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Venous thromboembolism (VTE), comprising both deep vein thrombosis (DVT) and pulmonary embolism (PE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. We used multiplex proteomics profiling to screen plasma from patients with suspected acute VTE, and a case-control study of patients followed up after ending anticoagulant treatment for a first VTE. With replication in 5 independent studies, together totalling 1137 patients and 1272 controls, we identify Complement Factor H Related Protein (CFHR5), a regulator of the alternative pathway of complement activation, as a novel VTE associated plasma biomarker. Using GWAS analysis of 2967 individuals we identified a genome-wide significant pQTL signal on chr1q31.3 associated with CFHR5 levels. We showed that higher CFHR5 levels are associated with increased thrombin generation in patient plasma and that recombinant CFHR5 enhances platelet activationin vitro. Thrombotic complications are a frequent feature of COVID-19; in hospitalised patients we found CFHR5 levels at baseline were associated with short-time prognosis of disease severity, defined as maximum level of respiratory support needed during hospital stay. Our results indicate a clinically important role for regulation of the alternative pathway of complement activation in the pathogenesis of VTE and pulmonary complications in acute COVID-19. Thus, CFHR5 is a potential diagnostic and/or risk predictive plasma biomarker reflecting underlying pathology in VTE and acute COVID-19.

The importance of defining cell-type-specific genes is well acknowledged. Technological advances facilitate high-resolution sequencing of single cells, but practical challenges remain. Adipose tissue is composed pri-marily of adipocytes, large buoyant cells requiring extensive, artefact-generating processing for separation and analysis. Thus, adipocyte data are frequently absent from single-cell RNA sequencing (scRNA-seq) data -sets, despite being the primary functional cell type. Here, we decipher cell-type-enriched transcriptomes from unfractionated human adipose tissue RNA-seq data. We profile all major constituent cell types, using 527 visceral adipose tissue (VAT) or 646 subcutaneous adipose tissue (SAT) samples, identifying over 2,300 cell-type-enriched transcripts. Sex-subset analysis uncovers a panel of male-only cell-type-enriched genes. By resolving expression profiles of genes differentially expressed between SAT and VAT, we identify mesothelial cells as the primary driver of this variation. This study provides an accessible method to profile cell-type-enriched transcriptomes using bulk RNA-seq, generating a roadmap for adipose tissue biology.

This article presents a case study of a decolonized curriculum development in the Art History programme at the small liberal arts institution Kalamazoo College (Michigan, USA). It discusses the curriculum plan, methods for learning, assessment and potential applications for this approach beyond the case study. Paying attention to questions about the origins of art history, and its long-established methods and canon within the Western academy, this article proposes that any approach to decolonizing an art history curriculum must take into account the frameworks and methods of the knowledge systems it employs, must continually assess, reflect and hold accountable those who participate in its implementation and maintenance, and, importantly, must recognize that decolonization work is a necessarily messy and ongoing process.

Importin proteins were originally characterized for their central role in protein transport through the nuclear pores, the only intracellular entry to the nucleus. This vital function must be tightly regulated to control access by transcription factors and other nuclear proteins to genomic DNA, to achieve appropriate modulation of cellular behaviors affecting cell fate. Importin-mediated nucleocytoplasmic transport relies on their specific recognition of cargoes, with each importin binding to distinct and overlapping protein subsets. Knowledge of importin function has expanded substantially in regard to three key developmental systems: embryonic stem cells, muscle cells and the germ line. In the decade since the potential for regulated nucleocytoplasmic transport to contribute to spermatogenesis was proposed, we and others have shown that the importins that ferry transcription factors into the nucleus perform additional roles, which control cell fate. This review presents key findings from studies of mammalian spermatogenesis that reveal potential new pathways by which male fertility and infertility arise. These studies of germline genesis illuminate new ways in which importin proteins govern cellular differentiation, including via directing proteins to distinct intracellular compartments and by determining cellular stress responses.

In today's highly competitive educational environment, becoming a physician requires that the students attend a high school that offers both a challenging curriculum and advanced course work. Ideally, the learning will occur in classroom environments with certified and nurturing teachers. Once accepted to college the students must survive two years of intense science coursework across the three disciplines of Biology, Chemistry and Physics and maintain a grade point average (GPA) of 3.5 or better. Still very few African American students reach these final steps on the challenging road to a career in medicine. This paper describes some of the historical and contemporary barriers African American physicians have faced as well as their underrepresentation as medical students including the differences in acceptance rates. The paper also discusses the impact of undergraduate science education on African American students’ medical school admissions. The importance of this review relates to the fact that there is currently an insufficient number of physicians and that African American physicians are underrepresented in that group.

A novel, simple, and sensitive assay was developed to monitor, quantitatively, the hyaluronidase and heparinase I-catalyzed cleavage of fluoresceinamine-labeled hyaluronic acid and heparin, respectively. The fluoresceinamine-labeled substrates were hydrophobically absorbed onto 4-microm polystyrene beads. In the presence of enzyme, the change in fluorescence output of the substrate-absorbed beads was monitored in a noncontinuous manner using a flow cytometer. Our results show that hyaluronidase and heparinase I can cleave their respective substrates on the beads in a concentration- and time-dependent manner. The assay is suitable for detecting the presence of these glycosaminoglycan-degrading enzymes in cell lysates, extracts, or purified fractions, for quantifying their amounts, and for investigating the activity of potential inhibitors.

18O exchange experiments were designed to identify the final intermediate in the catalytic mechanism of bacteriophage T4 deoxycytidylate (dCMP) hydroxymethylase (CH). CH catalyzes the formation of 5-(hydroxymethyl)-dCMP (HmdCMP) from dCMP and methylenetetrahydrofolate (CH2-THF). CH resembles thymidylate synthase (TS), an enzyme of known three-dimensional structure, in both amino acid sequence and the reaction catalyzed. The final intermediate in the reaction catalyzed by TS or CH has been proposed to be the nucleotide with an exocyclic 5-methylene group covalently linked to the enzyme. This intermediate is then hydrated to HmdCMP (by CH) or reduced to deoxythymidylate (by TS). We report here that CH catalyzes the incorporation of 18O from solvent water into the product, HmdCMP, in the presence of tetrahydrofolate (THF). The cause of this exchange is a reverse reaction followed by a resynthesis. CH also catalyzes the exchange of 18O from solvent water into HmdCMP in the absence of exogenous THF and in the presence of THF analogues that lack N-5. N-5 is the nitrogen that is likely to be bound to the methylene as it is transferred to dCMP. A CH variant that lacks the nucleophilic Cys 148 is incapable of promoting these 18O exchange reactions. The THF analogues lacking N-5 do not promote a CH-catalyzed reverse reaction. Rather, we propose that the CH-catalyzed 18O exchange reaction promoted by these THF analogues occurs via 5-methylene-dCMP linked to the enzyme through Cys 148. We conclude here that enzyme-bound 5-methylene-dCMP is the final intermediate during catalysis by CH, as has also been proposed for TS and dUMP.

The economic case for the production of biomass crops can only be established through a comprehensive analysis of the potential costs and returns of these crops. Using data from Ireland, this paper provides a Discounted Cash Flow (DCF) investment analysis for two of the most common biomass crops, willow and miscanthus. We find that miscanthus consistently generates investment returns greater than willow. Sensitivity analysis is used to examine the effects on the estimates of variation in key physical and financial parameters. The superseded enterprise, establishment grant level, yield level, price level, and length of production lifespan are shown to significantly influence the returns generated by investments in willow and miscanthus.

This paper reviews the economic performance of Irish dairy farms over the period 1998 to 2006 with the objective of identifying the factors influencing cost structure. Initial analysis reveals that a large variation in cost structure exists in the Irish dairy farming sector, and that this variation has increased over time. Econometric techniques are employed to examine the variation in cost structures and to identify the factors affecting farm profitability. National Farm Survey data from Ireland are used to analyse production costs. Average cost curves are shown for the Irish dairy industry and are compared to the results of similar analysis conducted for England and Wales. The results show that increasing yield per cow and stocking rate decreases costs implying that scale and improving efficiency is key to reducing cost. An analysis of cost mobility showed that cost structure was quite sticky, and that relative cost management improved little over the period, with the majority of high cost farmers remaining high cost.

Successful management of classical ballet dancers with overuse injuries requires an understanding of the art form, precise knowledge of anatomy and awareness of certain conditions. Turnout is the single most fundamental physical attribute in classical ballet and 'forcing turnout' frequently contributes to overuse injuries. Common presenting conditions arising from the foot and ankle include problems at the first metatarsophalangeal joint, second metatarsal stress fractures, flexor hallucis longus tendinitis and anterior and posterior ankle impingement syndromes. Persistent shin pain in dancers is often due to chronic compartment syndrome, stress fracture of the posteromedial or anterior tibia. Knee pain can arise from patellofemoral syndrome, patellar tendon insertional pathologies, or a combination of both. Hip and back problems are also prevalent in dancers. To speed injury recovery of dancers, it is important for the sports medicine team to cooperate fully. This permits the dancer to benefit from accurate diagnosis, technique correction where necessary, the full range of manual therapies to joint and soft tissue, appropriate strengthening programmes and maintenance of dance fitness during any time out of class with Pilates-based exercises and nutrition advice. Most overuse ballet conditions respond well to a combination of conservative therapies. Those dancers that do require surgical management still depend heavily on ballet-specific rehabilitation for a complete recovery.

1. 1. SAMP lyase and AMP deaminase were determined in parenchymal and kupffer cells of rats fed either basal or carcinogen-enriched diets. Results were calculated on a U/mg protein and U/cell basis. 2. 2. Data indicated that although deaminase increased 1 1 2 - to 2-fold in parenchymal cells on a U/mg protein and U/cell basis from rats fed carcinogen-enriched diets there was a greater increase in U/mg protein. 3. 3. In contrast, little to no increase was seen in kupffer cells. 4. 4. SAMP lyase, however, depicted a smaller increase in parenchymal cells of carcinogen-enriched diet fed rats, but a 4- to 5-fold elevation in kupffer cells regardless of whether the data were expressed in U/mg protein or U/cell. 5. 5. These data indicate that increased activity of AMP deaminase may be a result of resistance to degradation in parenchymal cells, whereas SAMP lyase elevations in kupffer cells may reflect an increase in enzyme concentration.