Miracle-dz/UniFAR-FTUs huggingface dataset:
NOCTURNIN Gene Diurnal Variation in Healthy Volunteers and Expression Levels in Shift Workers

Objective The NOCTURNIN gene links nutrient absorption and metabolism to the circadian clock. Shift workers are at a heightened risk of overweight and of developing obesity and metabolic syndrome. This study investigates the diurnal variation of NOCTURNIN in healthy volunteers and its expression levels in rotational shift and daytime workers. Methods NOCTURNIN expression levels were evaluated in peripheral blood lymphocytes from 15 healthy volunteers at 4-hour intervals for 24 h. Metabolic parameters and NOCTURNIN expression were measured in workers engaged in shift and daytime work. Results In the group of volunteers NOCTURNIN expression showed diurnal variation, with a peak at 8:00 AM. NOCTURNIN expression was higher in shift workers than in daytime workers. Multivariate analysis confirmed the role of shift work as an independent factor affecting NOCTURNIN expression. Notably, its level correlated directly with body mass index and inversely with total energy expenditure. Conclusions Measuring NOCTURNIN expression levels in human peripheral blood lymphocytes can improve investigations on the relationship between changes in circadian rhythm and metabolic disorders. Shift workers show higher NOCTURNIN levels than daytime workers.
Regulatory T Cells Control the Switch From in situ to Invasive Breast Cancer

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of breast cancer, and it only progresses to invasive breast cancer in around 40% of patients. While immune infiltrates have been observed in these early cancer lesions, their potential prognostic value is still unclear. Regulatory T (Treg) cells accumulate in advanced breast cancers, and predict poor outcome. We have shown before that ablation of Treg cells in established tumors leads to significant decrease in primary and metastatic tumor burden. In this work, we sought to investigate Treg cell function in the progression from non-invasive to invasive breast cancer lesions. To this end, we used the murine mammary tumor virus polyoma middle T (MMTV-PyMT) murine model of spontaneous, stage-wise breast carcinogenesis crossed to Foxp3DTR knock in mice, allowing Treg cell ablation by administration of diphtheria toxin. Transient targeting of Treg cells at the in situ carcinoma stage resulted in a significant increase in the number of tumor-bearing mammary glands and size of growing tumors compared with control mice. Whole mammary gland mounts and histological examination confirmed larger emergent tumor area in Treg cell-ablated mice, and revealed that these tumors were characterized by a more advanced tumor staging, with presence of early invasion, increased desmoplasia and collagen deposition. Furthermore, Treg cell ablation increased the percentage of cancer stem/progenitor cells in the mammary compartment. Interestingly, Treg cell ablation resulted in increased inflammatory cytokines IL-4 and IL-5 with a concomitant reduction in classically activated tumor associated macrophages. This TH2-biased immune regulatory mammary inflammation was consistent with the enhancement in tumor promotion that we observed. Overall, our study demonstrates that Treg cells oppose breast cancer progression at early stages, raising a cautionary note regarding the consideration of immune intervention targeted at boosting immune responses for DCIS.
MECP2 Duplication Causes Aberrant GABA Pathways, Circuits and Behaviors in Transgenic Monkeys: Neural Mappings to Patients with Autism

MECP2 gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remain unknown. Here we report a combination of gene–circuit–behavior analyses including MECP2 coexpression network, locomotive and cognitive behaviors, and EEG and fMRI findings in 5 MECP2 overexpressed monkeys (Macaca fascicularis; 3 females) and 20 wild-type monkeys (Macaca fascicularis; 11 females). Whole-genome expression analysis revealed MECP2 coexpressed genes significantly enriched in GABA-related signaling pathways, whereby reduced β-synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile, MECP2-induced hyperconnectivity in prefrontal and cingulate networks accounted for regressive deficits in reversal learning tasks. Furthermore, we stratified a cohort of 49 patients with autism and 72 healthy controls of 1112 subjects using functional connectivity patterns, and identified dysconnectivity profiles similar to those in monkeys. By establishing a circuit-based construct link between genetically defined models and stratified patients, these results pave new avenues to deconstruct clinical heterogeneity and advance accurate diagnosis in psychiatric disorders. SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a complex disorder with co-occurring symptoms caused by multiple genetic variations and brain circuit abnormalities. To dissect the gene–circuit–behavior causal chain underlying ASD, animal models are established by manipulating causative genes such as MECP2. However, it is unknown whether such models have captured any circuit-level pathology in ASD patients, as demonstrated by human brain imaging studies. Here, we use transgenic macaques to examine the causal effect of MECP2 overexpression on gene coexpression, brain circuits, and behaviors. For the first time, we demonstrate that the circuit abnormalities linked to MECP2 and autism-like traits in the monkeys can be mapped to a homogeneous ASD subgroup, thereby offering a new strategy to deconstruct clinical heterogeneity in ASD.
A Review of the Bioactivity of Plant Products Against Aedes aegypti (Diptera: Culicidae)

Abstract The mosquito Aedes aegypti L. (Diptera: Culicidae) is a disease vector for several pathogens that affect human health worldwide. Therefore, there is a need to produce synthetic chemicals that can effectively control mosquitoes; however, these chemicals can also cause a range of environmental and health problems. In the present review, we compiled all available information from the literature between 2005 and 2018 on plant products that have been used to control A. aegypti and tabulated their modes of action. This review classifies these plant-based products according to their bioactivities (toxicity, repellency, feeding deterrence, and oviposition deterrence) and provides new insights, findings, and patterns of their application. Plants contain a wide spectrum of chemical compounds that can effectively control mosquito populations; therefore, they should be developed to control diseases transmitted by mosquitoes. Plant products are mostly safe for human, animal, and environmental health. Moreover, because of the diversity and low use of plant-derived compounds as insect control agents, mosquitoes have not acquired resistance to them. The present review indicated that the bioactivities of many plant compounds can effectively control A. aegypti in laboratory conditions, and the comprehensive cataloging and classification of natural plant product bioactivities in this review will facilitate the search for new applications of these substances in insect pest control strategies.
Spatial, sexual, and rapid temporal differentiation in neuromast expression on lateral plates of Haida Gwaii threespine stickleback (Gasterosteus aculeatus)

Lateral lines, a major sensory modality in fishes, are diverse among taxa, but their intraspecific variation has received limited attention. We examined numbers of superficial neuromasts on the buttressing lateral plates (LP) of 1910 threespine stickleback (Gasterosteus aculeatus Linnaeus, 1758) from 26 ecologically and morphologically diverse populations on the Haida Gwaii archipelago, western Canada. Extending from previous studies, we predicted that (i) highly stained dystrophic localities would have threespine stickleback with elevated numbers of neuromasts per plate due to a greater reliance on non-visual sensory modalities and (ii) that LP count and neuromast numbers per plate would functionally covary with predatory assemblage. We found that there were no differences in neuromast count across major habitats (marine, lake, stream), but clear-water populations and those with predatory fish had significantly more neuromasts per plate than most populations in highly stained dystrophic lakes, the effects being accentuated on the first buttressing plate (LP4). We also report the first evidence that neuromast counts per plate are sexually dimorphic, with males having a greater density of neuromasts in most populations. Two transplant experiments between ecologically opposite habitats indicate that within 12 generations, neuromast counts per plate can rapidly shift in response to a change in habitat.
Comprehensive annotations of human herpesvirus 6A and 6B genomes reveal novel and conserved genomic features

Human herpesvirus 6 (HHV-6) A and B are highly ubiquitous betaherpesviruses, infecting the majority of the human population. Like other herpesviruses, they encompass large genomes and our understanding of their protein coding potential is far from complete. Here we employ ribosome profiling and systematic transcript analysis to experimentally define the HHV-6 translation products and to follow their temporal expression. We identify hundreds of new open reading frames (ORFs), including many upstream ORFs (uORFs) and internal ORFs (iORFs), generating a complete unbiased atlas of HHV-6 proteome. Furthermore, by integrating systematic data from the prototypic betaherpesvirus, human cytomegalovirus, we uncover numerous uORFs and iORFs that are conserved across betaherpesviruses and we show that uORFs are specifically enriched in late viral genes. Using our transcriptome measurements, we identified three highly abundant HHV-6 encoded long non-coding RNAs (lncRNAs), one of which generates a non-polyadenylated stable intron that appears to be a conserved feature of betaherpesviruses. Overall, our work reveals the complexity of HHV-6 genomes and highlights novel features that are conserved between betaherpesviruses, providing a rich resource for future functional studies.
DarkDivNet – A global research collaboration to explore the dark diversity of plant communities

DarkDivNet is a global research collaboration which explores dark diversity — the set of species that are absent from a site despite being suitable under the site conditions and present in the region. Participants of the network survey vascular plant diversity both at local (10 m × 10 m) and regional scales (radius 10 km) using a standardized approach. They also measure simple plant traits and collect soil samples. Observed and dark diversity together form the site‐specific species pool, and the ratio of observed diversity and dark diversity describes community completeness. We shall explore how observed and dark diversity, site‐specific species pool and community completeness vary across natural and anthropogenic gradients. We link plant diversity measures to the information obtained from environmental DNA: soil biota and plant taxa that occurred at the site before. We will refine existing dark diversity methods and use large vegetation databases to infer species habitat suitability. We expand the dark diversity concept from a purely taxonomy‐based approach to include the functional and phylogenetic aspects of diversity. DarkDivNet currently includes 161 planned sampling areas globally, but new participants are welcome. The main vegetation sampling period is scheduled until September 2020, with the first research papers being produced after that.
METABOLIZABLE ENERGY DETERMINATION IN BROILER CHICKENS

OF THESIS METABOLIZABLE ENERGY DETERMINATION IN BROILER CHICKENS Feed accounts for the highest cost associated in poultry production, with energy-containing feedstuffs being the most expensive portion of the cost of feeding. The increasing demand for poultry meat gives reason to determine accurate apparent metabolizable energy (AME) values for various feedstuff through measuring energy utilization in the birds. The adaptation length of birds fed an experimental diet may affect the determined AME value due to the diet matrix and physiochemical properties of the feedstuff. Therefore, the objective of this thesis was to evaluate a select group of energy-containing feedstuff with different diets and with factors such as coccidia challenge and exogenous enzyme supplementation that may influence the determined AME values in broiler chickens.
Non-cell autonomous OTX2 transcription factor regulates anxiety-related behaviors in the mouse

The Otx2 homeoprotein transcription factor is expressed in the dopaminergic neurons of the ventral tegmental area, a mesencephalic nucleus involved in the control of complex behaviors through its projections to limbic structures, including the ventral hippocampus, amygdala, nucleus accumbens and prefrontal cortex. We find adult mice heterozygous for Otx2 show a hypoanxious phenotype in light-dark box and elevated plus maze paradigms. However, the number of dopaminergic neurons, the integrity of their axons, their projection patterns in target structures, and the amounts of dopamine and dopamine metabolites in targets structures were not modified in the Otx2 mutant. Because OTX2 is expressed by the choroid plexus, secreted into cerebrospinal fluid and transferred to parvalbumin interneurons of the cortex, hippocampus, and amygdala, we investigated if the hypoanxiety of Otx2 heterozygous mice could result from the decreased synthesis of Otx2 in the choroid plexus. Indeed, hypoanxious phenotype was reversed by the overexpression of Otx2 specifically in choroid plexus of adult Otx2 heterozygous mice, while hypoanxious phenotype could be induced in adult wild type mice by lowering OTX2 levels in the cerebrospinal fluid. Taken together, OTX2 synthesis by the choroid plexus followed by its secretion into the cerebrospinal fluid is an important regulator of the anxiety phenotype in the mouse.
An overview of data-driven HADDOCK strategies in CAPRI rounds 38-45

Our information-driven docking approach HADDOCK has demonstrated a sustained performance since the start of its participation to CAPRI. This is due, in part, to its ability to integrate data into the modelling process, and to the robustness of its scoring function. We participated in CAPRI both as server and as manual predictors. In CAPRI rounds 38-45, we have used various strategies depending on the information at hand. These ranged from imposing restraints to a few residues identified from literature as being important for the interaction, to binding pockets identified from homologous complexes or template-based refinement / CA-CA restraint-guided docking from identified templates. When relevant, symmetry restraints were used to limit the conformational sampling. We also tested for a large decamer target a new implementation of the MARTINI coarse-grained force field in HADDOCK. Overall in the current rounds, we obtained acceptable or better predictions for 13 and 11 server and manual submissions, respectively, out of the 22 interfaces. Our server performance (acceptable models) was better (59%) than the manual (50%) one, in which we typically experiment with various combinations of protocols and data sources. Again, our simple scoring function based on a linear combination of intermolecular van der Waals and electrostatic energies and an empirical desolvation term demonstrated a good performance in the scoring experiment with a 63% success rate across all 22 interfaces. An analysis of model quality indicates that, while we are consistently performing well in generating acceptable models, there is room for improvement for generating/identifying higher quality models.
Relating Δ17O Values of Animal Body Water to Exogenous Water Inputs and Metabolism

The dynamics of animal body water and metabolism are integral aspects of biological function but are difficult to measure, particularly in free-ranging individuals. We demonstrate a new method to estimate inputs to body water via analysis of Δ17O, a measure of 17O/16O relative to 18O/16O. Animal body water is primarily a mixture of drinking or food water (meteoric water; Δ17O ≈ 0.030 per mille [‰]) and metabolic water synthesized from atmospheric oxygen (Δ17O ≈ –0.450‰). Greater drinking or food water intake should increase Δ17O toward 0.030‰, whereas greater metabolic rate should decrease Δ17O toward –0.450‰. We found that wild mammal Δ17O values generally increased with body mass, consistent with both a decline in mass-specific metabolic rate and an increase in water intake. Captive mouse (Peromyscus maniculatus) Δ17O values were higher than predicted but exhibited the expected relative change based on metabolic rate and water intake. Measurements of Δ17O may enable novel ecophysiological studies.
Determination of the genus Meloidogyne species and study of their impact on the market gardening in the area of Bamako, Mali

The development of market gardening is faced with many problems among which there are the nematodes of the genus Meloidogyne. The aim of this study is twofold: (a) determining the Meloidogyne species that are crowned by the perineal plates of female and (b) studying the impact of the multiplication of these nematodes on the tomato cv Roma (Lycopersicon esculentum L). Root samples were collected at five sites around Bamako, Mali. In a trial, nematode larvae were extracted from the roots of culture and then inoculated on tomato plants. A second tomato plants non-inoculated was used as control. Using a maceration-filtration method, three Meloidogyne spp. were identified: Meloidogyne arenaria, Meloidogyne javanica and Meloidogyne incognita. All of the inoculated plants reacted by the presence of galls that were not observed on the non-inoculated plants. Key words: Market gardening, genus Meloidogyne, galls, Lycopersicon esculentum, perineal plate, roots of culture, root samples.
Assessment of the breeding and wintering sites of Eurasian Woodcock (Scolopax rusticola) occurring in Hungary based on ringing recovery data

Using the latest dataset of the Hungarian Bird Ringing Centre, the aims of this study were to describe the monthly spatial pattern of woodcock occurrence and to assess the main wintering and breeding areas of the birds associated with Hungary in the last decade. Descriptive analyses were performed regarding the annual number of detections (ringing, recaptures and recoveries), and the relation between the annual number of woodcock ringers and the number of ringed birds was tested. Minimum convex polygons (MCP) were calculated for the detections of each month, and the variation of the monthly MCP size was evaluated. Distances of all detection locations were measured from the geographical central point of Hungary, and the distributions of these distances were compared among the months. The annual number of ringed birds increased, however it was not in relation with the number of people involved in ringing. The rate of recoveries was 7.5%. Two types of the reco very circumstances were registered: 89.9% by hunting, 10.1% found dead. MCPs were calculated for eight months. Each MCP overlapped with Hungary, to varying degrees, however remarkable differences were found in the MCP sizes among the different months. The largest areas were covered in December, January and February, while the areas in September and October were less than half of that size. The shortest distances to the country were registered in March, April, October, and November. Moderate distances were recorded in May and September, and the longest distances were found in December, January and February. Large amount of data is available about the wintering areas, and a wide wintering zone can be estimated. In contrast, there is no or only very little information about the areas covered in summer.
Effects of trap confinement on personality measurements in two terrestrial rodents

In recent years individual differences in the behavior of animals, or personalities, have been shown to influence the response of individuals to changing environments and have important ecological implications. As researchers strive to understand and predict the responses of individuals and populations to anthropogenic changes, personality studies in wild populations will likely continue to increase. Studies of personality in wild populations often require that animals are live-trapped before behavioral observation can occur; however, it is unknown what impact live trapping may have on the behavior of trapped individuals. Specifically, if the duration of trap confinement directly influences behavior, then by obtaining wild animals through live-trapping are we confounding the very measurements we are most interested in? To investigate this question, we performed a study using two small mammal species. We positioned high-definition trail cameras on Longworth small mammal traps in the field to observe capture events and record the time of capture. We then measured personality in captured deer mice (Peromyscus maniculatus) and southern red-backed voles (Myodes gapperi) using three standardized tests. With a repeatability analysis, we confirmed which behaviors could be considered personality traits, and through linear and generalized linear models, we found that the time an animal had spent confined to a trap before testing did not affect the majority of behaviors exhibited. Our results showed two weak behavioral effects of confinement duration on boldness and docility depending on whether an individual had been trapped previously. Our results suggest that personality measurements of wild, trapped small mammals are not determined by trapping procedures, but that researchers should control for whether an animal is naïve to trapping during analysis.
Integrated network pharmacology and targeted metabolomics to reveal the mechanism of nephrotoxicity of triptolide.

Triptolide (TP) is one of the important active components in Tripterygium wilfordii Hook. F. , which shows strong anti-inflammatory and immunomodulatory effects. However, a large number of literature studies have reported that TP is the main component causing nephrotoxicity, and the mechanism of nephrotoxicity has not yet been revealed. Therefore, it is of great practical significance to clarify the toxicity mechanism of TP. This study integrated network pharmacology and targeted metabolomics to reveal the nephrotoxicity mechanism of TP. Firstly, network pharmacology screening of 61 action targets related to TP induced nephrotoxicity, with 39 direct targets and 22 indirect targets, was performed. Subsequently, based on a large-scale protein-protein interaction (PPI) and molecular docking validation, the core targets were identified. Based on the above targets and enrichment analysis, the purine metabolism, Toll-like receptor signaling pathway and NF-κB signaling pathway were found play a pivotal role in TP-induced nephrotoxicity. Literature investigation showed that purine and pyrimidine metabolism pathways were closely related to kidney diseases. Therefore, by using the quantitative method of determining endogenous purine and pyrimidine previously established in the laboratory, a targeted metabolomic analysis of TP was carried out. Finally, six nephrotoxicity biomarkers, dihydroorotate, thymidine, 2-deoxyinosine, uric acid, adenosine and xanthine, were found. Combining the above results, the mechanisms underlying the nephrotoxicity of TP were speculated to be due to the over-consumption of xanthine and uric acid, which would result in enormous ROS being released in response to oxidative stress in the body. Furthermore, activation of the Toll-like receptor signalling pathway can promotes the phosphorylation of the downstream protein NF-κB and causes an inflammatory response that ultimately leads to nephrotoxicity.