Anthromes dispaying evidence of weekly cycles in active fire data cover 70% of the global land surface

Across the globe, human activities have been gaining importance relatively to climate and ecology as the main controls on fire regimes and consequently human activity became an important driver of the frequency, extent and intensity of vegetation burning worldwide. Our objective in the present study is to look for weekly cycles in vegetation fire activity at global scale as evidence of human agency, relying on the original MODIS active fire detections at 1 km spatial resolution (MCD14ML) and using novel statistical methodologies to detect significant periodicities in time series data. We tested the hypotheses that global fire activity displays weekly cycles and that the weekday with the fewest fires is Sunday. We also assessed the effect of land use and land cover on weekly fire cycle significance by testing those hypotheses separately for the Villages, Settlements, Croplands, Rangelands, Seminatural, and Wildlands anthromes. Based on a preliminary data analysis of the daily global active fire counts periodogram, we developed an harmonic regression model for the mean function of daily fire activity and assumed a linear model for the de-seasonalized time series. For inference purposes, we used a Bayesian methodology and constructed a simultaneous 95% credible band for the mean function. The hypothesis of a Sunday weekly minimum was directly investigated by computing the probabilities that the mean functions of every weekday (Monday to Saturday) are inside the credible band corresponding to mean Sunday fire activity. Since these probabilities are small, there is statistical evidence of significantly fewer fires on Sunday than on the other days of the week. Cropland, rangeland, and seminatural anthromes, which cover 70% of the global land area and account for 94% of the active fires analysed, display weekly cycles in fire activity. Due to lower land management intensity and less strict control over fire size and duration, weekly cycles in Rangelands and Seminatural anthromes, which jointly account for 53.46% of all fires, although statistically significant are weaker than those detected in Croplandsinfo:eu-repo/semantics/publishedVersio

The use of representative community samples to assess SARS-CoV-2 lineage competition: Alpha outcompetes Beta and wild-type in England from January to March 2021.

Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy and will be a high priority for public health for the foreseeable future. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained using a variety of methods all of which are known to contain biases. As a case study, using an approach which is largely free of biases, we here describe lineage dynamics and phylogenetic relationships of the Alpha and Beta variant in England during the first 3 months of 2021 using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the Alpha variant (first identified in Kent) becoming predominant, driven by a reproduction number 0.3 higher than for the prior wild-type. During January, positive samples were more likely to be Alpha in those aged 18 to 54 years old. Although individuals infected with the Alpha variant were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild-type, they were more likely to be antibody-positive 6 weeks after infection. Further, viral load was higher in those infected with the Alpha variant as measured by cycle threshold (Ct) values. The presence of infections with non-imported Beta variant (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing. These results highlight how sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance during periods of lineage diversity

BTN3A2 Expression in Epithelial Ovarian Cancer Is Associated with Higher Tumor Infiltrating T Cells and a Better Prognosis

BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR = 0.651, p = 0.006 and HR = 0.642, p = 0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR = 1.355 p = 0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells

Epithelial atypia in biopsies performed for microcalcifications. Practical considerations about 2,833 serially sectioned surgical biopsies with a long follow-up

This study analyzes the occurrence of epithelial atypia in 2,833 serially sectioned surgical breast biopsies (SB) performed for microcalcifications (median number of blocks per SB:26) and the occurrence of subsequent cancer after an initial diagnosis of epithelial atypia (median follow-up 160 months). Epithelial atypia (flat epithelial atypia, atypical ductal hyperplasia, and lobular neoplasia) were found in 971 SB, with and without a concomitant cancer in 301 (31%) and 670 (69%) SB, respectively. Thus, isolated epithelial atypia were found in 670 out of the 2,833 SB (23%). Concomitant cancers corresponded to ductal carcinomas in situ and micro-invasive (77%), invasive ductal carcinomas not otherwise specified (15%), invasive lobular carcinomas (4%), and tubular carcinomas (4%). Fifteen out of the 443 patients with isolated epithelial atypia developed a subsequent ipsilateral (n = 14) and contralateral (n = 1) invasive cancer. The high slide rating might explain the high percentages of epithelial atypia and concomitant cancers and the low percentage of subsequent cancer after a diagnosis of epithelial atypia as a single lesion. Epithelial atypia could be more a risk marker of concomitant than subsequent cancer

Distinct fibroblast lineages determine dermal architecture in skin development and repair

This work was funded by the Wellcome Trust (F.M.W., A.C.F.-S.), the Medical Research Council (MRC) (F.M.W., A.C.F.-S.) and the European Union FP7 programme: TUMIC (F.M.W.), HEALING (F.M.W.) and EpigeneSys (A.C.F.-S.). B.M.L. is the recipient of a FEBS long-term fellowship. K.K. is the recipient of a MRC PhD Studentship. The authors acknowledge financial support from the Department of Health via theNational Institute forHealth Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London (KCL) and King’s College Hospital NHS Foundation Trust. Input from M. Mastrogiannaki, A. Reimer and B. Trappmann is gratefully acknowledged

Best practice for motor imagery: a systematic literature review on motor imagery training elements in five different disciplines

<p>Abstract</p> <p>Background</p> <p>The literature suggests a beneficial effect of motor imagery (MI) if combined with physical practice, but detailed descriptions of MI training session (MITS) elements and temporal parameters are lacking. The aim of this review was to identify the characteristics of a successful MITS and compare these for different disciplines, MI session types, task focus, age, gender and MI modification during intervention.</p> <p>Methods</p> <p>An extended systematic literature search using 24 databases was performed for five disciplines: Education, Medicine, Music, Psychology and Sports. References that described an MI intervention that focused on motor skills, performance or strength improvement were included. Information describing 17 MITS elements was extracted based on the PETTLEP (physical, environment, timing, task, learning, emotion, perspective) approach. Seven elements describing the MITS temporal parameters were calculated: study duration, intervention duration, MITS duration, total MITS count, MITS per week, MI trials per MITS and total MI training time.</p> <p>Results</p> <p>Both independent reviewers found 96% congruity, which was tested on a random sample of 20% of all references. After selection, 133 studies reporting 141 MI interventions were included. The locations of the MITS and position of the participants during MI were task-specific. Participants received acoustic detailed MI instructions, which were mostly standardised and live. During MI practice, participants kept their eyes closed. MI training was performed from an internal perspective with a kinaesthetic mode. Changes in MI content, duration and dosage were reported in 31 MI interventions. Familiarisation sessions before the start of the MI intervention were mentioned in 17 reports. MI interventions focused with decreasing relevance on motor-, cognitive- and strength-focused tasks. Average study intervention lasted 34 days, with participants practicing MI on average three times per week for 17 minutes, with 34 MI trials. Average total MI time was 178 minutes including 13 MITS. Reporting rate varied between 25.5% and 95.5%.</p> <p>Conclusions</p> <p>MITS elements of successful interventions were individual, supervised and non-directed sessions, added after physical practice. Successful design characteristics were dominant in the Psychology literature, in interventions focusing on motor and strength-related tasks, in interventions with participants aged 20 to 29 years old, and in MI interventions including participants of both genders. Systematic searching of the MI literature was constrained by the lack of a defined MeSH term.</p

Comparative genetic, proteomic and phosphoproteomic analysis of C. <i>elegans </i>embryos with a focus on <i>ham</i>-1/STOX and <i>pig</i>-1/MELK in dopaminergic neuron development

Asymmetric cell divisions are required for cellular diversity and defects can lead to altered daughter cell fates and numbers. In a genetic screen for C. elegans mutants with defects in dopaminergic head neuron specification or differentiation, we isolated a new allele of the transcription factor HAM-1 [HSN (Hermaphrodite-Specific Neurons) Abnormal Migration]. Loss of both HAM-1 and its target, the kinase PIG-1 [PAR-1(I)-like Gene], leads to abnormal dopaminergic head neuron numbers. We identified discrete genetic relationships between ham-1, pig-1 and apoptosis pathway genes in dopaminergic head neurons. We used an unbiased, quantitative mass spectrometry-based proteomics approach to characterise direct and indirect protein targets and pathways that mediate the effects of PIG-1 kinase loss in C. elegans embryos. Proteins showing changes in either abundance, or phosphorylation levels, between wild-type and pig-1 mutant embryos are predominantly connected with processes including cell cycle, asymmetric cell division, apoptosis and actomyosin-regulation. Several of these proteins play important roles in C. elegans development. Our data provide an in-depth characterisation of the C. elegans wild-type embryo proteome and phosphoproteome and can be explored via the Encyclopedia of Proteome Dynamics (EPD) - an open access, searchable online database

BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and genistein in breast and prostate cancer cells

Indole-3-carbinol (I3C) and genistein are naturally occurring chemicals derived from cruciferous vegetables and soy, respectively, with potential cancer prevention activity for hormone-responsive tumours (e.g., breast and prostate cancers). Previously, we showed that I3C induces BRCA1 expression and that both I3C and BRCA1 inhibit oestrogen (E2)-stimulated oestrogen receptor (ER-α) activity in human breast cancer cells. We now report that both I3C and genistein induce the expression of both breast cancer susceptibility genes (BRCA1 and BRCA2) in breast (MCF-7 and T47D) and prostate (DU-145 and LNCaP) cancer cell types, in a time- and dose-dependent fashion. Induction of the BRCA genes occurred at low doses of I3C (20 μM) and genistein (0.5–1.0 μM), suggesting potential relevance to cancer prevention. A combination of I3C and genistein gave greater than expected induction of BRCA expression. Studies using small interfering RNAs (siRNAs) and BRCA expression vectors suggest that the phytochemical induction of BRCA2 is due, in part, to BRCA1. Functional studies suggest that I3C-mediated cytoxicity is, in part, dependent upon BRCA1 and BRCA2. Inhibition of E2-stimulated ER-α activity by I3C and genistein was dependent upon BRCA1; and inhibition of ligand-inducible androgen receptor (AR) activity by I3C and genistein was partially reversed by BRCA1-siRNA. Finally, we provide evidence suggesting that the phytochemical induction of BRCA1 expression is due, in part, to endoplasmic reticulum stress response signalling. These findings suggest that the BRCA genes are molecular targets for some of the activities of I3C and genistein

Rationale and design of the United Kingdom Heart Failure with Preserved Ejection Fraction Registry

\ua9 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.Objective: Heart failure with preserved ejection fraction (HFpEF) is a common heterogeneous syndrome that remains imprecisely defined and consequently has limited treatment options and poor outcomes. Methods: The UK Heart Failure with Preserved Ejection Fraction Registry (UK HFpEF) is a prospective data-enabled cohort and platform study. The study will develop a large, highly characterised cohort of patients with HFpEF. A biobank will be established. Deep clinical phenotyping, imaging, multiomics and centrally held national electronic health record data will be integrated at scale, in order to reclassify HFpEF into distinct subgroups, improve understanding of disease mechanisms and identify new biological pathways and molecular targets. Together, these will form the basis for developing diagnostics and targeted therapeutics specific to subgroups. It will be a platform for more effective and efficient trials, focusing on subgroups in whom targeted interventions are expected to be effective, with consent in place to facilitate rapid recruitment, and linkage for follow-up. Patients with a diagnosis of HFpEF made by a heart failure specialist, who have had natriuretic peptide levels measured and a left ventricular ejection fraction &gt;40% are eligible. Patients with an ejection fraction between 40% and 49% will be limited to no more than 25% of the cohort. Conclusions: UK HFpEF will develop a rich, multimodal data resource to enable the identification of disease endotypes and develop more effective diagnostic strategies, precise risk stratification and targeted therapeutics. Trial registration number: NCT05441839

Tracing the Origin of the Fungal α1 Domain Places Its Ancestor in the HMG-Box Superfamily: Implication for Fungal Mating-Type Evolution

BACKGROUND: Fungal mating types in self-incompatible Pezizomycotina are specified by one of two alternate sequences occupying the same locus on corresponding chromosomes. One sequence is characterized by a gene encoding an HMG protein, while the hallmark of the other is a gene encoding a protein with an α1 domain showing similarity to the Matα1p protein of Saccharomyces cerevisiae. DNA-binding HMG proteins are ubiquitous and well characterized. In contrast, α1 domain proteins have limited distribution and their evolutionary origin is obscure, precluding a complete understanding of mating-type evolution in Ascomycota. Although much work has focused on the role of the S. cerevisiae Matα1p protein as a transcription factor, it has not yet been placed in any of the large families of sequence-specific DNA-binding proteins. METHODOLOGY/PRINCIPAL FINDINGS: We present sequence comparisons, phylogenetic analyses, and in silico predictions of secondary and tertiary structures, which support our hypothesis that the α1 domain is related to the HMG domain. We have also characterized a new conserved motif in α1 proteins of Pezizomycotina. This motif is immediately adjacent to and downstream of the α1 domain and consists of a core sequence Y-[LMIF]-x(3)-G-[WL] embedded in a larger conserved motif. CONCLUSIONS/SIGNIFICANCE: Our data suggest that extant α1-box genes originated from an ancestral HMG gene, which confirms the current model of mating-type evolution within the fungal kingdom. We propose to incorporate α1 proteins in a new subclass of HMG proteins termed MATα_HMG