Miracle-dz/UniFAR-FTUs huggingface dataset:
High‐resolution profiles and nitrogen isotope tracing reveal a dominant source of nitrous oxide and multiple pathways of nitrogen gas formation in the central Arabian Sea

The oxygen minimum zone (OMZ) of the Arabian Sea is a significant source of nitrous oxide (N2O), yet the metabolism responsible for N2O production is unclear. High‐resolution profiles identified peaks and troughs of N2O and NO2‐ in the top 500 m of the water column. The first peak in N2O was not in the oxycline, but deeper at the oxic‐suboxic interface. Peaks and troughs were targeted with a suite of 15N incubations (15NO3‐, 15NO2‐, 15NH4+) to identify pathways of N2O and N2 formation. With 15NO2‐, 15N‐N2O was produced at all depths with a binomial distribution with respect to the NO2‐ pool. With 15NO3‐, the 15N was not binomially distributed. NO3‐ is first reduced to NO2‐ before reduction to N2O, and NO2‐ → N2O is the dominant metabolism responsible for N2O production. The N2O produced from 15NH4+ represented 2‐5% of that from 15NO2‐ at the top of the OMZ. In addition, the production of 45N2O, but no 46N2O, at some depths with 15NH4+, suggested a novel source akin to Nitrosomonas spp. under O2 limitation. Unlike N2O, the production of N2 with 15NO2‐ or 15NO3‐ was not binomially distributed and therefore was not entirely derived from the same source as N2O. Although indicative of an alternative N2 source to denitrification, the lack of significant production of labeled N2 with 15NH4+ discounts anaerobic ammonium oxidation (anammox), as we understand it. Dissolved organic nitrogen or nitrate/nitrite reduction to ammonium are suggested as the additional sources of N in N2 production.
Complete Mitochondrial Genome of Trichuris trichiura from Macaca sylvanus and Papio papio

Trichuriasis is among the most prevalent worldwide parasitism caused by helminths. For many years, Trichuris spp. have been described with a relatively narrow range of both morphological and biometrical features. The use of the complete mitochondrial genome (mitogenome) is an alternative and powerful molecular method for inferring phylogenies. Here, we present an overview of the contributions of mitogenome for Trichuris spp. from human and non-human primates. In addition, we carry out structural and phylogenetic comparative analyses with genomes of Trichuris species available in public datasets. The complete mt genomes of Trichuris trichiura and Trichuris sp. from Macaca sylvanus and T. trichiura from Papio papio are 14,091 bp, 14,047 bp and 14,089 bp in length, respectively. The three mt genomes are circular and consist of 37 genes—13 PCGs (cox1–3, nad1–6, nad4L, atp6, atp8 and cob), 22 transfer RNA genes (tRNAs), and two rRNAs (rrnL and rrnS). The molecular evidence presented here supports the hypothesis that T. trichiura de M. sylvanus (TMF31) and T. trichiura de P. papio (TPM1) were similar but genetically different with respect to Trichuris sp. from macaques (TMM5). The phylogenetic study also supported the evolution of the different Trichuris species. In conclusion, we suggest the existence of two cryptic species parasitizing M. sylvanus.
Germ cell ribonucleoprotein granules in different clades of life: From insects to mammals

Ribonucleoprotein (RNP) granules are no newcomers in biology. Found in all life forms, ranging across taxa, these membrane‐less “organelles” have been classified into different categories based on their composition, structure, behavior, function, and localization. Broadly, they can be listed as stress granules (SGs), processing bodies (PBs), neuronal granules (NGs), and germ cell granules (GCGs). Keeping in line with the topic of this review, RNP granules present in the germ cells have been implicated in a wide range of cellular functions including cellular specification, differentiation, proliferation, and so forth. The mechanisms used by them can be diverse and many of them remain partly obscure and active areas of research. GCGs can be of different types in different organisms and at different stages of development, with multiple types coexisting in the same cell. In this review, the different known subcategories of GCGs have been studied with respect to five distinct model organisms, namely, Drosophila, Caenorhabditis elegans, Xenopus, Zebrafish, and mammals. Of them, the cytoplasmic polar granules in Drosophila, P granules in C. elegans, balbiani body in Xenopus and Zebrafish, and chromatoid bodies in mammals have been specifically emphasized upon. A descriptive account of the same has been provided along with insights into our current understanding of their functional significance with respect to cellular events relating to different developmental and reproductive processes.
Gene networks and pathways for plasma lipid traits via multitissue multiomics systems analysis

Genome-wide association studies (GWASs) have implicated ∼380 genetic loci for plasma lipid regulation. However, these loci only explain 17–27% of the trait variance, and a comprehensive understanding of the molecular mechanisms has not been achieved. In this study, we utilized an integrative genomics approach leveraging diverse genomic data from human populations to investigate whether genetic variants associated with various plasma lipid traits, namely, total cholesterol, high and low density lipoprotein cholesterol (HDL and LDL), and triglycerides, from GWASs were concentrated on specific parts of tissue-specific gene regulatory networks. In addition to the expected lipid metabolism pathways, gene subnetworks involved in “interferon signaling,” “autoimmune/immune activation,” “visual transduction,” and “protein catabolism” were significantly associated with all lipid traits. In addition, we detected trait-specific subnetworks, including cadherin-associated subnetworks for LDL; glutathione metabolism for HDL; valine, leucine, and isoleucine biosynthesis for total cholesterol; and insulin signaling and complement pathways for triglyceride. Finally, by using gene-gene relations revealed by tissue-specific gene regulatory networks, we detected both known (e.g., APOH, APOA4, and ABCA1) and novel (e.g., F2 in adipose tissue) key regulator genes in these lipid-associated subnetworks. Knockdown of the F2 gene (coagulation factor II, thrombin) in 3T3-L1 and C3H10T1/2 adipocytes altered gene expression of Abcb11, Apoa5, Apof, Fabp1, Lipc, and Cd36; reduced intracellular adipocyte lipid content; and increased extracellular lipid content, supporting a link between adipose thrombin and lipid regulation. Our results shed light on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation and lipid-associated diseases.
The First Whole Genome Sequence and Characterisation of Avian Nephritis Virus Genotype 3

Avian nephritis virus (ANV) is classified in the Avastroviridae family with disease associations with nephritis, uneven flock growth and runting stunting syndrome (RSS) in chicken and turkey flocks, and other avian species. The whole genome of ANV genotype 3 (ANV-3) of 6959 nucleotides including the untranslated 5′ and 3′ regions and polyadenylated tail was detected in a metagenomic virome investigation of RSS-affected chicken broiler flocks. This report characterises the ANV-3 genome, identifying partially overlapping open reading frames (ORFs), ORF1a and ORF1b, and an opposing secondary pseudoknot prior to a ribosomal frameshift stemloop structure, with a separate ORF2, whilst observing conserved astrovirus motifs. Phylogenetic analysis of the Avastroviridae whole genome and ORF2 capsid polyprotein classified the first complete whole genome of ANV-3 within Avastroviridae genogroup 2.
Overexpression of the MSK1 Kinase in Patients With Chronic Lung Allograft Dysfunction and Its Confirmed Role in a Murine Model

Supplemental Digital Content is available in the text. Background. Chronic lung allograft dysfunction (CLAD) and its obstructive form, the obliterative bronchiolitis (OB), are the main long-term complications related to high mortality rate postlung transplantation. CLAD treatment lacks a significant success in survival. Here, we investigated a new strategy through inhibition of the proinflammatory mitogen- and stress-activated kinase 1 (MSK1) kinase. Methods. MSK1 expression was assessed in a mouse OB model after heterotopic tracheal allotransplantation. Pharmacological inhibition of MSK1 (H89, fasudil, PHA767491) was evaluated in the murine model and in a translational model using human lung primary fibroblasts in proinflammatory conditions. MSK1 expression was graded over time in biopsies from a cohort of CLAD patients. Results. MSK1 mRNA progressively increased during OB (6.4-fold at D21 posttransplantation). Inhibition of MSK1 allowed to counteract the damage to the epithelium (56% restoration for H89), and abolished the recruitment of MHCII+ (94%) and T cells (100%) at the early inflammatory phase of OB. In addition, it markedly decreased the late fibroproliferative obstruction in allografts (48%). MSK1 inhibitors decreased production of IL-6 (whose transcription is under the control of MSK1) released from human lung fibroblasts (96%). Finally, we confirmed occurrence of a 2.9-fold increased MSK1 mRNA expression in lung biopsies in patients at 6 months before CLAD diagnosis as compared to recipients with stable lung function. Conclusions. These findings suggest the overall interest of the MSK1 kinase either as a marker or as a potential therapeutic target in lung dysfunction posttransplantation.
Fracture Risk in Patients with Myasthenia Gravis: A Population-Based Cohort Study.

BACKGROUND Prednisone is a common treatment for myasthenia gravis (MG), and osteoporosis is a known potential risk of chronic prednisone therapy. OBJECTIVE Our aim was to evaluate the risk of serious fractures in a population-based cohort of MG patients. METHODS An inception cohort of patients with MG was identified from administrative health data in Ontario, Canada between April 1, 2002 and December 31, 2015. For each MG patient, we matched 4 general population comparators based on age, sex, and region of residence. Fractures were identified through emergency department and hospitalization data. Crude overall rates and sex-specific rates of fractures were calculated for the MG and comparator groups, as well as rates of specific fractures. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. RESULTS Among 3,823 incident MG patients (followed for a mean of 5 years), 188 (4.9%) experienced a fracture compared with 741 (4.8%) fractures amongst 15,292 matched comparators. Crude fracture rates were not different between the MG cohort and matched comparators (8.71 vs. 7.98 per 1000 patient years), overall and in men and women separately. After controlling for multiple covariates, MG patients had a significantly lower risk of fracture than comparators (HR 0.74, 95% CI 0.63-0.88). CONCLUSIONS In this large, population-based cohort of incident MG patients, MG patients were at lower risk of a major fracture than comparators. The reasons for this finding are unclear but may highlight the importance osteoporosis prevention.
Efficacy and safety of drug-eluting bead-transcatheter arterial chemoembolization using 100–300 μm versus 300–500 μm CalliSpheres microspheres in patients with advanced-stage hepatocellular carcinoma

Purpose: To evaluate the efficacy and safety of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) using 100–300 μm versus 300–500 μm CalliSpheres microspheres (CSMs) for treating multiple hepatocellular carcinoma (HCC) with the largest nodule measuring between 5 and 10 cm. Methods: Eighty-one advanced-stage HCC patients treated by DEB-TACE between January 2017 and March 2020 were retrospectively analyzed. There were 48 patients in the 100–300 μm group and 33 patients in the 300–500 μm group. Treatment response, liver function tests, and complications were compared between the two groups. Results: At 6 months, the response rates in the 100–300 μm group were higher than those in the 300–500 μm group (P < 0.05). Disease control rates in the 100–300 μm group were higher than those in the 300–500 μm group at 1, 3, and 6 months (P < 0.05). Progression-free survival (PFS) and overall survival (OS) were longer in the 100–300 μm group (P < 0.05). Visual analog score points were higher in the 300–500 μm group (P < 0.05). There were no significant differences in complications between the two groups. Conclusion: The use of small-diameter CSMs in multiple HCC with the largest nodule size of 5–10 cm provides better treatment response and longer PFS and OS for treating advanced-stage HCC.
Market Opportunities for Hay Milk: Factors Influencing Perceptions among Italian Consumers

Simple Summary Consumer’s awareness of milk quality has been largely increased by real food safety scares, environmental issues, and the effects of food on health. Consumers are asking about how the cows were fed and treated. In this framework, despite their appearing to be copious research in the current literature on milk, the consumer acceptance of hay milk in Italy is largely unexplored. Using a structured questionnaire, we found that aspects such as curiosity, the production place of food, the local culinary traditions, label, and environmental issues play an important role in the people’s consumption intentions for milk from hay-fed cows. This study could provide useful implications for food manufacturers and facilitate the design of marketing strategies for hay milk produced in the Centre and South of Italy. Abstract Central and South Italy are characterized by small-scale dairy farms and growing abandonment by farmers for other, better-paid, off-farm jobs. New marketing concepts for milk can be one solution to remunerate mountain farmers for their efforts. This study investigates the potential market for hay milk in Italy. In particular, we want to understand which variables drive the people’s willingness to consume hay milk, and if the European food quality certification schemes impact on people’s willingness to consume milk from hay-fed cows. Data were collected from a sample of consumers from Central and South Italy (n = 331) using a web-based survey. Later, a discrete choice probit model was applied. The main results indicate that aspects as curiosity, the production place of food, the local culinary traditions, label, and environmental issues play an important role in the people’s consumption intentions for milk from hay-fed cows. Moreover, the survey highlights that the respondents had positive opinion towards hay milk and highlighted some important marketing implications for the Italian milk sector. The study findings could encourage discussion about a niche market to boost local growth, initiating a process of improving livelihoods, certification of products, and use of the marketing tools addressed towards a specific milk consumer’s profile. In other words, the study could provide useful implications for food manufacturers and facilitate the design of marketing strategies for hay milk produced in Central and South Italy.
Non-Parametric Evaluation Methods of the Brain Activity of a Bottlenose Dolphin during an Assisted Therapy

Simple Summary Dolphin Assisted Therapies (DAT) can be used with any person or group with specific needs and it can be as disparate as people at risk of social exclusion, eating disorders, terminally ill, mental health disorders, among many others. This paper is focused on measuring and analyzing dolphins brain activity when DAT is taking place, in order to identify if there is any differences in female dolphin’s neuronal signal when it is interacting with control or intervention subjects. In addition, we designed a wireless and portable electroencephalographic single-channel signal capture device to monitor the brain activity of a female bottle-nose dolphin. Our findings also validate the evidence that the interaction between a patient with a certain disease or disorder and undergoes to a DAT modifies usual brain activity behavior of a female bottle-nose dolphin. Abstract Dolphin-Assisted Therapies (DAT) are alternative therapies aimed to reduce anxiety levels, stress relief and physical benefits. This paper is focused on measuring and analyzing dolphins brain activity when DAT is taking place in order to identify if there is any differences in female dolphin’s neuronal signal when it is interacting with control or intervention subjects, performing our research in Delfiniti, Ixtapa, Mexico facilities. We designed a wireless and portable electroencephalographic single-channel signal capture sensor to acquire and monitor the brain activity of a female bottle-nose dolphin. This EEG sensor was able to show that dolphin activity at rest is characterized by high spectral power at slow-frequencies bands. When the dolphin participated in DAT, a 23.53% increment in the 12–30 Hz frequency band was observed, but this only occurred for patients with some disease or disorder, given that 0.5–4 Hz band keeps it at 17.91% when there is a control patient. Regarding the fractal or Self-Affine Analysis, we found for all samples studied that at the beginning the dolphin’s brain activity behaved as a self-affine fractal described by a power-law until the fluctuations of voltage reached the crossovers, and after the crossovers these fluctuations left this scaling behavior. Hence, our findings validate the hypothesis that the participation in a DAT of a Patient with a certain disease or disorder modifies the usual behavior of a female bottle-nose dolphin.
Pharmacokinetics and Pharmacodynamics of Salvinorin A and Salvia divinorum: Clinical and Forensic Aspects

Salvia divinorum Epling and Játiva is a perennial mint from the Lamiaceae family, endemic to Mexico, predominantly from the state of Oaxaca. Due to its psychoactive properties, S. divinorum had been used for centuries by Mazatecans for divinatory, religious, and medicinal purposes. In recent years, its use for recreational purposes, especially among adolescents and young adults, has progressively increased. The main bioactive compound underlying the hallucinogenic effects, salvinorin A, is a non-nitrogenous diterpenoid with high affinity and selectivity for the κ-opioid receptor. The aim of this work is to comprehensively review and discuss the toxicokinetics and toxicodynamics of S. divinorum and salvinorin A, highlighting their psychological, physiological, and toxic effects. Potential therapeutic applications and forensic aspects are also covered in this review. The leaves of S. divinorum can be chewed, drunk as an infusion, smoked, or vaporised. Absorption of salvinorin A occurs through the oral mucosa or the respiratory tract, being rapidly broken down in the gastrointestinal system to its major inactive metabolite, salvinorin B, when swallowed. Salvinorin A is rapidly distributed, with accumulation in the brain, and quickly eliminated. Its pharmacokinetic parameters parallel well with the short-lived psychoactive and physiological effects. No reports on toxicity or serious adverse outcomes were found. A variety of therapeutic applications have been proposed for S. divinorum which includes the treatment of chronic pain, gastrointestinal and mood disorders, neurological diseases, and treatment of drug dependence. Notwithstanding, there is still limited knowledge regarding the pharmacology and toxicology features of S. divinorum and salvinorin A, and this is needed due to its widespread use. Additionally, the clinical acceptance of salvinorin A has been hampered, especially due to the psychotropic side effects and misuse, turning the scientific community to the development of analogues with better pharmacological profiles.
Comparisons of Polyexposure, Polygenic, and Clinical Risk Scores in Risk Prediction of Type 2 Diabetes

OBJECTIVE To establish a polyexposure score (PXS) for type 2 diabetes (T2D) incorporating 12 nongenetic exposures and examine whether a PXS and/or a polygenic risk score (PGS) improves diabetes prediction beyond traditional clinical risk factors. RESEARCH DESIGN AND METHODS We identified 356,621 unrelated individuals from the UK Biobank of White British ancestry with no prior diagnosis of T2D and normal HbA1c levels. Using self-reported and hospital admission information, we deployed a machine learning procedure to select the most predictive and robust factors out of 111 nongenetically ascertained exposure and lifestyle variables for the PXS in prospective T2D. We computed the clinical risk score (CRS) and PGS by taking a weighted sum of eight established clinical risk factors and >6 million single nucleotide polymorphisms, respectively. RESULTS In the study population, 7,513 had incident T2D. The C-statistics for the PGS, PXS, and CRS models were 0.709, 0.762, and 0.839, respectively. Individuals in the top 10% of PGS, PXS, and CRS had 2.00-, 5.90-, and 9.97-fold greater risk, respectively, compared to the remaining population. Addition of PGS and PXS to CRS improved T2D classification accuracy, with a continuous net reclassification index of 15.2% and 30.1% for cases, respectively, and 7.3% and 16.9% for controls, respectively. CONCLUSIONS For T2D, the PXS provides modest incremental predictive value over established clinical risk factors. However, the concept of PXS merits further consideration in T2D risk stratification and is likely to be useful in other chronic disease risk prediction models.
Human cytomegalovirus infection is associated with increased expression of the lissencephaly gene PAFAH1B1 encoding LIS1 in neural stem cells and congenitally infected brains

Congenital infection of the central nervous system by human cytomegalovirus (HCMV) is a leading cause of permanent sequelae, including mental retardation or neurodevelopmental abnormalities. The most severe complications include smooth brain or polymicrogyria, which are both indicative of abnormal migration of neural cells, although the underlying mechanisms remain to be determined. To gain better insight on the pathogenesis of such sequelae, we assessed the expression levels of a set of neurogenesis‐related genes, using HCMV‐infected human neural stem cells derived from embryonic stem cells (NSCs). Among the 84 genes tested, we found dramatically increased expression of the gene PAFAH1B1, encoding LIS1 (lissencephaly‐1), in HCMV‐infected versus uninfected NSCs. Consistent with these findings, western blotting and immunofluorescence analyses confirmed the increased levels of LIS1 in HCMV‐infected NSCs at the protein level. We next assessed the migratory abilities of HCMV‐infected NSCs and observed that infection strongly impaired the migration of NSCs, without detectable effect on their proliferation. Moreover, we observed increased immunostaining for LIS1 in brains of congenitally infected fetuses, but not in control samples, highlighting the clinical relevance of our findings. Of note, PAFAH1B1 mutations (resulting in either haploinsufficiency or gain of function) are primary causes of hereditary neurodevelopmental diseases. Notably, mutations resulting in PAFAH1B1 haploinsufficiency cause classic lissencephaly. Taken together, our findings suggest that PAFAH1B1 is a critical target of HCMV infection. They also shine a new light on the pathophysiological basis of the neurological outcomes of congenital HCMV infection, by suggesting that defective neural cell migration might contribute to the pathogenesis of the neurodevelopmental sequelae of infection. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.