Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional network analysis on brains reveals a potential regulatory role of PPP1R3F in autism spectrum disorders

ObjectiveThis study aims at identifying master regulators of transcriptional networks in autism spectrum disorders (ASDs). ResultsWith two sets of independent RNA-Seq data generated on cerebellum from patients with ASDs and control subjects (N = 39 and 45 for set 1, N = 24 and 38 for set 2, respectively), we carried out a network deconvolution of transcriptomic data, followed by virtual protein activity analysis. We identified PPP1R3F (Protein Phosphatase 1 Regulatory Subunit 3F) as a candidate master regulator affecting a large body of downstream genes that are associated with the disease phenotype. Pathway analysis on the identified targets of PPP1R3F in both datasets indicated alteration of endocytosis pathway. Despite a limited sample size, our study represents one of the first applications of network deconvolution approach to brain transcriptomic data to generate hypotheses that may be further validated by large-scale studies.
Karyotype evolution in Fusarium

The germ tube burst method (GTBM) was employed to examine karyotypes of 33 Fusarium species representative of 11 species complexes that span the phylogenetic breadth of the genus. The karyotypes revealed that the nucleolar organizing region (NOR), which includes the ribosomal rDNA region, was telomeric in the species where it was discernible. Variable karyotypes were detected in eight species due to variation in numbers of putative core and/or supernumerary chromosomes. The putative core chromosome number (CN) was most variable in the F. solani (CN = 9‒12) and F. buharicum (CN = 9+1 and 18-20) species complexes. Quantitative real-time PCR and genome sequence analysis rejected the hypothesis that the latter variation in CN was due to diploidization. The core CN in six other species complexes where two or more karyotypes were obtained was less variable or fixed. Karyotypes of 10 species in the sambucinum species complex, which is the most derived lineage of Fusarium, revealed that members of this complex possess the lowest CN in the genus. When viewed in context of the species phylogeny, karyotype evolution in Fusarium appears to have been dominated by a reduction in core CN in five closely related complexes that share a most recent common ancestor (tricinctum and incarnatum-equiseti CN = 8-9, chlamydosporum CN = 8, heterosporum CN = 7, sambucinum CN = 4-5) but not in the sister to these complexes (nisikadoi CN = 11, oxysporum CN = 11 and fujikuroi CN = 10-12). CN stability is best illustrated by the F. sambucinum subclade, where the only changes observed since it diverged from other fusaria appear to have involved two independent putative telomere to telomere fusions that reduced the core CN from five to four, once each in the sambucinum and graminearum subclades. Results of the present study indicate a core CN of 4 may be fixed in the latter subclade, which is further distinguished by the absence of putative supernumerary chromosomes. Karyotyping of fusaria in the not too distant future will be done by whole-genome sequencing such that each scaffold represents a complete chromosome from telomere to telomere. The CN data presented here should be of value to assist such full genome assembling.
Stachys sieboldii Extract Supplementation Attenuates Memory Deficits by Modulating BDNF-CREB and Its Downstream Molecules, in Animal Models of Memory Impairment

Cholinergic dysfunction, impaired brain-derived neurotrophic factor and cAMP response element binding protein (BDNF-CREB) signaling are one of the major pathological hallmarks of cognitive impairment. Therefore, improving cholinergic neurotransmission, and regulating the BDNF-CREB pathway by downregulating apoptosis genes is one strategy for inhibiting the etiology of dementia. This study evaluates the potential effects of Stachys sieboldii MIQ (SS) extract against cognitive dysfunction and its underlying mechanisms. SS supplementation for 33 days improved scopolamine-induced memory impairment symptoms in Morris water maze test and Y-maze test. SS reduced the acetylcholineesterase activity and significantly increase acetylcholine and cholineacetyltransferase activity in the brain. In the subsequent mechanism study, SS regulated the mRNA expression level of neuronal plasticity molecules such as (nerve growth factor) NGF, BDNF, CREB, and its downstream molecules such as Bcl-2 and Egr-1 by downregulating the neuronal apoptosis targets in both hippocampus and frontal cortex. Additionally, inward currents caused by SS in hippocampal CA1 neurons was partially blocked by the GABA receptor antagonist picrotoxin (50 μM), suggesting that SS acts on synaptic/extrasynaptic GABAA receptors. These findings indicate that SS may function in a way that is similar to nootropic drugs by inhibiting cholinergic abnormalities, and neuronal apoptosis targets and ultimately increasing the expression of BDNF-CREB.
The effect of high‐flow nasal oxygen on hospital length of stay in cardiac surgical patients at high risk for respiratory complications: a randomised controlled trial

There has been increased interest in the prophylactic and therapeutic use of high‐flow nasal oxygen in patients with, or at risk of, non‐hypercapnic respiratory failure. There are no randomised trials examining the efficacy of high‐flow nasal oxygen in high‐risk cardiac surgical patients. We sought to determine whether routine administration of high‐flow nasal oxygen, compared with standard oxygen therapy, leads to reduced hospital length of stay after cardiac surgery in patients with pre‐existing respiratory disease at high risk for postoperative pulmonary complications. Adult patients with pre‐existing respiratory disease undergoing elective cardiac surgery were randomly allocated to receive high‐flow nasal oxygen (n = 51) or standard oxygen therapy (n = 49). The primary outcome was hospital length of stay and all analyses were carried out on an intention‐to‐treat basis. Median (IQR [range]) hospital length of stay was 7 (6–9 [4–30]) days in the high‐flow nasal oxygen group and 9 (7–16 [4–120]) days in the standard oxygen group (p=0.012). Geometric mean hospital length of stay was 29% lower in the high‐flow nasal group (95%CI 11–44%, p = 0.004). High‐flow nasal oxygen was also associated with fewer intensive care unit re‐admissions (1/49 vs. 7/45; p = 0.026). When compared with standard care, prophylactic postoperative high‐flow nasal oxygen reduced hospital length of stay and intensive care unit re‐admission. This is the first randomised controlled trial examining the effect of prophylactic high‐flow nasal oxygen use on patient‐centred outcomes in cardiac surgical patients at high risk for postoperative respiratory complications.
Relationship between Methods of Loading and Unloading, Carcass Bruising, and Animal Welfare in the Transportation of Extensively Reared Beef Cattle

Simple Summary In Uruguay, extensive, welfare-friendly beef production is a substantial part of the economy and culture. Transport of beef cattle to the slaughterhouse compromises animal welfare. The objective of this study was to assess transport conditions related to carcass bruising. A total of 242 trucks with 8132 animals were assessed on loading, transport, unloading conditions, and carcass bruising. In 39.3% of the loadings only a flag was used. The fastest unloading time was performed using a flag only. Carcass bruises were assessed by trained observers inside the plant. Although the number of bruises was high, there were no grade 3 bruises, the deepest and severe ones. It appeared that animal welfare training of truck drivers worked out well and the use of flags to move animals increased compared to a previous study in 2008. Abstract In Uruguay, extensive, welfare-friendly beef production is a substantial part of the economy and culture. Transport of beef cattle to slaughterhouse compromises animal welfare. The objective of this study was to assess transport conditions related to carcass bruising. A total of 242 trucks with 8132 animals were assessed on loading, transport, unloading conditions, and carcass bruising. Average loading time was 26 min and 21 s and the perception of the truck drivers was correlated with the time took for loading and the use of devices. In 39.3% of the loadings only a flag was used. The average unloading time was 5 min and 54 s with a significant difference in time for the use of devices; only flag 3 min 51 s, cattle prod 6 min 43 s and sticks 8 min 09 s. Of the carcasses observed, 772 (9.5%) had no bruises, 873 (10.7%) had one bruise, 1312 (16.1%) two, 1231 (15.1%) three and 3944 (48.5%) had four or more bruises. Prevalence of bruises were highest on the Tuber-coxea (hip) (29.3%) following forequarter (22.4%), Tuber-ischiadicum (rear) (17.3%), ribs/flank (14.1%), rump/round (10.1%) and loin (6.8%). Bruises were 68.7% grade 1 and 31.3 % grade 2; there were no grade 3, the deepest ones, observed. It appeared that animal welfare training of truck drivers worked out well and the use of flags increased compared to a previous study in 2008.
Life‐history evolution under fluctuating density‐dependent selection and the adaptive alignment of pace‐of‐life syndromes

We present a novel perspective on life‐history evolution that combines recent theoretical advances in fluctuating density‐dependent selection with the notion of pace‐of‐life syndromes (POLSs) in behavioural ecology. These ideas posit phenotypic co‐variation in life‐history, physiological, morphological and behavioural traits as a continuum from the highly fecund, short‐lived, bold, aggressive and highly dispersive ‘fast’ types at one end of the POLS to the less fecund, long‐lived, cautious, shy, plastic and socially responsive ‘slow’ types at the other. We propose that such variation in life histories and the associated individual differences in behaviour can be explained through their eco‐evolutionary dynamics with population density – a single and ubiquitous selective factor that is present in all biological systems. Contrasting regimes of environmental stochasticity are expected to affect population density in time and space and create differing patterns of fluctuating density‐dependent selection, which generates variation in fast versus slow life histories within and among populations. We therefore predict that a major axis of phenotypic co‐variation in life‐history, physiological, morphological and behavioural traits (i.e. the POLS) should align with these stochastic fluctuations in the multivariate fitness landscape created by variation in density‐dependent selection. Phenotypic plasticity and/or genetic (co‐)variation oriented along this major POLS axis are thus expected to facilitate rapid and adaptively integrated changes in various aspects of life histories within and among populations and/or species. The fluctuating density‐dependent selection POLS framework presented here therefore provides a series of clear testable predictions, the investigation of which should further our fundamental understanding of life‐history evolution and thus our ability to predict natural population dynamics.
Unilateral Botulinum Neurotoxin-A Injection into the Striatum of C57BL/6 Mice Leads to a Different Motor Behavior Compared with Rats

Different morphological changes in the caudate-putamen (CPu) of naïve rats and mice were observed after intrastriatal botulinum neurotoxin-A (BoNT-A) injection. For this purpose we here studied various motor behaviors in mice (n = 46) longitudinally up to 9 months after intrastriatal BoNT-A administration as previously reported for rats, and compared both outcomes. Apomorphine- and amphetamine-induced rotational behavior, spontaneous motor behavior, as well as lateralized neglect were studied in mice after the injection of single doses of BoNT-A into the right CPu, comparing them with sham-injected animals. Unilateral intrastriatal injection of BoNT-A in mice induced significantly increased contralateral apomorphine-induced rotations for 1 to 3 months, as well as significantly increased contralateral amphetamine-induced rotations 1 to 9 months after injection. In rats (n = 28), unilateral BoNT-A injection also induced significantly increased contralateral apomorphine-induced rotations 3 months after injection, but did not provoke amphetamine-induced rotations at all. Lateralized sensorimotor integration, forelimb preference, and forelimb stepping were significantly impaired on the left side. The differences in motor behaviors between rats and mice may be caused by different BoNT-A effects on cholinergic and catecholaminergic fibers in rat and mouse striata, interspecies differences in striatal receptor densities, and different connectomes of the basal ganglia.
An Epidemiological Review of Diet and Cutaneous Malignant Melanoma

Incidence of cutaneous malignant melanoma has continued to rise despite public efforts to promote sun protection behaviors among populations at risk. However, dietary factors may also affect the development of melanoma. In the past few decades, findings from epidemiologic and experimental research have linked consumption of several foods and other nutrients to the risk of melanoma. Caffeine has been associated with a lower risk of melanoma, and citrus fruits and alcohol with increased risk. Associations between polyunsaturated fatty acid, niacin/nicotinamide, folate, and vitamin D with melanoma remain controversial. Diet likely influences melanoma development through several potential mechanisms, such as enhancing UV-induced apoptosis and increasing photosensitivity. We conducted a narrative review to summarize recent epidemiologic studies of diet and melanoma based on published literature. Given the high prevalence of the food items and nutrients covered in this review and the decades-long rising melanoma incidence worldwide, the associations we discuss may have important public health implications in terms of reducing melanoma incidence through dietary modification. Cancer Epidemiol Biomarkers Prev; 27(10); 1115–22. ©2018 AACR.
Malaria in pregnancy shapes the development of foetal and infant immunity

Malaria, particularly Plasmodium falciparum, continues to disproportionately affect pregnant women. In addition to the profoundly deleterious impact of maternal malaria on the health of the mother and foetus, malaria infection in pregnancy has been shown to affect the development of the foetal and infant immune system and may alter the risk of malaria and nonmalarial outcomes during infancy. This review summarizes our current understanding of how malaria infection in pregnancy shapes the protective components of the maternal immune system transferred to the foetus and how foetal exposure to parasite antigens impacts the development of foetal and infant immunity. It also reviews existing evidence linking malaria infection in pregnancy to malaria and nonmalarial outcomes in infancy and how preventing malaria in pregnancy may alter these outcomes. A better understanding of the consequences of malaria infection in pregnancy on the development of foetal and infant immunity will inform control strategies, including intermittent preventive treatment in pregnancy and vaccine development.
Effect of cabergoline alginate nanocomposite on the transgenic Drosophila melanogaster model of Parkinson’s disease

Abstract Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. Dopamine agonists help the patients with PD by reversing the dopamine depletion and related motor deficits. In the present work, cabergoline, a potent ergot dopamine agonist, was given in the form of cabergoline alginate nanocomposite (CANC) to the PD model flies to study its effects on climbing ability, activity pattern, life span, lipid peroxidation, glutathione (GSH) content, glutathione-S-transferase (GST) activity, dopamine content, protein carbonyl content, mean gray-scale values, and caspase-3 and caspase-9 activities. Cabergoline alginate nanocomposite was synthesized by adding the cabergoline solution in the warm aqueous solution of sodium alginate; The synthesized CANC was characterized using fourier transform (FTIR) infrared spectroscopy, transmission electron microscopy (TEM), and UV–Visible spectroscopic techniques. The synthesized CANC having the final doses of 1, 2, and 3 μM was supplemented with diet and the flies were allowed to feed on it for 24 days. Cabergoline alginate nanocomposite significantly increases climbing ability, reduces lipid peroxidation, GST activity, protein carbonyl content, caspase 3/9 activity, mean gray-scale values, and increases the GSH as well as dopamine content in a dose-dependent manner. The results of this study suggest that CANC is potent in delaying and reducing the symptoms of PD.
Social Support patterns in Primary Health Care : differences between having physical diseases or mental disorders

The social support network is a health protective factor involving physical, mental and psychological aspects, providing a better quality of life, favoring better adaptation to adverse conditions, promoting resilience and mobilizing resources for a more effective coping with negative life events that can lead to illness. We aimed to analyze the association between physical diseases, common mental disorders and the social support network of patients serviced at primary care facilities in the cities of Rio de Janeiro and São Paulo through a cross-sectional study with 1,466 patients in the 18-65 years age group. We used the Social Network Index (SNI) to assess the support network through the categories of isolation and integration. The doctor/nurse completed the questionnaire to evaluate the physical disease diagnosis, while the Hospital Anxiety and Depression Scale was used to detect mental disorders. We found that the pattern of social support was different depending on the presence of physical diseases or mental disorders. Negative associations were found between diabetes and isolation; integration and anxiety; integration and depression. Positive associations were identified between isolation and anxiety and isolation and depression.
The role of stochastic sequestration dynamics for intrinsic noise filtering in signaling network motifs

The relation between design principles of signaling network motifs and their robustness against intrinsic noise still remains illusive. In this work we investigate the role of cascading for coping with intrinsic noise due to stochasticity in molecular reactions. We use stochastic approaches to quantify fluctuations in the terminal kinase of phosphorylation-dephosphorylation cascade motifs and demonstrate that cascading highly affects these fluctuations. We show that this purely stochastic effect can be explained by time-varying sequestration of upstream kinase molecules. In particular, we discuss conditions on time scales and parameter regimes which lead to a reduction of output fluctuations. Our results are put into biological context by adapting rate parameters of our modeling approach to biologically feasible ranges for general binding-unbinding and phosphorylation-dephosphorylation mechanisms. Overall, this study reveals a novel role of stochastic sequestration for dynamic noise filtering in signaling cascade motifs.
Angiographic derived endothelial shear stress: a new predictor of atherosclerotic disease progression

AIMS To examine the efficacy of angiography derived endothelial shear stress (ESS) in predicting atherosclerotic disease progression. METHODS AND RESULTS Thirty-five patients admitted with ST-elevation myocardial infarction that had three-vessel intravascular ultrasound (IVUS) immediately after revascularization and at 13 months follow-up were included. Three dimensional (3D) reconstruction of the non-culprit vessels were performed using (i) quantitative coronary angiography (QCA) and (ii) methodology involving fusion of IVUS and biplane angiography. In both models, blood flow simulation was performed and the minimum predominant ESS was estimated in 3 mm segments. Baseline plaque characteristics and ESS were used to identify predictors of atherosclerotic disease progression defied as plaque area increase and lumen reduction at follow-up. Fifty-four vessels were included in the final analysis. A moderate correlation was noted between ESS estimated in the 3D QCA and the IVUS-derived models (r = 0.588, P < 0.001); 3D QCA accurately identified segments exposed to low (<1 Pa) ESS in the IVUS-based reconstructions (AUC: 0.793, P < 0.001). Low 3D QCA-derived ESS (<1.75 Pa) was associated with an increase in plaque area, burden, and necrotic core at follow-up. In multivariate analysis, low ESS estimated either in 3D QCA [odds ratio (OR): 2.07, 95% confidence interval (CI): 1.17-3.67; P = 0.012) or in IVUS (<1 Pa; OR: 2.23, 95% CI: 1.23-4.03; P = 0.008) models, and plaque burden were independent predictors of atherosclerotic disease progression; 3D QCA and IVUS-derived models had a similar accuracy in predicting disease progression (AUC: 0.826 vs. 0.827, P = 0.907). CONCLUSIONS 3D QCA-derived ESS can predict disease progression. Further research is required to examine its value in detecting vulnerable plaques.
Effects of hypoxia on swimming and sensing in a weakly electric fish

ABSTRACT Low dissolved oxygen (hypoxia) can severely limit fish performance, especially aerobically expensive behaviours including swimming and acquisition of sensory information. Fishes can reduce oxygen requirements by altering these behaviours under hypoxia, but the underlying mechanisms can be difficult to quantify. We used a weakly electric fish as a model system to explore potential effects of hypoxia on swim performance and sensory information acquisition, which enabled us to non-invasively record electric signalling activity used for active acquisition of sensory information during swimming. To quantify potential effects of hypoxia, we measured critical swim speed (Ucrit) and concurrent electric signalling activity under high- and low-dissolved oxygen concentrations in a hypoxia-tolerant African mormyrid fish, Marcusenius victoriae. Fish were maintained under normoxia for 6 months prior to experimental treatments, and then acclimated for 8 weeks to normoxia or hypoxia and tested under both conditions (acute: 4 h exposure). Acute hypoxia exposure resulted in a significant reduction in both Ucrit and electric signalling activity in fish not acclimated to hypoxia. However, individuals acclimated to chronic hypoxia were characterized by a higher Ucrit under both hypoxia and normoxia than fish acclimated to normoxia. Following a 6 month re-introduction to normoxia, hypoxia-acclimated individuals still showed increased performance under acute hypoxic test conditions, but not under normoxia. Our results highlight the detrimental effects of hypoxia on aerobic swim performance and sensory information acquisition, and the ability of fish to heighten aerobic performance through acclimation processes that can still influence performance even months after initial exposure. Summary: Chronic hypoxia exposure in a weakly electric fish increases aspects of aerobic performance and mitigates potentially limiting effects of hypoxia on swimming and signalling at aerobically demanding swim speeds.