Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence Implicating Non-Dioxin-Like Congeners as the Key Mediators of Polychlorinated Biphenyl (PCB) Developmental Neurotoxicity

Despite being banned from production for decades, polychlorinated biphenyls (PCBs) continue to pose a significant risk to human health. This is due to not only the continued release of legacy PCBs from PCB-containing equipment and materials manufactured prior to the ban on PCB production, but also the inadvertent production of PCBs as byproducts of contemporary pigment and dye production. Evidence from human and animal studies clearly identifies developmental neurotoxicity as a primary endpoint of concern associated with PCB exposures. However, the relative role(s) of specific PCB congeners in mediating the adverse effects of PCBs on the developing nervous system, and the mechanism(s) by which PCBs disrupt typical neurodevelopment remain outstanding questions. New questions are also emerging regarding the potential developmental neurotoxicity of lower chlorinated PCBs that were not present in the legacy commercial PCB mixtures, but constitute a significant proportion of contemporary human PCB exposures. Here, we review behavioral and mechanistic data obtained from experimental models as well as recent epidemiological studies that suggest the non-dioxin-like (NDL) PCBs are primarily responsible for the developmental neurotoxicity associated with PCBs. We also discuss emerging data demonstrating the potential for non-legacy, lower chlorinated PCBs to cause adverse neurodevelopmental outcomes. Molecular targets, the relevance of PCB interactions with these targets to neurodevelopmental disorders, and critical data gaps are addressed as well.
Current and future treatments of pulmonary arterial hypertension

Therapeutic options for pulmonary arterial hypertension (PAH) have increased over the last decades. The advent of pharmacological therapies targeting the prostacyclin, endothelin, and NO pathways has significantly improved outcomes. However, for the vast majority of patients, PAH remains a life‐limiting illness with no prospect of cure. PAH is characterised by pulmonary vascular remodelling. Current research focusses on targeting the underlying pathways of aberrant proliferation, migration, and apoptosis. Despite success in preclinical models, using a plethora of novel approaches targeting cellular GPCRs, ion channels, metabolism, epigenetics, growth factor receptors, transcription factors, and inflammation, successful transfer to human disease with positive outcomes in clinical trials is limited. This review provides an overview of novel targets addressed by clinical trials and gives an outlook on novel preclinical perspectives in PAH.
Global gene flow releases invasive plants from environmental constraints on genetic diversity

Significance We found that long-distance dispersal and repeated introductions by humans have shaped adaptive potential in a globally distributed invasive species. Some plant species, therefore, do not need strong demographic changes to overcome environmental constraints that exist in the native range; simply mixing genetic stock from multiple populations can provide an adaptive advantage. This work highlights the value of preventing future introduction events for problematic invasive species, even if the species already exists in an area. When plants establish outside their native range, their ability to adapt to the new environment is influenced by both demography and dispersal. However, the relative importance of these two factors is poorly understood. To quantify the influence of demography and dispersal on patterns of genetic diversity underlying adaptation, we used data from a globally distributed demographic research network comprising 35 native and 18 nonnative populations of Plantago lanceolata. Species-specific simulation experiments showed that dispersal would dilute demographic influences on genetic diversity at local scales. Populations in the native European range had strong spatial genetic structure associated with geographic distance and precipitation seasonality. In contrast, nonnative populations had weaker spatial genetic structure that was not associated with environmental gradients but with higher within-population genetic diversity. Our findings show that dispersal caused by repeated, long-distance, human-mediated introductions has allowed invasive plant populations to overcome environmental constraints on genetic diversity, even without strong demographic changes. The impact of invasive plants may, therefore, increase with repeated introductions, highlighting the need to constrain future introductions of species even if they already exist in an area.
The Kinetics of Amyloid Fibril Formation by de Novo Protein Albebetin and Its Mutant Variants

Engineering of amyloid structures is one of the new perspective areas of protein engineering. Studying the process of amyloid formation can help find ways to manage it in the interests of medicine and biotechnology. One of the promising candidates for the structural basis of artificial functional amyloid fibrils is albebetin (ABB), an artificial protein engineered under the leadership of O.B. Ptitsyn. Various aspects of the amyloid formation of this protein and some methods for controlling this process are investigated in this paper. Four stages of amyloid fibrils formation by this protein from the first non-fibrillar aggregates to mature fibrils and large micron-sized complexes have been described in detail. Dependence of albebetin amyloids formation on external conditions and some mutations also have been described. The introduction of similar point mutations in the two structurally identical α-β-β motifs of ABB lead to different amiloidogenesis kinetics. The inhibitory effect of a disulfide bond and high pH on amyloid fibrils formation, that can be used to control this process, was shown. The results of this work are a good basis for the further design and use of ABB-based amyloid constructs.
New data about home range and movements of Oligoryzomys flavescens (Rodentia: Cricetidae) help to understand the spread and transmission of Andes virus that causes Hantavirus Pulmonary Syndrome

Hantavirus pulmonary syndrome is an emerging infectious disease caused by viruses of the genus Orthohantavirus. The rodent Oligoryzomys flavescens is distributed along four countries of South America. In Argentina, O. flavescens acts as a reservoir of three genotypes of ANDV orthohantavirus. The aims of this work were to estimate home range size and movements—with spool‐and‐line and radiotelemetry—of infected and non‐infected O. flavescens in order to understand the spread and transmission of the virus. O. flavescens use a wide area to satisfice its requirements, reaching a home range of 1.82 ha during spring. Orthohantavirus infection did not change the behaviour of individuals. We observed a great overlapping in the home range of infected and non‐infected individuals resulting in a high probability of virus dispersion on rodent population. These results show that human health risks could be high on island environments and knowledge about the movement ecology of O. flavescens provides useful information on prevention.
Blood Contamination in CSF and Its Impact on Quantitative Analysis of Alpha-Synuclein

Analysis of cerebrospinal fluid (CSF) is important for diagnosis of neurological diseases. Especially for neurodegenerative diseases, abnormal protein abundance in CSF is an important biomarker. However, the quality of CSF is a key factor for the analytic outcome. Any external contamination has tremendous impact on the analysis and the reliability of the results. In this study, we evaluated the effect of blood contamination in CSF with respect to protein biomarker identification. We compared three distinct measures: Combur10-Test® strips, a specific hemoglobin ELISA, and bottom-up mass spectrometry (MS)-based proteomics for the determination of the general blood contamination level. In parallel, we studied the impact of blood contamination on the detectability of alpha-synuclein (aSyn), a highly abundant protein in blood/erythrocytes and a potential biomarker for Parkinson’s disease. Comparable results were achieved, with all three approaches enabling detection of blood levels in CSF down to 0.001%. We found higher aSyn levels with increasing blood contamination, highlighting the difficulty of authentic quantification of this protein in CSF. Based on our results, we identified other markers for blood contamination beyond hemoglobin and defined a grading system for blood levels in CSF samples, including a lower limit of tolerable blood contamination for MS-based biomarker studies.
Extracellular Vesicles Derived from Senescent Fibroblasts Attenuate the Dermal Effect on Keratinocyte Differentiation

The skin is a multilayered and primary defensive organ. Intimate intercellular communication in the skin is necessary to ensure effective surveillance. Extracellular vesicles (EVs) are being explored for their involvement in intercellular skin communication. The aim of this study was to evaluate how human dermal fibroblasts (HDFs) accelerate EV production during senescence and the effects of senescence-associated EVs on epidermal homeostasis. Replicative senescent HDFs were assessed with senescence-associated β-galactosidase staining and the expression of senescence-related markers. Isolated EVs were characterized by dynamic light scattering and EV marker expression. EVs secreted from untreated young or senescent HDFs, or from those treated with a nSMase inhibitor, antioxidant, and lysosomal activity regulators, were determined by sandwich ELISA for CD81. Human epidermal keratinocytes were treated with young- and senescent HDF-derived EVs. Compared to young HDFs, senescent HDFs produced relatively high levels of EVs due to the increased nSMase activity, oxidative stress, and altered lysosomal activity. The nSMase inhibitor, antioxidant, and agents that recovered lysosomal activity reduced EV secretion in senescent HDFs. Relative to young HDF-derived EVs, senescent HDF-derived EVs were less supportive in keratinocyte differentiation and barrier function but increased proinflammatory cytokine IL-6 levels. Our study suggests that dermis-derived EVs may regulate epidermal homeostasis by reflecting cellular status, which provides insight as to how the dermis communicates with the epidermis and influences skin senescence.
A Pilot Study on the Effects of l-Carnitine and Trimethylamine-N-Oxide on Platelet Mitochondrial DNA Methylation and CVD Biomarkers in Aged Women

l-carnitine supplementation has been used for cardiovascular health protection for a long time. Recently, trimethylamine-N-oxide (TMAO), which is an end product of l-carnitine metabolism via the activity of microbiota, has been identified as a cardiovascular disease (CVD) biomarker. The aim of this study was to assess the effect of 6 months of l-carnitine supplementation in a group of aged women engaged in a regular physical training. Platelet mitochondrial DNA methylation, an emerging and innovative biomarker, lipid profile and TMAO levels have been measured. TMAO increased after l-carnitine supplementation (before 344.3 ± 129.8 ng/mL vs. after 2216.8 ± 1869.0 ng/mL; n = 9; paired t-test, p = 0.02). No significant effects on TMAO were exerted by training alone (n = 9) or by l-leucine supplementation (n = 12). TMAO levels after 6 months of l-carnitine supplementation were associated with higher low-density lipoprotein-cholesterol (LDL-c) (Spearman Rho = 0.518, p = 0.003) and total cholesterol (TC) (Spearman Rho = 0.407, p = 0.026) levels. l-carnitine supplementation increased D-loop methylation in platelets (+6.63%; paired t-test, p = 0.005). D-loop methylation was not directly correlated to the TMAO augmentation observed in the supplemented group, but its increase inversely correlated with TC (Pearson coefficient = −0.529, p = 0.029) and LDL-c (Pearson coefficient = −0.439, p = 0.048). This evidence supports the hypothesis that the correlation between l-carnitine, TMAO and atherosclerosis might be more complex than already postulated, and the alteration of mitochondrial DNA (mtDNA) methylation in platelets could be involved in the pathogenesis of this multifactorial disease.
Effects of exogenous compound sprays on cherry cracking: skin properties and gene expression.

BACKGROUND Cherry fruit cracking is a costly problem for cherry growers. The effect of repeated sprayings (gibberellic acid - GA3 , abscisic acid - ABA, salicylic acid - SA, glycine betaine - GB and Ascophyllum nodosum - AN) combined with CaCl2 , on 'Sweetheart' cherry fruit cracking characteristics was investigated. Cracking was quantified in terms of cracking incidence, crack morphology, confocal scanning laser microscopy, cuticular wax content and cell wall modification and cuticular wax gene expression. RESULTS All spray treatments reduced cracking compared to the untreated control (H2 O), with less cheek cracks and the least cracking incidence observed for ABA+CaCl2 - and GB + CaCl2 -treated fruits, indicating an added benefit to reduce cracking compared to spraying with CaCl2 alone. In addition, GB + CaCl2 -treated fruits showed higher fruit diameter. ABA+CaCl2 and GB + CaCl2 sprays showed higher wax content and higher cuticle and epidermal thickness compared to the control, including increased expression of wax synthase (ABA+CaCl2 ) and expansin 1 (GB + CaCl2 ). CONCLUSION In general, factors that improve the cuticle thickness appear to be important at the fruit colouring stage. At the fruit ripening stage, larger cell size of the epidermis, hypodermis and parenchyma cells lowers cracking incidence, pointing at the importance of flexibility and elasticity of the epidermis. This article is protected by copyright. All rights reserved.
CRK2 and C-terminal phosphorylation of NADPH oxidase RBOHD regulate ROS production in Arabidopsis

Reactive oxygen species (ROS) are important messengers in eukaryotic organisms and their production is tightly controlled. Active extracellular ROS production by NADPH oxidases in plants is triggered by receptor-like protein kinase (RLK)-dependent signaling networks. Here we show that the cysteine-rich RLK CRK2 kinase activity is required for plant growth and CRK2 exists in a preformed complex with the NADPH oxidase RBOHD in Arabidopsis. Functional CRK2 is required for the full elicitor-induced ROS burst and consequently the crk2 mutant is impaired in defense against the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Our work demonstrates that CRK2 regulates plant innate immunity. We identified in vitro CRK2-dependent phosphorylation sites in the C-terminal region of RBOHD. Phosphorylation of S703 RBOHD is enhanced upon flg22 treatment and substitution of S703 with alanine reduced ROS production in Arabidopsis. Phylogenetic analysis suggests that phospho-sites in C-terminal region of RBOHD are conserved throughout the plant lineage and between animals and plants. We propose that regulation of NADPH oxidase activity by phosphorylation of the C-terminal region might be an ancient mechanism.
Occupational Factors Associated with Health-Related Quality of Life in Nursing Professionals: A Multi-Centre Study

Background: Nursing professionals are exposed to stressful situations arising from the work context that may affect health-related quality of life (HRQoL). The objective of this study was to analyse the relationship between sociodemographic and work-related variables regarding HRQoL in nursing professionals. Methods: A multi-centre, cross-sectional descriptive design was used. The participants consisted 1521 nurses working in healthcare centres, in both primary care and hospital care, in the eight provinces of the Andalusian Public Health System (APHS), Spain. Sociodemographic and work-related variables were analysed: Compassion fatigue, compassion satisfaction and burnout were measured using the professional quality of life questionnaire (ProQOL), and HRQoL was measured using the SF-12 health questionnaire. Results: Compassion fatigue, burnou, and, to a lesser extent, compassion satisfaction significantly influence the physical and mental components of HRQoL. The simple regression analysis showed that burnout and compassion fatigue were significantly associated with the mental component of HRQoL. Gender influenced the mental component of HRQoL. The rest of the sociodemographic and work-related variables were not significantly related to HRQoL. Conclusion: Work-related stress and repeated contact with situations of suffering influence HRQoL. Health systems must implement programmes to increase the emotional well-being of workers.
Different Patterns of Left Ventricular Hypertrophy in Metabolically Healthy and Insulin-Resistant Obese Subjects

Obese subjects showed different cardiovascular risk depending by different insulin sensitivity status. We investigated the difference in left ventricular mass and geometry between metabolically healthy (MHO) and unhealthy (MUHO) obese subjects. From a cohort of 876 obese subjects (48.3 ± 14.1 years) without cardio-metabolic disease and stratified according to increasing values of Matsuda index after 75 g oral glucose tolerance test, we defined MHO (n = 292) those in the upper tertile and MUHO (n = 292) those in the lower tertile. All participants underwent echocardiographic measurements. Left ventricular mass was calculated by Devereux equation and normalized by height2,7 and left ventricular hypertrophy (LVH) was defined by values >44 g/m2.7 for females and >48 g/m2.7 for males. Left ventricular geometric pattern was defined as concentric or eccentric if relative wall thickness was higher or lower than 0.42, respectively. MHO developed more commonly a concentric remodeling (19.9 vs. 9.9%; p = 0.001) and had a reduced risk for LVH (OR 0.46; p < 0.0001) than MUHO, in which the eccentric type was more prevalent (40.4 vs. 5.1%; p < 0.0001). We demonstrated that obese subjects—matched for age, gender and BMI—have different left ventricular mass and geometry due to different insulin sensitivity status, suggesting that diverse metabolic phenotypes lead to alternative myocardial adaptation.
Accurate, Very Low Computational Complexity Spike Sorting Using Unsupervised Matched Subspace Learning

This paper presents an adaptable dictionary-based feature extraction approach for spike sorting offering high accuracy and low computational complexity for implantable applications. It extracts and learns identifiable features from evolving subspaces through matched unsupervised subspace filtering. To provide compatibility with the strict constraints in implantable devices such as the chip area and power budget, the dictionary contains arrays of {–1, 0 and 1} and the algorithm need only process addition and subtraction operations. Three types of such dictionary were considered. To quantify and compare the performance of the resulting three feature extractors with existing systems, a neural signal simulator based on several different libraries was developed. For noise levels σN between 0.05 and 0.3 and groups of 3 to 6 clusters, all three feature extractors provide robust high performance with average classification errors of less than 8% over five iterations, each consisting of 100 generated data segments. To our knowledge, the proposed adaptive feature extractors are the first able to classify reliably 6 clusters for implantable applications. An ASIC implementation of the best performing dictionary-based feature extractor was synthesized in a 65-nm CMOS process. It occupies an area of 0.09 mm2 and dissipates up to about 10.48 μW from a 1 V supply voltage, when operating with 8-bit resolution at 30 kHz operating frequency.
Development of a Rapid On-site Method for the Detection of Chicken Meat in Processed Ground Meat Products Using a Direct Ultrafast PCR System.

In this study, we developed a rapid on-site detection method using direct ultrafast PCR coupled with a microfluidic chip to identify the presence of chicken meat in processed ground meat products. Chicken-specific PCR primer targeting mitochondrial 16S rRNA gene was newly designed, and its specificity was confirmed against 17 other animal species and 4 different chicken meat samples from different countries of origin. The sensitivity of the chicken-specific ultrafast PCR was 0.1 pg of chicken DNA. To evaluate the limit of detection (LOD) of the direct ultrafast PCR method, different percentages of chicken meat mixed with pork or beef were prepared. The LOD of the direct ultrafast PCR method for the chicken meat/pork and chicken meat/beef mixtures was 0.1% for both raw meat and autoclaved meat. This method was used for 15 commercialized processed ground meat products. In this method, the target sequence was successfully amplified, and the presence of chicken meat in processed ground meat products was identified within approximately 25 min, including the time for sample preparation. Thus, our study shows that this developed direct ultrafast PCR method is a rapid and accurate method for on-site detection of chicken DNA in commercial food products.
Characterisation of endogenous Claudin‐1 expression, motility and susceptibility to hepatitis C virus in CRISPR knock‐in cells

Claudin‐1 (CLDN1) is a four‐span transmembrane protein localised at cell–cell tight junctions (TJs), playing an important role in epithelial impermeability and tissue homoeostasis under physiological conditions. Moreover, CLDN1 expression is up‐regulated in several cancers, and the level of CLDN1 expression has been proposed as a prognostic marker of patient survival.
Religiosity and Psychotic Ideation in Stable Schizophrenia: A Role for Empathic Perspective-Taking

The relationship between religiosity and different components of empathy was explored in schizophrenia patients. A total of 81 stable schizophrenia patients and 95 controls from the nearby community completed self-reported questionnaires assessing religiosity and empathy (through the Interpersonal Reactivity Index, IRI). Patients with schizophrenia showed higher religiousness than controls and they presented less perspective-taking and empathic concern but increased personal distress in IRI scores. Regression analyses unveiled an association between religiosity and perspective-taking in schizophrenics after adjusting for age, gender, and psychotic symptoms. In conclusion, religiosity in patients with schizophrenia may be linked to variations in perspective- taking as a component of empathy.
A Fast and Scalable Workflow for SNPs Detection in Genome Sequences Using Hadoop Map-Reduce

Next generation sequencing (NGS) technologies produce a huge amount of biological data, which poses various issues such as requirements of high processing time and large memory. This research focuses on the detection of single nucleotide polymorphism (SNP) in genome sequences. Currently, SNPs detection algorithms face several issues, e.g., computational overhead cost, accuracy, and memory requirements. In this research, we propose a fast and scalable workflow that integrates Bowtie aligner with Hadoop based Heap SNP caller to improve the SNPs detection in genome sequences. The proposed workflow is validated through benchmark datasets obtained from publicly available web-portals, e.g., NCBI and DDBJ DRA. Extensive experiments have been performed and the results obtained are compared with Bowtie and BWA aligner in the alignment phase, while compared with GATK, FaSD, SparkGA, Halvade, and Heap in SNP calling phase. Experimental results analysis shows that the proposed workflow outperforms existing frameworks e.g., GATK, FaSD, Heap integrated with BWA and Bowtie aligners, SparkGA, and Halvade. The proposed framework achieved 22.46% more efficient F-score and 99.80% consistent accuracy on average. More, comparatively 0.21% mean higher accuracy is achieved. Moreover, SNP mining has also been performed to identify specific regions in genome sequences. All the frameworks are implemented with the default configuration of memory management. The observations show that all workflows have approximately same memory requirement. In the future, it is intended to graphically show the mined SNPs for user-friendly interaction, analyze and optimize the memory requirements as well.