The Controversies of Deaccession in Museums: The Pre-Columbian Collection at the University of Texas at Austin

Examination of the legal, ethical, and social context and implications of deaccession in museums. Case study on the orphaned pre-Columbian collection at the University of Texas at Austin, deaccessioned from the Texas Memorial Museum.Art and Art Histor

Matrigel modulates a stem cell phenotype and promotes tumor cell formation in a mantle cell lymphoma cell line

Tumors may be maintained by subpopulations of cells possessing stem cell-like properties. We evaluated the stem cell-like and tumor-forming properties of side population (SP) and CD133+/ CD44+ cells in Granta 519, a human mantle cell lymphoma cell line. The in-vitro Cobblestone Area Forming Cell (CAFC) assay, designed to detect stem and progenitor cells, revealed that SP cells contained the greatest proportion of stem cell-like cells. The addition of Matrigel to CAFC assays of SP and non-SP cells both increased their respective stem cell frequencies in comparison to those cultures without Matrigel, and additionally resulted in observed stem cell frequencies which were the same between SP and non-SP cells. Contrary, Matrigel decreased the stem cell frequencies of CD133+/CD44+ or CD133-/CD44- cells. In-vivo assays revealed tumor formation from Matrigel-mixed SP and non-SP cells, and in one instance, occurred with as few as one Matrigel-mixed SP cell. Vehicle-mixed injections of SP and non-SP tumor cells resulted in tumor formation from SP cells only. Tumor formation did not occur from Matrigel nor hyaluronan (cellular substrate for CD44-expressing cells)-mixed populations of CD133+/CD44+ or CD133-/CD44- cells. These data demonstrate that Matrigel modulates a stem cell phenotype and promotes tumor formation from SP and non-SP cells. The tumor micro-environmental niche and tumor cell to micro-environmental interactions may be important future targets for novel chemotherapeutic agent

Bridging the West Midlands’ Digital Skills Gap:A Roadmap Towards a Digital Skills Innovation District

Amid an escalating skills shortage that threatens the long-term socioeconomic prosperity of the UK, the West Midlands both epitomises the national challenge and, at the same time, offers myriad opportunities to enact lasting change. When it comes to skills, the regional characteristics are stark. The West Midlands is behind the UK average in qualification levels, with pupils typically averaging lower numbers of substantial Level 3 qualifications than the rest of England. The region is predicted to demonstrate the slowest rate of reduction in those with ‘no qualification’ status between 2017-2027, while the NEET (Not in Education, Employment or Training) rate continues to grow. The West Midlands is significantly behind the rest of the country in A-Level attainment, a statistic exacerbated by the underrepresentation of disadvantaged learners in higher-level apprenticeships. Those who do attain a higher education qualification in the West Midlands are less likely to stay in the region upon graduation than elsewhere in the UK.Of particular and growing importance are digital skills. Not only does the region’s tech sector have the potential to add £2.7bn in regional economic growth and 52,000 jobs over the next four years, digital skills are becoming increasingly critical to all sectors, from Business, Professional and Financial Services to health, advanced manufacturing to energy. And yet employers across the region today are reporting serious challenges in securing the levels of talent needed to ensure they remain at the cutting edge of technological delivery. It’s clear that business-as-usual will not be enough to resolve the region’s skills challenges. This project is the first step in tackling these mounting issues. While the challenges are clear, so too is the shared appetite across the region’s universities, private and public sectors to invest in new ways of turning the West Midlands’ skills outlook around. This report details the outputs of research carried out by the University of Birmingham to capture insights from cross-sectoral representatives in the West Midlands. We outline how regions across the UK and father afield are maximising collaborative R&D power to tackle regional challenges, and examine how the West Midlands can best tap into its established ecosystem of leading businesses, universities, further education providers, and civic bodies to realise a step change in how we solve the region’s skills problem. Our ultimate recommendation is to establish a dedicated Digital Skills Innovation District in Birmingham: an ambitious, long-term skills project that is developed by the region for the region. The district would be a thriving hub for industry, higher and further education, and civic organisations to develop and deliver new educational interventions which target the region’s most pressing skills challenges. It would seek to inspire learners young and old to explore new educational and professional pathways, and constantly learn from all regional stakeholders in order to grow and evolve over time. The innovation district would be sector agnostic, recognising the importance of digital skills to all employers, while at the same time mapping onto key regional sectors wherever possible to ensure continued contribution to economic stability and growth. And the district would also demonstrate the shared commitment and ambition across our organisational ecosystem to achieve the aims of devolution and the Levelling Up agenda, presenting a united front in tackling the regional skills challenges that would attract investment to achieve meaningful long-term success. This report details the steps needed to make this ambition a reality

Bridging the West Midlands’ Digital Skills Gap:A Roadmap Towards a Digital Skills Innovation District

Amid an escalating skills shortage that threatens the long-term socioeconomic prosperity of the UK, the West Midlands both epitomises the national challenge and, at the same time, offers myriad opportunities to enact lasting change. When it comes to skills, the regional characteristics are stark. The West Midlands is behind the UK average in qualification levels, with pupils typically averaging lower numbers of substantial Level 3 qualifications than the rest of England. The region is predicted to demonstrate the slowest rate of reduction in those with ‘no qualification’ status between 2017-2027, while the NEET (Not in Education, Employment or Training) rate continues to grow. The West Midlands is significantly behind the rest of the country in A-Level attainment, a statistic exacerbated by the underrepresentation of disadvantaged learners in higher-level apprenticeships. Those who do attain a higher education qualification in the West Midlands are less likely to stay in the region upon graduation than elsewhere in the UK.Of particular and growing importance are digital skills. Not only does the region’s tech sector have the potential to add £2.7bn in regional economic growth and 52,000 jobs over the next four years, digital skills are becoming increasingly critical to all sectors, from Business, Professional and Financial Services to health, advanced manufacturing to energy. And yet employers across the region today are reporting serious challenges in securing the levels of talent needed to ensure they remain at the cutting edge of technological delivery. It’s clear that business-as-usual will not be enough to resolve the region’s skills challenges. This project is the first step in tackling these mounting issues. While the challenges are clear, so too is the shared appetite across the region’s universities, private and public sectors to invest in new ways of turning the West Midlands’ skills outlook around. This report details the outputs of research carried out by the University of Birmingham to capture insights from cross-sectoral representatives in the West Midlands. We outline how regions across the UK and father afield are maximising collaborative R&D power to tackle regional challenges, and examine how the West Midlands can best tap into its established ecosystem of leading businesses, universities, further education providers, and civic bodies to realise a step change in how we solve the region’s skills problem. Our ultimate recommendation is to establish a dedicated Digital Skills Innovation District in Birmingham: an ambitious, long-term skills project that is developed by the region for the region. The district would be a thriving hub for industry, higher and further education, and civic organisations to develop and deliver new educational interventions which target the region’s most pressing skills challenges. It would seek to inspire learners young and old to explore new educational and professional pathways, and constantly learn from all regional stakeholders in order to grow and evolve over time. The innovation district would be sector agnostic, recognising the importance of digital skills to all employers, while at the same time mapping onto key regional sectors wherever possible to ensure continued contribution to economic stability and growth. And the district would also demonstrate the shared commitment and ambition across our organisational ecosystem to achieve the aims of devolution and the Levelling Up agenda, presenting a united front in tackling the regional skills challenges that would attract investment to achieve meaningful long-term success. This report details the steps needed to make this ambition a reality

The relationships between women’s reproductive factors:a Mendelian randomisation analysis

BACKGROUND: Women’s reproductive factors include their age at menarche and menopause, the age at which they start and stop having children and the number of children they have. Studies that have linked these factors with disease risk have largely investigated individual reproductive factors and have not considered the genetic correlation and total interplay that may occur between them. This study aimed to investigate the nature of the relationships between eight female reproductive factors. METHODS: We used data from the UK Biobank and genetic consortia with data available for the following reproductive factors: age at menarche, age at menopause, age at first birth, age at last birth, number of births, being parous, age first had sexual intercourse and lifetime number of sexual partners. Linkage disequilibrium score regression (LDSC) was performed to investigate the genetic correlation between reproductive factors. We then applied Mendelian randomisation (MR) methods to estimate the causal relationships between these factors. Sensitivity analyses were used to investigate directionality of the effects, test for evidence of pleiotropy and account for sample overlap. RESULTS: LDSC indicated that most reproductive factors are genetically correlated (r(g) range: |0.06–0.94|), though there was little evidence for genetic correlations between lifetime number of sexual partners and age at last birth, number of births and ever being parous (r(g) < 0.01). MR revealed potential causal relationships between many reproductive factors, including later age at menarche (1 SD increase) leading to a later age at first sexual intercourse (beta (B) = 0.09 SD, 95% confidence intervals (CI) = 0.06,0.11), age at first birth (B = 0.07 SD, CI = 0.04,0.10), age at last birth (B = 0.06 SD, CI = 0.04,0.09) and age at menopause (B = 0.06 SD, CI = 0.03,0.10). Later age at first birth was found to lead to a later age at menopause (B = 0.21 SD, CI = 0.13,0.29), age at last birth (B = 0.72 SD, CI = 0.67, 0.77) and a lower number of births (B = −0.38 SD, CI = −0.44, −0.32). CONCLUSION: This study presents evidence that women’s reproductive factors are genetically correlated and causally related. Future studies examining the health sequelae of reproductive factors should consider a woman’s entire reproductive history, including the causal interplay between reproductive factors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02293-5

The COVID-19 pandemic and the menstrual cycle: research gaps and opportunities

International audienceSince the beginning of the COVID-19 pandemic, discussions on social media and blogs have indicated that women have experienced menstrual changes, including altered menstrual duration, frequency, regularity, and volume (heavier bleeding and clotting), increased dysmenorrhea, and worsened premenstrual syndrome. There have been a small number of scientific studies of variable quality reporting on menstrual cycle features during the pandemic, but it is still unclear whether apparent changes are due to COVID-19 infection/illness itself, or other pandemic-related factors like increased psychological stress and changes in health behaviours. It is also unclear to what degree current findings are explained by reporting bias, recall bias, selection bias and confounding factors. Further research is urgently needed. We provide a list of outstanding research questions and potential approaches to address them. Findings can inform policies to mitigate against gender inequalities in health and society, allowing us to build back better post-COVID

Language processing skills linked to FMR1 variation: A study of gaze-language coordination during rapid automatized naming among women with the FMR1 premutation

This work is licensed under a Creative Commons Attribution 4.0 International License.The FMR1 premutation (PM) is relatively common in the general population. Evidence suggests that PM carriers may exhibit subtle differences in specific cognitive and language abilities. This study examined potential mechanisms underlying such differences through the study of gaze and language coordination during a language processing task (rapid automatized naming; RAN) among female carriers of the FMR1 PM. RAN taps a complex set of underlying neuropsychological mechanisms, with breakdowns implicating processing disruptions in fundamental skills that support higher order language and executive functions, making RAN (and analysis of gaze/language coordination during RAN) a potentially powerful paradigm for revealing the phenotypic expression of the FMR1 PM. Forty-eight PM carriers and 56 controls completed RAN on an eye tracker, where they serially named arrays of numbers, letters, colors, and objects. Findings revealed a pattern of inefficient language processing in the PM group, including a greater number of eye fixations (namely, visual regressions) and reduced eye-voice span (i.e., the eyes’ lead over the voice) relative to controls. Differences were driven by performance in the latter half of the RAN arrays, when working memory and processing load are the greatest, implicating executive skills. RAN deficits were associated with broader social-communicative difficulties among PM carriers, and with FMR1-related molecular genetic variation (higher CGG repeat length, lower activation ratio, and increased levels of the fragile X mental retardation protein; FMRP). Findings contribute to an understanding of the neurocognitive profile of PM carriers and indicate specific gene-behavior associations that implicate the role of the FMR1 gene in language-related processes.NIH R01DC010191NIH R01MH091131NIH P30 HD0311

DNA methylation and body mass index:investigating identified methylation sites at HIF3A in a causal framework

Multiple differentially methylated sites and regions associated with adiposity have now been identified in large-scale cross-sectional studies. We tested for replication of associations between previously identified CpG sites at HIF3A and adiposity in ∼1,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Availability of methylation and adiposity measures at multiple time points, as well as genetic data, allowed us to assess the temporal associations between adiposity and methylation and to make inferences regarding causality and directionality. Overall, our results were discordant with those expected if HIF3A methylation has a causal effect on BMI and provided more evidence for causality in the reverse direction (i.e., an effect of BMI on HIF3A methylation). These results are based on robust evidence from longitudinal analyses and were also partially supported by Mendelian randomization analysis, although this latter analysis was underpowered to detect a causal effect of BMI on HIF3A methylation. Our results also highlight an apparent long-lasting intergenerational influence of maternal BMI on offspring methylation at this locus, which may confound associations between own adiposity and HIF3A methylation. Further work is required to replicate and uncover the mechanisms underlying the direct and intergenerational effect of adiposity on DNA methylation.Rebecca C. Richmond, Gemma C. Sharp, Mary E. Ward, Abigail Fraser, Oliver Lyttleton, Wendy L. McArdle, Susan M. Ring, Tom R. Gaunt, Debbie A. Lawlor, George Davey Smith, and Caroline L. Relto

Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells.

Huntington's disease is a neurodegenerative disorder caused by CAG expansion that results in expansion of a polyglutamine tract at the extreme N terminus of huntingtin (htt). htt with polyglutamine expansion is proapoptotic in different cell types. Here, we show that caspase inhibitors diminish the toxicity of htt. Additionally, we define htt itself as an important caspase substrate by generating a site-directed htt mutant that is resistant to caspase-3 cleavage at positions 513 and 530 and to caspase-6 cleavage at position 586. In contrast to cleavable htt, caspase-resistant htt with an expanded polyglutamine tract has reduced toxicity in apoptotically stressed neuronal and nonneuronal cells and forms aggregates at a much reduced frequency. These results suggest that inhibiting caspase cleavage of htt may therefore be of potential therapeutic benefit in Huntington's disease

A novel hypothesis-generating approach for detecting phenotypic associations using epigenetic data.

Aim: Hypotheses about what phenotypes to include in causal analyses, that in turn can have clinical and policy implications, can be guided by hypothesis-free approaches leveraging the epigenome, for example. Materials & methods: Minimally adjusted epigenome-wide association studies (EWAS) using ALSPAC data were performed for example conditions, dysmenorrhea and heavy menstrual bleeding (HMB). Differentially methylated CpGs were searched in the EWAS Catalog and associated traits identified. Traits were compared between those with and without the example conditions in ALSPAC. Results: Seven CpG sites were associated with dysmenorrhea and two with HMB. Smoking and adverse childhood experience score were associated with both conditions in the hypothesis-testing phase. Conclusion: Hypothesis-generating EWAS can help identify associations for future analyses