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

A detailed phenotypic analysis of immune cell populations in the bronchoalveolar lavage fluid of atopic asthmatics after segmental allergen challenge

BACKGROUND: Atopic asthma is characterized by intermittent exacerbations triggered by exposure to allergen. Exacerbations are characterized by an acute inflammatory reaction in the airways, with recruitment of both innate and adaptive immune cells. These cell populations as well as soluble factors are critical for initiating and controlling the inflammatory processes in allergic asthma. Detailed data on the numbers and types of cells recruited following allergen challenge is lacking. In this paper we present an extensive phenotypic analysis of the inflammatory cell infiltrate present in the bronchoalveolar lavage (BAL) fluid following bronchoscopically directed allergen challenge in mild atopic asthmatics. METHODS: A re-analysis of pooled data obtained prior to intervention in our randomized, placebo controlled, double blinded study (costimulation inhibition in asthma trial [CIA]) was performed. Twenty-four subjects underwent bronchoscopically directed segmental allergen challenge followed by BAL collection 48 hours later. The BAL fluid was analyzed by multi-color flow cytometry for immune cell populations and multi-plex ELISA for cytokine detection. RESULTS: Allergen instillation induced pro-inflammatory cytokines (IL-6) and immune modulating cytokines (IL-2, IFN-γ, and IL-10) along with an increase in lymphocytes and suppressor cells (Tregs and MDSC). Interestingly, membrane expression of CD30 was identified on lymphocytes, especially Tregs, but not eosinophils. Soluble CD30 was also detected in the BAL fluid after allergen challenge in adult atopic asthmatics. CONCLUSIONS: After segmental allergen challenge of adult atopic asthmatics, cell types associated with a pro-inflammatory as well as an anti-inflammatory response are detected within the BAL fluid of the lung

Biotic and stable-isotope characterization of the Toarcian Ocean Anoxic Event through a carbonate–clastic sequence from Somerset, UK

This study focuses on a condensed sequence of alternating carbonate–clastic sediments of the Barrington Member, Beacon Limestone Formation (latest Pliensbachian to early Toarcian) from Somerset (SW England). Abundant ammonites confirm (apart from the absence of the Clevelandicum and Tenuicostatum ammonite subchronozones) the presence of Hawskerense Subchronozone to Fallaciosum–Bingmanni subchronozones. Well-preserved, sometimes diverse assemblages of ostracods, foraminifera, nannofossils and lowdiversity dinoflagellate assemblages support the chronostratigraphic framework. Stable-isotope analyses demonstrate the presence of a carbon isotope excursion, relating to the Toarcian Oceanic Anoxic Event, within the early Toarcian. Faunal, geochemical and sedimentological evidence suggest that deposition largely took place in a relatively deep-water (subwave base), mid-outer shelf environment under a well-mixed water column. However, reduced benthic diversity, the presence of weakly laminated sediments and changes in microplankton assemblage composition within the Toarcian Oceanic Anoxic Event indicates dysoxic, but probably never anoxic, bottom-water conditions during this event. The onset of the carbon isotope excursion coincides with extinction in the nannofossils and benthos, including the disappearance of the ostracod suborder Metacopina. Faunal evidence indicates connectivity with the Mediterranean region, not previously recorded for the UK during the early Toarcian

Impaired tumor necrosis factor-α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze

BACKGROUND: Infants with severe respiratory syncytial virus (RSV) bronchiolitis have an increased risk of recurrent wheezing and asthma. We aimed to evaluate the relationships between regulatory T cell (Treg) percentage and cytokine production of in vitro-stimulated CD4+ T cells during acute bronchiolitis and the development of recurrent wheezing in the first 3 years of life. METHODS: We obtained peripheral blood from 166 infants hospitalized with their first episode of RSV-confirmed bronchiolitis. Granzyme B (GZB) expression, and interleukin-10, interferon-γ, tumor necrosis factor-α (TNF-α), IL-4, and IL-5 production by in vitro anti-CD3/CD28- and anti-CD3/CD46-activated CD4+ T cells, and percentage of peripheral Treg (CD4+CD25 RESULTS: Sixty-seven percent (n = 111) of children had wheezing after their initial RSV infection, with 30% having recurrent wheezing. The percentage of peripheral Treg (CD4+CD25 CONCLUSIONS: We demonstrated lower TNF-α production by in vitro stimulated CD4+ T cells during severe RSV bronchiolitis in children that subsequently developed recurrent wheezing, compared with children with no subsequent wheeze. These findings support the role of CD4+ T cell immunity in the development of subsequent wheezing in these children

Global Phylogeography of the Dusky Shark Carcharhinus obscurus: Implications for Fisheries Management and Monitoring the Shark Fin Trade

Genetic stock structure information is needed to delineate management units and monitor trade in sharks, many of which are heavily exploited and declining. The dusky shark Carcharhinus obscurus is a large apex predator that is sought after for its fins and is considered highly susceptible to overexploitation. The International Union for the Conservation of Nature (IUCN) classifies this species as ‘Vulnerable’ globally and ‘Endangered’ in the northwest Atlantic. We make the first assessment of global stock structure of C. obscurus by analyzing part of the mitochondrial control region (mtCR) in 255 individuals sampled from 8 geographically dispersed locations. We found 25 mtCR haplotypes and rejected a null hypothesis of panmixia (analysis of molecular variance, ΦST = 0.55, p \u3c 0.000001), detecting significant differentiation between 3 management units: US Atlantic (USATL), South Africa (SAF), and Australia (AUS). We also found preliminary evidence of population structure between the USATL and southwest Atlantic (Brazil). There were no shared haplotypes between the western Atlantic and Indo-Pacific. These analyses suggest that replenishment of the collapsed USATL management unit via immigration of females from elsewhere is unlikely. Mixed stock analysis (MSA) simulations show that reconstruction of the relative contributions of USATL, SAF, and AUS management units to the Asian fin trade is possible using these mtCR sequences. We suggest avenues for obtaining samples to conduct MSA of the shark fin trade, which could enhance management of dusky sharks and other species that are exploited for their fins

Increased Expression of Cytotoxic T-Lymphocyte-Associated Protein 4 by T Cells, Induced by B7 in Sera, Reduces Adaptive Immunity in Patients With Acute Liver Failure.

BACKGROUND & AIMS: Patients with acute liver failure (ALF) have defects in innate immune responses to microbes (immune paresis) and are susceptible to sepsis. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4), which interacts with the membrane receptor B7 (also called CD80 and CD86), is a negative regulator of T-cell activation. We collected T cells from patients with ALF and investigated whether inhibitory signals down-regulate adaptive immune responses in patients with ALF. METHODS: We collected peripheral blood mononuclear cells from patients with ALF and controls from September 2013 through September 2015 (45 patients with ALF, 20 patients with acute-on-chronic liver failure, 15 patients with cirrhosis with no evidence of acute decompensation, 20 patients with septic shock but no cirrhosis or liver disease, and 20 healthy individuals). Circulating CD4+ T cells were isolated and analyzed by flow cytometry. CD4+ T cells were incubated with antigen, or agonist to CD3 and dendritic cells, with or without antibody against CTLA4; T-cell proliferation and protein expression were quantified. We measured levels of soluble B7 molecules in supernatants of isolated primary hepatocytes, hepatic sinusoidal endothelial cells, and biliary epithelial cells from healthy or diseased liver tissues. We also measured levels of soluble B7 serum samples from patients and controls, and mice with acetaminophen-induced liver injury using enzyme-linked immunosorbent assays. RESULTS: Peripheral blood samples from patients with ALF had a higher proportion of CD4+ CTLA4+ T cells than controls; patients with infections had the highest proportions. CD4+ T cells from patients with ALF had a reduced proliferative response to antigen or CD3 stimulation compared to cells from controls; incubation of CD4+ T cells from patients with ALF with an antibody against CTLA4 increased their proliferative response to antigen and to CD3 stimulation, to the same levels as cells from controls. CD4+ T cells from controls up-regulated expression of CTLA4 after 24-48 hours culture with sera from patients with ALF; these sera were found to have increased concentrations of soluble B7 compared to sera from controls. Necrotic human primary hepatocytes exposed to acetaminophen, but not hepatic sinusoidal endothelial cells and biliary epithelial cells from patients with ALF, secreted high levels of soluble B7. Sera from mice with acetaminophen-induced liver injury contained high levels of soluble B7 compared to sera from mice without liver injury. Plasma exchange reduced circulating levels of soluble B7 in patients with ALF and expression of CTLA4 on T cells. CONCLUSIONS: Peripheral CD4+ T cells from patients with ALF have increased expression of CTLA4 compared to individuals without ALF; these cells have a reduced response to antigen and CD3 stimulation. We found sera of patients with ALF and from mice with liver injury to have high concentrations of soluble B7, which up-regulates CTLA4 expression by T cells and reduces their response to antigen. Plasma exchange reduces levels of B7 in sera from patients with ALF and might be used to restore antimicrobial responses to patients

Identification of novel subgroup a variants with enhanced receptor binding and replicative capacity in primary isolates of anaemogenic strains of feline leukaemia virus

<b>BACKGROUND:</b> The development of anaemia in feline leukaemia virus (FeLV)-infected cats is associated with the emergence of a novel viral subgroup, FeLV-C. FeLV-C arises from the subgroup that is transmitted, FeLV-A, through alterations in the amino acid sequence of the receptor binding domain (RBD) of the envelope glycoprotein that result in a shift in the receptor usage and the cell tropism of the virus. The factors that influence the transition from subgroup A to subgroup C remain unclear, one possibility is that a selective pressure in the host drives the acquisition of mutations in the RBD, creating A/C intermediates with enhanced abilities to interact with the FeLV-C receptor, FLVCR. In order to understand further the emergence of FeLV-C in the infected cat, we examined primary isolates of FeLV-C for evidence of FeLV-A variants that bore mutations consistent with a gradual evolution from FeLV-A to FeLV-C.<p></p> <b>RESULTS:</b> Within each isolate of FeLV-C, we identified variants that were ostensibly subgroup A by nucleic acid sequence comparisons, but which bore mutations in the RBD. One such mutation, N91D, was present in multiple isolates and when engineered into a molecular clone of the prototypic FeLV-A (Glasgow-1), enhanced replication was noted in feline cells. Expression of the N91D Env on murine leukaemia virus (MLV) pseudotypes enhanced viral entry mediated by the FeLV-A receptor THTR1 while soluble FeLV-A Env bearing the N91D mutation bound more efficiently to mouse or guinea pig cells bearing the FeLV-A and -C receptors. Long-term in vitro culture of variants bearing the N91D substitution in the presence of anti-FeLV gp70 antibodies did not result in the emergence of FeLV-C variants, suggesting that additional selective pressures in the infected cat may drive the subsequent evolution from subgroup A to subgroup C.<p></p> <b>CONCLUSIONS:</b> Our data support a model in which variants of FeLV-A, bearing subtle differences in the RBD of Env, may be predisposed towards enhanced replication in vivo and subsequent conversion to FeLV-C. The selection pressures in vivo that drive the emergence of FeLV-C in a proportion of infected cats remain to be established

The Role of Parental Cognitive, Behavioral, and Motor Profiles in Clinical Variability in Individuals with Chromosome 16p11.2 Deletions

Importance Most disorders caused by copy number variants (CNVs) display significant clinical variability, often referred to as incomplete penetrance and variable expressivity. Genetic and environmental sources of this variability are not well understood. Objectives To investigate the contributors to phenotypic variability in probands with CNVs involving the same genomic region; to measure the effect size for de novo mutation events; and to explore the contribution of familial background to resulting cognitive, behavioral, and motor performance outcomes in probands with de novo CNVs. Design, Setting, and Participants Family-based study design with a volunteer sample of 56 individuals with de novo 16p11.2 deletions and their noncarrier parents and siblings from the Simons Variation in Individuals Project. Main Outcomes and Measures We used linear mixed-model analysis to measure effect size and intraclass correlation to determine the influence of family background for a de novo CNV on quantitative traits representing the following 3 neurodevelopmental domains: cognitive ability (Full-Scale IQ), social behavior (Social Responsiveness Scale), and neuromotor performance (Purdue Pegboard Test). We included an anthropometric trait, body mass index, for comparison. Results A significant deleterious effect of the 16p11.2 deletion was demonstrated across all domains. Relative to the biparental mean, the effect sizes were −1.7 SD for cognitive ability, 2.2 SD for social behavior, and −1.3 SD for neuromotor performance (P \u3c .001). Despite large deleterious effects, significant positive correlations between parents and probands were preserved for the Full-Scale IQ (0.42 [P = .03]), the verbal IQ (0.53 [P = .004]), and the Social Responsiveness Scale (0.52 [P = .009]) scores. We also observed a 1-SD increase in the body mass index of probands compared with siblings, with an intraclass correlation of 0.40 (P = .07). Conclusions and Relevance Analysis of families with de novo CNVs provides the least confounded estimate of the effect size of the 16p11.2 deletion on heritable, quantitative traits and demonstrates a 1- to 2-SD effect across all neurodevelopmental dimensions. Significant parent-proband correlations indicate that family background contributes to the phenotypic variability seen in this and perhaps other CNV disorders and may have implications for counseling families regarding their children’s developmental and psychiatric prognoses. Use of biparental mean scores rather than general population mean scores may be more relevant to examine the effect of a mutation or any other cause of trait variation on a neurodevelopmental outcome and possibly on systems of diagnosis and trait ascertainment for developmental disorders