GeneChip analyses point to novel pathogenetic mechanisms in mantle cell lymphoma

The translocation t(11;14)(q13;q32) is the genetic hallmark of mantle cell lymphoma (MCL) but is not sufficient for inducing lymphomagenesis. Here we performed genome-wide 100K GeneChip Mapping in 26 t(11;14)-positive MCL and six MCL cell lines. Partial uniparental disomy (pUPD) was shown to be a recurrent chromosomal event not only in MCL cell lines but also in primary MCL. Remarkably, pUPD affected recurrent targets of deletion like 11q, 13q and 17p. Moreover, we identified 12 novel regions of recurrent gain and loss as well as 12 high-level amplifications and eight homozygously deleted regions hitherto undescribed in MCL. Interestingly, GeneChip analyses identified different genes, encoding proteins involved in microtubule dynamics, such as MAP2, MAP6 and TP53, as targets for chromosomal aberration in MCL. Further investigation, including mutation analyses, fluorescence in situ hybridisation as well as epigenetic and expression studies, revealed additional aberrations frequently affecting these genes. In total, 19 of 20 MCL cases, which were subjected to genetic and epigenetic analyses, and five of six MCL cell lines harboured at least one aberration in MAP2, MAP6 or TP53. These findings provide evidence that alterations of microtubule dynamics might be one of the critical events in MCL lymphomagenesis contributing to chromosomal instability

The effect of extreme spring weather on body condition and stress physiology in Lapland longspurs and white-crowned sparrows breeding in the Arctic

AbstractClimate change is causing rapid shifts in temperature while also increasing the frequency, duration, and intensity of extreme weather. In the northern hemisphere, the spring of 2013 was characterized as extreme due to record high snow cover and low temperatures. Studies that describe the effects of extreme weather on phenology across taxa are limited while morphological and physiological responses remain poorly understood. Stress physiology, as measured through baseline and stress-induced concentrations of cortisol or corticosterone, has often been studied to understand how organisms respond to environmental stressors. We compared body condition and stress physiology of two long-distance migrants breeding in low arctic Alaska – the white-crowned sparrow (Zonotrichia leucophrys) and Lapland longspur (Calcarius lapponicus) – in 2013, an extreme weather year, with three more typical years (2011, 2012, and 2014). The extended snow cover in spring 2013 caused measureable changes in phenology, body condition and physiology. Arrival timing for both species was delayed 4–5days compared to the other three years. Lapland longspurs had reduced fat stores, pectoralis muscle profiles, body mass, and hematocrit levels, while stress-induced concentrations of corticosterone were increased. Similarly, white-crowned sparrows had reduced pectoralis muscle profiles and hematocrit levels, but in contrast to Lapland longspurs, had elevated fat stores and no difference in mass or stress physiology relative to other study years. An understanding of physiological mechanisms that regulate coping strategies is of critical importance for predicting how species will respond to the occurrence of extreme events in the future due to global climate change

Structural characteristics and contractual terms of specialist palliative homecare in Germany

Background Multi-professional specialist palliative homecare (SPHC) teams care for palliative patients with complex symptoms. In Germany, the SPHC directive regulates care provision, but model contracts for each federal state are heterogeneous regarding staff requirements, cooperation with other healthcare providers, and financial reimbursement. The structural characteristics of SPHC teams also vary. Aim We provide a structured overview of the existing model contracts, as well as a nationwide assessment of SPHC teams and their structural characteristics. Furthermore, we explore whether these characteristics serve to find specifc patterns of SPHC team models, based on empirical data. Methods This study is part of the multi-methods research project “SAVOIR”, funded by the German Innovations Fund. Most model contracts are publicly available. Structural characteristics (e.g. number, professions, and affiliations of team members, and external cooperation) were assessed via an online database (“Wegweiser Hospiz- und Palliativversorgung”) based on voluntary information obtained from SPHC teams. All the data were updated by phone during the assessment process. Data were descriptively analysed regarding staff, cooperation requirements, and reimbursement schemes, while latent class analysis (LCA) was used to identify structural team models. Results Model contracts have heterogeneous contract partners and terms related to staff requirements (number and qualifications) and cooperation with other services. Fourteen reimbursement schemes were available, all combining different payment models. Of the 283 SPHC teams, 196 provided structural characteristics. Teams reported between one and 298 members (mean: 30.3, median: 18), mainly nurses and physicians, while 37.8% had a psychosocial professional as a team member. Most teams were composed of nurses and physicians employed in different settings; for example, staff was employed by the team, in private practices/nursing services, or in hospitals. Latent class analysis identified four structural team models, based on the team size, team members’ affiliation, and care organisation. Conclusion Both the contractual terms and teams’ structural characteristics vary substantially, and this must be considered when analysing patient data from SPHC. The identified patterns of team models can form a starting point from which to analyse different forms of care provision and their impact on care quality

The stress response is attenuated during inclement weather in parental, but not in pre-parental, Lapland longspurs (Calcarius lapponicus) breeding in the Low Arctic

AbstractBirds breeding at high latitudes can be faced with extreme weather events throughout the breeding season. In response to environmental perturbations, vertebrates activate the hypothalamic-pituitary-adrenal (HPA) axis and synthesize corticosterone, which promotes changes in behavior and physiology to help the animal survive. The parental care hypothesis suggests that the HPA axis activity should be downregulated during the parental stage of breeding to prevent nest abandonment. However, it is unknown what happens to HPA axis activity in response to severe weather at the transition from the pre-parental to parental stages of breeding. We sampled baseline corticosterone levels and the time course of corticosterone elevation over 60min of restraint stress and assessed body condition and fat stores in Lapland longspurs (Calcarius lapponicus) breeding in the Low Arctic in the presence and absence of snowstorms. The results showed that during the pre-parental stage, HPA axis activity was up-regulated in response to snowstorms, with corticosterone levels continuing to increase through 60min of restraint. However, once birds were parental, HPA axis activity was unaffected by snowstorms and levels peaked at 10min. Fat levels and body condition did not change in response to snowstorms but fat levels declined in males during the pre-parental stage. These data suggest that the parental care hypothesis can be applied to severe storm events; parental birds restrained the activity of the HPA axis, likely to focus on the reproductive effort that is already underway, while pre-parental birds greatly upregulated HPA axis activity in response to snowstorms to maximize self-preservation

Real-time monitoring shows substantial excess all-cause mortality during second wave of COVID-19 in Europe, October to December 2020.

The European monitoring of excess mortality for public health action (EuroMOMO) network monitors weekly excess all-cause mortality in 27 European countries or subnational areas. During the first wave of the coronavirus disease (COVID-19) pandemic in Europe in spring 2020, several countries experienced extraordinarily high levels of excess mortality. Europe is currently seeing another upsurge in COVID-19 cases, and EuroMOMO is again witnessing a substantial excess all-cause mortality attributable to COVID-19.Funding statement: The EuroMOMO network hub at Statens Serum Institut receives funding from European Centre for Disease Prevention and Control, Solna, Sweden, through a framework contract 2017-2020.S

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

The Human Phenotype Ontology in 2017.

Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human Phenotype Ontology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology