Repeated nuclear translocations underlie photoreceptor positioning and lamination of the outer nuclear layer in the mammalian retina

In development, almost all stratified neurons must migrate from their birthplace to the appropriate neural layer. Photoreceptors reside in the most apical layer of the retina, near their place of birth. Whether photoreceptors require migratory events for fine-positioning and/or retention within this layer is not well understood. Here, we show that photoreceptor nuclei of the developing mouse retina cyclically exhibit rapid, dynein-1-dependent translocation toward the apical surface, before moving more slowly in the basal direction, likely due to passive displacement by neighboring retinal nuclei. Attenuating dynein 1 function in rod photoreceptors results in their ectopic basal displacement into the outer plexiform layer and inner nuclear layer. Synapse formation is also compromised in these displaced cells. We propose that repeated, apically directed nuclear translocation events are necessary to ensure retention of post-mitotic photoreceptors within the emerging outer nuclear layer during retinogenesis, which is critical for correct neuronal lamination

RNA:protein ratio of the unicellular organism as a characteristic of phosphorous and nitrogen stoichiometry and of the cellular requirement of ribosomes for protein synthesis

Background Mean phosphorous:nitrogen (P:N) ratios and relationships of P:N ratios with the growth rate of organisms indicate a surprising similarity among and within microbial species, plants, and insect herbivores. To reveal the cellular mechanisms underling this similarity, the macromolecular composition of seven microorganisms and the effect of specific growth rate (SGR) on RNA:protein ratio, the number of ribosomes, and peptide elongation rate (PER) were analyzed under different conditions of exponential growth. Results It was found that P:N ratios calculated from RNA and protein contents in these particular organisms were in the same range as the mean ratios reported for diverse organisms and had similar positive relationships with growth rate, consistent with the growth-rate hypothesis. The efficiency of protein synthesis in microorganisms is estimated as the number of active ribosomes required for the incorporation of one amino acid into the synthesized protein. This parameter is calculated as the SGR:PER ratio. Experimental and theoretical evidence indicated that the requirement of ribosomes for protein synthesis is proportional to the RNA:protein ratio. The constant of proportionality had the same values for all organisms, and was derived mechanistically from the characteristics of the protein-synthesis machinery of the cell (the number of nucleotides per ribosome, the average masses of nucleotides and amino acids, the fraction of ribosomal RNA in the total RNA, and the fraction of active ribosomes). Impairment of the growth conditions decreased the RNA:protein ratio and increased the overall efficiency of protein synthesis in the microorganisms. Conclusion Our results suggest that the decrease in RNA:protein and estimated P:N ratios with decrease in the growth rate of the microorganism is a consequence of an increased overall efficiency of protein synthesis in the cell resulting from activation of the general stress response and increased transcription of cellular maintenance genes at the expense of growth related genes. The strong link between P:N stoichiometry, RNA:protein ratio, ribosomal requirement for protein synthesis, and growth rate of microorganisms indicated by the study could be used to characterize the N and P economy of complex ecosystems such as soils and the oceans

Impact of age on outcome after colorectal cancer surgery in the elderly - a developing country perspective

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is a major source of morbidity and mortality in the elderly population and surgery is often the only definitive management option. The suitability of surgical candidates based on age alone has traditionally been a source of controversy. Surgical resection may be considered detrimental in the elderly solely on the basis of advanced age. Based on recent evidence suggesting that age alone is not a predictor of outcomes, Western societies are increasingly performing definitive procedures on the elderly. Such evidence is not available from our region. We aimed to determine whether age has an independent effect on complications after surgery for colorectal cancer in our population.</p> <p>Methods</p> <p>A retrospective review of all patients who underwent surgery for pathologically confirmed colorectal cancer at Aga Khan University Hospital, Karachi between January 1999 and December 2008 was conducted. Using a cut-off of 70 years, patients were divided into two groups. Patient demographics, tumor characteristics and postoperative complications and 30-day mortality were compared. Multivariate logistic regression analysis was performed with clinically relevant variables to determine whether age had an independent and significant association with the outcome.</p> <p>Results</p> <p>A total of 271 files were reviewed, of which 56 belonged to elderly patients (≥ 70 years). The gender ratio was equal in both groups. Elderly patients had a significantly higher comorbidity status, Charlson score and American society of anesthesiologists (ASA) class (all p < 0.001). Upon multivariate analysis, factors associated with more complications were ASA status (95% CI = 1.30-6.25), preoperative perforation (95% CI = 1.94-48.0) and rectal tumors (95% CI = 1.21-5.34). Old age was significantly associated with systemic complications upon univariate analysis (p = 0.05), however, this association vanished upon multivariate analysis (p = 0.36).</p> <p>Conclusion</p> <p>Older patients have more co-morbid conditions and higher ASA scores, but increasing age itself is not independently associated with complications after surgery for CRC. Therefore patient selection should focus on the clinical status and ASA class of the patient rather than age.</p

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Indicated prevention interventions for anxiety in children and adolescents: a review and meta-analysis of school-based programs

Anxiety disorders are among the most common youth mental health disorders. Early intervention can reduce elevated anxiety symptoms. School-based interventions exist but it is unclear how effective targeted approaches are for reducing symptoms of anxiety. This review and meta-analysis aimed to determine the effectiveness of school-based indicated interventions for symptomatic children and adolescents. The study was registered with PROSPERO [CRD42018087628]. We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Library for randomised-controlled trials comparing indicated programs for child and adolescent (5–18 years) anxiety to active or inactive control groups. Data were extracted from papers up to December 2019. The primary outcome was efficacy (mean change in anxiety symptom scores). Sub-group and sensitivity analyses explored intervention intensity and control type. We identified 20 studies with 2076 participants. Eighteen studies were suitable for meta-analysis. A small positive effect was found for indicated programs compared to controls on self-reported anxiety symptoms at post-test (g = − 0.28, CI = − 0.50, − 0.05, k = 18). This benefit was maintained at 6 (g = − 0.35, CI = − 0.58, − 0.13, k = 9) and 12 months (g = − 0.24, CI = − 0.48, 0.00, k = 4). Based on two studies, > 12 month effects were very small (g = − 0.01, CI = − 0.38, 0.36). No differences were found based on intervention intensity or control type. Risk of bias and variability between studies was high (I2 = 78%). Findings show that school-based indicated programs for child and adolescent anxiety can produce small beneficial effects, enduring for up to 12 months. Future studies should include long-term diagnostic assessments

Effect of root age on the biomechanics of seminal and nodal roots of barley (<i>Hordeum vulgare L.</i>) in contrasting soil environments

Acknowledgments The James Hutton Institute receives funding from the Scottish Government. The authors would also like to thank Jim McNicol from Biomathematics and Statistics Scotland for his advice on statistical analysis.Peer reviewedPostprin

Suicide among adults aged 30–49: A psychological autopsy study in Hong Kong

<p>Abstract</p> <p>Background</p> <p>A surge in suicide rates in middle age people in Hong Kong and many Asian countries was recently observed. However, there is a paucity of suicide research on this subgroup of people in Asia.</p> <p>Methods</p> <p>The next-of-kin of 85 suicide cases and 85 community subjects aged 30–49 years were interviewed by a psychological autopsy approach. Information was triangulated by interview notes, coroner's court files, and police investigation reports.</p> <p>Results</p> <p>A multiple logistic regression analysis identified the following risk factors for suicide among the middle age people in Hong Kong: the presence of at least one psychiatric disorder (OR = 37.5, 95% CI 11.5–121.9, p < 0.001), indebtedness (OR = 9.4, 95% CI 2.2–40.8, p < 0.01), unemployment (OR = 4.8, 95% CI 1.3–17.5, p < 0.05), never married (OR = 4.2, 95% CI 1.1–16.3, p < 0.05), and lived alone (OR = 3.9, 95% CI 1.2–13.4, p < 0.05).</p> <p>Conclusion</p> <p>The data show that socio-economical factors had a strong impact on suicide in the target group. Further research is needed to explore any positive qualities that protect the middle-aged from suicide. The prevention of suicide in the middle-aged requires multiple strategies.</p

Regulation of Mycobacterium-Specific Mononuclear Cell Responses by 25-Hydroxyvitamin D3

The active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has been shown to be an important regulator of innate and adaptive immune function. In addition, synthesis of 1,25(OH)2D3 from 25-hydroxyvitamin D3 (25(OH)D3) by the enzyme 1α-hydroxylase in monocytes upon activation by TLR signaling has been found to regulate innate immune responses of monocytes in an intracrine fashion. In this study we wanted to determine what cells expressed 1α-hydroxylase in stimulated peripheral blood mononuclear cell (PBMC) cultures and if conversion of 25(OH)D3 to 1,25(OH)2D3 in PBMC cultures regulated antigen-specific immune responses. Initially, we found that stimulation of PBMCs from animals vaccinated with Mycobacterium bovis (M. bovis) BCG with purified protein derivative of M. bovis (M. bovis PPD) induced 1α-hydroxylase gene expression and that treatment with a physiological concentration of 25(OH)D3 down-regulated IFN-γ and IL-17F gene expression. Next, we stimulated PBMCs from M. bovis BCG-vaccinated and non-vaccinated cattle with M. bovis PPD and sorted them by FACS according to surface markers for monocytes/macrophages (CD14), B cells (IgM), and T cells (CD3). Sorting the PBMCs revealed that 1α-hydroxylase expression was induced in the monocytes and B cells, but not in the T cells. Furthermore, treatment of stimulated PBMCs with 25(OH)D3 down-regulated antigen-specific IFN-γ and IL-17F responses in the T cells, even though 1α-hydroxylase expression was not induced in the T cells. Based on evidence of no T cell 1α-hydroxylase we hypothesize that activated monocytes and B cells synthesize 1,25(OH)2D3 and that 1,25(OH)2D3 down-regulates antigen-specific expression of IFN-γ and IL-17F in T cells in a paracrine fashion

Fertility History and Physical and Mental Health Changes in European Older Adults

Previous studies have shown that aspects of reproductive history, such as earlier parenthood and high parity, are associated with poorer health in mid and later life. However, it is unclear which dimensions of health are most affected by reproductive history, and whether the pattern of associations varies for measures of physical, psychological and cognitive health. Such variation might provide more insight into possible underlying mechanisms. We use longitudinal data for men and women aged 50–79 years in ten European countries from the Survey of Health, Ageing and Retirement in Europe to analyse associations between completed fertility history and self-reported and observed health indicators measured 2–3 years apart (functional limitations, chronic diseases, grip strength, depression and cognition), adjusting for socio-demographic, and health factors at baseline. Using multiple imputation and pattern mixture modelling, we tested the robustness of estimates to missing data mechanisms. The results are partly consistent with previous studies and show that women who became mothers before age 20 had worse functional health at baseline and were more likely to suffer functional health declines. Parents of 4 or more children had worse physical, psychological and cognitive health at baseline and were more likely to develop circulatory disease over the follow-up period. Men who delayed fatherhood until age 35 or later had better health at baseline but did not experience significantly different health declines. This study improves our understanding of linkages between fertility histories and later life health and possible implications of changes in fertility patterns for population health. However, research ideally using prospective life course data is needed to further elucidate possible mechanisms, considering interactions with partnership histories, health behaviour patterns and socio-economic trajectories

Global Priorities for Conserving the Evolutionary History of Sharks, Rays, and Chimaeras

In an era of accelerated biodiversity loss and limited conservation resources, systematic prioritization of species and places is essential. In terrestrial vertebrates, evolutionary distinctness has been used to identify species and locations that embody the greatest share of evolutionary history. We estimate evolutionary distinctness for a large marine vertebrate radiation on a dated taxon-complete tree for all 1,192 chondrichthyan fishes (sharks, rays and chimaeras) by augmenting a new 610-species molecular phylogeny using taxonomic constraints. Chondrichthyans are by far the most evolutionarily distinct of all major radiations of jawed vertebrates—the average species embodies 26 million years of unique evolutionary history. With this metric, we identify 21 countries with the highest richness, endemism and evolutionary distinctness of threatened species as targets for conservation prioritization. On average, threatened chondrichthyans are more evolutionarily distinct—further motivating improved conservation, fisheries management and trade regulation to avoid significant pruning of the chondrichthyan tree of life