The bacterial community associated with adult vine weevil (Otiorhynchus sulcatus) in UK populations growing on strawberry is dominated by Candidatus Nardonella

Otiorhynchus sulcatus (Fabricius) (Coleoptera: Curculionidae), commonly known as black vine weevil or simply vine weevil, is an important pest of soft fruit and ornamental crops. This species is endemic to temperate areas of Europe but has spread to many other areas over the last century, including North America and Australasia. The ability of vine weevils to adapt to such different environments is difficult to reconcile with the parthenogenetic reproduction strategy, which is likely to underpin a low genetic diversity. It is therefore tempting to hypothesize that weevil adaptation to different environments is mediated, at least partly, by the microbial communities inhabiting these insects. As a first step towards testing this hypothesis we characterized the composition of the bacterial microbiota in weevils from populations feeding on strawberry plants across four geographically separate locations in the UK. We performed 16S rRNA gene Illumina amplicon sequencing, generating 2 882 853 high‐quality reads. Ecological indices, namely Chao1 and Shannon, revealed that the populations used for this study harboured a low diversity and an uneven bacterial microbiota. Furthermore, β‐diversity analysis failed to identify a clear association between microbiota composition and location. Notably, a single operational taxonomic unit phylogenetically related to Candidatus Nardonella accounted for 81% of the total sequencing reads for all tested insects. Our results indicate that vine weevil bacterial microbiota resembles that of other insects as it has low diversity and it is dominated by few taxa. A prediction of this observation is that location per se may not be a determinant of the microbiota inhabiting weevil populations. Rather, other or additional selective pressures, such as the plant species used as a food source, ultimately shape the weevil bacterial microbiota. Our results will serve as a reference framework to investigate other or additional hypotheses aimed at elucidating vine weevil adaptation to its environment

Supersymmetric Charged Clouds in AdS_5

We consider supersymmetric holographic flows that involve background gauge fields dual to chemical potentials in the boundary field theory. We use a consistent truncation of gauged N=8 supergravity in five dimensions and we give a complete analysis of the supersymmetry conditions for a large family of flows. We examine how the well-known supersymmetric flow between two fixed points is modified by the presence of the chemical potentials and this yields a new, completely smooth, solution that interpolates between two global AdS spaces of different radii and with different values of the chemical potential. We also examine some black-hole-like singular flows and a new non-supersymmetric black hole solution. We comment on the interpretation of our new solutions in terms of giant gravitons and discuss the implications of our work for finding black-hole solutions in AdS geometries.Comment: 31 pages, 6 figures; minor corrections, updated reference

Exploring Australian teachers’ perceptions of physical literacy: a mixed-methods study

Background: Physical literacy (PL) has generated substantial international interest across sport, health and education sectors. Teachers play a crucial role in supporting children’s PL growth. Despite PL featuring in several physical education curricular texts, research into teacher understanding and perception of the concept is scarce. This study aimed to explore the understanding and perception of PL among Australian teachers of health and physical education (including generalists and specialists). Methods: Utilizing an explanatory sequential mixed-methods study design, the first phase involved an online survey of 174 Australian teachers. The survey, developed from relevant literature, aimed to elicit an understanding of teachers’ awareness, understanding, and perceptions of PL, and comprised a combination of open-ended, yes/no, Likert, and multiple-choice response options. The second phase involved semi-structured telephone interviews with nine survey participants, to build on survey responses. Interviews lasting on average 37 (range 28–58) minutes were digitally recorded and transcribed verbatim. For quantitative data, bivariate comparisons were made using chi-square tests to examine the relationships between teacher training (generalist versus specialist), age group, years of teaching experience, and teacher PL understanding. Interview data were analyzed using an inductive thematic approach to identify emergent theme clusters. Results: Respondents (n = 122, male 48.4%) were mostly specialist trained teachers, with 10–14 years of teaching experience. Quantitative findings revealed that while most teachers were aware of PL, many only partially understood the concept, often interpreting it as an understanding of bodily movements and/or the benefits of physical activity participation. There were no differences in PL understanding by teacher training, age group, or years of teaching experience. Two main themes, identified from qualitative interviews, which provided further explanation of teachers’ understanding and perception of PL were: (a) ‘physical literacy has been a bit of a buzzword’: perceptions of the PL concept and (b) ‘It's a concept that needs to be ingrained’: implementing PL in schools. Teachers acknowledged the potential importance and applicability of PL, however, expressed scepticism (e.g. buzzword) about the concept. Narrow understanding of the concept persisted during interviews. In terms of its implementation within schools, teachers highlighted the need for curriculum alignment, provision of resources and professional development opportunities, and policy changes. In recognizing these implementation strategies, teachers further noted potential barriers that could hinder PL implementation including time constraints, workload and busyness, and the lack of prioritization of physical education (PE) within schools. Conclusion: Study findings revealed the urgent need to clarify the concept of PL for teachers given their critical role in ensuring effective and successful translation of research into educational practice. Resources, professional dialogue, and continuing professional development opportunities can support teachers’ overall understanding and implementation of PL. This is important for potentially maximizing children’s PL development across the lifespan

Eukaryotic Cells Producing Ribosomes Deficient in Rpl1 Are Hypersensitive to Defects in the Ubiquitin-Proteasome System

It has recently become clear that the misassembly of ribosomes in eukaryotic cells can have deleterious effects that go far beyond a simple shortage of ribosomes. In this work we find that cells deficient in ribosomal protein L1 (Rpl1; Rpl10a in mammals) produce ribosomes lacking Rpl1 that are exported to the cytoplasm and that can be incorporated into polyribosomes. The presence of such defective ribosomes leads to slow growth and appears to render the cells hypersensitive to lesions in the ubiquitin-proteasome system. Several genes that were reasonable candidates for degradation of 60S subunits lacking Rpl1 fail to do so, suggesting that key players in the surveillance of ribosomal subunits remain to be found. Interestingly, in spite of rendering the cells hypersensitive to the proteasome inhibitor MG132, shortage of Rpl1 partially suppresses the stress-invoked temporary repression of ribosome synthesis caused by MG132.United States. National Institutes of Health (GM25532)United States. National Institutes of Health (ARRAGM25532-S1)United States. National Institutes of Health (GM085177)United States. National Institutes of Health (CAI-3330)Natural Sciences and Engineering Research Council of Canada (NSERC

Young Adults With Anterior Ischemic Optic Neuropathy: A Multicenter Optic Disc Drusen Study.

PURPOSE: Optic disc drusen (ODD), present in 2% of the general population, have occasionally been reported in patients with nonarteritic anterior ischemic optic neuropathy (NA-AION). The purpose of this study was to examine the prevalence of ODD in young patients with NA-AION. DESIGN: Retrospective, cross-sectional multicenter study. METHODS: All patients with NA-AION 50 years old or younger, seen in neuro-ophthalmology clinics of the international ODDS (Optic Disc Drusen Studies) Consortium between April 1, 2017, and March 31, 2019, were identified. Patients were included if ODD were diagnosed by any method, or if ODD were excluded by enhanced-depth imaging optical coherence tomography (EDI-OCT) using ODDS Consortium guidelines. NA-AION eyes with ODD were termed "ODD-AION"; those without were termed "NODD-AION". RESULTS: A total of 65 patients (127 eyes) with NA-AION were included (mean 41 years old). Of the 74 eyes with NA-AION, 51% had ODD-AION, whereas 43% of fellow eyes without NA-AION had ODD (P = .36). No significant differences were found between ODD-AION and NODD-AION eyes in terms of Snellen best-corrected VA or perimetric mean deviation. According to EDI-OCT results, 28% of eyes with NODD-AION had peripapillary hyperreflective ovoid mass-like structures (PHOMS); 7% had hyperreflective lines, whereas 54% with ODD-AION had PHOMS; and 66% had hyperreflective lines (P = .006 and P < .001, respectively). CONCLUSIONS: Most of these young NA-AION patients had ODD. This indicates that ODD may be an independent risk factor for the development of NA-AION, at least in younger patients. This study suggests ODD-AION be recognized as a novel diagnosis

N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease

BACKGROUND: Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this neural death is unknown, but genetic predisposition and environmental factors may cause the disease. Sequence variations in N-acetyltransferase 2 (NAT2) gene leading to slow acetylation process have been associated with PD, but results are contradictory. METHODS: We analyzed three NAT2 genetic variations, c.481C>T, c.590G>A (p.R197Q) and c.857G>A (p.G286E), which are known to result in a slow acetylator phenotype. Using validated PCR-RFLP assays, we genotyped 243 healthy unrelated Caucasian control subjects and 124 PD patients for these genetic variations. Further, we have undertaken a systematic review of NAT2 studies on PD and we incorporated our results in a meta-analysis consisting of 10 studies, 1,206 PD patients and 1,619 control subjects. RESULTS: Overall, we did not find significant differences in polymorphic acetylation genotypes in PD and control subjects. In the meta-analysis of slow acetylators from 10 studies and representing 604/1206 PD vs. 732/1619 control subjects, a marginally significant odds ratio (OR) of 1.32 (95% CI 1.12–1.54, p < 0.05) was obtained. Re-analysis of the data to exclude the only two studies showing positive association of slow acetylators to PD, resulted in a non-significant OR (1.07, 95% CI 0.9–1.28). Furthermore, meta-analysis of studies for c.590G>A, where both allele and genotype frequencies in PD vs. control subjects were analyzed, did not give significant summary odds ratios as well. CONCLUSION: We found little evidence for differences in polymorphic acetylation genotypes in PD and control subjects. Results of the meta-analyses did not also provide conclusive evidence for an overall association of NAT2 slow acetylator genotypes to PD

Polygenic basis and biomedical consequences of telomere length variation

Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 new). Genetically determined differences in LTL were associated with multiple biological traits, ranging from height to bone marrow function, as well as several diseases spanning neoplastic, vascular and inflammatory pathologies. Finally, we estimated that, at the age of 40 years, people with an LTL >1 s.d. shorter than the population mean had a 2.5-year-lower life expectancy compared with the group with ≥1 s.d. longer LDL. Overall, we furnish new insights into the genetic regulation of LTL, reveal wide-ranging influences of LTL on physiological traits, diseases and longevity, and provide a powerful resource available to the global research community

Human RNA Polymerase II-Association Factor 1 (hPaf1/PD2) Regulates Histone Methylation and Chromatin Remodeling in Pancreatic Cancer

Change in gene expression associated with pancreatic cancer could be attributed to the variation in histone posttranslational modifications leading to subsequent remodeling of the chromatin template during transcription. However, the interconnected network of molecules involved in regulating such processes remains elusive. hPaf1/PD2, a subunit of the human PAF-complex, involved in the regulation of transcriptional elongation has oncogenic potential. Our study explores the possibility that regulation of histone methylation by hPaf1 can contribute towards alteration in gene expression by nucleosomal rearrangement. Here, we show that knockdown of hPaf1/PD2 leads to decreased di- and tri-methylation at histone H3 lysine 4 residues in pancreatic cancer cells. Interestingly, hPaf1/PD2 colocalizes with MLL1 (Mixed Lineage Leukemia 1), a histone methyltransferase that methylates H3K4 residues. Also, a reduction in hPaf1 level resulted in reduced MLL1 expression and a corresponding decrease in the level of CHD1 (Chromohelicase DNA-binding protein 1), an ATPase dependent chromatin remodeling enzyme that specifically binds to H3K4 di and trimethyl marks. hPaf1/PD2 was also found to interact and colocalize with CHD1 in both cytoplasmic and nuclear extracts of pancreatic cancer cells. Further, reduced level of CHD1 localization in the nucleus in hPaf1/PD2 Knockdown cells could be rescued by ectopic expression of hPaf1/PD2. Micrococcal nuclease digestion showed an altered chromatin structure in hPaf1/PD2-KD cells. Overall, our results suggest that hPaf1/PD2 in association with MLL1 regulates methylation of H3K4 residues, as well as interacts and regulates nuclear shuttling of chromatin remodeling protein CHD1, facilitating its function in pancreatic cancer cells

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions