Miracle-dz/UniFAR-FTUs huggingface dataset:
Leptospira species promote a pro‐inflammatory phenotype in human neutrophils

Leptospirosis is a global zoonosis caused by pathogenic Leptospira. Neutrophils are key cells against bacterial pathogens but can also contribute to tissue damage. Because the information regarding the role of human neutrophils in leptospirosis is scant, we comparatively analysed the human neutrophil's response to saprophytic Leptospira biflexa serovar Patoc (Patoc) and the pathogenic Leptospira interrogans serovar Copenhageni (LIC).
Mobile phone use and incidence of brain tumour histological types, grading or anatomical location: a population-based ecological study

Objective Some studies have reported increasing trends in certain brain tumours and a possible link with mobile phone use has been suggested. We examined the incidence time trends of brain tumour in Australia for three distinct time periods to ascertain the influence of improved diagnostic technologies and increase in mobile phone use on the incidence of brain tumours. Design In a population-based ecological study, we examined trends of brain tumour over the periods 1982–1992, 1993–2002 and 2003–2013. We further compared the observed incidence during the period of substantial mobile phone use (2003–2013) with predicted (modelled) incidence for the same period by applying various relative risks, latency periods and mobile phone use scenarios. Setting National Australian incidence registration data on primary cancers of the brain diagnosed between 1982 and 2013. Population 16 825 eligible brain cancer cases aged 20–59 from all of Australia (10 083 males and 6742 females). Main outcome measures Annual percentage change (APC) in brain tumour incidence based on Poisson regression analysis. Results The overall brain tumour rates remained stable during all three periods. There was an increase in glioblastoma during 1993–2002 (APC 2.3, 95% CI 0.8 to 3.7) which was likely due to advances in the use of MRI during that period. There were no increases in any brain tumour types, including glioma (−0.6, –1.4 to 0.2) and glioblastoma (0.8, –0.4 to 2.0), during the period of substantial mobile phone use from 2003 to 2013. During that period, there was also no increase in glioma of the temporal lobe (0.5, –1.3 to 2.3), which is the location most exposed when using a mobile phone. Predicted incidence rates were higher than the observed rates for latency periods up to 15 years. Conclusions In Australia, there has been no increase in any brain tumour histological type or glioma location that can be attributed to mobile phones.
Nonomuraea lactucae sp. nov., a novel actinomycete isolated from rhizosphere soil of lettuce (Lactuca sativa).

A novel actinobacterium, designated strain NEAU-YG30T, was isolated from the rhizosphere soil of lettuce collected in Heilongjiang province, north-east China. The taxonomic position of the strain was investigated using a polyphasic approach. On the basis of 16S rRNA gene sequence analysis, strain NEAU-YG30T belongs to the genus Nonomuraea, and shared highest sequence similarity to Nonomuraea muscovyensis KCTC 29233T (97.9 %) and Nonomuraea indica CCTCC AA 209050T (97.6 %). The major menaquinone was identified as MK-9(H4). The major fatty acids were 10-methyl C17 : 0, C17 : 0, iso-C16 : 0 2-OH, iso-C16 : 0 and C16 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, hydroxyl-phosphatidylethanolamine, phosphatidylinositol, an unidentified phospholipid and three unidentified lipids. The genomic DNA G+C content of strain NEAU-YG30T was 70.5 mol%. DNA-DNA hybridization values between them were less than 70 %. On the basis of phenotypic, genotypic and phylogenetic data, strain NEAU-YG30T can be characterized to represent a novel species of the genus Nonomuraea, for which the name Nonomuraealactucae sp. nov. is proposed. The type strain is NEAU-YG30T (=JCM 32549T=CGMCC 4.7506T).
Errors in estimating usual sodium intake by the Kawasaki formula alter its relationship with mortality: implications for public health.

Background Several cohort studies with inaccurate estimates of sodium reported a J-shaped relationship with mortality. We compared various estimated sodium intakes with that measured by the gold-standard method of multiple non-consecutive 24-h urine collections and assessed their relationship with mortality. Methods We analysed the Trials of Hypertension Prevention follow-up data. Sodium intake was assessed in four ways: (i) average measured (gold standard): mean of three to seven 24-h urinary sodium measurements during the trial periods; (ii) average estimated: mean of three to seven estimated 24-h urinary sodium excretions from sodium concentration of 24-h urine using the Kawasaki formula; (iii) first measured: 24-h urinary sodium measured at the beginning of each trial; (iv) first estimated: 24-h urinary sodium estimated from sodium concentration of the first 24-h urine using the Kawasaki formula. We included 2974 individuals aged 30-54 years with pre-hypertension, not assigned to sodium intervention. Results During a median follow-up of 24 years, 272 deaths occurred. The average sodium intake measured by the gold-standard method was 3769 ± 1282 mg/d. The average estimated sodium over-estimated the intake by 1297 mg/d (95% confidence interval: 1267-1326). The average estimated value was systematically biased with over-estimation at lower levels and under-estimation at higher levels. The average measured sodium showed a linear relationship with mortality. The average estimated sodium appeared to show a J-shaped relationship with mortality. The first measured and the first estimated sodium both flattened the relationship. Conclusions Accurately measured sodium intake showed a linear relationship with mortality. Inaccurately estimated sodium changed the relationship and could explain much of the paradoxical J-shaped findings reported in some cohort studies.
A unique nanoparticulate TLR9 agonist enables a HA split vaccine to confer Fc&ggr;R-mediated protection against heterologous lethal influenza virus infection

The development of a universal influenza vaccine that can provide a robust and long-lasting protection against a broader range of influenza virus strains is a global public health priority. One approach to improve vaccine efficacy is to use an adjuvant to boost immune responses to the target antigens; nevertheless, the role of adjuvants in the context of influenza vaccines is not fully understood. We have previously developed the K3-schizophyllan (SPG) adjuvant, which is composed of nanoparticulated oligodeoxynucleotides K3, a TLR9 agonist, with SPG, a non-agonistic β-glucan ligand of Dectin-1. In this study, K3-SPG given with conventional influenza hemagglutinin (HA) split vaccine (K3-SPG HA) conferred protection against antigenically mismatched heterologous virus challenge. While K3-SPG HA elicited robust cross-reactive HA-specific IgG2c and CD8 T-cell responses, CD8 T-cell depletion had no impact on this cross-protection. In contrast, K3-SPG HA was not able to confer protection against heterologous virus challenge in FcRγ-deficient mice. Our results indicated that FcγR-mediated antibody responses induced by the HA antigen and K3-SPG adjuvant were important for potent protection against antigenically mismatched influenza virus infection. Thus, we demonstrated that the K3-SPG-adjuvanted vaccine strategy broadens protective immunity against influenza and provides a basis for the development of next-generation influenza vaccines.
Multi-level remodeling of transcriptional landscapes in aging and longevity

In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and gene expression has been observed to be deregulated with aging. In this review, we discuss the current knowledge on the transcriptional alterations that have been described to occur with age in metazoans. First, we discuss age-related transcriptional changes in protein-coding genes, the expected functional impact of such changes, and how known pro-longevity interventions impact these changes. Second, we discuss the changes and impact of emerging aspects of transcription in aging, including age-related changes in splicing, lncRNAs and circRNAs. Third, we discuss the changes and potential impact of transcription of transposable elements with aging. Fourth, we highlight small ncRNAs and their potential impact on the regulation of aging phenotypes. Understanding the aging transcriptome will be key to identify important regulatory targets, and ultimately slow-down or reverse aging and extend healthy lifespan in humans.
Antipsychotics and pituitary tumors: an analysis of the European pharmacovigilance database (EudraVigilance)

One of the possible long-term consequences of antipsychotic-induced hyperprolactinemia is the development of pituitary tumors – prolactinomas. So far, two pharmacovigilance studies of spontaneous adverse event report databases have suggested an increased risk, whereas a longitudinal study carried out with risperidone showed no evidence of increased risk of tumors with mass effect. Besides, information on amisulpride and paliperidone is lacking. Thus, in this study, we aimed to analyze the European pharmacovigilance database (EudraVigilance) to shed light on this issue. We searched for all suspected spontaneous cases of pituitary tumors associated with antipsychotics in EudraVigilance up to 23 March 2017. To assess the association between pituitary tumor cases and each antipsychotic, we calculated the proportional reporting ratios. Among 4 964 866 events of all types recorded in EudraVigilance, we found 292 cases of pituitary tumors associated with antipsychotics. All atypical antipsychotics except clozapine fulfilled the criteria to generate a safety signal. The highest proportional reporting ratio values were found for amisulpride 51.57 (36.3–73.2), risperidone 21.83 (18.4–25.8), and paliperidone 19.95 (14.7–27.1). Sulpiride and haloperidol showed a higher risk among typical antipsychotics 12.4 (5.89–26.1) and 7.0 (4.35–11.3). Notably, we found that a mass effect was present in 16% of the cases. Besides, 18 cases occurred in patients aged below 18 years. Our analysis of the data in EudraVigilance confirms the safety signal detected by previous studies. Interestingly, for the first time, we show that the association seems to be the strongest for amisulpride and that a mass effect was present in around 16% of the cases.
AHNS series: Do you know your guidelines? Guideline recommendations for recurrent and persistent head and neck cancer after primary treatment

Locoregional recurrent/persistent head and neck cancer following primary treatment is a significant challenge as it is usually difficult to treat and has worse outcomes compared to the primary setting. Surgical resection of a local or regional recurrence offers the best chance of cure when feasible. Local recurrence outcomes vary by subsite with laryngeal recurrences having the best prognoses and hypopharynx having the worst. Instances of persistent neck masses following primary nonsurgical treatment can be evaluated with positron emission tomography (PET) with CT (PET‐CT) when there is no definitive diagnosis of a recurrence/persistence. Reirradiation with or without chemotherapy can be considered for primary treatment when surgery is not an option, for adjuvant treatment following salvage surgery, or for palliation. Immunotherapy represents a newer class of chemotherapeutic agents. Current guidelines recommend enrollment in clinical trials especially when surgery is not an option as outcomes remain universally poor in the recurrent/persistent setting.
Deep convolutional networks do not classify based on global object shape

Deep convolutional networks (DCNNs) are achieving previously unseen performance in object classification, raising questions about whether DCNNs operate similarly to human vision. In biological vision, shape is arguably the most important cue for recognition. We tested the role of shape information in DCNNs trained to recognize objects. In Experiment 1, we presented a trained DCNN with object silhouettes that preserved overall shape but were filled with surface texture taken from other objects. Shape cues appeared to play some role in the classification of artifacts, but little or none for animals. In Experiments 2–4, DCNNs showed no ability to classify glass figurines or outlines but correctly classified some silhouettes. Aspects of these results led us to hypothesize that DCNNs do not distinguish object’s bounding contours from other edges, and that DCNNs access some local shape features, but not global shape. In Experiment 5, we tested this hypothesis with displays that preserved local features but disrupted global shape, and vice versa. With disrupted global shape, which reduced human accuracy to 28%, DCNNs gave the same classification labels as with ordinary shapes. Conversely, local contour changes eliminated accurate DCNN classification but caused no difficulty for human observers. These results provide evidence that DCNNs have access to some local shape information in the form of local edge relations, but they have no access to global object shapes.
SREBP-1a–stimulated lipid synthesis is required for macrophage phagocytosis downstream of TLR4-directed mTORC1

Significance There is a growing appreciation for a fundamental connection between lipid metabolism and the innate immune response. Phagocytosis is a key macrophage innate immune response to pathogen exposure, and cytoplasmic membrane expansion is required to surround and capture the target pathogen prior to internalization. Sterol regulatory element binding proteins (SREBPs) are gene regulatory factors that sense the intracellular lipid environment and modulate key genes that drive fatty acid and cholesterol synthesis to maintain lipid homeostasis. In this study, we show that, in mutant cells that lack a key SREBP isoform, phagocytosis is impaired, and we track the defect to altered lipid composition of membrane phospholipids that results in decreased interaction between membrane lipid rafts and the actin cytoskeletal network. There is a growing appreciation for a fundamental connection between lipid metabolism and the immune response. Macrophage phagocytosis is a signature innate immune response to pathogen exposure, and cytoplasmic membrane expansion is required to engulf the phagocytic target. The sterol regulatory element binding proteins (SREBPs) are key transcriptional regulatory proteins that sense the intracellular lipid environment and modulate expression of key genes of fatty acid and cholesterol metabolism to maintain lipid homeostasis. In this study, we show that TLR4-dependent stimulation of macrophage phagocytosis requires mTORC1-directed SREBP-1a−dependent lipid synthesis. We also show that the phagocytic defect in macrophages from SREBP-1a−deficient mice results from decreased interaction between membrane lipid rafts and the actin cytoskeleton, presumably due to reduced accumulation of newly synthesized fatty acyl chains within major membrane phospholipids. We show that mTORC1-deficient macrophages also have a phagocytic block downstream from TLR4 signaling, and, interestingly, the reduced level of phagocytosis in both SREBP-1a− and mTORC1-deficient macrophages can be restored by ectopic SREBP-1a expression. Taken together, these observations indicate SREBP-1a is a major downstream effector of TLR4−mTORC1 directed interactions between membrane lipid rafts and the actin cytoskeleton that are required for pathogen-stimulated phagocytosis in macrophages.
Evolution of transmission mode in conditional mutualisms with spatial variation in symbiont quality

While some symbioses are always mutualistic or parasitic, others have costs and benefits that depend on environmental factors. The environmental context may itself vary in space, in some cases causing a symbiont to be a mutualist in one location and a parasite in another. Such spatially conditional mutualisms pose a dilemma for hosts, who might evolve (higher or lower) horizontal or vertical transmission to increase their chances of being infected only where the symbiont is beneficial. To determine how transmission in hosts might evolve, we modeled transmission evolution where the symbiont had a spatially conditional effect on either host lifespan or fecundity. We found that over ecological time, symbionts that affected lifespan but not fecundity led to high frequencies of infected hosts in areas where the symbiont was beneficial and low frequencies elsewhere. In response, hosts evolved increased horizontal transmission only when the symbiont affected lifespan. We also modeled transmission evolution in symbionts, which evolved high horizontal and vertical transmission, indicating a possible host-symbiont conflict over transmission mode. Our results suggest an eco-evolutionary feedback where the component of host fitness that a conditionally mutualistic symbiont influences affects its distribution in the population, and, through this, the transmission mode that evolves.
RNA-mediated gene fusion in mammalian cells

Significance This report provides striking evidence that expression of a chimeric RNA mimicking a fusion RNA can drive the formation of gene fusions in mammalian cells. However, it is the antisense rather than sense chimeric RNAs that effectively drive gene fusion. The discovery that the cellular AZI1 RNA, not AZI1 protein, can act as an “initiator” RNA to induce TMPRSS2–ERG gene fusion indicates that this mechanism may have important biological relevance to oncogenesis. RNA-mediated gene fusion, a mechanism that relies on sequence-specific interactions, can account for the “specificity” of genes that were selected to undergo gene fusion. The results could also have fundamental implications in mammalian genome stability, as well as gene-editing technology via mechanisms native to mammalian cells. One of the hallmarks of cancer is the formation of oncogenic fusion genes as a result of chromosomal translocations. Fusion genes are presumed to form before fusion RNA expression. However, studies have reported the presence of fusion RNAs in individuals who were negative for chromosomal translocations. These observations give rise to “the cart before the horse” hypothesis, in which the genesis of a fusion RNA precedes the fusion gene. The fusion RNA then guides the genomic rearrangements that ultimately result in a gene fusion. However, RNA-mediated genomic rearrangements in mammalian cells have never been demonstrated. Here we provide evidence that expression of a chimeric RNA drives formation of a specified gene fusion via genomic rearrangement in mammalian cells. The process is: (i) specified by the sequence of chimeric RNA involved, (ii) facilitated by physiological hormone levels, (iii) permissible regardless of intrachromosomal (TMPRSS2–ERG) or interchromosomal (TMPRSS2–ETV1) fusion, and (iv) can occur in normal cells before malignant transformation. We demonstrate that, contrary to “the cart before the horse” model, it is the antisense rather than sense chimeric RNAs that effectively drive gene fusion, and that this disparity can be explained by transcriptional conflict. Furthermore, we identified an endogenous RNA AZI1 that functions as the “initiator” RNA to induce TMPRSS2–ERG fusion. RNA-driven gene fusion demonstrated in this report provides important insight in early disease mechanisms, and could have fundamental implications in the biology of mammalian genome stability, as well as gene-editing technology via mechanisms native to mammalian cells.
Effects of local authority expenditure on childhood obesity

Abstract Background Under the 2013 reforms introduced by the Health and Social Care Act (2012), public health responsibilities in England were transferred from the National Health Service to local authorities (LAs). Ring-fenced grants were introduced to support the new responsibilities. The aim of our study was to test whether the level of expenditure in 2013/14 affected the prevalence of childhood obesity in 2016/17. Methods We used National Child Measurement Programme definitions of childhood obesity and datasets. We used LA revenue returns data to derive three measures of per capita expenditure: childhood obesity (<19); physical activity (<19) and the Children’s 5–19 Public Health Programme. We ran separate negative binomial models for two age groups of children (4–5 year olds; 10–11 year olds) and conducted sensitivity analyses. Results With few exceptions, the level of spend in 2013/14 was not significantly associated with the level of childhood obesity in 2016/17. We identified some positive associations between spend on physical activity and the Children’s Public Health Programme at baseline (2013/14) and the level of childhood obesity in children aged 4–5 in 2016/17, but the effect was not evident in children aged 10–11. In both age groups, LA levels of childhood obesity in 2016/17 were significantly and positively associated with obesity levels in 2013/14. As these four cohorts comprise entirely different pupils, this underlines the importance of local drivers of childhood obesity. Conclusions Higher levels of local expenditure are unlikely to be effective in reducing childhood obesity in the short term.
Model Microbial Consortia as Tools for Understanding Complex Microbial Communities

A major biological challenge in the postgenomic era has been untangling the composition and functions of microbes that inhabit complex communities or microbiomes. Multi-omics and modern bioinformatics have provided the tools to assay molecules across different cellular and community scales; however, mechanistic knowledge over microbial interactions often remains elusive. This is due to the immense diversity and the essentially undiminished volume of not-yet-cultured microbes. Simplified model communities hold some promise in enabling researchers to manage complexity so that they can mechanistically understand the emergent properties of microbial community interactions. In this review, we surveyed several approaches that have effectively used tractable model consortia to elucidate the complex behavior of microbial communities. We go further to provide some perspectives on the limitations and new opportunities with these approaches and highlight where these efforts are likely to lead as advances are made in molecular ecology and systems biology.