Loss of TET2 increases B-1 cell number and IgM production while limiting CDR3 diversity

Recent studies have demonstrated a role for Ten-Eleven Translocation-2 (TET2), an epigenetic modulator, in regulating germinal center formation and plasma cell differentiation in B-2 cells, yet the role of TET2 in regulating B-1 cells is largely unknown. Here, B-1 cell subset numbers, IgM production, and gene expression were analyzed in mice with global knockout of TET2 compared to wildtype (WT) controls. Results revealed that TET2-KO mice had elevated numbers of B-1a and B-1b cells in their primary niche, the peritoneal cavity, as well as in the bone marrow (B-1a) and spleen (B-1b). Consistent with this finding, circulating IgM, but not IgG, was elevated in TET2-KO mice compared to WT. Analysis of bulk RNASeq of sort purified peritoneal B-1a and B-1b cells revealed reduced expression of heavy and light chain immunoglobulin genes, predominantly in B-1a cells from TET2-KO mice compared to WT controls. As expected, the expression of IgM transcripts was the most abundant isotype in B-1 cells. Yet, only in B-1a cells there was a significant increase in the proportion of IgM transcripts in TET2-KO mice compared to WT. Analysis of the CDR3 of the BCR revealed an increased abundance of replicated CDR3 sequences in B-1 cells from TET2-KO mice, which was more clearly pronounced in B-1a compared to B-1b cells. V-D-J usage and circos plot analysis of V-J combinations showed enhanced usage of VH11 and VH12 pairings. Taken together, our study is the first to demonstrate that global loss of TET2 increases B-1 cell number and IgM production and reduces CDR3 diversity, which could impact many biological processes and disease states that are regulated by IgM

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Supernatural Psychology: Roads Less Traveled

A fascinating analysis of the psychology behind the popular TV series Supernatural. Following the adventures of two brothers who investigate deeply strange and paranormal mysteries in their never-ending road trip, the TV show Supernatural has many fans eager to better understand the psychology behind the series’ themes and characters. Through 20 essays, this collection examines such issues as The role grief and trauma play in the protagonists’ lives The importance of music to the narrative What motivates someone to hunt monsters and why we want to believe in magic The various archangels and archetypes depicted How people can cope with tragedy, loss, addiction, and fear to become heroes who do the right thing The dynamics of fandom: how fans relate to the narrative, characters, and actors, and continue to engage with series through fanfic, social media, and other practiceshttps://digitalcommons.tamusa.edu/psyc_books/1004/thumbnail.jp

The Effects of Diet on the Biochemical Constituents of Beef

Crossbred steers (n = 64) were grazed on warm- or cool-season grasses, without or with energy supplementation of wet distillers grains with solubles (WDGS), and were finished on a corn-based diet with or without 35% WDGS. Grass-type was the major contributor in determining the biochemical composition of L. dorsi steaks, with warm-season grasses causing increased concentrations of moisture and zinc and decreased concentrations of magnesium. Aging 28 days instead of 7 days increased pH and caused an increased concentration of carbohydrates, and non-heme and heme iron in B. femoris steaks. Diet, especially grass type, during grazing, can alter the end composition of beef

Media content created for Museums without Walls: An interactive resource exploring connections between Orkney and the Hudson's Bay Company

During the summer of 2021 the Stromness Museum together with the University of Dundee launched a pilot project to explore around 80 objects in their collections relating to Orkney’s history with the Hudson’s Bay Company in Canada. Our aim was to design an interactive online resource which brought together 3D scans and photographs of the museum’s collections together with insights and stories from different perspectives, including Orcadian, Cree, Métis and Inuit voices. What resulted was a compelling and diverse variety of material offering fresh insights and contemporary connections to this complex period of shared history.  The resource is freely available online and as a touchscreen exhibit inside the Stromness Museum in Orkney. https://www.stromnessmuseum.org.uk/sites/stromnessmuseum.org.uk/files/hbc/index.html Data and file overview The archived material consists of 3D scanned objects from the Museum’s collections in .glb format; photographs of objects and family photographs relating to personal accounts featured in the resource; soundbites from various people interviewed for the resource about their family heritage and the Hudson’s Bay Company; curator written blurbs; and artwork relating to the resource interface. Sharing and access information The material (with the exception of a walk-through screen capture video) is not publicly accessible for download and re-use without requested consent. This is because much of the materials concern Indigenous objects, stories and imagery and we do not wish for this to be re-used elsewhere without prior consent from the individuals represented. All material is available to view (but not download and re-use) on the Stromness Museum’s website: (https://www.stromnessmuseum.org.uk/sites/stromnessmuseum.org.uk/files/hbc/index.html) Methodological information Our approach for generating material as part of this project followed a collaborative co-curation methodology which facilitated curation of the resource to be led by the contributions and engagements of the individuals and communities we worked with. The content maps and walk-through screen capture video are made available under a CC-BY-NC license, for full details of this license copy and paste the following link into your browser, https://creativecommons.org/licenses/by-nc/4.0

Subaqueous foraging among carnivorous dinosaurs

Secondary aquatic adaptations evolved independently more than 30 times from terrestrial vertebrate ancestors1,2. For decades, non-avian dinosaurs were believed to be an exception to this pattern. Only a few species have been hypothesized to be partly or predominantly aquatic3,4,5,6,7,8,9,10,11. However, these hypotheses remain controversial12,13, largely owing to the difficulty of identifying unambiguous anatomical adaptations for aquatic habits in extinct animals. Here we demonstrate that the relationship between bone density and aquatic ecologies across extant amniotes provides a reliable inference of aquatic habits in extinct species. We use this approach to evaluate the distribution of aquatic adaptations among non-avian dinosaurs. We find strong support for aquatic habits in spinosaurids, associated with a marked increase in bone density, which precedes the evolution of more conspicuous anatomical modifications, a pattern also observed in other aquatic reptiles and mammals14,15,16. Spinosaurids are revealed to be aquatic specialists with surprising ecological disparity, including subaqueous foraging behaviour in Spinosaurus and Baryonyx, and non-diving habits in Suchomimus. Adaptation to aquatic environments appeared in spinosaurids during the Early Cretaceous, following their divergence from other tetanuran theropods during the Early Jurassic17

Adrenal Tumors in Adults

Although most adrenal tumors are not diagnostic dilemmas, there are cases that are challenging. This may be due to the tissue provided, for example fragmented tissue received in the setting of morcellation, or it may be due to inherently challenging histology, such as in cases with equivocal features of malignancy. Additionally, much has been learned about the molecular alterations of adrenal tumors, especially pheochromocytomas. Many of these alterations represent germline mutations with significant clinical implications for patients and their families. The aim of this review is to provide an overview of the most common adrenal tumors in adults so that pathologists can tackle these interesting tumors