Transition to Self-compatibility Associated With Dominant S-allele in a Diploid Siberian Progenitor of Allotetraploid Arabidopsis kamchatica Revealed by Arabidopsis lyrata Genomes.

A transition to selfing can be beneficial when mating partners are scarce, for example, due to ploidy changes or at species range edges. Here, we explain how self-compatibility evolved in diploid Siberian Arabidopsis lyrata, and how it contributed to the establishment of allotetraploid Arabidopsis kamchatica. First, we provide chromosome-level genome assemblies for two self-fertilizing diploid A. lyrata accessions, one from North America and one from Siberia, including a fully assembled S-locus for the latter. We then propose a sequence of events leading to the loss of self-incompatibility in Siberian A. lyrata, date this independent transition to ∼90 Kya, and infer evolutionary relationships between Siberian and North American A. lyrata, showing an independent transition to selfing in Siberia. Finally, we provide evidence that this selfing Siberian A. lyrata lineage contributed to the formation of the allotetraploid A. kamchatica and propose that the selfing of the latter is mediated by the loss-of-function mutation in a dominant S-allele inherited from A. lyrata.

Recognition of CD1d-sulfatide mediated by a type II natural killer T cell antigen receptor.

Natural killer T cells (NKT cells) are divided into type I and type II subsets on the basis of differences in their T cell antigen receptor (TCR) repertoire and CD1d-antigen specificity. Although the mode by which type I NKT cell TCRs recognize CD1d-antigen has been established, how type II NKT cell TCRs engage CD1d-antigen is unknown. Here we provide a basis for how a type II NKT cell TCR, XV19, recognized CD1d-sulfatide. The XV19 TCR bound orthogonally above the A' pocket of CD1d, in contrast to the parallel docking of type I NKT cell TCRs over the F' pocket of CD1d. At the XV19 TCR-CD1d-sulfatide interface, the TCRα and TCRß chains sat centrally on CD1d, where the malleable CDR3 loops dominated interactions with CD1d-sulfatide. Accordingly, we highlight the diverse mechanisms by which NKT cell TCRs can bind CD1d and account for the distinct antigen specificity of type II NKT cells.

A comparative study of tissue protein synthesis rates in an Antarctic, Harpagifer antarcticus and a temperate, Lipophrys pholis teleost.

The affect of temperature on tissue protein synthesis rates has been reported in temperate and tropical, but not Antarctic fishes. Previous studies have generally demonstrated low growth rates in Antarctic fish species in comparison to temperate relatives and elevated levels of protein turnover. This study investigates how low temperatures effect tissue protein synthesis and hence tissue growth in a polar fish species. Groups of Antarctic, Harpagifer antarcticus and temperate, Lipophrys pholis, were acclimated to a range of overlapping water temperatures and protein synthesis was measure in white muscle (WM), liver and gastrointestinal tract (GIT). WM protein synthesis rates increased linearly with temperature in both species (H. antarcticus 0.16-0.23%.d-1, L. pholis, 0.31-0.76%.d-1), while liver (H. antarcticus 0.24-0.27%.d-1, L. pholis, 0.44-1.03%.d-1) and GIT were unaffected by temperature in H. antarcticus but increased non-linearly in L.pholis (H. antarcticus 0.22-0.26%.d-1, L. pholis, 0.40-0.86%.d-1). RNA to protein ratios were unaffected by temperature in H. antarcticus but increased weakly, in L.pholis WM and liver. In L.pholis, RNA translational efficiency increased significantly with temperature in all tissues, but only in liver in H. antarcticus. At the overlapping temperature of 3 °C, protein synthesis (WM 26%, Liver, 39%, GIT, 35%) and RNA translational efficiency (WM 273%, Liver, 271%, GIT, 300%) were significantly lower in H. antarcticus than L.pholis, while RNA to protein ratios were significantly higher (WM 270%, Liver 170%, GIT 186%). Tissue specific effects of temperature are detectable in both species. This study provides the first evidence, that tissue protein synthesis rates are constrained in Antarctic fishes.

Recognition of ß-linked self glycolipids mediated by natural killer T cell antigen receptors.

The most potent foreign antigens for natural killer T cells (NKT cells) are α-linked glycolipids, whereas NKT cell self-reactivity involves weaker recognition of structurally distinct ß-linked glycolipid antigens. Here we provide the mechanism for the autoreactivity of T cell antigen receptors (TCRs) on NKT cells to the mono- and tri-glycosylated ß-linked agonists ß-galactosylceramide (ß-GalCer) and isoglobotrihexosylceramide (iGb3), respectively. In binding these disparate antigens, the NKT cell TCRs docked onto CD1d similarly, achieving this by flattening the conformation of the ß-linked ligands regardless of the size of the glycosyl head group. Unexpectedly, the antigenicity of iGb3 was attributable to its terminal sugar group making compensatory interactions with CD1d. Thus, the NKT cell TCR molds the ß-linked self ligands to resemble the conformation of foreign α-linked ligands, which shows that induced-fit molecular mimicry can underpin the self-reactivity of NKT cell TCRs to ß-linked antigens.

Perceptions, beliefs, and current practices regarding neonatal skin care and emollient use in eastern Uganda: a qualitative study.

BACKGROUND: The skin is a major route of infection in the neonatal period, especially in low birthweight (LBW) infants. Appropriate and safe neonatal skin care practices are required to reduce this risk. The perceptions and beliefs of mothers and other caregivers towards various neonatal skin care practices in our setting have been documented. Data from Asia suggests that the application of emollient to the skin of LBW infants can promote growth, reduce serious neonatal infections, and potentially reduce mortality. This is the first study to explore the acceptability of emollients and massage as part of neonatal skin care in a low-resource setting in sub-Saharan Africa (SSA) that is representative of the majority of government health facilities in Uganda and many in SSA. OBJECTIVE: To explore perceptions, beliefs, and current practices regarding neonatal skin care and emollient use in eastern Uganda. METHODS: We conducted a qualitative study consisting of three focus group discussions (30 participants), eight in-depth interviews with mothers/caregivers of preterm and term neonates and 12 key informant interviews with midwives, doctors and community health workers involved in neonatal care, to explore the perceptions and practices surrounding neonatal skin care and emollient use. Data collected were transcribed and analyzed using thematic content analysis. RESULTS: Mothers perceived that skin care began in utero. Skincare practices depended on the place of delivery; for deliveries in a health facility the skincare practices were mainly based on the health worker's advice. Vernix caseosa was often washed off due to its perceived undesirability and was attributed to sexual intercourse in the last trimester. Despite their deleterious attributes found in previous studies, petrolatum-based oils, petrolatum-based jellies and talcum baby powders were the most commonly reported items used in neonatal skin care. In our population, there was high acceptability of emollient therapy use; however, neonatal massage was treated with scepticism as mothers feared damaging the vulnerable neonate. Mothers suggested massage and emollient application be undertaken by health workers, if it becomes an intervention. CONCLUSIONS: In eastern Uganda, the perceptions and beliefs of mothers/caregivers toward neonatal skincare influenced their practices of which some could potentially be beneficial, and others harmful. Emollient use would be easily accepted if adequate sensitisation is conducted and using the gatekeepers such as health workers.

A microstructural investigation of an industrial attractive gel at pressure and temperature.

Oil-continuous drilling fluids used in the oil and gas industry are formulated to be pseudoplastic with a relatively weak yield stress. These fluids are required to maintain their properties over wide temperature and pressure ranges yet there are few methods that can sensitively study the inherent structure and mechanical properties in the fluids under such conditions. Here we study a model oil-continuous drilling fluid formulation as a function of both temperature (up to 153 °C) and pressure (up to 1330 bar) with Diffusive Wave Spectroscopy (DWS). The system comprises a colloidal gel network of clay particles and trapped emulsion droplets. As a function of temperature the system undergoes local structural changes reflected in the DWS dynamics which are also consistent with macroscopic rheological measurements. On cycling to high pressure the system exhibits similar structural and dynamic changes with a strong hysteresis. Although multiple scattering in multicomponent non-ergodic samples does not directly yield self diffusion probe dynamics, the use of microrheology analysis here appears to be in good agreement with direct rheological measurements of the sample linear viscoelasticity at ambient pressure. Thus DWS microrheology succesfully probes irreversible changes in the structure and the mechanical response of the drilling fluid formulation under a high pressure cycle.

Community health workers and health equity in low- and middle-income countries: systematic review and recommendations for policy and practice.

BACKGROUND: The deployment of Community Health Workers (CHWs) is widely promoted as a strategy for reducing health inequities in low- and middle-income countries (LMIC). Yet there is limited evidence on whether and how CHW programmes achieve this. This systematic review aimed to synthesise research findings on the following questions: (1) How effective are CHW interventions at reaching the most disadvantaged groups in LMIC contexts? and (2) What evidence exists on whether and how these programmes reduce health inequities in the populations they serve? METHODS: We searched six academic databases for recent (2014-2020) studies reporting on CHW programme access, utilisation, quality, and effects on health outcomes/behaviours in relation to potential stratifiers of health opportunities and outcomes (e.g., gender, socioeconomic status, place of residence). Quantitative data were extracted, tabulated, and subjected to meta-analysis where appropriate. Qualitative findings were synthesised using thematic analysis. RESULTS: One hundred sixty-seven studies met the search criteria, reporting on CHW interventions in 33 LMIC. Quantitative synthesis showed that CHW programmes successfully reach many (although not all) marginalized groups, but that health inequalities often persist in the populations they serve. Qualitative findings suggest that disadvantaged groups experienced barriers to taking up CHW health advice and referrals and point to a range of strategies for improving the reach and impact of CHW programmes in these groups. Ensuring fair working conditions for CHWs and expanding opportunities for advocacy were also revealed as being important for bridging health equity gaps. CONCLUSION: In order to optimise the equity impacts of CHW programmes, we need to move beyond seeing CHWs as a temporary sticking plaster, and instead build meaningful partnerships between CHWs, communities and policy-makers to confront and address the underlying structures of inequity. TRIAL REGISTRATION: PROSPERO registration number CRD42020177333 .

Downstream sequence-dependent RNA cleavage and pausing by RNA polymerase I.

The sequence of the DNA template has long been thought to influence the rate of transcription by DNA-dependent RNA polymerases, but the influence of DNA sequence on transcription elongation properties of eukaryotic RNA polymerase I (Pol I) from Saccharomyces cerevisiae has not been defined. In this study, we observe changes in dinucleotide production, transcription elongation complex stability, and Pol I pausing in vitro in response to downstream DNA. In vitro studies demonstrate that AT-rich downstream DNA enhances pausing by Pol I and inhibits Pol I nucleolytic cleavage activity. Analysis of Pol I native elongating transcript sequencing data in Saccharomyces cerevisiae suggests that these downstream sequence elements influence Pol I in vivo Native elongating transcript sequencing studies reveal that Pol I occupancy increases as downstream AT content increases and decreases as downstream GC content increases. Collectively, these data demonstrate that the downstream DNA sequence directly impacts the kinetics of transcription elongation prior to the sequence entering the active site of Pol I both in vivo and in vitro.

Gel breakdown in a formulated product via accumulated strain.

Almost any formulated product is sufficiently complex that definitive elucidation of all interactions and microstructural evolutions is difficult at best and more likely intractable. Drilling fluids are no exception. Nevertheless, detailed experiment and comparison with simpler systems studied in the literature enable rational pictures to be deduced. We study the breakdown of a gelled formulated product, a drilling fluid, under the action of repeated deformation, i.e. weakly nonlinear oscillation. Our data may be rationalised by postulating that the fluid behaves as an arrested phase separating material whose natural slow structural evolution, aging and coarsening, is accelerated by the imposed sinusoidal strain consistent with previous work on well characterised systems. During the observed evolution the elastic modulus exhibits a maximum which appears correlated with a maximal connected heterogeneity of structure.

The changing form of Antarctic biodiversity.

Antarctic biodiversity is much more extensive, ecologically diverse and biogeographically structured than previously thought. Understanding of how this diversity is distributed in marine and terrestrial systems, the mechanisms underlying its spatial variation, and the significance of the microbiota is growing rapidly. Broadly recognizable drivers of diversity variation include energy availability and historical refugia. The impacts of local human activities and global environmental change nonetheless pose challenges to the current and future understanding of Antarctic biodiversity. Life in the Antarctic and the Southern Ocean is surprisingly rich, and as much at risk from environmental change as it is elsewhere.

NETSeq reveals heterogeneous nucleotide incorporation by RNA polymerase I.

DNA sequence motifs that affect RNA polymerase transcription elongation are well studied in prokaryotic organisms and contribute directly to regulation of gene expression. Despite significant work on the regulation of eukaryotic transcription, the effect of DNA template sequence on RNA polymerase I (Pol I) transcription elongation remains unknown. In this study, we examined the effects of DNA sequence motifs on Pol I transcription elongation kinetics in vitro and in vivo. Specifically, we characterized how the spy rho-independent terminator motif from Escherichia coli directly affects Saccharomyces cerevisiae Pol I activity, demonstrating evolutionary conservation of sequence-specific effects on transcription. The insight gained from this analysis led to the identification of a homologous sequence in the ribosomal DNA of S. cerevisiae We then used native elongating transcript sequencing (NETSeq) to determine whether Pol I encounters pause-inducing sequences in vivo. We found hundreds of positions within the ribosomal DNA (rDNA) that reproducibly induce pausing in vivo. We also observed significantly lower Pol I occupancy at G residues in the rDNA, independent of other sequence context, indicating differential nucleotide incorporation rates for Pol I in vivo. These data demonstrate that DNA template sequence elements directly influence Pol I transcription elongation. Furthermore, we have developed the necessary experimental and analytical methods to investigate these perturbations in living cells going forward.

A molecular basis for NKT cell recognition of CD1d-self-antigen.

The antigen receptor for natural killer T cells (NKT TCR) binds CD1d-restricted microbial and self-lipid antigens, although the molecular basis of self-CD1d recognition is unclear. Here, we have characterized NKT TCR recognition of CD1d molecules loaded with natural self-antigens (Ags) and report the 2.3 Å resolution structure of an autoreactive NKT TCR-phosphatidylinositol-CD1d complex. NKT TCR recognition of self- and foreign antigens was underpinned by a similar mode of germline-encoded recognition of CD1d. However, NKT TCR autoreactivity is mediated by unique sequences within the non-germline-encoded CDR3ß loop encoding for a hydrophobic motif that promotes self-association with CD1d. Accordingly, NKT cell autoreactivity may arise from the inherent affinity of the interaction between CD1d and the NKT TCR, resulting in the recognition of a broad range of CD1d-restricted self-antigens. This demonstrates that multiple self-antigens can be recognized in a similar manner by autoreactive NKT TCRs.

Bureaucratic encounters "after neoliberalism": Examining the supportive turn in social housing governance.

It is well established that encounters between welfare bureaucracies and their clients have been reconfigured under neoliberalism to address the problem of "welfare dependency." Contemporary bureaucratic encounters therefore entail measures to activate clients' entrepreneurial/self-governing capacities, and conditionality/sanctioning practices to deal with clients who behave "irresponsibly." Despite the dominance of the neoliberal model, recent research has identified a counter-trend in the practices of housing services away from entrepreneurializing and punitive strategies and towards a more supportive approach. This paper examines this counter-trend and its implications for neoliberal welfare governance. To do this, it presents findings from research into social housing governance in Queensland, Australia, where the neoliberal focus on welfare independence, conditionality and sanctioning has been tempered by a new supportive approach focused on assisting vulnerable clients to maintain and benefit from access to welfare/housing support. Following Larner, we argue that this shift signals the emergence of an "after neoliberal" governmental formation, wherein key features of neoliberal governmentality are replaced by, or redeployed in the service of, progressive initiatives that address neoliberalism's failings at the street level, but leave broader neoliberal policy settings undisturbed. We also challenge recent sociological accounts that construe supportive welfare practices as a function of an all-encompassing neoliberal project, arguing instead for appreciation of the contingency of these developments and the progressive political affordances that they entail.

Agency in advanced liberal services: grounding sociological knowledge in homeless people's accounts.

This paper aims to understand how people who are homeless respond to advanced liberal social services that endeavour to promote their autonomy and responsible actions. We prioritize the experiences and positions of people who are homeless, and what agentic action means to them. Sociological literature is selective about what accounts are deemed agentic. Agency is associated with accounts that resist or subvert dominant neoliberal framings of homelessness as failure of individuals. When people experiencing homelessness or poverty themselves foreground autonomy or responsibility, sociologists treat them as cultural dopes who have internalized neoliberal discourse. Our analysis is driven by an ethnographic study in an Australian homelessness shelter. We demonstrate how people who are homeless neither outright reject nor completely embrace advanced liberal practices to influence their actions and promote autonomy. People engaged in relational reasoning. Paternalist and advanced liberal social services were both lauded and rejected for their capacities and limitations to realize a good life. We contribute to the discussion for sociology to value people's accounts and experiences, rather than broader social process explaining their accounts. From the perspectives of people who are homeless, we show that just because something appears neoliberal does not mean it should be automatically rejected.

Does women's caste make a significant contribution to adolescent pregnancy in Nepal? A study of Dalit and non-Dalit adolescents and young adults in Rupandehi district.

BACKGROUND: Adolescent pregnancy is a public health concern worldwide. There are disparities in the occurrence of adolescence pregnancy in different social groups and settings; however, few studies have focused on the contribution of a woman's caste in early pregnancy in Nepal. This study aimed to examine the association between caste and adolescent pregnancy; and investigate factors that influence this among women of Dalit and non-Dalit caste groups. METHODS: A cross sectional survey among 457 women, age between 14 and 24 years was carried out in Rupandehi district of Nepal. Bivariate and multivariate logistic regression analysis using a stepwise entry method was performed to assess the association of women's caste, ethnicity and other socio-demographic and individual factors with early pregnancy. RESULTS: Over two thirds of the participants (69%) were pregnant during adolescence. The highest percentage of adolescent pregnancies were reported among women from Janajati groups (77%) and the lowest in Brahmin/Chhetri caste groups (45%); while 72.5% of women from Dalit caste groups reported adolescent pregnancy. When adjusted for demographic and individual variables, early pregnancy was less likely among women who were from Brahman/Chhetri (OR: 0.60; 95% CI: 0.30, 1.22) and Madhesi/Muslim (OR 0.56; 95% CI: 0.23, 1.36) compared to women from the Dalit caste, but multivariate regression analysis found none of these were statistically significant. Women who had secondary level education (OR: 0.34; 95% CI: 0.17, 0.65), had married after 17 years of age (OR: 0.02; 95% CI: 0.01, 0.14) and had attended fairs/clubs (OR: 0.40; CI: 0.21, 0.79) were significantly less likely to experience early age pregnancy. Women who drank alcohol (OR: 5.18; 95% CI: 1.02, 26.32) were significantly more likely to become pregnant during adolescence compared to women who did not drink alcohol. CONCLUSIONS: Women's caste had no direct contributory role in the early pregnancy of the sample. Education, age at marriage and individual behaviours were the key contributing factors. Reducing the number of adolescent pregnancies requires addressing the factors that lead to and perpetuate child marriage; keeping girls within education systems for longer; increase the knowledge and control of girls over their own reproductive health and planning; and actions that promote gender respect within relationships, decision-making and negotiation among both girls and boys.

Gourds and squashes (Cucurbita spp.) adapted to megafaunal extinction and ecological anachronism through domestication.

The genus Cucurbita (squashes, pumpkins, gourds) contains numerous domesticated lineages with ancient New World origins. It was broadly distributed in the past but has declined to the point that several of the crops' progenitor species are scarce or unknown in the wild. We hypothesize that Holocene ecological shifts and megafaunal extinctions severely impacted wild Cucurbita, whereas their domestic counterparts adapted to changing conditions via symbiosis with human cultivators. First, we used high-throughput sequencing to analyze complete plastid genomes of 91 total Cucurbita samples, comprising ancient (n = 19), modern wild (n = 30), and modern domestic (n = 42) taxa. This analysis demonstrates independent domestication in eastern North America, evidence of a previously unknown pathway to domestication in northeastern Mexico, and broad archaeological distributions of taxa currently unknown in the wild. Further, sequence similarity between distant wild populations suggests recent fragmentation. Collectively, these results point to wild-type declines coinciding with widespread domestication. Second, we hypothesize that the disappearance of large herbivores struck a critical ecological blow against wild Cucurbita, and we take initial steps to consider this hypothesis through cross-mammal analyses of bitter taste receptor gene repertoires. Directly, megafauna consumed Cucurbita fruits and dispersed their seeds; wild Cucurbita were likely left without mutualistic dispersal partners in the Holocene because they are unpalatable to smaller surviving mammals with more bitter taste receptor genes. Indirectly, megafauna maintained mosaic-like landscapes ideal for Cucurbita, and vegetative changes following the megafaunal extinctions likely crowded out their disturbed-ground niche. Thus, anthropogenic landscapes provided favorable growth habitats and willing dispersal partners in the wake of ecological upheaval.

Design and Performance of a Pinned Photodiode CMOS Image Sensor Using Reverse Substrate Bias.

A new pinned photodiode (PPD) CMOS image sensor with reverse biased p-type substrate has been developed and characterized. The sensor uses traditional PPDs with one additional deep implantation step to suppress the parasitic reverse currents, and can be fully depleted. The first prototypes have been manufactured on an 18 µm thick, 1000 Ω·cm epitaxial silicon wafers using 180 nm PPD image sensor process. Both front-side illuminated (FSI) and back-side illuminated (BSI) devices were manufactured in collaboration with Teledyne e2v. The characterization results from a number of arrays of 10 µm and 5.4 µm PPD pixels, with different shape, the size and the depth of the new implant are in good agreement with device simulations. The new pixels could be reverse-biased without parasitic leakage currents well beyond full depletion, and demonstrate nearly identical optical response to the reference non-modified pixels. The observed excessive charge sharing in some pixel variants is shown to not be a limiting factor in operation. This development promises to realize monolithic PPD CIS with large depleted thickness and correspondingly high quantum efficiency at near-infrared and soft X-ray wavelengths.

Percutaneous Transvenous Mitral Valve-in-Valve Implantation Using Commercially Available Transcatheter Valve. First Australian Experience.

In patients with a degenerative mitral bioprosthesis and prohibitive surgical risk there is emerging evidence for the feasibility of valve-in-valve procedures via a percutaneous transvenous transseptal approach. This paper describes the first time this procedure has been performed in Australia.

Drivers of interannual variability in virioplankton abundance at the coastal western Antarctic peninsula and the potential effects of climate change.

An 8-year time-series in the Western Antarctic Peninsula (WAP) with an approximately weekly sampling frequency was used to elucidate changes in virioplankton abundance and their drivers in this climatically sensitive region. Virioplankton abundances at the coastal WAP show a pronounced seasonal cycle with interannual variability in the timing and magnitude of the summer maxima. Bacterioplankton abundance is the most influential driving factor of the virioplankton, and exhibit closely coupled dynamics. Sea ice cover and duration predetermine levels of phytoplankton stock and thus, influence virioplankton by dictating the substrates available to the bacterioplankton. However, variations in the composition of the phytoplankton community and particularly the prominence of Diatoms inferred from silicate drawdown, drive interannual differences in the magnitude of the virioplankton bloom; likely again mediated through changes in the bacterioplankton. Their findings suggest that future warming within the WAP will cause changes in sea ice that will influence viruses and their microbial hosts through changes in the timing, magnitude and composition of the phytoplankton bloom. Thus, the flow of matter and energy through the viral shunt may be decreased with consequences for the Antarctic food web and element cycling.

Do Growing Rods for Idiopathic Early Onset Scoliosis Improve Activity and Participation for Children?

OBJECTIVE: To investigate whether growing rod surgery for children with progressive idiopathic early onset scoliosis (EOS) effects activity and participation, and investigate factors that may affect this. STUDY DESIGN: Multicenter retrospective cohort study using prospectively collected data on 60 children with idiopathic EOS and significant scoliosis (defined as a Cobb angle >40°). Thirty underwent brace treatment, and 30, growth rod surgery. Questionnaire and radiographic data were recorded at 1 year. The validated Activities Scale for Kids performance version (ASKp) questionnaire was used to measure activity and participation. RESULTS: In the brace group, Cobb angle increased from 60° to 68°. There was no change in ASKp score. In the operative group, Cobb angle decreased from 67° to 45°. ASKp decreased from 91 to 88 (P < .01). Presence of spinal pain correlated with greater reduction in activity and participation scores in both groups, as did occurrence of complications in the operative group (P < .05). Both treatments permitted growth of the immature spine. CONCLUSIONS: In children with significant idiopathic EOS (Cobb angle>40°), growth rod surgery was associated with a reduction in activity and participation and Cobb angle, whereas brace treatment was associated with an increase in Cobb angle and no change in activity and participation. Pain was the most important factor affecting activity and participation in both groups.