Single cell transcriptomics comes of age

Single cell transcriptomics technologies have vast potential in advancing our understanding of biology and disease. Here, Sarah Aldridge and Sarah Teichmann review the last decade of technological advancements in single-cell transcriptomics and highlight some of the recent discoveries enabled by this technology

The City That (Didn’t) Make It Work: An Analysis Of State-Sponsored Resegregation In Charlotte-Mecklenburg Schools

A 1984 editorial published in the Charlotte Observer proclaimed that Charlotte’s “proudest achievement is its fully integrated school system…one of the nation’s finest, recognized throughout the United States for quality innovation, and most of all, for overcoming the most difficult challenge American public education has ever faced” (Mickelson, Smith, & Hawn Nelson, 2015a, p. 2). However, the Charlotte-Mecklenburg School system (CMS) has become largely resegregated; in 2015, more than half of the students of color in Charlotte-Mecklenburg attended hypersegregated schools (Helms, 2015). This thesis aims to examine the resegregation of public education in Charlotte, and focuses on understanding the social, political, and economic causes of resegregation. Using Bonilla-Silva’s (2001) theory of “new racism” as a frame of analysis and reviews of existing literature, this thesis examines the ways that decisions made by elected officials and government bodies work to uphold existing systems of racial inequity and guarantee disadvantages for students of color in the American public education system by directly or indirectly isolating students of color into segregated schools. As a result of these decisions at the local, state, and national level, Charlotte’s public schools have transitioned from a national example of desegregation to a highly segregated, inequitable school system

Degradation of tetraphenylphosphonium bromide at high pH and its effect on radionuclide solubility

Recently, tetraphenylphosphonium bromide (TPPB) has been used to remove technetium from some radioactive waste streams. However, before TPPB could 15 be approved for use it was necessary to show that TPPB and its degradation products would not have a significant detrimental effect on post-closure performance of a radioactive waste repository. TPPB is known to be stable at neutral pH, however, under alkaline conditions it degrades by an alkaline hydrolysis mechanism to triphenylphosphonium oxide (TPPO). Degradation can 20 also occur by radiolysis to produce triphenylphosphine (TPP). The kinetics of the alkaline hydrolysis degradation of TPPB is described and the solubility of europium, iodine, nickel, technetium(VII) and uranium(VI) in aqueous solutions of TPPB and its degradation products is reported. These results were used to support the use of TPPB in removing technetium from some waste streams

Uptake of COVID-19 vaccinations amongst 3,433,483 children and young people: meta-analysis of UK prospective cohorts

SARS-CoV-2 infection in children and young people (CYP) can lead to life-threatening COVID-19, transmission within households and schools, and the development of long COVID. Using linked health and administrative data, we investigated vaccine uptake among 3,433,483 CYP aged 5–17 years across all UK nations between 4th August 2021 and 31st May 2022. We constructed national cohorts and undertook multi-state modelling and meta-analysis to identify associations between demographic variables and vaccine uptake. We found that uptake of the first COVID-19 vaccine among CYP was low across all four nations compared to other age groups and diminished with subsequent doses. Age and vaccination status of adults living in the same household were identified as important risk factors associated with vaccine uptake in CYP. For example, 5–11 year-olds were less likely to receive their first vaccine compared to 16–17 year-olds (adjusted Hazard Ratio [aHR]: 0.10 (95%CI: 0.06–0.19)), and CYP in unvaccinated households were less likely to receive their first vaccine compared to CYP in partially vaccinated households (aHR: 0.19, 95%CI 0.13–0.29)

The lives of young carers in England omnibus survey report. Appendices to research report

The lives of young carers in England omnibus survey report. Appendices to research repor

Eating Disorders and Intrasexual Competition: Testing an Evolutionary Hypothesis among Young Women

The sexual competition hypothesis (SCH) contends that intense female intrasexual competition (ISC) is the ultimate cause of eating disorders. The SCH explains the phenomenon of the pursuit of thinness as an adaptation to ISC in the modern environment. It argues that eating disorders are pathological phenomena that arise from the mismatch between the modern environment and the inherited female adaptations for ISC. The present study has two aims. The first is to examine the relationship between disordered eating behavior (DEB) and ISC in a sample of female undergraduates. The second is to establish whether there is any relationship between disordered eating behavior and life history (LH) strategy. Participants completed a battery of questionnaires examining eating-related attitudes and behaviors, ISC, and LH strategy. A group of 206 female undergraduates were recruited. A structural equation model was constructed to analyze the data. ISC for mates was significantly associated with DEB, as predicted by the SCH. DEB was found to be predicted by fast LH strategy, which was only partially mediated by the SCH. The results of this study are supportive of the SCH and justify research on a clinical sample

Complex wing motion during stridulation in the katydid Nastonotus foreli (Orthoptera: Tettigoniidae: Pseudophyllinae)

Male Katydids (Orthoptera: Tettigoniidae) rub together their specialised forewings to produce sound, a process known as stridulation. During wing closure, a lobe on the anal margin of the right forewing (a scraper), engages with a teeth-covered file on the left forewing. The movement of the scraper across the file produces vibrations which are amplified by a large wing cell adjacent to the scraper, the mirror. Katydids are known to stridulate with either sustained or interrupted sweeps of the file, generating resonant pure-tone (narrowband frequency) or non-resonant (broadband frequencies) calls. However, some species can conserve some purity in their calls despite incorporating discrete pulses and silent intervals. This mechanism is exhibited by many Pseudophyllinae, such as Nastonotus spp., Cocconotus spp., Triencentrus spp. and Eubliastes spp. This study aims to measure and quantify the mechanics of wing stridulation in Nastonotus foreli, a Neotropical katydid that can produce complex, relatively narrowband calls at ≈20kHz. It was predicted that this species will use a stridulatory mechanism involving elastic energy whereby the scraper bends and flicks along the file in periodic bursts. The calling behaviour and wing mechanics of seven males were studied using a combination of technologies (e.g. micro-scanning laser Doppler vibrometry, advanced microscopy, ultrasound-sensitive equipment and optical motion detectors) to quantify wing mechanics and structure. Analysis of recordings revealed no clear relationship between wing velocity and carrier frequency, and a pronounced distinction between wing velocity and scraper velocity during wing closure, suggesting that the scraper experiences considerable deformation. This is characteristic of the elastic scraper mechanism of stridulation. Curiously, N. foreli might have evolved to employ elastic energy to double the duration of the call, despite possessing muscles that can reach velocities high enough to produce the same frequency without the help of elastic energy

Seasonality and immunity to laboratory-confirmed seasonal coronaviruses (HCoV-NL63, HCoV-OC43, and HCoV-229E): results from the Flu Watch cohort study

Background: There is currently a pandemic caused by the novel coronavirus SARS-CoV-2. The intensity and duration of this first wave in the UK may be dependent on whether SARS-CoV-2 transmits more effectively in the winter than the summer and the UK Government response is partially built upon the assumption that those infected will develop immunity to reinfection in the short term. In this paper we examine evidence for seasonality and immunity to laboratory-confirmed seasonal coronavirus (HCoV) from a prospective cohort study in England. Methods: In this analysis of the Flu Watch cohort, we examine seasonal trends for PCR-confirmed coronavirus infections (HCoV-NL63, HCoV-OC43, and HCoV-229E) in all participants during winter seasons (2006-2007, 2007-2008, 2008-2009) and during the first wave of the 2009 H1N1 influenza pandemic (May-Sep 2009). We also included data from the pandemic and �post-pandemic� winter seasons (2009-2010 and 2010-2011) to identify individuals with two confirmed HCoV infections and examine evidence for immunity against homologous reinfection. Results: We tested 1,104 swabs taken during respiratory illness and detected HCoV in 199 during the first four seasons. The rate of confirmed HCoV infection across all seasons was 390 (95% CI 338-448) per 100,000 person-weeks; highest in the Nov-Mar 2008/9 season at 674 (95%CI 537-835). The highest rate was in February at 759 (95% CI 580-975). Data collected during May-Sep 2009 showed there was small amounts of ongoing transmission, with four cases detected during this period. Eight participants had two confirmed infections, of which none had the same strain twice. Conclusion: Our results provide evidence that HCoV infection in England is most intense in winter, but that there is a small amount of ongoing transmission during summer periods. We found some evidence of immunity against homologous reinfection.</ns3:p

Protein Complexes and Proteolytic Activation of the Cell Wall Hydrolase RipA Regulate Septal Resolution in Mycobacteria

Peptidoglycan hydrolases are a double-edged sword. They are required for normal cell division, but when dysregulated can become autolysins lethal to bacteria. How bacteria ensure that peptidoglycan hydrolases function only in the correct spatial and temporal context remains largely unknown. Here, we demonstrate that dysregulation converts the essential mycobacterial peptidoglycan hydrolase RipA to an autolysin that compromises cellular structural integrity. We find that mycobacteria control RipA activity through two interconnected levels of regulation in vivo—protein interactions coordinate PG hydrolysis, while proteolysis is necessary for RipA enzymatic activity. Dysregulation of RipA protein complexes by treatment with a peptidoglycan synthase inhibitor leads to excessive RipA activity and impairment of correct morphology. Furthermore, expression of a RipA dominant negative mutant or of differentially processed RipA homologues reveals that RipA is produced as a zymogen, requiring proteolytic processing for activity. The amount of RipA processing differs between fast-growing and slow-growing mycobacteria and correlates with the requirement for peptidoglycan hydrolase activity in these species. Together, the complex picture of RipA regulation is a part of a growing paradigm for careful control of cell wall hydrolysis by bacteria during growth, and may represent a novel target for chemotherapy development

A silent orchestra: convergent song loss in Hawaiian crickets is repeated, morphologically varied, and widespread

Host-parasite interactions are predicted to drive the evolution of defences and counter-defences, but the ability of either partner to adapt depends on new and advantageous traits arising. The loss of male song in Hawaiian field crickets (Teleogryllus oceanicus) subject to fatal parasitism by eavesdropping flies (Ormia ochracea) is a textbook example of rapid evolution in one such arms race. Male crickets ordinarily sing to attract females by rubbing their forewings together, which produces sound by exciting acoustic resonating structures formed from modified wing veins (‘normal-wing’). The resulting song is the target of strong sexual selection by conspecific females. However, male song also attracts female flies that squirt larvae onto males or nearby female crickets; the larvae then burrow into, consume, and ultimately kill the host. The flies thus impose strong natural selection on male song, producing silent males, which have spread rapidly in populations on two islands – Kauai and Oahu. On both islands, song loss is caused by genetic mutations that drastically reduce or eliminate sound-producing structures on the male forewing by feminising wing venation – these males are called ‘flatwing’. On recent visits to parasitized cricket populations, we discovered two additional wing phenotypes – ‘small-wing’ and ‘curly-wing’. These two phenotypes differ noticeably from flatwing, and from each other, but all have the effect of eliminating or reducing acoustic signals that attract the parasitoid fly. These discoveries illustrate how the evolutionary process can repeatedly, and through a remarkable variety of independent mechanisms, drive adaptation to the same selection pressure