Defining Lineage Potential and Fate Behavior of Precursors during Pancreas Development

Pancreas development involves a coordinated process in which an early phase of cell segregation is followed by a longer phase of lineage restriction, expansion, and tissue remodeling. By combining clonal tracing and whole-mount reconstruction with proliferation kinetics and single-cell transcriptional profiling, we define the functional basis of pancreas morphogenesis. We show that the large-scale organization of mouse pancreas can be traced to the activity of self-renewing precursors positioned at the termini of growing ducts, which act collectively to drive serial rounds of stochastic ductal bifurcation balanced by termination. During this phase of branching morphogenesis, multipotent precursors become progressively fate-restricted, giving rise to self-renewing acinar-committed precursors that are conveyed with growing ducts, as well as ductal progenitors that expand the trailing ducts and give rise to delaminating endocrine cells. These findings define quantitatively how the functional behavior and lineage progression of precursor pools determine the large-scale patterning of pancreatic sub-compartments

Evaluation of stem rot in 339 Bornean tree species: implications of size, taxonomy, and soil-related variation for aboveground biomass estimates

Fungal decay of heart wood creates hollows and areas of reduced wood density within the stems of living trees known as stem rot. Although stem rot is acknowledged as a source of error in forest aboveground biomass (AGB) estimates, there are few data sets available to evaluate the controls over stem rot infection and severity in tropical forests. Using legacy and recent data from 3180 drilled, felled, and cored stems in mixed dipterocarp forests in Sarawak, Malaysian Borneo, we quantified the frequency and severity of stem rot in a total of 339 tree species, and related variation in stem rot with tree size, wood density, taxonomy, and species’ soil association, as well as edaphic conditions. Predicted stem rot frequency for a 50 cm tree was 53% of felled, 39% of drilled, and 28% of cored stems, demonstrating differences among methods in rot detection ability. The percent stem volume infected by rot, or stem rot severity, ranged widely among trees with stem rot infection (0.1–82.8 %) and averaged 9% across all trees felled. Tree taxonomy explained the greatest proportion of variance in both stem rot frequency and severity among the predictors evaluated in our models. Stem rot frequency, but not severity, increased sharply with tree diameter, ranging from 13% in trees 10–30 cm DBH to 54%in stems ≥ 50 cm DBH across all data sets. The frequency of stem rot increased significantly in soils with low pH and cation concentrations in topsoil, and stem rot was more common in tree species associated with dystrophic sandy soils than with nutrient-rich clays. When scaled to forest stands, the maximum percent of stem biomass lost to stem rot varied significantly with soil properties, and we estimate that stem rot reduces total forest AGB estimates by up to 7% relative to what would be predicted assuming all stems are composed strictly of intact wood. This study demonstrates not only that stem rot is likely to be a significant source of error in forest AGB estimation, but also that it strongly covaries with tree size, taxonomy, habitat association, and soil resources, underscoring the need to account for tree community composition and edaphic variation in estimating carbon storage in tropical forests

A novel long non-coding natural antisense RNA is a negative regulator of Nos1 gene expression

Long non-coding natural antisense transcripts (NATs) are widespread in eukaryotic species. Although recent studies indicate that long NATs are engaged in the regulation of gene expression, the precise functional roles of the vast majority of them are unknown. Here we report that a long NAT (Mm-antiNos1 RNA) complementary to mRNA encoding the neuronal isoform of nitric oxide synthase (Nos1) is expressed in the mouse brain and is transcribed from the non-template strand of the Nos1 locus. Nos1 produces nitric oxide (NO), a major signaling molecule in the CNS implicated in many important functions including neuronal differentiation and memory formation. We show that the newly discovered NAT negatively regulates Nos1 gene expression. Moreover, our quantitative studies of the temporal expression profiles of Mm-antiNos1 RNA in the mouse brain during embryonic development and postnatal life indicate that it may be involved in the regulation of NO-dependent neurogenesis

Atypical audiovisual speech integration in infants at risk for autism

The language difficulties often seen in individuals with autism might stem from an inability to integrate audiovisual information, a skill important for language development. We investigated whether 9-month-old siblings of older children with autism, who are at an increased risk of developing autism, are able to integrate audiovisual speech cues. We used an eye-tracker to record where infants looked when shown a screen displaying two faces of the same model, where one face is articulating/ba/and the other/ga/, with one face congruent with the syllable sound being presented simultaneously, the other face incongruent. This method was successful in showing that infants at low risk can integrate audiovisual speech: they looked for the same amount of time at the mouths in both the fusible visual/ga/− audio/ba/and the congruent visual/ba/− audio/ba/displays, indicating that the auditory and visual streams fuse into a McGurk-type of syllabic percept in the incongruent condition. It also showed that low-risk infants could perceive a mismatch between auditory and visual cues: they looked longer at the mouth in the mismatched, non-fusible visual/ba/− audio/ga/display compared with the congruent visual/ga/− audio/ga/display, demonstrating that they perceive an uncommon, and therefore interesting, speech-like percept when looking at the incongruent mouth (repeated ANOVA: displays x fusion/mismatch conditions interaction: F(1,16) = 17.153, p = 0.001). The looking behaviour of high-risk infants did not differ according to the type of display, suggesting difficulties in matching auditory and visual information (repeated ANOVA, displays x conditions interaction: F(1,25) = 0.09, p = 0.767), in contrast to low-risk infants (repeated ANOVA: displays x conditions x low/high-risk groups interaction: F(1,41) = 4.466, p = 0.041). In some cases this reduced ability might lead to the poor communication skills characteristic of autism

Physics, Topology, Logic and Computation: A Rosetta Stone

In physics, Feynman diagrams are used to reason about quantum processes. In the 1980s, it became clear that underlying these diagrams is a powerful analogy between quantum physics and topology: namely, a linear operator behaves very much like a "cobordism". Similar diagrams can be used to reason about logic, where they represent proofs, and computation, where they represent programs. With the rise of interest in quantum cryptography and quantum computation, it became clear that there is extensive network of analogies between physics, topology, logic and computation. In this expository paper, we make some of these analogies precise using the concept of "closed symmetric monoidal category". We assume no prior knowledge of category theory, proof theory or computer science.Comment: 73 pages, 8 encapsulated postscript figure

'Motivate': the effect of a Football in the Community delivered weight loss programme on over 35-year old men and women's cardiovascular risk factors

The purpose of this study was to examine whether an innovative, inclusive and integrated 12-week exercise, behaviour change and nutrition advice-based weight management programme could significantly improve the cardiovascular risk factors of overweight and obese men and women over the age of 35. One hundred and ninety-four men and 98 women (mean age = 52.28 ± 9.74 and 51.19 ± 9.04) attending a community-based intervention delivered by Notts County Football in the Community over one year, took part in the study. Height (m), weight (kg), fitness (meters covered during a 6 min walk) and waist circumference (cm) were measured at weeks 1 and 12 as part of the intervention. Changes in body weight, waist circumference and fitness for men and women were measured by a 2-way repeated measures ANOVA, with significance set to p < 0.05.Weight, waist circumference and fitness significantly improved over time in both men (4.96 kg, 6.29 cm, 70.22 m; p < 0.05) and women (4.26 kg, 5.90 cm, 35.29 m; p < 0.05). The results demonstrated that the FITC lead weight loss intervention was successful in significantly improving cardiovascular risk factors in both men and women. In particular, the weight loss reductions achieved were comparable to those seen in similar, more costly men-only programmes. This is the first study to demonstrate the efficacy of such an intervention in an inclusive, mixed gender programme and more specifically, in women

Social Value at Universities: Policy and Practice Guidance

Universities globally can be major hubs of social and economic activity which drive change in society. We know that they can create multiple and diverse routes into employment, can have significant purchasing power which can inform standards across supply chains, can create learning opportunities which directly nourish and enrich local communities, and can deliver research and innovation which impact health for the better. However, the measurable difference these make to lives – and how universities and the funding bodies account for this impact - is still unknown. We created the Global Symposia for Social Value at Universities in 2022, as a way to accelerate the movement. Over 130 joined from 12 countries to contribute to the analysis, from different disciplines such as health, arts, environmental sciences, alongside private, public and third sector stakeholders. There were two symposiums. The first was related to understanding policy and practice across disciplines at universities; the second was focused on one of the biggest sectors, business and management studies. This report presents the findings from both symposiums from the perspective of different stakeholders: 1. what is currently being done that is valued 2. recommendations for improvement The Global Symposia at Universities 2022 was co-hosted between Social Value UK and Liverpool John Moores University, the British Academy of Management (Sustainable and Responsible Business SIG), Principles for Responsible Management Education (Working Group on Poverty), University Vocational Awards Council, Social Value International, The Academy of Business in Society, American International Accreditation Association for Schools and Colleges, and the National Society for Experiential Education. Maddy England and Clare Bentley at Social Value UK were also central to delivering this guidance. Supported by Liverpool John Moores University’s Quality Research Funds

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty