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Abstract Phosphoprotein phosphatase (PPP) enzymes are ubiquitous proteins involved in cellular signaling pathways and other functions. Here we have traced the origin of the PPP sequences of Eukaryotes and their radiation. Using a bacterial PPP Hidden Markov Model (HMM) we uncovered “BacterialPPP-Like” sequences in Archaea. A HMM derived from eukaryotic PPP enzymes revealed additional, unique sequences in Archaea and Bacteria that were more like the eukaryotic PPP enzymes then the bacterial PPPs. These sequences formed the basis of phylogenetic tree inference and sequence structural analysis allowing the history of these sequence types to be elucidated. Our phylogenetic tree data strongly suggest that eukaryotic PPPs ultimately arose from ancestors in the Asgard archaea. We have clarified the radiation of PPPs within Eukaryotes, substantially expanding the range of known organisms with PPP subtypes (Bsu1, PP7, PPEF/RdgC) previously thought to have a more restricted distribution. Surprisingly, sequences from the Methanosarcinaceae (Euryarchaeota) form a strongly supported sister group to eukaryotic PPPs in our phylogenetic analysis. This strongly suggests an intimate association between an Asgard ancestor and that of the Methanosarcinaceae. This is highly reminiscent of the syntrophic association recently demonstrated between the cultured Lokiarchaeal species Prometheoarchaeum and a methanogenic bacterial species.

As high-speed internet becomes increasingly important as a resource for cardiovascular disease (CVD) prevention and management services, gaps in digital infrastructure may have detrimental impact on health outcomes. Using national census and CDC data from 2018 we evaluated state-level rates of household internet access and age-adjusted cardiac mortality. After adjusting for state level demographic variables, and rates of education, income, and health insurance, internet access rates were inversely associated with age adjusted CVD mortality, showing that the potential for internet access to affect CVD management deserves further study.

Gestational alloimmune liver disease resulting in neonatal haemochromatosis is a rare but often lethal neonatal and fetal condition and is the leading cause of fetal and neonatal liver injury. Chelation-antioxidant treatment, intravenous immunoglobulin therapy and exchange transfusions, as well as liver transplantation have been used as treatments for the affected newborn at birth. In the reported case, a woman with previous neonatal death at 34 weeks of gestation due to gestational alloimmune liver disease commenced weekly doses of intravenous immunoglobulin (1 mg/kg) from 15 weeks in a subsequent pregnancy. A healthy baby boy was delivered following induction of labour at 36 weeks and 5 days of gestation. Following the same protocol, another healthy baby boy was delivered at 37 weeks of gestation. This case report emphasises the clinical utility of antenatal prophylaxis with intravenous immunoglobulin in women at high risk of recurrent gestational alloimmune liver disease.

Cancer somatic mutations can generate neoantigens that distinguish malignant from normal cells. However, the personalized identification and validation of neoantigens remains a major challenge. Here we discover neoantigens in human mantle-cell lymphomas by using an integrated genomic and proteomic strategy that interrogates tumour antigen peptides presented by major histocompatibility complex (MHC) class I and class II molecules. We applied this approach to systematically characterize MHC ligands from 17 patients. Remarkably, all discovered neoantigenic peptides were exclusively derived from the lymphoma immunoglobulin heavy- or light-chain variable regions. Although we identified MHC presentation of private polymorphic germline alleles, no mutated peptides were recovered from non-immunoglobulin somatically mutated genes. Somatic mutations within the immunoglobulin variable region were almost exclusively presented by MHC class II. We isolated circulating CD4+ T cells specific for immunoglobulin-derived neoantigens and found these cells could mediate killing of autologous lymphoma cells. These results demonstrate that an integrative approach combining MHC isolation, peptide identification, and exome sequencing is an effective platform to uncover tumour neoantigens. Application of this strategy to human lymphoma implicates immunoglobulin neoantigens as targets for lymphoma immunotherapy.

Abstract The Diabetes and Antenatal Milk Expressing (DAME) randomised controlled trial (RCT) was conducted in 2011–2015, at six sites in Melbourne, Australia to explore the effect of advising women with diabetes in pregnancy to express breast milk from 36 weeks gestation. Infants whose mothers were randomised to express in pregnancy were more likely to be exclusively breast milk fed during their hospital stay, and there was no evidence of harm. This paper explores women's views and experiences of antenatal expressing. In this two‐arm RCT, 635 women with diabetes in pregnancy who were otherwise of low medical risk were randomised at 36–37 weeks gestation to usual care (not expressing, n = 316), or the intervention, where women were advised to hand express for 10 min twice daily until birth (n = 319). Semistructured face‐to‐face interviews were conducted with 10 women who expressed antenatally. They were asked about their experiences of antenatal expressing, including how they felt about the overall experience, the amount of breast milk they expressed, making time to express, and their experience of breastfeeding. Thematic analysis of the in‐depth interviews identified six themes: (1) learning and adapting expressing, (2) feelings and sensations associated with expressing, (3) support, (4) dis/empowerment, (5) health, and (6) the value of breast milk. Women had both positive and negative experiences of antenatal expressing. If health professionals are advising antenatal expressing to women, it is important they understand the range of outcomes and experiences.

To examine the effects of increased strength on mechanical work, the metabolic cost of transport (Cost), and mechanical efficiency (ME) during running. Fourteen physically active men (22.0 ± 2.0 years, 79.3 ± 11.1 kg) were randomized to a strength-training group (SG, n = 7), who participated in a maximal strength training protocol lasting 8 weeks, and a control group (CG, n = 7), which did not perform any training intervention. Metabolic and kinematic data were collected simultaneously while running at a constant speed (2.78 m·s-1). The ME was defined as the ratio between mechanical power (Pmec) and metabolic power (Pmet). The repeated measures two-way ANOVA did not show any significant interaction between groups, despite some large effect sizes (d): internal work (Wint, p = 0.265, d = -1.37), external work (Wext, p = 0.888, d = 0.21), total work (Wtot, p = 0.931, d = -0.17), Pmec (p = 0.917, d = -0.17), step length (SL, p = 0.941, d = 0.24), step frequency (SF, p = 0.814, d = -0.18), contact time (CT, p = 0.120, d = -0.79), aerial time (AT, p = 0.266, d = 1.12), Pmet (p = 0.088, d = 0.85), and ME (p = 0.329, d = 0.54). The exception was a significant decrease in Cost (p = 0.047, d = 0.84) in SG. The paired t-test and Wilcoxon test only detected intragroup differences (pre- vs. post-training) for SG, showing a higher CT (p = 0.041), and a lower Cost (p = 0.003) and Pmet (p = 0.004). The results indicate that improved neuromuscular factors related to strength training may be responsible for the higher metabolic economy of running after 8 weeks of intervention. However, this process was unable to alter running mechanics in order to indicate a significant improvement in ME.

Fast-response infrared gas analyzers (IRGAs) have been widely used over 3 decades in many ecosystems for long-term monitoring of water vapor fluxes in the surface layer of the atmosphere. While some of the early IRGA sensors are still used in these national and/or regional eco-flux networks, optically improved IRGA sensors are newly employed in the same networks. The purpose of this study was to evaluate the performance of water vapor density and flux data from three generations of IRGAs – LI-7500, LI-7500A, and LI-7500RS (LI-COR Bioscience, Inc., Nebraska, USA) – over the course of a growing season in Bushland, Texas, USA, in an irrigated maize canopy for 90 d. Water vapor density measurements were in generally good agreement, but temporal drift occurred in different directions and magnitudes. Means exhibited mostly shift changes that did not impact the flux magnitudes, while their variances of water vapor density fluctuations were occasionally in poor agreement, especially following rainfall events. LI-7500 cospectra were largest compared to LI-7500RS and LI-7500A, especially under unstable and neutral static stability. Agreement among the sensors was best under the typical irrigation-cooled boundary layer, with a 14 % interinstrument coefficient of variability under advective conditions. Generally, the smallest variances occurred with the LI-7500RS, and high-frequency spectral corrections were larger for these measurements, resulting in similar fluxes between the LI-7500A and LI-7500RS. Fluxes from the LI-7500 were best representative of growing season ET based on a world-class lysimeter reference measurement, but using the energy balance ratio as an estimate of systematic bias corrected most of the differences among measured fluxes.

Abstract Background The Mongolian jird (Meriones unguiculatus) has long been recognized as a permissive host for the filarial parasite Brugia malayi; however, it is nonpermissive to another filarial parasite, canine heartworm (Dirofilaria immitis). By elucidating differences in the early response to infection, we sought to identify mechanisms involved in the species-specific clearance of these parasites. We hypothesized that the early clearance of D. immitis in intraperitoneal infection of the jird is immune mediated and parasite species dependent. Methods Jird peritoneal exudate cells (PECs) were isolated and their attachment to parasite larvae assessed in vitro under various conditions: D. immitis and B. malayi cultured separately, co-culture of both parasites, incubation before addition of cells, culture of heat-killed parasites, and culture with PECs isolated from jirds with mature B. malayi infection. The cells attaching to larvae were identified by immunohistochemistry. Results In vitro cell attachment to live D. immitis was high (mean = 99.6%) while much lower for B. malayi (mean = 5.56%). This species-specific attachment was also observed when both filarial species were co-cultured, with no significant change from controls (U (9, 14) = 58.5, p = 0.999). When we replicated these experiments with PECs derived from jirds subcutaneously infected with B. malayi, the results were similar (99.4% and 4.72% of D. immitis and B. malayi, respectively, exhibited cell attachment). Heat-killing the parasites significantly reduced cell attachment to D. immitis (mean = 71.9%; U (11, 14) = 7.5, p < 0.001) while increasing attachment to B. malayi (mean = 16.7%; U (9, 15) = 20, p = 0.002). Cell attachment to both species was reduced when larvae were allowed a 24-h pre-incubation period prior to the addition of cells. The attaching cells were identified as macrophages by immunohistochemistry. Conclusions These results suggest a strongly species-dependent response from which B. malayi could not confer protection by proxy in co-culture. The changes in cell attachment following heat-killing and pre-incubation suggest a role for excretory/secretory products in host immune evasion and/or antigenicity. The nature of this attachment is the subject of ongoing study and may provide insight into filarial host specificity.

Increasingly, policy makers, educators, and school systems are embracing LGBTQ+ individuals and issues in the classroom. This fall, California's K-12 classrooms began using LGBTQ-inclusive textbooks, and, for the last three years, a San Francisco high school has offered an LGBTQ Studies course, likely the first in the country and a pilot for others in the district. Though far from typical, these efforts -- and the LGBTQ Studies course in particular -- present an opportunity to see how inclusive LGBTQ+ curriculum is playing out in schools, offering guidance on how best to encourage understanding and acceptance of gender and sexuality among students.

This paper examines the consolidation and settlement behaviour of soft clay deposits treated with granular columns (single and in groups). Two Rowe cell loading chambers were used to conduct the investigations on samples of kaolin and a local Belfast natural estuarine alluvium called 'sleech'. Tests were carried out on unreinforced samples and then reinforced samples with single and multiple column configurations. The test duration for each test was between 3 and 4 months, depending on the test material and the granular column configuration. The settlement reduction factors based on primary and secondary consolidation were examined. The study suggests that the effectiveness of granular columns at mitigating primary and/or secondary settlement is directly related to the loading intensity, the stress history and the creep characteristics of the subsoil. It was also found that the stress concentration ratio reduced with the stress level. Secondary consolidation also has some effects on the stress concentration ratio. [ABSTRACT FROM AUTHOR]

Peroxisomes are eukaryotic specific organelles that perform diverse metabolic functions including fatty acid β-oxidation, reactive species metabolism, photorespiration, and responses to stress. However, the potential regulation of these functions by post-translational modifications, including protein phosphorylation, has had limited study. Recently, we identified and catalogued a large number of peroxisomal phosphorylated proteins, implicating the presence of protein kinases in this organelle. Here, we employed available prediction models coupled with sequence conservation analysis to identify 31 protein kinases from the Arabidopsis kinome (all protein kinases) that contain a putative, non-canonical peroxisomal targeting signal type 1 (PTS1). From this, twelve C-terminal domain-PTS1s were demonstrated to be functional in vivo, targeting enhanced yellow fluorescent protein to peroxisomes, increasing the list of presumptive peroxisomal protein kinases to nineteen. Of the twelve protein kinases with functional PTS1s, we obtained full length clones for eight and demonstrated that seven target to peroxisomes in vivo. Screening homozygous mutants of the presumptive nineteen protein kinases revealed one candidate (GPK1) that harbors a sugar-dependence phenotype, suggesting it is involved in regulating peroxisomal fatty acid β-oxidation. These results present new opportunities for investigating the regulation of peroxisome functions.