Wellcome Open Research最新文献

We present a genome assembly from a female Commophila aeneana (Orange Beauty; Arthropoda; Insecta; Lepidoptera; Tortricidae). The assembly consists of two haplotypes with total lengths of 429.47 megabases and 322.66 megabases. Most of haplotype 1 (99.82%) is scaffolded into 25 chromosomal pseudomolecules, including the W and Z sex chromosomes., and most of haplotype 2 (99.71%) is scaffolded into 23 chromosomal pseudomolecules. The mitochondrial genome has also been assembled, with a length of 16.5 kilobases.

We present a genome assembly from an individual Cornu aspersum (Brown garden snail; Mollusca; Gastropoda; Stylommatophora; Helicidae). The genome sequence has a total length of 2 908.45 megabases. Most of the assembly (98.95%) is scaffolded into 27 chromosomal pseudomolecules. The mitochondrial genome has also been assembled, with a length of 14.04 kilobases. This assembly was generated as part of the Darwin Tree of Life project, which produces reference genomes for eukaryotic species found in Britain and Ireland.

We present a genome assembly from an individual male Brachypalpoides lentus (hoverfly; Arthropoda; Insecta; Diptera; Syrphidae). The assembly contains two haplotypes with total lengths of 1 315.37 megabases and 1 154.75 megabases. Most of haplotype 1 (95.66%) is scaffolded into 6 chromosomal pseudomolecules, including the X and Y sex chromosomes. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 15.88 kilobases. This assembly was generated as part of the Darwin Tree of Life project, which produces reference genomes for eukaryotic species found in Britain and Ireland.

We present a genome assembly from a female specimen of Aphodius granarius (dung beetle; Arthropoda; Insecta; Coleoptera; Scarabaeidae). The genome sequence has a total length of 397.20 megabases. The assembly is scaffolded into 10 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled, with a length of 22.13 kilobases.

We present a genome assembly from an individual female Calliphora vicina (bluebottle blow fly; Arthropoda; Insecta; Diptera; Calliphoridae). The genome sequence is 706.5 megabases in span. Most of the assembly is scaffolded into 6 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 16.72 kilobases in length. Gene annotation of this assembly on Ensembl identified 13,436 protein coding genes.

The COVID-19 pandemic led to a multitude of immediate social restrictions for many across the world. In the UK, the lives of children and young people were quickly impacted when COVID-19 restrictions led to school closures for most children and restrictions on social interactions. The Born in Bradford COVID-19 longitudinal research study explored the impact of the COVID-19 pandemic on the lives of children and their families living in Bradford. Surveys were administered during the first wave of the pandemic (March to June 2020) and compared to findings from before the pandemic (February 2017 to March 2020). The current study examined the social and emotional wellbeing of children ( M age: 10.5 years) from before to during the pandemic, measured using the parent completed Strengths and Difficulties Questionnaire (SDQ). Regression analyses looked at associations between a range of social determinants of health and changes in SDQ scores. The results showed that the odds of experiencing difficulties were lower for children of Pakistani heritage compared to White British children (OR 0.55, 95% CI 0.35-0.86). Girls were less likely to experience difficulties compared to boys (OR 0.60, 95% CI 0.41-0.88), as were older, compared to younger children (per year: OR 0.81, 95% CI 0.68-0.96) and those living in the most deprived quintile of IMD (OR 3.03, 95% CI 1.79-5.15). There were associations between experiencing difficulties and: food insecurity; financial worry; getting below recommended levels of physical activity; and having less than the recommended amount of sleep. These findings raise concerns about the longer-term impacts of the pandemic on children's wellbeing and increasing inequity in child outcomes. The increased impact on the most disadvantaged, underscores the importance of recognising and meeting the support needs of children and families to ensure that inequalities are not widened further, and children are given the opportunity to reach their full potential.

Background: Neuroblastoma is the most common extracranial solid tumour in infants and children, accounting for approximately 15% of paediatric cancer mortality. These tumours are unique in that a subset, namely stage MS, frequently undergo spontaneous regression or differentiation. Differentiation therapy, where cancer cells are re-routed back down their correct developmental pathway, is therefore a promising therapeutic avenue. We have previously shown that the CDK4/6 inhibitor palbociclib induces both decreased proliferation and enhanced neuronal differentiation of neuroblastoma cells in vitro. When combined with retinoic acid, already used clinically for maintenance therapy, this differentiation is enhanced.

Methods: Here, we investigate two additional CDK4/6 inhibitors, abemaciclib and ribociclib, to induce differentiation of the relapsed, high-risk MYCN-amplified neuroblastoma cell line SK-N-BE(2)C, with and without retinoic acid. We culture SK-N-BE(2)C cells in both adherent and three-dimensional culture and monitor proliferation and differentiation using readouts including live-imaging, immunocytochemistry, qRT-PCR and EdU incorporation.

Results: We find the CDK4/6 inhibitors palbociclib, abemaciclib and ribociclib all enhance retinoic acid-induced differentiation in both adherent SK-N-BE(2)C cells and 3D spheroids.

Conclusions: CDK4/6 inhibitors display a class effect in inducing neuronal differentiation together with retinoic acid, both in adherent neuroblastoma cell lines and three-dimensional tumour spheroids. This is an important consideration for potentially developing CDK inhibitor-induced differentiation as a therapy in the clinic.

Background: Adolescent depression and anxiety are highly prevalent, recurrent, and disabling mental health conditions. Current treatment outcomes are suboptimal, often leaving young people with residual symptoms and high relapse rates. To inform future development of more effective preventative strategies, the Emotional Vulnerability in Adolescents (EVA) study aimed to identify vulnerability markers for adolescent depression and anxiety. Specifically, it examined the associations between mental health outcomes and potentially modifiable biopsychosocial factors. The present report provides an overview of the study design and methodology, summarised the demographic, clinical, and mechanistic characteristics of the sample, and examined individual differences by age, gender, and personal and familial history of mental health at baseline.

Methods: Data collection was conducted across three-time points (baseline, 6-months and a 60-month follow-up). A total of 425 adolescents (60.5% female) aged 12 -18 years (Mean = 15.06, SD = 1.75) were recruited at baseline. A comprehensive battery of measures to assess a range of bio-psycho-social factors was employed.

Results: We replicated previous findings in suggesting that females and those with a personal or familial history of mental health difficulties have higher levels of depression and anxiety and lower levels of well-being. These vulnerable sub-groups were also found to differ from their counterparts in a number of biopsychosocial factors; specifically they showed poorer sleep quality, lower levels of resilience, and higher levels of rumination, stress, neuroticism, external shame, bullying experiences, neural-cognitive biases, and dysfunctional attitudes. Furthermore, symptoms of depression and anxiety increased with age and peaked around age 15; age was also associated with an increased risk for eating disorders.

Conclusions: The present findings highlight the importance of considering individual differences in developing future preventative and intervention strategies by targeting underlying mechanisms that are more specifically prominent in each individual subgroup of the population.

Background: Health systems in low-and middle-income countries (LMICs) face chronic Human Resources for Health (HRH) shortages. This is especially worse in rural and primary healthcare settings. The Cuban government since 1960s has been implementing a policy strategy for producing healthcare workers for export, to boost their economy, support humanitarian efforts and boost their global diplomatic influence. Several LMICs have since established health cooperation programs with Cuba to import health workers to address their shortages. This review aimed to examine the emergence, design, utility, outcomes, and lessons learned from the implementation of these programs.

Methods: We conducted a scoping review using the Joanna Briggs Institute (JBI) methodology and searched for literature across four databases. Two independent reviewers screened and selected relevant articles based on pre-defined criteria. We extracted data and synthesized findings using thematic analysis.

Results: We included 71 articles after screening 3509 articles. Cuban health cooperation programs have been implemented in many LMICs in South America, Africa, Southeast Asia, and the Pacific region. These programs are formalized primarily through bilateral agreements and implemented as exchange initiatives. This involves importing Cuban healthcare workers and sending collaborating country students to study in Cuba. These programs aimed to address HRH shortages, maldistribution, inadequate training capacity, and respond to medical emergencies in the host countries. Cuban healthcare workers, primarily family physicians, within the host countries; are deployed in primary healthcare settings, increasing the rural health workforce, and improving healthcare access and outcomes. Challenges included opposition from local medical professionals, underutilization due to poorly coordinated recruitment, and language barrier in non-Spanish speaking countries.

Conclusion: Cuban health cooperations in LMICs have shown diverse results based on their structures. Long-term comprehensive programs have proven to be more successful in boosting the healthcare workforce and enhancing health outcomes. Key factors for optimizing HRH health cooperation include effective collaborative decision-making and need-based deployment in alignment with national health system goals.

Background: Collagen fibrils are the primary supporting scaffolds of vertebrate tissues, but the mechanism of assembly is unclear.

Methods: Here, using CRISPR-tagging of type I collagen, high-resolution light imaging, and SILAC labelling, we elucidated the cellular mechanism underlying the spatiotemporal assembly of collagen fibrils in cultured fibroblasts.

Results: Our findings reveal the multifaceted trafficking of collagen, including constitutive secretion, intracellular pooling, and plasma membrane-directed fibrillogenesis. Notably, we differentiated the processes of collagen secretion and fibril assembly and identified the crucial involvement of endocytosis in the regulation of fibril formation. By employing Col1a1 knockout fibroblasts, we demonstrated the incorporation of exogenous collagen into the nucleation sites at the plasma membrane through these recycling mechanisms.

Conclusions: Our study sheds light on a complex and previously unidentified collagen assembly process and its regulation of health and disease. Mass spectrometry data were available via ProteomeXchange with the identifier PXD036794.