Excavating the 'Rutland Sea Dragon': The largest ichthyosaur skeleton ever found in the UK (Whitby Mudstone Formation, Toarcian, Lower Jurassic)

An almost complete ichthyosaur skeleton 10 m long was discovered in January 2021 at the Rutland Water Nature Reserve in the county of Rutland, UK. This was excavated by a small team of palaeontologists in the summer of the same year. Nicknamed ‘The Rutland Sea Dragon’, this almost fully articulated skeleton is an example of the large-bodied Early Jurassic ichthyosaur Temnodontosaurus. The specimen was analysed in situ, recorded (including a 3D scan using photogrammetry), excavated and removed from the site in a series of large plaster field jackets to preserve taphonomic information. Significantly, the specimen is the largest ichthyosaur skeleton to have been found in the UK and it may be the first recorded example of Temnodontosaurus trigonodon to be found in the country, extending its known geographic range significantly. It also represents the most complete skeleton of a large prehistoric reptile to have been found in the UK. We provide an account of the discovery and describe the methods used for excavating, recording and lifting the large skeleton which will aid palaeontologists facing similar challenges when collecting extensive remains of large and fragile fossil vertebrates. We also discuss the preliminary research findings and the global impact this discovery has had through public engagement

Macrophages orchestrate the expansion of a proangiogenic perivascular niche during cancer progression

Tumor-associated macrophages (TAMs) are a highly plastic stromal cell type that support cancer progression. Using single-cell RNA sequencing of TAMs from a spontaneous murine model of mammary adenocarcinoma (MMTV-PyMT), we characterize a subset of these cells expressing lymphatic vessel endothelial hyaluronic acid receptor 1 (Lyve-1) that spatially reside proximal to blood vasculature. We demonstrate that Lyve-1+ TAMs support tumor growth and identify a pivotal role for these cells in maintaining a population of perivascular mesenchymal cells that express α-smooth muscle actin and phenotypically resemble pericytes. Using photolabeling techniques, we show that mesenchymal cells maintain their prevalence in the growing tumor through proliferation and uncover a role for Lyve-1+ TAMs in orchestrating a selective platelet-derived growth factor–CC–dependent expansion of the perivascular mesenchymal population, creating a proangiogenic niche. This study highlights the inter-reliance of the immune and nonimmune stromal network that supports cancer progression and provides therapeutic opportunities for tackling the disease

Determinants of postnatal spleen tissue regeneration and organogenesis

Abstract The spleen is an organ that filters the blood and is responsible for generating blood-borne immune responses. It is also an organ with a remarkable capacity to regenerate. Techniques for splenic auto-transplantation have emerged to take advantage of this characteristic and rebuild spleen tissue in individuals undergoing splenectomy. While this procedure has been performed for decades, the underlying mechanisms controlling spleen regeneration have remained elusive. Insights into secondary lymphoid organogenesis and the roles of stromal organiser cells and lymphotoxin signalling in lymph node development have helped reveal similar requirements for spleen regeneration. These factors are now considered in the regulation of embryonic and postnatal spleen formation, and in the establishment of mature white pulp and marginal zone compartments which are essential for spleen-mediated immunity. A greater understanding of the cellular and molecular mechanisms which control spleen development will assist in the design of more precise and efficient tissue grafting methods for spleen regeneration on demand. Regeneration of organs which harbour functional white pulp tissue will also offer novel opportunities for effective immunotherapy against cancer as well as infectious diseases

Oncological outcome after free jejunal flap reconstruction for carcinoma of the hypopharynx

It has been a common practice among the oncologist to reduce the dosage of adjuvant radiotherapy for patients after free jejunal flap reconstruction. The current aims to study potential risk of radiation to the visceral flap and the subsequent oncological outcome. Between 1996 and 2010, consecutive patients with carcinoma of the hypopharynx requiring laryngectomy, circumferential pharyngectomy and post-operative irradiation were recruited. Ninety-six patients were recruited. TNM tumor staging at presentation was: stage II (40.6%), stage III (34.4%) and stage IV (25.0%). Median follow-up period after surgery was 68 months. After tumor ablation, reconstruction was performed using free jejunal flap (60.4%), pectoralis major myocutaneous (PM) flap (31.3%) and free anterolateral thigh (ALT) flap (8.3%). All patients underwent adjuvant radiotherapy within 6.4 weeks after surgery. The mean total dose of radiation given to those receiving cutaneous and jejunal flap reconstruction was 62.2 Gy and 54.8 Gy, respectively. There was no secondary ischaemia or necrosis of the flaps after radiotherapy. The 5-year actuarial loco-regional tumor control for the cutaneous flap and jejunal flap group was: stage II (61 vs. 69%, p = 0.9), stage III (36 vs. 46%, p = 0.2) and stage IV (32 vs. 14%, p = 0.04), respectively. Reduction of radiation dosage in free jejunal group adversely affects the oncological control in stage IV hypopharyngeal carcinoma. In such circumstances, tubed cutaneous flaps are the preferred reconstructive option, so that full-dose radiotherapy can be given

ILC3 function as a double-edged sword in inflammatory bowel diseases

Inflammatory bowel diseases (IBD), composed mainly of Crohn’s disease (CD) and ulcerative colitis (UC), are strongly implicated in the development of intestinal inflammation lesions. Its exact etiology and pathogenesis are still undetermined. Recently accumulating evidence supports that group 3 innate lymphoid cells (ILC3) are responsible for gastrointestinal mucosal homeostasis through moderate generation of IL-22, IL-17, and GM-CSF in the physiological state. ILC3 contribute to the progression and aggravation of IBD while both IL-22 and IL-17, along with IFN-γ, are overexpressed by the dysregulation of NCR− ILC3 or NCR+ ILC3 function and the bias of NCR+ ILC3 towards ILC1 as well as regulatory ILC dysfunction in the pathological state. Herein, we feature the group 3 innate lymphoid cells’ development, biological function, maintenance of gut homeostasis, mediation of IBD occurrence, and potential application to IBD therapy

Hierarchy of Hofstadter states and replica quantum Hall ferromagnetism in graphene superlattices

Self-similarity and fractals have fascinated researchers across various disciplines. In graphene placed on boron nitride and subjected to a magnetic field, self-similarity appears in the form of numerous replicas of the original Dirac spectrum, and their quantization gives rise to a fractal pattern of Landau levels, referred to as the Hofstadter butterfly. Here we employ capacitance spectroscopy to probe directly the density of states (DoS) and energy gaps in this spectrum. Without a magnetic field, replica spectra are seen as pronounced DoS minima surrounded by van Hove singularities. The Hofstadter butterfly shows up as recurring Landau fan diagrams in high fields. Electron-electron interactions add another twist to the self-similar behaviour. We observe suppression of quantum Hall ferromagnetism, a reverse Stoner transition at commensurable fluxes and additional ferromagnetism within replica spectra. The strength and variety of the interaction effects indicate a large playground to study many-body physics in fractal Dirac systems.Comment: Nature Phys. (2014

JNK3 Maintains Expression of the Insulin Receptor Substrate 2 (IRS2) in Insulin-Secreting Cells: Functional Consequences for Insulin Signaling

We have recently shown that silencing of the brain/islet specific c-Jun N-terminal Kinase3 (JNK3) isoform enhances both basal and cytokine-induced beta-cell apoptosis, whereas silencing of JNK1 or JNK2 has opposite effects. While it is known that JNK1 or JNK2 may promote apoptosis by inhibiting the activity of the pro-survival Akt pathway, the effect of JNK3 on Akt has not been documented. This study aims to determine the involvement of individual JNKs and specifically JNK3 in the regulation of the Akt signaling pathway in insulin-secreting cells. JNK3 silencing strongly decreases Insulin Receptor Substrate 2 (IRS2) protein expression, and blocks Akt2 but not Akt1 activation by insulin, while the silencing of JNK1 or JNK2 activates both Akt1 and Akt2. Concomitantly, the silencing of JNK1 or JNK2, but not of JNK3, potently phosphorylates the glycogen synthase kinase3 (GSK3β). JNK3 silencing also decreases the activity of the transcription factor Forkhead BoxO3A (FoxO3A) that is known to control IRS2 expression, in addition to increasing c-Jun levels that are known to inhibit insulin gene expression. In conclusion, we propose that JNK1/2 on one hand and JNK3 on the other hand, have opposite effects on insulin-signaling in insulin-secreting cells; JNK3 protects beta-cells from apoptosis and dysfunction mainly through maintenance of a normal IRS2 to Akt2 signaling pathway. It seems that JNK3 mediates its effects mainly at the transcriptional level, while JNK1 or JNK2 appear to mediate their pro-apoptotic effect in the cytoplasm

GO4genome: A Prokaryotic Phylogeny Based on Genome Organization

Determining the phylogeny of closely related prokaryotes may fail in an analysis of rRNA or a small set of sequences. Whole-genome phylogeny utilizes the maximally available sample space. For a precise determination of genome similarity, two aspects have to be considered when developing an algorithm of whole-genome phylogeny: (1) gene order conservation is a more precise signal than gene content; and (2) when using sequence similarity, failures in identifying orthologues or the in situ replacement of genes via horizontal gene transfer may give misleading results. GO4genome is a new paradigm, which is based on a detailed analysis of gene function and the location of the respective genes. For characterization of genes, the algorithm uses gene ontology enabling a comparison of function independent of evolutionary relationship. After the identification of locally optimal series of gene functions, their length distribution is utilized to compute a phylogenetic distance. The outcome is a classification of genomes based on metabolic capabilities and their organization. Thus, the impact of effects on genome organization that are not covered by methods of molecular phylogeny can be studied. Genomes of strains belonging to Escherichia coli, Shigella, Streptococcus, Methanosarcina, and Yersinia were analyzed. Differences from the findings of classical methods are discussed