likely compensating for the lowered plasma oncotic pressure caused by hypoalbuminemia in FcRn-deficient mice. Determining the magnitude of FcRn-mediated effects on albumin turnover, we then measured the steady-state plasma concentrations of biosynthetically labeled albumin and transferrin during [[sup.3]H]leucine infusion. The concentration of albumin was ~40% lower in FcRn-deficient mice compared with normal mice. Furthermore, the ~40% lower plasma albumin concentration in FcRn-deficient mice along with the ~20% increase in albumin production indicate, by the mass-balance equation, that albumin degradation in FcRn-deficient mice is twice that of normal mice. These studies of biosynthetically labeled, and thus native, albumin support our previous finding that FcRn protects albumin from degradation. Permitting quantification of the magnitude of FcRn-mediated recycling, they further indicate that FcRn has extraordinary capacity: the amount of albumin saved from degradation by FeRn-mediated recycling is the same as that produced by the liver. production; clearance; steady-state; kinetics; Fc receptor

Published
2006

22. Network Localization of Unconscious Visual Perception in Blindsight.

Author

Kletenik, Isaiah, Ferguson, Michael A., Bateman, James R., Cohen, Alexander L., Lin, Christopher, Tetreault, Aaron, Pelak, Victoria S., Anderson, Clark Alan, Prasad, Sashank, Darby, Richard Ryan, and Fox, Michael D.

Subjects
SUBLIMINAL perception, VISUAL perception, FUNCTIONAL connectivity, VISUAL fields, BRAIN injuries
Abstract

Objective: Blindsight is a disorder where brain injury causes loss of conscious but not unconscious visual perception. Prior studies have produced conflicting results regarding the neuroanatomical pathways involved in this unconscious perception. Methods: We performed a systematic literature search to identify lesion locations causing visual field loss in patients with blindsight (n = 34) and patients without blindsight (n = 35). Resting state functional connectivity between each lesion location and all other brain voxels was computed using a large connectome database (n = 1,000). Connections significantly associated with blindsight (vs no blindsight) were identified. Results: Functional connectivity between lesion locations and the ipsilesional medial pulvinar was significantly associated with blindsight (family wise error p = 0.029). No significant connectivity differences were found to other brain regions previously implicated in blindsight. This finding was independent of methods (eg, flipping lesions to the left or right) and stimulus type (moving vs static). Interpretation: Connectivity to the ipsilesional medial pulvinar best differentiates lesion locations associated with blindsight versus those without blindsight. Our results align with recent data from animal models and provide insight into the neuroanatomical substrate of unconscious visual abilities in patients. ANN NEUROL 2022;91:217–224 [ABSTRACT FROM AUTHOR]

Published
2022
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26. Accuracy and Precision of an Optoacoustic Prototype in Determining Endotracheal Tube Position in Children.

Author

Volsko, Teresa A., Petrov, Yuriy, McNinch, Neil L., Prough, Donald S., Anderson, Clark R., and Bigham, Michael T.

Subjects
AUDIO equipment, CHEST X rays, STATISTICAL correlation, INTENSIVE care units, INTUBATION, LONGITUDINAL method, PEDIATRICS, RESEARCH evaluation, STATISTICAL sampling, STATISTICS, T-test (Statistics), TRACHEA intubation, PILOT projects, PRODUCT design, DATA analysis, RESEARCH bias, DATA analysis software, ACCURACY, DESCRIPTIVE statistics
Abstract

BACKGROUND: Confirmation of endotracheal tube (ETT) tip position and timely identification and correction of malposition is an essential component of care for endotracheally intubated and mechanically ventilated children. We evaluated the ability of a prototype optoacoustic medical device to determine ETT tip position. We hypothesized that the precision of optoacoustic assessment of ETT tip position would be comparable to chest radiography. METHODS: We recruited children aged newborn to 16 y who were admitted to the pediatric ICU requiring tracheal intubation and undergoing a chest radiograph for clinical purposes. After positioning each child on a chest radiograph plate, a sterile optical fiber, temporarily inserted through the ETT, emitted laser pulses perpendicular to the fiber and to the ETT, generating acoustic (ultrasound) waves in overlying tissue when the tip of the fiber passed beneath an acoustic sensor in the sternal notch. The distance from the ETT tip to the peak acoustic signal was used to calculate the distance from the ETT tip to the carina, which was compared with the same distance calculated by the radiologist reading the chest radiograph. Pearson's correlation coefficient, paired t tests, a Bland-Altman plot were used to compare the measures (P < .05 was considered statistically significant). RESULTS: Twenty-six subjects were enrolled: 15 (57.7%) were male, median (interquartile range) age, weight, and height were 9 months (4-24), 9.6 kg (5.7-13.0), and 75 cm (62-90), respectively. All ETTs were cuffed (internal diameter range 3.0-5.0 mm). The relationship between optoacoustic and chest radiograph measurements was strong (r = 0.91, P < .001). Bias was 0.1 cm with narrow limits of agreement between measures (0.58 cm and 0.76 cm). CONCLUSIONS: The optoacoustic prototype accurately determined ETT tip position and was comparable in precision to chest radiograph. [ABSTRACT FROM AUTHOR]

Published
2018
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27. Penetrating trauma in children on the United States-Mexico border: Hispanic ethnicity is not a risk factor.

Author

Vo, Loc-Uyen T., Anderson, Clark, Howe, Jarett K., Tyroch, Alan H., Thomas, Samantha, Vernia, Hannah, and Fitzgerald, Tamara N.

Subjects
*CHILDREN'S injuries, *ETHNIC identity of Hispanic Americans, *PENETRATING wounds, *SOCIAL status, *RACE discrimination
Abstract

Introduction: The United States-Mexico border is perceived as dangerous by the media and current political leaders. Hispanic ethnicity, low socioeconomic status, male gender and adolescent age have previously been identified as risk factors for penetrating trauma (PT).Methods: A retrospective review of PT was performed in a border region. Children 0-17 years old, admitted to the region's only level I trauma center between 2001 and 2016 were included. Standardized morbidity ratio was used to compare observed to expected morbidity.Results: There were 417 PT admissions. 197 (47%) were non-accidental, 34 (8%) suicide attempts and 186 (45%) accidental. There were 12 homicides, 7 suicides and no accidental deaths. The region contains over 280,000 children, thus yielding a homicide rate of 0.26 per 100,000. The U.S. pediatric homicide rate was 2.6-4.0 over this period. Adolescents 13-17 years old accounted for 237 (57%) admissions, 152 (78%) of non-accidental admissions and 12 (63%) deaths. Most admissions (N = 321, 77%) and 15 of the deaths (79%) were males. Non-accidental injuries were more frequent in ZIP codes associated with low incomes. Hispanic patients accounted for 173 (88%) of non-accidental trauma. However, 40 (20%) non-accidental injuries occurred in Mexico and 157 (80%) injuries occurred in an 82% Hispanic region. Therefore, the standardized morbidity ratio for Hispanic ethnicity was 1.048 (CL 0.8-1.2, P = 0.6).Conclusion: On the United States-Mexico border, the pediatric homicide rate was less than 1/10 the national average. Male adolescents are at risk for non-accidental PT. In a Hispanic majority population, Hispanic ethnicity was not a risk factor for PT. It is possible that economic disparity, rather than race/ethnicity, is a risk factor for PT. [ABSTRACT FROM AUTHOR]

Published
2018
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29. Radiation and Anti-Cancer Vaccines: A Winning Combination.

Author

Cadena, Alexandra, Cushman, Taylor R., Anderson, Clark, Barsoumian, Hampartsoum B., Welsh, James W., and Cortez, Maria Angelica

Subjects
CANCER vaccines, ANTINEOPLASTIC agents, CANCER radiotherapy, TOLL-like receptors, DNA damage
Abstract

The emerging combination of radiation therapy with vaccines is a promising new treatment plan in the fight against cancer. While many cancer vaccines such as MUC1, p53 CpG oligodeoxynucleotide, and SOX2 may be great candidates for antitumor vaccination, there still remain many investigations to be done into possible vaccine combinations. One fruitful partnership that has emerged are anti-tumor vaccines in combination with radiation. Radiation therapy was previously thought to be only a tool for directly or indirectly damaging DNA and therefore causing cancer cell death. Now, with much preclinical and clinical data, radiation has taken on the role of an in situ vaccine. With both cancer vaccines and radiation at our disposal, more and more studies are looking to combining vaccine types such as toll-like receptors, viral components, dendritic-cell-based, and subunit vaccines with radiation. While the outcomes of these combinatory efforts are promising, there is still much work to be covered. This review sheds light on the current state of affairs in cancer vaccines and how radiation will bring its story into the future. [ABSTRACT FROM AUTHOR]

Published
2018
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30. Inhibiting Aurora Kinases Reduces Tumor Growth and Suppresses Tumor Recurrence after Chemotherapy in Patient-Derived Triple-Negative Breast Cancer Xenografts

Author

Anderson Clark, Didier Decaudin, Franck Assayag, Sophie Chateau-Joubert, Edward Spooner, Jean-Jacques Fontaine, Xiaohong Liu, Ivan Bièche, Samantha Goodstal, Angela Romanelli, Jean-Luc Servely, Marie-France Poupon, Patricia de Cremoux, Elisabetta Marangoni, EMD Serono Inc., Hôpital Saint-Louis, École nationale vétérinaire d'Alfort (ENVA), Département Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA), Université Paris Diderot - Paris 7 (UPD7), Hôpital René HUGUENIN (Saint-Cloud), and Institut Curie [Paris]

Subjects
CA15-3, Cancer Research, medicine.medical_treatment, [SDV]Life Sciences [q-bio], PROTEIN, Targeted therapy, Mice, 0302 clinical medicine, Aurora kinase, Aurora Kinases, PF-03814735, Antineoplastic Combined Chemotherapy Protocols, Molecular Targeted Therapy, Triple-negative breast cancer, GENE-EXPRESSION, 0303 health sciences, ACUTE MYELOGENOUS LEUKEMIA, Kinase, Immunohistochemistry, 3. Good health, APOPTOSIS, Oncology, 030220 oncology & carcinogenesis, MCF-7 Cells, Female, CHECKPOINT, Mice, Nude, Breast Neoplasms, Cell Growth Processes, Protein Serine-Threonine Kinases, ENDOREDUPLICATION, 03 medical and health sciences, Breast cancer, Cell Line, Tumor, medicine, Animals, Humans, [INFO]Computer Science [cs], Protein Kinase Inhibitors, 030304 developmental biology, B KINASE, Chemotherapy, business.industry, ANEUPLOIDY, Cancer, medicine.disease, Xenograft Model Antitumor Assays, Immunology, CELLS, Cancer research, business
Abstract

Triple-negative breast cancers (TNBC) have an aggressive phenotype with a relatively high rate of recurrence and poor overall survival. To date, there is no approved targeted therapy for TNBCs. Aurora kinases act as regulators of mammalian cell division. They are important for cell-cycle progression and are frequently overexpressed or mutated in human tumors, including breast cancer. In this study, we investigated the therapeutic potential of targeting Aurora kinases in preclinical models of human breast cancers using a pan-inhibitor of Aurora kinases, AS703569. In vitro, AS703569 was tested in 15 human breast cancer cell lines. TNBC cell lines were more sensitive to AS703569 than were other types of breast cancer cells. Inhibition of proliferation was associated with cell-cycle arrest, aneuploidy, and apoptosis. In vivo, AS703569 administered alone significantly inhibited tumor growth in seven of 11 patient-derived breast cancer xenografts. Treatment with AS703569 was associated with a decrease of phospho-histone H3 expression. Finally, AS703569 combined to doxorubicin–cyclophosphamide significantly inhibited in vivo tumor recurrence, suggesting that Aurora kinase inhibitors could be used both in monotherapy and in combination settings. In conclusion, these data indicate that targeting Aurora kinases could represent a new effective approach for TNBC treatment. Mol Cancer Ther; 11(12); 2693–703. ©2012 AACR.

Published
2012

32. FcRn in the yolk sac endoderm of mouse is required for IgG transport to fetus1

Author

Kim, Jonghan, Mohanty, Sudhasri, Ganesan, Latha P., Hua, Keding, Jarjoura, David, Hayton, William L., Robinson, John M., and Anderson, Clark L.

Subjects
Male, Mice, Knockout, Placenta, Endoderm, Histocompatibility Antigens Class I, Mice, Transgenic, Receptors, Fc, Article, Mice, Inbred C57BL, Mice, Protein Transport, Fetus, Pregnancy, Immunoglobulin G, embryonic structures, Animals, Humans, Female, Maternal-Fetal Exchange, reproductive and urinary physiology, Yolk Sac
Abstract

In adults, the nonclassical MHC class I molecule, FcRn, binds both IgG and albumin and rescues both from a degradative fate, endowing both proteins with high plasma concentrations. FcRn also transports IgG from mother to young during gestation. Anticipating that a detailed understanding of gestational IgG transport in the mouse may give us a useful model to understand FcRn function in the human placenta, we have studied FcRn in the mouse yolk sac placenta in detail. Analyzing day 19-20 fetuses of the three FcRn genotypes resulting from matings of FcRn(+/-) parents, we found that FcRn(-/-) fetuses showed negligible IgG concentrations (1.5 microg/ml), whereas IgG concentrations in FcRn(+/-) fetuses were about a half (176 microg/ml) that of FcRn(+/+) fetuses (336 microg/ml), indicating that FcRn is responsible for virtually all IgG transport from mother to fetus. Immunofluorescence and immunoblotting studies indicated that FcRn is expressed in the endoderm of the yolk sac placenta but not in other cells of the yolk sac placenta or in the chorioallantoic placenta. IgG was found in the endoderm of both FcRn(+/+) and FcRn(-/-) yolk sac placentas and in the mesenchyme of FcRn(+/+) but was missing from the mesenchyme of FcRn(-/-) yolk sac placentas, indicating that IgG enters the endoderm constitutively but is moved out of the endoderm by FcRn. The similarities of these results to human placental FcRn expression and function are striking.

Published
2009

34. Mouse liver sinusoidal endothelium eliminates hiV-like Particles from Blood at a rate of 100 Million per Minute by a second-Order Kinetic Process.

Author

Mates, Jessica M., Zhili Yao, Cheplowitz, Alana M., Suer, Ozan, Phillips, Gary S., Kwiek, Jesse J., Rajaram, Murugesan V. S., Jonghan Kim, Robinson, John M., Ganesan, Latha P., and Anderson, Clark L.

Subjects
HIV, LABORATORY mice, ENDOTHELIAL cells
Abstract

We crafted human immunodeficiency virus (HIV)-like particles of diameter about 140 nm, which expressed two major HIV-1 proteins, namely, env and gag gene products, and used this reagent to simulate the rate of decay of HIV from the blood stream of BALB/c male mice. We found that most (~90%) of the particles were eliminated (cleared) from the blood by the liver sinusoidal endothelial cells (LSECs), the remainder from Kupffer cells; suggesting that LSECs are the major liver scavengers for HIV clearance from blood. Decay was rapid with kinetics suggesting second order with respect to particles, which infers dimerization of a putative receptor on LSEC. The number of HIV-like particles required for saturating the clearance mechanism was approximated. The capacity for elimination of blood-borne HIV-like particles by the sinusoid was 112 million particles per minute. Assuming that the sinusoid endothelial cells were about the size of glassadherent macrophages, then elimination capacity was more than 540 particles per hour per endothelial cell. [ABSTRACT FROM AUTHOR]

Published
2017
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35. Basking in reflected glory: the election of president Obama and naming behaviour.

Author

Anderson-Clark, Tracy N. and Green, Raymond J.

Subjects
*AFRICAN American personal names, *RACIAL identity of African Americans, *PERSONAL names, *AFRICAN American mothers, *SELF-esteem -- Social aspects, *PSYCHOLOGY, UNITED States presidential election, 2008
Abstract

The influence of the 2008 election of President Barack Obama on the naming of children born to African American mothers was investigated. Results indicated that children born after the election were given names that sounded more ‘African American’ than were children born before the election. In addition, African American mother’s Collective Self-Esteem scores were positively correlated with the ethnic sound of a child’s name. It was concluded that this difference in naming behaviour could be viewed through a social identity theory approach and might indicate a desire to ‘bask in the reflected glory’ of President Obama’s election. [ABSTRACT FROM PUBLISHER]

Published
2017
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38. Regulation of Phagocytosis by FcνRIIb and Phosphatases.

Author

Tridandapani, Susheela and Anderson, Clark L.

Abstract

Phagocytosis of immune-complexes is a dynamic process that is accompanied by the generation of inflammatory/tissue damaging products. Recent advances in the field indicate that this process is subject to regulation by inhibitory Fcν receptors and intracellular phosphatases, including the inositol phosphatases SHIP-1, SHIP-2 and PTEN, and the protein tyrosine phosphatase SHP-1. This chapter will describe the role of the inhibitory Fc receptor, FcνRIIb, and the phosphatases in modulating the signaling events leading to phagocytosis and the accompanying inflammation. [ABSTRACT FROM AUTHOR]

Published
2005
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39. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two: National Harbor, MD, USA. 9-13 November 2016

Author

Ager, Casey, Reilley, Matthew, Nicholas, Courtney, Bartkowiak, Todd, Jaiswal, Ashvin, Curran, Michael, Albershardt, Tina C., Bajaj, Anshika, Archer, Jacob F., Reeves, Rebecca S., Ngo, Lisa Y., Berglund, Peter, ter Meulen, Jan, Denis, Caroline, Ghadially, Hormas, Arnoux, Thomas, Chanuc, Fabien, Fuseri, Nicolas, Wilkinson, Robert W., Wagtmann, Nicolai, Morel, Yannis, Andre, Pascale, Atkins, Michael B., Carlino, Matteo S., Ribas, Antoni, Thompson, John A., Choueiri, Toni K., Hodi, F. Stephen, Hwu, Wen-Jen, McDermott, David F., Atkinson, Victoria, Cebon, Jonathan S., Fitzharris, Bernie, Jameson, Michael B., McNeil, Catriona, Hill, Andrew G., Mangin, Eric, Ahamadi, Malidi, van Vugt, Marianne, van Zutphen, Mariëlle, Ibrahim, Nageatte, Long, Georgina V., Gartrell, Robyn, Blake, Zoe, Simoes, Ines, Fu, Yichun, Saito, Takuro, Qian, Yingzhi, Lu, Yan, Saenger, Yvonne M., Budhu, Sadna, De Henau, Olivier, Zappasodi, Roberta, Schlunegger, Kyle, Freimark, Bruce, Hutchins, Jeff, Barker, Christopher A., Wolchok, Jedd D., Merghoub, Taha, Burova, Elena, Allbritton, Omaira, Hong, Peter, Dai, Jie, Pei, Jerry, Liu, Matt, Kantrowitz, Joel, Lai, Venus, Poueymirou, William, MacDonald, Douglas, Ioffe, Ella, Mohrs, Markus, Olson, William, Thurston, Gavin, Capasso, Cristian, Frascaro, Federica, Carpi, Sara, Tähtinen, Siri, Feola, Sara, Fusciello, Manlio, Peltonen, Karita, Martins, Beatriz, Sjöberg, Madeleine, Pesonen, Sari, Ranki, Tuuli, Kyruk, Lukasz, Ylösmäki, Erkko, Cerullo, Vincenzo, Cerignoli, Fabio, Xi, Biao, Guenther, Garret, Yu, Naichen, Muir, Lincoln, Zhao, Leyna, Abassi, Yama, Cervera-Carrascón, Víctor, Siurala, Mikko, Santos, João, Havunen, Riikka, Parviainen, Suvi, Hemminki, Akseli, Dalgleish, Angus, Mudan, Satvinder, DeBenedette, Mark, Plachco, Ana, Gamble, Alicia, Grogan, Elizabeth W., Krisko, John, Tcherepanova, Irina, Nicolette, Charles, Dhupkar, Pooja, Yu, Ling, Kleinerman, Eugenie S., Gordon, Nancy, Grenga, Italia, Lepone, Lauren, Gameiro, Sofia, Knudson, Karin M., Fantini, Massimo, Tsang, Kwong, Hodge, James, Donahue, Renee, Schlom, Jeffrey, Evans, Elizabeth, Bussler, Holm, Mallow, Crystal, Reilly, Christine, Torno, Sebold, Scrivens, Maria, Foster, Cathie, Howell, Alan, Balch, Leslie, Knapp, Alyssa, Leonard, John E., Paris, Mark, Fisher, Terry, Hu-Lieskovan, Siwen, Smith, Ernest, Zauderer, Maurice, Fogler, William, Franklin, Marilyn, Thayer, Matt, Saims, Dan, Magnani, John L., Gong, Jian, Gray, Michael, Fromm, George, de Silva, Suresh, Giffin, Louise, Xu, Xin, Rose, Jason, Schreiber, Taylor H., Gameiro, Sofia R., Clavijo, Paul E., Allen, Clint T., Hodge, James W., Tsang, Kwong Y., Grogan, Jane, Manieri, Nicholas, Chiang, Eugene, Caplazi, Patrick, Yadav, Mahesh, Hagner, Patrick, Chiu, Hsiling, Waldman, Michelle, Klippel, Anke, Thakurta, Anjan, Pourdehnad, Michael, Gandhi, Anita, Henrich, Ian, Quick, Laura, Young, Rob, Chou, Margaret, Hotson, Andrew, Willingham, Stephen, Ho, Po, Choy, Carmen, Laport, Ginna, McCaffery, Ian, Miller, Richard, Tipton, Kimberly A., Wong, Kenneth R., Singson, Victoria, Wong, Chihunt, Chan, Chanty, Huang, Yuanhiu, Liu, Shouchun, Richardson, Jennifer H., Kavanaugh, W. Michael, West, James, Irving, Bryan A., Jaini, Ritika, Loya, Matthew, Eng, Charis, Johnson, Melissa L., Adjei, Alex A., Opyrchal, Mateusz, Ramalingam, Suresh, Janne, Pasi A., Dominguez, George, Gabrilovich, Dmitry, de Leon, Laura, Hasapidis, Jeannette, Diede, Scott J., Ordentlich, Peter, Cruickshank, Scott, Meyers, Michael L., Hellmann, Matthew D., Kalinski, Pawel, Zureikat, Amer, Edwards, Robert, Muthuswamy, Ravi, Obermajer, Nataša, Urban, Julie, Butterfield, Lisa H., Gooding, William, Zeh, Herbert, Bartlett, David, Zubkova, Olga, Agapova, Larissa, Kapralova, Marina, Krasovskaia, Liudmila, Ovsepyan, Armen, Lykov, Maxim, Eremeev, Artem, Bokovanov, Vladimir, Grigoryeva, Olga, Karpov, Andrey, Ruchko, Sergey, Shuster, Alexandr, Khalil, Danny N., Campesato, Luis Felipe, Li, Yanyun, Lazorchak, Adam S., Patterson, Troy D., Ding, Yueyun, Sasikumar, Pottayil, Sudarshan, Naremaddepalli, Gowda, Nagaraj, Ramachandra, Raghuveer, Samiulla, Dodheri, Giri, Sanjeev, Eswarappa, Rajesh, Ramachandra, Murali, Tuck, David, Wyant, Timothy, Leshem, Jasmin, Liu, Xiu-fen, Bera, Tapan, Terabe, Masaki, Bossenmaier, Birgit, Niederfellner, Gerhard, Reiter, Yoram, Pastan, Ira, Xia, Leiming, Xia, Yang, Hu, Yangyang, Wang, Yi, Bao, Yangyi, Dai, Fu, Huang, Shiang, Hurt, Elaine, Hollingsworth, Robert E., Lum, Lawrence G., Chang, Alfred E., Wicha, Max S., Li, Qiao, Mace, Thomas, Makhijani, Neil, Talbert, Erin, Young, Gregory, Guttridge, Denis, Conwell, Darwin, Lesinski, Gregory B., Gonzales, Rodney JM Macedo, Huffman, Austin P., Wang, Ximi K., Reshef, Ran, MacKinnon, Andy, Chen, Jason, Gross, Matt, Marguier, Gisele, Shwonek, Peter, Sotirovska, Natalija, Steggerda, Susanne, Parlati, Francesco, Makkouk, Amani, Bennett, Mark K., Emberley, Ethan, Huang, Tony, Li, Weiqun, Neou, Silinda, Pan, Alison, Zhang, Jing, Zhang, Winter, Marshall, Netonia, Marron, Thomas U., Agudo, Judith, Brown, Brian, Brody, Joshua, McQuinn, Christopher, Farren, Matthew, Komar, Hannah, Shakya, Reena, Ludwug, Thomas, Morillon, Y. 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A., Sayers, Thomas J., Vasilakos, John P., Alston, Tesha, Dovedi, Simon, Elvecrog, James, Grigsby, Iwen, Herbst, Ronald, Johnson, Karen, Moeckly, Craig, Mullins, Stefanie, Siebenaler, Kristen, SternJohn, Julius, Tilahun, Ashenafi, Tomai, Mark A., Vogel, Katharina, Vietsch, Eveline E., Wellstein, Anton, Wythes, Martin, Crosignani, Stefano, Tumang, Joseph, Alekar, Shilpa, Bingham, Patrick, Cauwenberghs, Sandra, Chaplin, Jenny, Dalvie, Deepak, Denies, Sofie, De Maeseneire, Coraline, Feng, JunLi, Frederix, Kim, Greasley, Samantha, Guo, Jie, Hardwick, James, Kaiser, Stephen, Jessen, Katti, Kindt, Erick, Letellier, Marie-Claire, Li, Wenlin, Maegley, Karen, Marillier, Reece, Miller, Nichol, Murray, Brion, Pirson, Romain, Preillon, Julie, Rabolli, Virginie, Ray, Chad, Ryan, Kevin, Scales, Stephanie, Srirangam, Jay, Solowiej, Jim, Stewart, Al, Streiner, Nicole, Torti, Vince, Tsaparikos, Konstantinos, Zheng, Xianxian, Driessens, Gregory, Gomes, Bruno, Kraus, Manfred, Xu, Chunxiao, Zhang, Yanping, Kradjian, Giorgio, Qin, Guozhong, Qi, Jin, Xu, Xiaomei, Marelli, Bo, Yu, Huakui, Guzman, Wilson, Tighe, Rober, Salazar, Rachel, Lo, Kin-Ming, English, Jessie, Radvanyi, Laszlo, Lan, Yan, Postow, Michael, Senbabaoglu, Yasin, Gasmi, Billel, Zhong, Hong, Liu, Cailian, Hirschhorhn-Cymerman, Daniel, Zha, Yuanyuan, Malnassy, Gregory, Fulton, Noreen, Park, Jae-Hyun, Stock, Wendy, Nakamura, Yusuke, Liu, Hongtao, Ju, Xiaoming, Kosoff, Rachelle, Ramos, Kimberly, Coder, Brandon, Petit, Robert, Princiotta, Michael, Perry, Kyle, Zou, Jun, Arina, Ainhoa, Fernandez, Christian, Zheng, Wenxin, Beckett, Michael A., Mauceri, Helena J., Fu, Yang-Xin, Weichselbaum, Ralph R., Lewis, Whitney, Han, Yanyan, Wu, Yeting, Yang, Chou, Huang, Jing, Wu, Dongyun, Li, Jin, Liang, Xiaoling, Zhou, Xiangjun, Hou, Jinlin, Hassan, Raffit, Jahan, Thierry, Antonia, Scott J., Kindler, Hedy L., Alley, Evan W., Honarmand, Somayeh, Liu, Weiqun, Leong, Meredith L., Whiting, Chan C., Nair, Nitya, Enstrom, Amanda, Lemmens, Edward E., Tsujikawa, Takahiro, Kumar, Sushil, Coussens, Lisa M., Murphy, Aimee L., Brockstedt, Dirk G., Koch, Sven D., Sebastian, Martin, Weiss, Christian, Früh, Martin, Pless, Miklos, Cathomas, Richard, Hilbe, Wolfgang, Pall, Georg, Wehler, Thomas, Alt, Jürgen, Bischoff, Helge, Geissler, Michael, Griesinger, Frank, Kollmeier, Jens, Papachristofilou, Alexandros, Doener, Fatma, Fotin-Mleczek, Mariola, Hipp, Madeleine, Hong, Henoch S., Kallen, Karl-Josef, Klinkhardt, Ute, Stosnach, Claudia, Scheel, Birgit, Schroeder, Andreas, Seibel, Tobias, Gnad-Vogt, Ulrike, Zippelius, Alfred, Park, Ha-Ram, Ahn, Yong-Oon, Kim, Tae Min, Kim, Soyeon, Kim, Seulki, Lee, Yu Soo, Keam, Bhumsuk, Kim, Dong-Wan, Heo, Dae Seog, Pilon-Thomas, Shari, Weber, Amy, Morse, Jennifer, Kodumudi, Krithika, Liu, Hao, Mullinax, John, Sarnaik, Amod A., Pike, Luke, Bang, Andrew, Balboni, Tracy, Taylor, Allison, Spektor, Alexander, Wilhite, Tyler, Krishnan, Monica, Cagney, Daniel, Alexander, Brian, Aizer, Ayal, Buchbinder, Elizabeth, Awad, Mark, Ghandi, Leena, Schoenfeld, Jonathan, Lessey-Morillon, Elizabeth, Ridnour, Lisa, Segal, Neil H., Sharma, Manish, Le, Dung T., Ferris, Robert L., Zelenetz, Andrew D., Levy, Ronald, Lossos, Izidore S., Jacobson, Caron, Ramchandren, Radhakrishnan, Godwin, John, Colevas, A. 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Nicholas, Cron, Kyle R., Sivan, Ayelet, Aquino-Michaels, Keston, Orecchioni, Marco, Bedognetti, Davide, Hendrickx, Wouter, Fuoco, Claudia, Spada, Filomena, Sgarrella, Francesco, Cesareni, Gianni, Marincola, Francesco, Kostarelos, Kostas, Bianco, Alberto, Delogu, Lucia, Roelands, Jessica, Boughorbel, Sabri, Decock, Julie, Presnell, Scott, Wang, Ena, Marincola, Franco M., Kuppen, Peter, Ceccarelli, Michele, Rinchai, Darawan, Chaussabel, Damien, Miller, Lance, Nguyen, Andrew, Sanborn, J. Zachary, Vaske, Charles, Rabizadeh, Shahrooz, Niazi, Kayvan, Benz, Steven, Patel, Shashank, Restifo, Nicholas, White, James, Angiuoli, Sam, Sausen, Mark, Jones, Sian, Sevdali, Maria, Simmons, John, Velculescu, Victor, Diaz, Luis, Zhang, Theresa, Sims, Jennifer S., Barton, Sunjay M., Kadenhe-Chiweshe, Angela, Dela Cruz, Filemon, Turk, Andrew T., Mazzeo, Christopher F., Kung, Andrew L., Bruce, Jeffrey N., Yamashiro, Darrell J., Connolly, Eileen P., Baird, Jason, Crittenden, Marka, Friedman, David, Xiao, Hong, Leidner, Rom, Bell, Bryan, Young, Kristina, Gough, Michael, Bian, Zhen, Kidder, Koby, Liu, Yuan, Curran, Emily, Chen, Xiufen, Corrales, Leticia P., Kline, Justin, Aguilar, Ethan G., Guerriero, Jennifer, Sotayo, Alaba, Ponichtera, Holly, Pourzia, Alexandra, Schad, Sara, Carrasco, Ruben, Lazo, Suzan, Bronson, Roderick, Letai, Anthony, Kornbluth, Richard S., Gupta, Sachin, Termini, James, Guirado, Elizabeth, Stone, Geoffrey W., Meyer, Christina, Helming, Laura, Wilson, Nicholas, Hofmeister, Robert, Neubert, Natalie J., Tillé, Laure, Barras, David, Soneson, Charlotte, Baumgaertner, Petra, Rimoldi, Donata, Gfeller, David, Delorenzi, Mauro, Fuertes Marraco, Silvia A., Speiser, Daniel E., Abraham, Tara S., Xiang, Bo, Magee, Michael S., Waldman, Scott A., Snook, Adam E., Blogowski, Wojciech, Zuba-Surma, Ewa, Budkowska, Marta, Salata, Daria, Dolegowska, Barbara, Starzynska, Teresa, Chan, Leo, Somanchi, Srinivas, McCulley, Kelsey, Lee, Dean, Buettner, Nico, Shi, Feng, Myers, Paisley T., Curbishley, Stuart, Penny, Sarah A., Steadman, Lora, Millar, David, Speers, Ellen, Ruth, Nicola, Wong, Gabriel, Thimme, Robert, Adams, David, Cobbold, Mark, Thomas, Remy, Al-Muftah, Mariam, Wong, Michael KK, Morse, Michael, Clark, Joseph I., Kaufman, Howard L., Daniels, Gregory A., Hua, Hong, Rao, Tharak, Dutcher, Janice P., Kang, Kai, Saunthararajah, Yogen, Velcheti, Vamsidhar, Kumar, Vikas, Anwar, Firoz, Verma, Amita, Chheda, Zinal, Kohanbash, Gary, Sidney, John, Okada, Kaori, Shrivastav, Shruti, Carrera, Diego A., Liu, Shuming, Jahan, Naznin, Mueller, Sabine, Pollack, Ian F., Carcaboso, Angel M., Sette, Alessandro, Hou, Yafei, Okada, Hideho, Field, Jessica J., Zeng, Weiping, Shih, Vincent FS, Law, Che-Leung, Senter, Peter D., Gardai, Shyra J., Okeley, Nicole M., Abelin, Jennifer G., Saeed, Abu Z., Malaker, Stacy A., Shabanowitz, Jeffrey, Ward, Stephen T., Hunt, Donald F., Profusek, Pam, Wood, Laura, Shepard, Dale, Grivas, Petros, Kapp, Kerstin, Volz, Barbara, Oswald, Detlef, Wittig, Burghardt, Schmidt, Manuel, Sefrin, Julian P., Hillringhaus, Lars, Lifke, Valeria, Lifke, Alexander, Skaletskaya, Anna, Ponte, Jose, Chittenden, Thomas, Setiady, Yulius, Sivado, Eva, Thomas, Vincent, El Alaoui, Meddy, Papot, Sébastien, Dumontet, Charles, Dyson, Mike, McCafferty, John, El Alaoui, Said, Bommareddy, Praveen K., Zloza, Andrew, Kohlhapp, Frederick, Silk, Ann W., Jhawar, Sachin, Paneque, Tomas, Newman, Jenna, Beltran, Pedro, Cao, Felicia, Hong, Bang-Xing, Rodriguez-Cruz, Tania, Song, Xiao-Tong, Gottschalk, Stephen, Calderon, Hugo, Illingworth, Sam, Brown, Alice, Fisher, Kerry, Seymour, Len, Champion, Brian, Eriksson, Emma, Wenthe, Jessica, Hellström, Ann-Charlotte, Paul-Wetterberg, Gabriella, Loskog, Angelica, Milenova, Ioanna, Ståhle, Magnus, Jarblad-Leja, Justyna, Ullenhag, Gustav, Dimberg, Anna, Moreno, Rafael, Alemany, Ramon, Goyal, Sharad, Silk, Ann, Mehnert, Janice, Gabrail, Nashat, Bryan, Jennifer, Medina, Daniel, Mitchell, Leah, Yagiz, Kader, Lopez, Fernando, Mendoza, Daniel, Munday, Anthony, Gruber, Harry, Jolly, Douglas, Fuhrmann, Steven, Radoja, Sasa, Tan, Wei, Pourchet, Aldo, Frey, Alan, Mohr, Ian, Mulvey, Matthew, Andtbacka, Robert H. 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Chris S., Burrill, Joel, Skoble, Justin, Katibah, George, deVries, Michele, Lauer, Peter, Dubensky, Thomas W., Chen, Xin, Zhou, Li, Ren, Xiubao, Aggarwal, Charu, Mangrolia, Drishty, Cohen, Roger, Weinstein, Gregory, Morrow, Matthew, Bauml, Joshua, Kraynyak, Kim, Boyer, Jean, Yan, Jian, Lee, Jessica, Humeau, Laurent, Oyola, Sandra, Duff, Susan, Weiner, David, Yang, Zane, Bagarazzi, Mark, McNeel, Douglas G., Eickhoff, Jens, Jeraj, Robert, Staab, Mary Jane, Straus, Jane, Rekoske, Brian, Liu, Glenn, Melssen, Marit, Grosh, William, Varhegyi, Nikole, Galeassi, Nadejda, Deacon, Donna H., Gaughan, Elizabeth, Ghisoli, Maurizio, Barve, Minal, Mennel, Robert, Wallraven, Gladice, Manning, Luisa, Senzer, Neil, Nemunaitis, John, Ogasawara, Masahiro, Ota, Shuichi, Peace, Kaitlin M., Hale, Diane F., Vreeland, Timothy J., Jackson, Doreen O., Berry, John S., Trappey, Alfred F., Herbert, Garth S., Clifton, Guy T., Hardin, Mark O., Toms, Anne, Qiao, Na, Litton, Jennifer, Peoples, George E., Mittendorf, Elizabeth A., Ghamsari, Lila, Flano, Emilio, Jacques, Judy, Liu, Biao, Havel, Jonathan, Makarov, Vladimir, Chan, Timothy A., Flechtner, Jessica B., Facciponte, John, Ugel, Stefano, De Sanctis, Francesco, Coukos, George, Paris, Sébastien, Pottier, Agnes, Levy, Laurent, Lu, Bo, Cappuccini, Federica, Pollock, Emily, Bryant, Richard, Hamdy, Freddie, Hill, Adrian, Redchenko, Irina, Sultan, Hussein, Kumai, Takumi, Fesenkova, Valentyna, Celis, Esteban, Fernando, Ingrid, Palena, Claudia, David, Justin M., Gabitzsch, Elizabeth, Jones, Frank, Gulley, James L., Herranz, Mireia Uribe, Wada, Hiroshi, Shimizu, Atsushi, Osada, Toshihiro, Fukaya, Satoshi, Sasaki, Eiji, Abolhalaj, Milad, Askmyr, David, Lundberg, Kristina, Albrekt, Ann-Sofie, Greiff, Lennart, Lindstedt, Malin, Flies, Dallas B., Higuchi, Tomoe, Ornatowski, Wojciech, Harris, Jaryse, Adams, Sarah F., Aguilera, Todd, Rafat, Marjan, Castellini, Laura, Shehade, Hussein, Kariolis, Mihalis, Jang, Dadi, vonEbyen, Rie, Graves, Edward, Ellies, Lesley, Rankin, Erinn, Koong, Albert, Giaccia, Amato, Ajina, Reham, Wang, Shangzi, Smith, Jill, Pierobon, Mariaelena, Jablonski, Sandra, Petricoin, Emanuel, Weiner, Louis M., Sherry, Lorcan, Waller, John, Anderson, Mark, Bigley, Alison, Bernatchez, Chantale, Haymaker, Cara, Kluger, Harriet, Tetzlaff, Michael, Jackson, Natalie, Gergel, Ivan, Tagliaferri, Mary, Hwu, Patrick, Snzol, Mario, Hurwitz, Michael, Barberi, Theresa, Martin, Allison, Suresh, Rahul, Barakat, David, Harris-Bookman, Sarah, Drake, Charles, Friedman, Alan, Berkey, Sara, Downs-Canner, Stephanie, Edwards, Robert P., Curiel, Tyler, Odunsi, Kunle, Bruno, Tullia C., Moore, Brandon, Squalls, Olivia, Ebner, Peggy, Waugh, Katherine, Mitchell, John, Franklin, Wilbur, Merrick, Daniel, McCarter, Martin, Palmer, Brent, Kern, Jeffrey, Vignali, Dario, Slansky, Jill, Chan, Anissa S. H., Qiu, Xiaohong, Fraser, Kathryn, Jonas, Adria, Ottoson, Nadine, Gordon, Keith, Kangas, Takashi O., Leonardo, Steven, Ertelt, Kathleen, Walsh, Richard, Uhlik, Mark, Graff, Jeremy, Bose, Nandita, Gupta, Ravi, Mandloi, Nitin, Paul, Kiran, Patil, Ashwini, Sathian, Rekha, Mohan, Aparna, Manoharan, Malini, Chaudhuri, Amitabha, Chen, Yu, Lin, Jing, Ye, Yun-bin, Xu, Chun-wei, Chen, Gang, Guo, Zeng-qing, Komarov, Andrey, Chenchik, Alex, Makhanov, Michael, Frangou, Costa, Zheng, Yi, Coltharp, Carla, Unfricht, Darryn, Dilworth, Ryan, Fridman, Leticia, Liu, Linying, Rajopadhye, Milind, Miller, Peter, Concha-Benavente, Fernando, Bauman, Julie, Trivedi, Sumita, Srivastava, Raghvendra, Ohr, James, Heron, Dwight, Duvvuri, Uma, Kim, Seungwon, Torrey, Heather, Mera, Toshi, Okubo, Yoshiaki, Vanamee, Eva, Foster, Rosemary, Faustman, Denise, Stack, Edward, Izaki, Daisuke, Beck, Kristen, Jia, Dan Tong, Armenta, Paul, White-Stern, Ashley, Marks, Douglas, Taback, Bret, Horst, Basil, Glickman, Laura Hix, Kanne, David B., Gauthier, Kelsey S., Desbien, Anthony L., Francica, Brian, Leong, Justin L., Sung, Leonard, Metchette, Ken, Kasibhatla, Shailaja, Pferdekamper, Anne Marie, Zheng, Lianxing, Cho, Charles, Feng, Yan, McKenna, Jeffery M., Tallarico, John, Bender, Steven, Ndubaku, Chudi, McWhirter, Sarah M., Gugel, Elena Gonzalez, Bell, Charles J. M., Munk, Adiel, Muniz, Luciana, Bhardwaj, Nina, Zhao, Fei, Evans, Kathy, Xiao, Christine, Holtzhausen, Alisha, Hanks, Brent A., Scholler, Nathalie, Yin, Catherine, Van der Meijs, Pien, Prantner, Andrew M., Krejsa, Cecile M., Smith, Leia, Johnson, Brian, Branstetter, Daniel, Stein, Paul L., Jaen, Juan C., Tan, Joanne BL, Chen, Ada, Park, Timothy, Powers, Jay P., Sexton, Holly, Xu, Guifen, Young, Steve W., Schindler, Ulrike, Deng, Wentao, Klinke, David John, Komar, Hannah M., Serpa, Gregory, Elnaggar, Omar, Hart, Philip, Schmidt, Carl, Dillhoff, Mary, Jin, Ming, Ostrowski, Michael C., Koti, Madhuri, Au, Katrina, Peterson, Nichole, Truesdell, Peter, Reid-Schachter, Gillian, Graham, Charles, Craig, Andrew, Francis, Julie-Ann, Kotlan, Beatrix, Balatoni, Timea, Farkas, Emil, Toth, Laszlo, Ujhelyi, Mihaly, Savolt, Akos, Doleschall, Zoltan, Horvath, Szabolcs, Eles, Klara, Olasz, Judit, Csuka, Orsolya, Kasler, Miklos, Liszkay, Gabriella, Barnea, Eytan, Blakely, Collin, Flynn, Patrick, Goodman, Reid, Bueno, Raphael, Sugarbaker, David, Jablons, David, Broaddus, V. Courtney, West, Brian, Kunk, Paul R., Obeid, Joseph M., Winters, Kevin, Pramoonjago, Patcharin, Stelow, Edward B., Bauer, Todd W., Rahma, Osama E., Lamble, Adam, Kosaka, Yoko, Huang, Fei, Saser, Kate A., Adams, Homer, Tognon, Christina E., Laderas, Ted, McWeeney, Shannon, Loriaux, Marc, Tyner, Jeffery W., Druker, Brian J., Lind, Evan F., Liu, Zhuqing, Lu, Shanhong, Kane, Lawrence P., Shayan, Gulidanna, Femel, Julia, Lane, Ryan, Booth, Jamie, Lund, Amanda W., Rodriguez, Anthony, Engelhard, Victor H., Metelli, Alessandra, Wu, Bill X., Fugle, Caroline W., Saleh, Rachidi, Sun, Shaoli, Wu, Jennifer, Liu, Bei, Li, Zihai, Morris, Zachary S., Guy, Emily I., Heinze, Clinton, Kler, Jasdeep, Gressett, Monica M., Werner, Lauryn R., Gillies, Stephen D., Korman, Alan J., Loibner, Hans, Hank, Jacquelyn A., Rakhmilevich, Alexander L., Harari, Paul M., Sondel, Paul M., Huelsmann, Erica, Broucek, Joseph, Brech, Dorothee, Straub, Tobias, Irmler, Martin, Beckers, Johannes, Buettner, Florian, Schaeffeler, Elke, Schwab, Matthias, Noessner, Elfriede, Wolfreys, Alison, Da Costa, Andre, Silva, John, Crosby, Andrea, Staelens, Ludovicus, Craggs, Graham, Cauvin, Annick, Mason, Sean, Paterson, Alison M., Lake, Andrew C., Armet, Caroline M., O’Connor, Rachel W., Hill, Jonathan A., Normant, Emmanuel, Adam, Ammar, Biniszkiewicz, Detlev M., Chappel, Scott C., Palombella, Vito J., Holland, Pamela M., Becker, Annette, Leleti, Manmohan R., Newcomb, Eric, Tan, Joanne B. L., Rapisuwon, Suthee, Radfar, Arash, Gardner, Kellie, Gibney, Geoffrey, Atkins, Michael, Rennier, Keith R., Crowder, Robert, Wang, Ping, Pachynski, Russell K., Carrero, Rosa M. Santana, Rivas, Sarai, Beceren-Braun, Figen, Anthony, Scott, Schluns, Kimberly S., Sawant, Deepali, Chikina, Maria, Yano, Hiroshi, Workman, Creg, Salerno, Elise, Mauldin, Ileana, Deacon, Donna, Shea, Sofia, Pinczewski, Joel, Gajewski, Thomas, Spranger, Stefani, Horton, Brendan, Suzuki, Akiko, Leland, Pamela, Joshi, Bharat H., Puri, Raj K., Sweis, Randy F., Bao, Riyue, Luke, Jason, Theodoraki, Marie-Nicole, Mogundo, Frances-Mary, Won, Haejung, Moreira, Dayson, Gao, Chan, Zhao, Xingli, Duttagupta, Priyanka, Jones, Jeremy, D’Apuzzo, Massimo, and Pal, Sumanta

Published
2016
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40. Abundant Intracellular IgG in Enterocytes and Endoderm Lacking FcRn.

Author

Mohanty, Sudhasri, Kim, Jonghan, Ganesan, Latha P., Phillips, Gary S., Robinson, John M., and Anderson, Clark L.

Subjects
INTRACELLULAR membranes, IMMUNOGLOBULIN G, ENTEROCYTES, ENDODERM, GENE expression, DIGESTIVE organs
Abstract

FcRn, a non-classical MHCI molecule, transports IgG from mother to young and regulates the rate of IgG degradation throughout life. Brambell proposed a mechanism that unified these two functions, saying that IgG was pinocytosed nonspecifically by the cell into an FcRn-expressing endosome, where, at low pH, it bound to FcRn and was exocytosed. This theory was immediately challenged by claims that FcRn specificity for ligand could be conferred at the cell surface in neonatal jejunum. Assessing Brambell's hypothesis we found abundant nonspecifically endocytosed IgG present in the cytoplasm of FcRn−/− enterocytes. Further, IgG was present in the intercellular clefts and the cores of FcRn+/+ but not FcRn−/− jejunum. FcRn specificity for ligand could be determined within the cell. [ABSTRACT FROM AUTHOR]

Published
2013
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41. Rapid and Efficient Clearance of Blood-borne Virus by Liver Sinusoidal Endothelium.

Author

Ganesan, Latha P., Mohanty, Sudhasri, Kim, Jonghan, Clark, K. Reed, Robinson, John M., and Anderson, Clark L.

Subjects
VIRUSES, LIVER, BLOODBORNE infections, ENDOTHELIUM, CELLS
Abstract

The liver removes quickly the great bulk of virus circulating in blood, leaving only a small fraction to infect the host, in a manner characteristic of each virus. The scavenger cells of the liver sinusoids are implicated, but the mechanism is entirely unknown. Here we show, borrowing a mouse model of adenovirus clearance, that nearly all infused adenovirus is cleared by the liver sinusoidal endothelial cell (LSEC). Using refined immunofluorescence microscopy techniques for distinguishing macrophages and endothelial cells in fixed liver, and identifying virus by two distinct physicochemical methods, we localized adenovirus 1 minute after infusion mainly to the LSEC (~90%), finding ~10% with Kupffer cells (KC) and none with hepatocytes. Electron microscopy confirmed our results. In contrast with much prior work claiming the main scavenger to be the KC, our results locate the clearance mechanism to the LSEC and identify this cell as a key site of antiviral activity. [ABSTRACT FROM AUTHOR]

Published
2011
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43. The Relationship Between First Names and Teacher Expectations for Achievement Motivation.

Author

Anderson-Clark, Tracy N., Green, Raymond J., and Henley, Tracy B.

Subjects
*NAMES, *TEACHER expectations, *EDUCATIONAL evaluation, *TEACHER evaluation, *ACHIEVEMENT motivation, *EDUCATIONAL psychology, *GRADING of students, *MOTIVATION (Psychology), *PERFORMANCE
Abstract

This study examines perceptions of achievement motivation as influenced by first name and student ethnicity. One hundred thirty elementary school teachers were given a vignette of a fifth-grade student and instructed to judge the behavior and characteristics of the student. Results showed that there was a significant main effect for an ethnic first name. Overall, significantly lower achievement scores were given by raters whose descriptions used an African American-sounding name rather than a Caucasian-sounding name. [ABSTRACT FROM AUTHOR]

Published
2008
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44. Familial hypercatabolic hypoproteinemia caused by deficiency of the neonatal Fc receptor, FcRn, due to a mutant β-microglobulin gene.

Author

Wani, Manzoor A., Haynes, Lynn D., Jonghan Kim, Bronson, C. L., Chaudhury, Chaity, Mohanty, Sudhasri, Waidmann, Thomas A., Robinson, John M., and Anderson, Clark L.

Subjects
ALBUMINS, FAMILIAL diseases, FC receptors, CELL receptors, LYMPHOCYTES, MACROPHAGES
Abstract

Two siblings, products of a consanguineous marriage, were markedly deficient in both albumin and lgG because of rapid degradation of these proteins, suggesting a lack of the neonatal Fc receptor, FcRn. FcRn is a heterodimeric receptor composed of a nonclassical MHC class I α-chain and β2-microglobulin (β2m) that binds two ligands, lgG and albumin, and extends the catabolic half-lives of both. Eight relatives of the siblings were moderately lgG-deficient. From sera archived for 35 years, we sequenced the two siblings' genes for the heterodimeric FcRn. We found that, although the a-chain gene sequences of the siblings were normal, the β2m genes contained a single nucleotide transversion that would mutate a conserved alanine to proline at the midpoint of the signal sequence. Concentrations of soluble β2m and HLA in the siblings' sera were <1% of normal. Transfection assays of β2m-deficient cultured cells with β2m cDNA indicated that the mutant β2m supported <20% of normal expression of β2m, MHC class I, and FcRn proteins. We concluded that a β2m gene mutation underlies the hypercatabolism and reduced serum levels of albumin and lgG in the two siblings with familial hypercatabolic hypoproteinemia. This experiment of nature affirms our hypothesis that FcRn binds lgG and albumin, salvages both from a degradative fate, and maintains their physiologic concentrations. [ABSTRACT FROM AUTHOR]

Published
2006
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45. Albumin turnover: FcRn-mediated recycling saves as much albumin from degradation as the liver produces.

Author

Jonghan Kim, Bronson, C. L., Hayton, William L., Radmacher, Michael D., oopenian, Derry C., Robinson, John M., and Anderson, Clark L.

Subjects
SERUM albumin, ALBUMINS, LIVER, MAJOR histocompatibility complex, IRON in the body, MICE, BIOSYNTHESIS
Abstract

It is now understood that the nonclassical major histocompatibility complex-I molecule FcRn binds albumin and retrieves it from an intracellular degradative fate. Whether FcRn in the liver modulates albumin turnover through effects on biosynthesis and production is not known. Thus we quantified the appearance of biosynthetically labeled albumin in plasma after an intravenous bolus injection of [³H]leucine in FcRn-deficient mice. The production rates for both albumin (FcRn substrate) and transferrin (nonsubstrate) are increased by ∼20% in FcRn-deficient mice compared with normal mice, likely compensating for the lowered plasma oncotic pressure caused by hypoalbuminemia in FcRn-deficient mice. Determining the magnitude of FcRn-mediated effects on albumin turnover, we then measured the steady-state plasma concentrations of biosynthetically labeled albumin and transferrin during [³H]leucine infusion. The concentration of albumin was ∼40% lower in FcRn-deficient mice compared with normal mice. Furthermore, the ∼40% lower plasma albumin concentration in FcRn-deficient mice along with the ∼20% increase in albumin production indicate, by the mass-balance equation, that albumin degradation in FcRn-deficient mice is twice that of normal mice. These studies of biosynthetically labeled, and thus native, albumin support our previous finding that FcRn protects albumin from degradation. Permitting quantification of the magnitude of FcRn-mediated recycling, they further indicate that FcRn has extraordinary capacity: the amount of albumin saved from degradation by FcRn-mediated recycling is the same as that produced by the liver. [ABSTRACT FROM AUTHOR]

Published
2006
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47. Competitive Social Strategies in Groups of Deprived and Experienced Rhesus Monkeys.

Author

Anderson, Clark O. and Mason, William A.

Subjects
RHESUS monkeys, WATER consumption, ANIMAL behavior, SOCIAL groups, SOCIAL status, SOCIAL perception
Abstract

Behavior during competition for water was observed in 2 social groups of young rhesus monkeys (3 females, 3 males in each). Monkeys in one group were socially deprived and those in the other were socially experienced (raised with mother and agemates). Social status, based on dyadic recording of displacements at the water bottle, was predictive of a number of measures related to water consumption and social orientation in both groups, but this measure was less reliable and predictive for the experienced group than for the deprived group. A major reason for the comparatively low predictive value and reliability of status among experienced monkeys was their ability to influence the behavior of higher status members through responses directed to a 3rd patty and other elaborate social strategies, many of which depended on responding to status relations between 2nd and 3rd parties. The fact that such strategies were only observed in the experienced group is a clear indication that the development of higher orders of social cognition is dependent on early social experience. [ABSTRACT FROM AUTHOR]

Published
1978
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48. Effects of Maternal Mobility, Partner, and Endocrine State on Social Responsiveness of Adolescent Rhesus Monkeys.

Author

Anderson, Clark O., Kenney, Ann McM., and Mason, William A.

Subjects
ANIMAL social behavior, RHESUS monkeys, SOCIAL interaction, SOCIETAL reaction, ANIMALS, BEHAVIOR
Abstract

The social behavior of rhesus monkeys raised for the 1st year of life with mobile (MS) or stationary (SS) cloth surrogate mothers was investigated when the animals reached 4-5 yr of age. The MS males generally refrained from social interaction during initial pairings with females, whereas SS males interacted frequently, but were more often the targets of attacks and chases from adult females than were MS males. The MS males were more likely to vary their social behavior according to the behavior of the social partner and seemed to benefit more from extended social exposure than their SS counterparts. The MS females were more similar to wild-born females than were SS females in nearly every behavior category and dimension tested. These results suggest that rearing with mobile artificial mothers improves the chances of later adaptive social adjustments in socially restricted monkeys. [ABSTRACT FROM AUTHOR]

Published
1977
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