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A comprehensive survey of programs for preparing science teachers at colleges and universities in the United States was conducted to provide information on the current status of such programs. Analyzed were (1) the practice teaching experience in these institutions, (2) the methods courses in science education, and (3) the characteristics of the instructors of these methods courses. Some 992 institutions were surveyed and 73 per cent of these returned at least a partial response. The two-part questionnaire was directed both to the person responsible for the overall program and to the instructors of the methods courses in the institution. Over 90 tables present information obtained in the survey. (GR)

AimsAortic stenosis is characterized by fibrosis and calcification of the valve, with a higher proportion of fibrosis observed in women. Stenotic bicuspid aortic valves progress more rapidly than tricuspid valves which may also influence the relative composition of the valve. We aimed to investigate the influence of cusp morphology on quantitative aortic valve composition quantified from contrast-enhanced computed tomography angiography in severe aortic stenosis. Methods and resultsPatients undergoing transcatheter aortic valve implantation with bicuspid and tricuspid valves were propensity matched 1:1 by age, sex, and comorbidities. Computed tomography angiograms were analyzed using semi-automated software to quantify fibrotic and calcific scores (volume/valve annular area) and the fibro-calcific ratio (fibrotic score/calcific score). The study population (n=140) was elderly (76±10 years, 62% male) and had a peak aortic jet velocity of 4.1±0.7 m/s. Compared to those with tricuspid valves (n=70), patients with bicuspid valves (n=70) had higher fibrotic scores (204 [interquartile range 118-267] versus 144[99-208] mm3/cm2, p=0.006) with similar calcific scores (p=0.614). Women had greater fibrotic scores than men in bicuspid (224[181-307] versus 169[109- 247] mm3/cm2; p=0.042) but not tricuspid valves (p=0.232). Men had greater calcific scores than women in both bicuspid (203[124-355] versus 130[70-182] mm3/cm2; p=0.008) and tricuspid (177[136-249] versus 100[62-150] mm3/cm2; p=0.004) valves. Among both valve types, women had greater fibro-calcific ratio compared to men (tricuspid 1.86[0.94-2.56] versus 0.86[0.54-1.24], p=0.001 and bicuspid 1.78[1.21-2.90] versus 0.74[0.44-1.53], p=0.001).ConclusionsIn severe aortic stenosis, bicuspid valves have proportionately more fibrosis than tricuspid valves, especially in women.

Ultrasound stimulated microbubbles (USMB) are being investigated for their potential to promote the uptake of anticancer agents into tumor tissue by exploiting their ability to enhance microvascular permeability. At sufficiently high ultrasound transmit amplitudes it has also recently been shown that USMB treatments can, on their own, induce vascular damage, shutdown blood flow, and inhibit tumor growth. The objective of this study is to examine the antitumor effects of ‘antivascular’ USMB treatments in conjunction with chemotherapy, which differs from previous work which has sought to enhance drug uptake with USMBs by increasing vascular permeability. Conceptually this is a strategy similar to combining vascular disrupting agents with a chemotherapy, and we have selected the taxane docetaxel (Taxotere) for evaluating this approach as it has previously been shown to have potent antitumor effects when combined with small molecule vascular disrupting agents. Experiments were conducted on PC3 tumors implanted in athymic mice. USMB treatments were performed at a frequency of 1 MHz employing sequences of 50 ms bursts (0.00024 duty cycle) at 1.65 MPa. USMB treatments were administered on a weekly basis for 4 weeks with docetaxel (DTX) being given intravenously at a dose level of 5 mg/kg. The USMB treatments, either alone or in combination with DTX, induced an acute reduction in tumor perfusion which was accompanied at the 24 hour point by significantly enhanced necrosis and apoptosis. Longitudinal experiments showed a modest prolongation in survival but no significant growth inhibition occurred in DTX–only and USMB-only treatment groups relative to control tumors. The combined USMB-DTX treatment group produced tumor shrinkage in weeks 4–6, and significant growth inhibition and survival prolongation relative to the control (p

Funder: Wellcome-MRC, Institute of Metabolic Science, Metabolic Research Laboratories, Imaging Core, Insulin-induced GLUT4 translocation to the plasma membrane in muscle and adipocytes is crucial for whole-body glucose homeostasis. Currently, GLUT4 trafficking assays rely on overexpression of tagged GLUT4. Here we describe a high-content imaging platform for studying endogenous GLUT4 translocation in intact adipocytes. This method enables high fidelity analysis of GLUT4 responses to specific perturbations, multiplexing of other trafficking proteins and other features including lipid droplet morphology. Using this multiplexed approach we showed that Vps45 and Rab14 are selective regulators of GLUT4, but Trarg1, Stx6, Stx16, Tbc1d4 and Rab10 knockdown affected both GLUT4 and TfR translocation. Thus, GLUT4 and TfR translocation machinery likely have some overlap upon insulin-stimulation. In addition, we identified Kif13A, a Rab10 binding molecular motor, as a novel regulator of GLUT4 traffic. Finally, comparison of endogenous to overexpressed GLUT4 highlights that the endogenous GLUT4 methodology has an enhanced sensitivity to genetic perturbations and emphasises the advantage of studying endogenous protein trafficking for drug discovery and genetic analysis of insulin action in relevant cell types.

Atlantic bluefin tuna (Thunnus thynnus) are commercially and ecologically valuable, but management is complicated by their highly migratory lifestyle. Recent collections of bluefin tuna larvae in the Slope Sea off northeastern United States have opened questions about how this region contributes to population dynamics. We analyzed larvae collected in the Slope Sea and the Gulf of Mexico in 2016 to estimate larval abundance and growth rates and used a high-resolution regional ocean circulation model to estimate spawning locations and larval transport. We did not detect a regional difference in growth rates, but found that Slope Sea larvae were larger than Gulf of Mexico larvae prior to exogenous feeding. Slope Sea larvae generally backtracked to locations north of Cape Hatteras and would have been retained within the Slope Sea until the early juvenile stage. Overall, our results provide supporting evidence that the Slope Sea is a major spawning ground that is likely to be important for population dynamics. Further study of larvae and spawning adults in the region should be prioritized to support management decisions.

PURPOSE: SouthSeq is a translational research study that performed genome sequencing (GS) for infants with symptoms suggestive of a genetic disorder. Recruitment targeted racial/ethnic minorities and rural, medically underserved areas in the Southeastern US that are historically under-represented in genomic medicine research. METHODS: GS and analysis were performed for 367 infants to detect disease-causal variation concurrent with standard of care evaluation and testing. RESULTS: Definitive diagnostic (DD) or likely diagnostic (LD) genetic findings were identified in 30% of infants and 14% harbored an uncertain result. Only 43% of DD/LD findings were identified via concurrent clinical genetic testing suggesting that GS testing is better for obtaining early genetic diagnosis. We also identified phenotypes that correlate with the likelihood of receiving a DD/LD finding, such as craniofacial, ophthalmologic, auditory, skin, and hair abnormalities. We did not observe any differences in diagnostic rates between racial/ethnic groups. CONCLUSION: We describe one of the largest-to-date GS cohorts of ill infants, enriched for African American and rural patients. Our results demonstrate the utility of GS as it provides early in life detection of clinically relevant genetic variation not identified via current clinical genetic testing, particularly for infants exhibiting certain phenotypic features.

Provides background information, defining areas within organ systems where physiological waterfalls exist. Describes pressure-flow relationships of elastic tubes (blood vessels, airways, renal tubules, various ducts). (CS)

Insulin resistance is one of the earliest pathological features of a suite of diseases including type 2 diabetes collectively referred to as metabolic syndrome. There is a growing body of evidence from both pre-clinical studies and human cohorts indicating that reactive oxygen species, such as the superoxide radical anion and hydrogen peroxide are key players in the development of insulin resistance. Here we review the evidence linking mitochondrial reactive oxygen species generated within mitochondria with insulin resistance in adipose tissue and skeletal muscle, two major insulin sensitive tissues. We outline the relevant mitochondria-derived reactive species, how the mitochondrial redox state is regulated, and methodologies available to measure mitochondrial reactive oxygen species. Importantly, we highlight key experimental issues to be considered when studying the role of mitochondrial reactive oxygen species in insulin resistance. Evaluating the available literature on both mitochondrial reactive oxygen species/redox state and insulin resistance in a variety of biological systems, we conclude that the weight of evidence suggests a likely role for mitochondrial reactive oxygen species in the etiology of insulin resistance in adipose tissue and skeletal muscle. However, major limitations in the methods used to study reactive oxygen species in insulin resistance as well as the lack of data linking mitochondrial reactive oxygen species and cytosolic insulin signaling pathways are significant obstacles in proving the mechanistic link between these two processes. We provide a framework to guide future studies to provide stronger mechanistic information on the link between mitochondrial reactive oxygen species and insulin resistance as understanding the source, localization, nature, and quantity of mitochondrial reactive oxygen species, their targets and downstream signaling pathways may pave the way for important new therapeutic strategies.

Large groups of animals aggregate around resource hotspots, with group size often influenced by the heterogeneity of the environment. In most cases, the foraging success of individuals within groups is interdependent, scaling either constructively or destructively with group size. Here we used biologging tags, acoustic prey mapping, passive acoustic recording of social cues and remote sensing of surface currents to investigate an alternative scenario in which large, dense aggregations of southeast Atlantic humpback whales, Megaptera novaeangliae, and northeast Pacific blue whales, Balaenoptera musculus, were each associated with ephemeral krill aggregations large enough such that their availability to predators appeared to be influenced more by environmental features than by consumption, implying independence of group size and consumption rates. We found that the temporal scale and spatial extent of oceanographic drivers were consistent with the temporal scale and locations of predator aggregations, and additionally found that groups formed above bathymetric features known to promote zooplankton concentration. Additionally, we found calling behaviour counter-indicative of competition: blue whale foraging calls were anomalously high during observed aggregation time periods, suggesting signalling behaviour that could alert conspecifics to the location of high-quality resources. Modelled results suggest that the use of social information reduces the time required for individuals to discover and exploit high-quality resources, allowing for more efficient foraging without apparent costs to the caller. Thus, rorqual whales foraging in these environments appear to exhibit a social foraging strategy whereby a behaviour with negligible individual costs (signalling) provides information that enhances group foraging efficiency. The population density dependence of this social foraging strategy may help explain why some rorqual species were at first slow to recover from human exploitation, but have since increased more rapidly.

In the North American Northern Great Plains, Kentucky bluegrass (Poa pratensis L.) and smooth bromegrass (Bromus inermis Leyss. subsp. inermis) pose a serious threat to native grassland integrity and function. This study's objectives were to 1) determine drought resistance of non-native grassland and invaded-native tallgrass prairie during 1 and 2 yr of drought and 2) determine drought resilience of non-native grassland and invaded-native tallgrass prairie after 1 yr of drought and 1 yr of recovery with 100% of average precipitation. Three rainout shelters, 3.6 m x 4 m, were installed on non-native and invaded-native grassland in eastern South Dakota to simulate drought conditions by excluding ambient rainfall. The shelter system was constructed on a track whereby the shelter automatically moved over the experimental plots when it rained and moved away from the plots when it stopped raining. Weekly watering treatments consisted of ambient, 75%, 100%, 125%, and 250% of the 30-yr average in 2013 and 2014 (Experiment I). Also, in 2014 a second set of the 75%, 100%, and 125% watering treatments were watered to 100% of the 30-yr average (Experiment II). Drought reduced biomass production in both non-native and invaded-native grassland sites. When plots were watered to 100% of the 30-yr average, the non-native site had similar amount of biomass compared with the drought year, but the invaded-native site had lower biomass. This response provides more evidence regarding the aggressive nature of these two introduced cool-season grasses and a mechanism to explain their continual dominance and expansion in this region.

Objectives The role of B cells in COVID‐19, beyond the production of specific antibodies against SARS-CoV-2, is still not well understood. Here, we describe the novel landscape of circulating double-negative (DN) CD27− IgD− B cells in COVID‐19 patients, representing a group of atypical and neglected subpopulations of this cell lineage. Methods Using multiparametric flow cytometry, we determined DN B cell subset amounts from 91 COVID-19 patients, correlated those with cytokines, clinical and laboratory parameters, and segregated them by principal components analysis. Results We detected significant increments in the DN2 and DN3 B cell subsets, while we found a relevant decrease in the DN1 B cell subpopulation, according to disease severity and patient outcomes. These DN cell numbers also appeared to correlate with pro- or anti-inflammatory signatures, respectively, and contributed to the segregation of the patients into disease severity groups. Conclusion This study provides insights into DN B cell subsets’ potential role in immune responses against SARS‐CoV‐2, particularly linked to the severity of COVID‐19. Supplementary Information The online version contains supplementary material available at 10.1007/s00011-021-01525-3.

This research was funded by Cyprus University of Technology internal funding program, to Nicolas Ioannou; and by the Rural and Environment Science and Analytical Services, Division of the Scottish Government, to David Cooke. Cyprus is the southernmost island country of Europe, located in the Mediterranean. Despite its limited area, potato production is considered an integral source of the national agricultural revenue. During 2010-2012, a late blight epidemic period for the country, the population structure of Phytophthora infestans was analyzed via a sample of 539 isolates collected from all of the main potato-cultivating regions of Cyprus. We determined mating type, mefenoxam sensitivity, and genetic polymorphism at 12 simple sequence repeat (SSRs) loci. Although both mating types were detected in the country, a gradual but dynamic shift toward A2 dominance was manifested over time. The pathogen population also demonstrated reduced sensitivity to the phenylamide fungicide, since 96.2% of the tested isolates had high (70.3%) and intermediate (25.9%) resistance to mefenoxam, which suggests that it should be replaced with other active ingredients in local disease management strategies. The genotypic analysis also revealed the predominance of the highly aggressive mefenoxam-insensitive EU_13_A2 lineage across the country, with a frequency of 79.2%. Other samples comprised an older lineage EU_2_A1 (19.5%), a very low proportion of EU_23_A1 (0.37%), and others that did not match any known lineage (0.92%). SSRs data supported triploid genomes among the dominant lineages, and patterns of their asexual population history were also apparent. A high subclonal variation of the 13_A2 population was detected, which suggested introduction events of this widespread genotype to Cyprus from major tuber-exporting countries. Present data indicate the severe impact of inoculum migration to the structure of the local population; thus, current phytosanitary procedures should be reconsidered and possibly attuned. This is the first comprehensive study to elucidate the diversity of P. infestans in Cyprus and could serve as a baseline for future monitoring of this highly adaptive plant pathogen, given that late blight management strategies should be constantly refined according to the traits of the dominant genotypes of P. infestans.

Ependymomas encompass a heterogeneous group of central nervous system (CNS) neoplasms that occur along the entire neuroaxis. In recent years, extensive (epi-)genomic profiling efforts have identified several molecular groups of ependymoma that are characterized by distinct molecular alterations and/or patterns. Based on unsupervised visualization of a large cohort of genome-wide DNA methylation data, we identified a highly distinct group of pediatric-type tumors (n = 40) forming a cluster separate from all established CNS tumor types, of which a high proportion were histopathologically diagnosed as ependymoma. RNA sequencing revealed recurrent fusions involving the pleomorphic adenoma gene-like 1 (PLAGL1) gene in 19 of 20 of the samples analyzed, with the most common fusion being EWSR1:PLAGL1 (n = 13). Five tumors showed a PLAGL1:FOXO1 fusion and one a PLAGL1:EP300 fusion. High transcript levels of PLAGL1 were noted in these tumors, with concurrent overexpression of the imprinted genes H19 and IGF2, which are regulated by PLAGL1. Histopathological review of cases with sufficient material (n = 16) demonstrated a broad morphological spectrum of tumors with predominant ependymoma-like features. Immunohistochemically, tumors were GFAP positive and OLIG2- and SOX10 negative. In 3/16 of the cases, a dot-like positivity for EMA was detected. All tumors in our series were located in the supratentorial compartment. Median age of the patients at the time of diagnosis was 6.2 years. Median progression-free survival was 35 months (for 11 patients with data available). In summary, our findings suggest the existence of a novel group of supratentorial neuroepithelial tumors that are characterized by recurrent PLAGL1 fusions and enriched for pediatric patients.

Background: Vulvovaginal candidiasis (VVC) is the second most common vulvovaginitis (VV). About 20% of women will experience recurrent infections in their lifetime with non-albicans Candida (NAC) species being one of the causative agents. Although studies have looked at risk factors for recurrent VVC they are limited in scope. In this study, we explore whether risks of recurrent VVC are increased with NAC infections compared to Candida albicans infections. Methods: Through an institutional review board-approved retrospective chart review, we identified 174 women with positive yeast cultures and followed their charts to assess recurrent visits and treatments. We also assessed several baseline variables such as race, age, body mass index (BMI), obstetric history, probiotic use, contraceptive use, mycological therapy, steroid use, hormone replacement therapy, menopausal status, and medical comorbidities. Results: Women with NAC VV were more likely to have multiple visits for recurring infections compared to women who had C. albicans VV (66% vs. 34%). The women with multiple recurrences were younger, had a lower BMI, had lower parity, and endorsed higher use of probiotics. Conclusion: Women with positive NAC cultures were more likely to have multiple visits to their physicians for VV complaints. Identifying the causative species using vaginal fungal cultures can more accurately guide therapy and lead to better outcomes for these patients.

Inhibitors targeting the epidermal growth factor receptor (EGFR) are an effective therapy for patients with non-small cell lung cancer harboring drug-sensitive activating mutations in the EGFR kinase domain. Drug resistance due to treatment-acquired mutations has motivated the development of successive generations of inhibitors that bind in the ATP site. The third-generation agent osimertinib is now a first-line treatment for this disease. Recently, allosteric inhibitors have been developed to overcome drug-resistant mutations that confer a resistance to osimertinib. Here, we present the structure-guided design and synthesis of a mutant-selective lead compound, which consists of a pyridinyl imidazole-fused benzylisoindolinedione scaffold that simultaneously occupies the orthosteric and allosteric sites. The compound potently inhibits enzymatic activity in L858R/T790M/C797S mutant EGFR (4.9 nM), with a significantly lower activity for wild-type EGFR (47 nM). Additionally, this compound achieves modest cetuximab-independent and mutant-selective cellular efficacies on the L858R (1.2 μM) and L858R/T790M (4.4 μM) variants.

Zinc (Zn) is essential for normal plant growth and development. The Zn-regulated transporter, iron-regulated transporter (IRT)-like protein (ZIP) family members are involved in Zn transport and cellular Zn homeostasis throughout the domains of life. In this study, we have characterized four ZIP transporters from Arabidopsis thaliana (IRT3, ZIP4, ZIP6, and ZIP9) to better understand their functional roles. The four ZIP proteins can restore the growth defect of a yeast Zn uptake mutant and are upregulated under Zn deficiency. Single and double mutants show no phenotypes under Zn-sufficient or Zn-limited growth conditions. In contrast, triple and quadruple mutants show impaired growth irrespective of external Zn supply due to reduced Zn translocation from root to shoot. All four ZIP genes are highly expressed during seed development, and siliques from all single and higher-order mutants exhibited an increased number of abnormal seeds and decreased Zn levels in mature seeds relative to wild type. The seed phenotypes could be reversed by supplementing the soil with Zn. Our data demonstrate that IRT3, ZIP4, ZIP6, and ZIP9 function redundantly in maintaining Zn homeostasis and seed development in A. thaliana.

The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (

Large clinical trials have demonstrated the overall safety of vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, reports have emerged of autoimmune phenomena, including vaccine-associated myocarditis,1 immune thrombocytopenia,2 and immune thrombotic thrombocytopenia.3 4 Here we present a novel case of a young woman who developed life-threatening autoimmune hemolytic anemia (AIHA) after her first dose of a SARS-CoV-2 mRNA vaccine. Notably, initial direct antiglobulin testing was negative using standard anti-IgG reagents, which are "blind" to certain immunoglobulin (IgG) isotypes. Further testing using an antiglobulin reagent that detects all IgG isotypes was strongly positive and confirmed the diagnosis of AIHA. The patient required transfusion with 13 units of packed red blood cells, as well as treatment with corticosteroids, rituximab, mycophenolate mofetil, and immune globulin. As efforts to administer SARS-CoV-2 vaccines continue globally, clinicians must be aware of potential autoimmune sequelae of these therapies. This article is protected by copyright. All rights reserved.

Background Patients with suspected acute coronary syndrome in whom myocardial infarction has been excluded are at risk of future adverse cardiac events. Objectives This study evaluated the usefulness of high-sensitivity cardiac troponin I (hs-cTnI) to select patients for further investigation after myocardial infarction has been excluded. Methods This is a prospective cohort study of patients presenting to the emergency department with suspected acute coronary syndrome and hs-cTnI concentrations below the sex-specific 99th percentile. Patients were recruited in a 2:1 fashion, stratified by peak hs-cTnI concentration above and below the risk stratification threshold of 5 ng/L. All patients underwent coronary computed tomography angiography (CCTA) after hospital discharge. Results Overall, 250 patients were recruited (61.4 ± 12.2 years 31% women) in whom 62.4% (156 of 250 patients) had coronary artery disease (CAD). Patients with intermediate hs-cTnI concentrations (between 5 ng/L and the sex-specific 99th percentile) were more likely to have CAD than those with hs-cTnI concentrations, Central Illustration

Topical 17-beta-estradiol (E2) regulates the hair cycle, hair shaft differentiation, and sebum production. Vitamin A also regulates sebum production. Vitamin A metabolism proteins localized to the pilosebaceous unit (PSU; hair follicle and sebaceous gland); and were regulated by E2 in other tissues. This study tests the hypothesis that E2 also regulates vitamin A metabolism in the PSU. First, aromatase and estrogen receptors localized to similar sites as retinoid metabolism proteins during mid-anagen. Next, female and male wax stripped C57BL/6J mice were topically treated with E2, the estrogen receptor antagonist ICI 182,780 (ICI), letrozole, E2 plus letrozole, or vehicle control (acetone) during mid-anagen. E2 or one of its inhibitors regulated most of the vitamin A metabolism genes and proteins examined in a sex-dependent manner. Most components were higher in females and reduced with ICI in females. ICI reductions occurred in the premedulla, sebaceous gland, and epidermis. Reduced E2 also reduced RA receptors in the sebaceous gland and bulge in females. However, reduced E2 increased the number of retinal dehydrogenase 2 positive hair follicle associated dermal dendritic cells in males. These results suggest that estrogen regulates vitamin A metabolism in the skin. Interactions between E2 and vitamin A have implications in acne treatment, hair loss, and skin immunity.

The mesothelium lines body cavities and surrounds internal organs, widely contributing to homeostasis and regeneration. Mesothelium disruptions cause visceral anomalies and mesothelioma tumors. Nonetheless, the embryonic emergence of mesothelia remains incompletely understood. Here, we track mesothelial origins in the lateral plate mesoderm (LPM) using zebrafish. Single-cell transcriptomics uncovers a post-gastrulation gene expression signature centered on hand2 in distinct LPM progenitor cells. We map mesothelial progenitors to lateral-most, hand2-expressing LPM and confirm conservation in mouse. Time-lapse imaging of zebrafish hand2 reporter embryos captures mesothelium formation including pericardium, visceral, and parietal peritoneum. We find primordial germ cells migrate with the forming mesothelium as ventral migration boundary. Functionally, hand2 loss disrupts mesothelium formation with reduced progenitor cells and perturbed migration. In mouse and human mesothelioma, we document expression of LPM-associated transcription factors including Hand2, suggesting re-initiation of a developmental program. Our data connects mesothelium development to Hand2, expanding our understanding of mesothelial pathologies. We thank Single Cell Discoveries for executing the single-cell RNA-sequencing, as well as the Center for Microscopy and Image Analysis (ZMB) and the Cytometry Facility (FCF) of the University of Zurich for technical support and equipment. We also thank Dr. Deborah Yelon, Dr. Richard M. White, Dr. Charles K. Kaufman, and the members of the Mosimann lab for critical input on the manuscript. Species schematics in Figs. 1 and 7 were adjusted from templates provided by PhyloPic (phylopic.org). Zebrafish schematics in Fig. 1 were adjusted from BioRender (biorender.com). This work has been supported by Swiss National Science Foundation (SNSF) professorship PP00P3_139093, SNSF R’Equip grant 316030_150838 (Light Sheet Fluorescence Microscopy), SNSF CRSII5_180345, a Marie Curie Career Integration Grant from the European Commission (CIG PCIG14-GA-2013-631984), the Canton of Zurich, the UZH Foundation for Research in Science and the Humanities, the Swiss Heart Foundation, the ZUNIV FAN/ UZH Alumni, the University of Colorado School of Medicine, Department of Pediatrics and Section of Developmental Biology, and the Helen and Arthur E. Johnson Foundation and Children’s Hospital Colorado Foundation to C.M.; the Swiss Bridge Foundation to A.B. and C.M; a UZH CanDoc to S.N.; EuFishBioMed and Company of Biologists travel fellowships to K.D.P.; SNSF postdoc mobility fellowship P400PB_191057 to J.K.R.; Human Frontier Science Program (HFSP) long-term postdoctoral fellowship LT000078/ 2016 to S.R.N.; SNSF grant 320030_182690 and Stiftung für Angewandte Krebsforschung to E.F.B.; SNSF 310030L_182575 and ERC Starting Grant 2013 337703 to N.M.; SNSF grants 310030_175841 and CRSII5_177208 and University of Zurich’s Research Priority Program Evolution in Action to M.D.R.. Sí

It is a great challenge to scale up current cell therapy processes developed in 2D systems, and bioreactor technology could play an essential role in the scale-up of cell therapeutic products. Cell quality is critical to the therapeutic efficacy and their critical quality attributes (CQAs) are tightly related to their manufacturing processes. Employment of appropriate bioreactors for cellular products would enhance the productivity, reduce the cost as well as ensure the product CQAs. The article reviews current commercially available bioreactors and their applications for regenerative therapeutic products. Regulatory, quality, and manufacturing aspects of these bioreactors are discussed.

The FMR1 premutation (PM:55-199 CGG) is associated with fragile X-associated tremor/ataxia syndrome (FXTAS) and when maternally transmitted is at risk of expansion to a hypermethylated full mutation (FM: ≥ 200 CGG) that causes fragile X syndrome (FXS). We describe a maternally transmitted PM (77 CGG) that was passed to a son (103 CGG), and to a daughter (220-1822 CGG), who were affected with FXTAS and FXS, respectively. The male with the PM showed low-level mosaicism for normal size of 30 and 37 CGG. This male had two offspring: one female mosaic for PM and FM (56, 157, >200 CGG) and another with only a 37 CGG allele detected in multiple tissues, neither with a clinical phenotype. The female with the 37 CGG allele showed normal levels of FMR1 methylation and mRNA and passed this 37 CGG allele to one of her daughters, who was also unaffected. These findings show that post-zygotic paternal retraction can lead to low-level mosaicism for normal size alleles, with these normal alleles being functional when passed over two generations.

Infection is the second leading cause of death in patients with cancer. Loss of efficacy in antibiotics due to antibiotic resistance in bacteria is an urgent threat against the continuing success of cancer therapy. In this review, the authors focus on recent updates on the impact of antibiotic resistance in the cancer setting, particularly on the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.). This review highlights the health and financial impact of antibiotic resistance in patients with cancer. Furthermore, the authors recommend measures to control the emergence of antibiotic resistance, highlighting the risk factors associated with cancer care. A lack of data in the etiology of infections, specifically in oncology patients in United States, is identified as a concern, and the authors advocate for a centralized and specialized surveillance system for patients with cancer to predict and prevent the emergence of antibiotic resistance. Finding better ways to predict, prevent, and treat antibiotic-resistant infections will have a major positive impact on the care of those with cancer.