Miracle-dz/UniFAR-FTUs huggingface dataset:
Differences in neurotoxic outcomes of organophosphorus pesticides revealed via multi-dimensional screening in adult and regenerating planarians

Organophosphorus pesticides (OPs) are a chemically diverse class of commonly used insecticides. Epidemiological studies suggest that low dose chronic prenatal and infant exposures can lead to life-long neurological damage and behavioral disorders. While inhibition of acetylcholinesterase (AChE) is the shared mechanism of acute OP neurotoxicity, OP-induced developmental neurotoxicity (DNT) can occur independently and/or in the absence of significant AChE inhibition, implying that OPs affect alternative targets. Moreover, different OPs can cause different adverse outcomes, suggesting that different OPs act through different mechanisms. These findings emphasize the importance of comparative studies of OP toxicity. Freshwater planarians are an invertebrate system that uniquely allows for automated, rapid and inexpensive testing of adult and developing organisms in parallel to differentiate neurotoxicity from DNT. Effects found only in regenerating planarians would be indicative of DNT, whereas shared effects may represent neurotoxicity. We leverage this unique feature of planarians to investigate potential differential effects of OPs on the adult and developing brain by performing a comparative screen to test 7 OPs (acephate, chlorpyrifos, dichlorvos, diazinon, malathion, parathion and profenofos) across 10 concentrations in quarter-log steps. Neurotoxicity was evaluated using a wide range of quantitative morphological and behavioral readouts. AChE activity was measured using an Ellman assay. The toxicological profiles of the 7 OPs differed across the OPs and between adult and regenerating planarians. Toxicological profiles were not correlated with levels of AChE inhibition. Twenty-two “mechanistic control compounds” known to target pathways suggested in the literature to be affected by OPs (cholinergic neurotransmission, serotonin neurotransmission, endocannabinoid system, cytoskeleton, adenyl cyclase and oxidative stress) and 2 negative controls were also screened. When compared with the mechanistic control compounds, the phenotypic profiles of the different OPs separated into distinct clusters. The phenotypic profiles of adult vs regenerating planarians exposed to the OPs clustered differently, suggesting some developmental-specific mechanisms. These results further support findings in other systems that OPs cause different adverse outcomes in the (developing) brain and build the foundation for future comparative studies focused on delineating the mechanisms of OP neurotoxicity in planarians.
Glycolysis revisited: from steady state growth to glucose pulses

Kinetic metabolic models of central metabolism have been proposed to understand how Saccharomyces cerevisiae navigates through nutrient perturbations. Yet, these models lacked important variables that constrain metabolism under relevant physiological conditions and thus have limited operational use such as in optimization of industrial fermentations. In this work, we developed a physiologically informed kinetic model of yeast glycolysis connected to central carbon metabolism by including the effect of anabolic reactions precursors, mitochondria and the trehalose cycle. A parameter estimation pipeline was developed, consisting of a divide and conquer approach, supplemented with regularization and global optimization. We show how this first mechanistic description of a growing yeast cell captures experimental dynamics at different growth rates and under a strong glucose perturbation, is robust to parametric uncertainty and explains the contribution of the different pathways in the network. Our work suggests that by combining multiple types of data and computational methods, complex but physiologically representative and robust models can be achieved.
Dopamine in the dorsal bed nucleus of stria terminalis signals Pavlovian sign-tracking and reward violations

Midbrain and striatal dopamine signals have been extremely well characterized over the past several decades, yet novel dopamine signals and functions in reward learning and motivation continue to emerge. A similar characterization of real-time sub-second dopamine signals in areas outside of the striatum has been limited. Recent advances in fluorescent sensor technology and fiber photometry permit measurement of dopamine binding correlates, which can divulge basic functions of dopamine signaling in non-striatal dopamine terminal regions, like the dorsal bed nucleus of the stria terminalis (dBNST). Here, we record GRABDA signals in the dBNST during a Pavlovian lever autoshaping task. We observe greater Pavlovian cue-evoked dBNST GRABDA signals in sign-tracking (ST) compared to goal-tracking/intermediate (GT/INT) rats and the magnitude of cue-evoked dBNST GRABDA signals decrease immediately following reinforcer-specific satiety. When we deliver unexpected reward or omit expected reward, we find that dBNST dopamine signals encode bidirectional reward prediction errors in GT/INT rats, but only positive prediction errors in ST rats. Since sign- and goal-tracking approach strategies are associated with distinct drug relapse vulnerabilities, we examined the effects of experimenter-administered fentanyl on dBNST dopamine associative encoding. Systemic fentanyl injections do not disrupt dBNST cue discrimination but generally potentiate dBNST dopamine signals. These results reveal multiple dBNST dopamine correlates of learning and motivation that depend on the Pavlovian approach strategy employed.
Cochlear implant material effects on inflammatory cell function and foreign body response

Objectives The objectives of this study were to assess the effects of cochlear implant (CI) biomaterials on the function of macrophages and fibroblasts, two key mediators of the foreign body response (FBR) and to determine how these materials influence fibrous tissue growth and new bone formation within the cochlea. Methods Macrophages and fibroblasts were cultured on polydimethylsiloxane (PDMS) and platinum substrates and human CI electrodes in vitro. Cell count, cell proliferation, cytokine production, and cell adhesion were measured. CI electrodes were implanted into murine cochleae for one week without electrical stimulation. Implanted cochleae were harvested for 3D X-ray microscopy with the CI left in-situ. The location of new bone growth within the scala tympani (ST) with reference to different portions of the implant (PDMS vs platinum) was quantified. Results Cell counts of macrophages and fibroblasts were significantly higher on platinum substrates and platinum contacts of CI electrodes. Fibroblast proliferation was greater on platinum relative to PDMS, and cells grown on platinum formed more/larger focal adhesions. 3D x-ray microscopy showed neo-ossification in the peri-implant areas of the ST. Volumetric quantification of neo-ossification showed a trend toward greater bone formation adjacent to the platinum electrodes compared to areas opposite or away from the platinum electrode bearing surfaces. Conclusions Fibrotic reactions are biomaterial specific, as demonstrated by the differences in cell adhesion, proliferation, and fibrosis on platinum and PDMS. The inflammatory reaction to platinum contacts on CI electrodes likely contributes to fibrosis to a greater degree than PDMS, and platinum contacts may influence the deposition of new bone, as demonstrated in the in vivo data. This information can potentially be used to influence the design of future generations of neural prostheses.
Genomic analysis of a synthetic reversed sequence reveals default chromatin states in yeast and mammalian cells

Up to 93% of the human genome may show evidence of transcription, yet annotated transcripts account for less than 5%. It is unclear what makes up this major discrepancy, and to what extent the excess transcription has a definable biological function, or is just a pervasive byproduct of non-specific RNA polymerase binding and transcription initiation. Understanding the default state of the genome would be informative in determining whether the observed pervasive activity has a definable function. The genome of any modern organism has undergone billions of years of evolution, making it unclear whether any observed genomic activity, or lack thereof, has been selected for. We sought to address this question by introducing a completely novel 100-kb locus into the genomes of two eukaryotic organisms, S. cerevisiae and M. musculus, and characterizing its genomic activity based on chromatin accessibility and transcription. The locus was designed by reversing (but not complementing) the sequence of the human HPRT1 locus, including ∼30-kb of both upstream and downstream regulatory regions, allowing retention of sequence features like repeat frequency and GC content but ablating coding information and transcription factor binding sites. We also compared this reversed locus with a synthetic version of the normal human HPRT1 locus in both organismal contexts. Despite neither the synthetic HPRT1 locus nor its reverse version coding for any promoters evolved for gene expression in yeast, we observed widespread transcriptional activity of both loci. This activity was observed both when the loci were present as episomes and when chromosomally integrated, although it did not correspond to any of the known HPRT1 functional regulatory elements. In contrast, when integrated in the mouse genome, the synthetic HPRT1 locus showed transcriptional activity corresponding precisely to the HPRT1 coding sequence, while the reverse locus displayed no activity at all. Together, these results show that genomic sequences with no coding information are active in yeast, but relatively inactive in mouse, indicating a potentially major difference in “default genomic states” between these two divergent eukaryotes.
Demystifying the Role of Prognostic Biomarkers in Breast Cancer through Integrated Transcriptome and Pathway Enrichment Analyses

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of death in women. There has been discovered an increasing number of molecular targets for BC prognosis and therapy. However, it is still urgent to identify new biomarkers. Therefore, we evaluated biomarkers that may contribute to the diagnosis and treatment of BC. We searched TCGA datasets and identified differentially expressed genes (DEGs) by comparing tumor (100 samples) and non-tumor (100 samples) tissues using the Deseq2 package. Pathway and functional enrichment analysis of the DEGs were done using DAVID (The Database for Annotation, Visualization, and Integrated Discovery) database. The protein-protein interaction (PPI) network was identified using the STRING database and visualized through Cytoscape software. Hub gene analysis of the PPI network was done using Cytohubba plugins. The associations between the identified genes and overall survival (OS) were analyzed using Kaplan–Meier plot. Finally, we have identified hub genes at the transcriptome level. A total of 824 DEGs were identified, which were mostly enriched in cell proliferation, signal transduction, and cell division. The PPI network comprised 822 nodes and 12145 edges. Elevated expression of the 5 hub genes AURKA, BUB1B, CCNA2, CCNB2, and PBK are related to poor OS in breast cancer patients. A promoter methylation study showed these genes to be hypomethylated. Validation through genetic alteration and missense mutations resulted in chromosomal instability leading to improper chromosome segregation causing aneuploidy. The enriched functions and pathways included the cell cycle, oocyte meiosis, and the p53 signaling pathway. The identified five hub genes in breast cancer have the potential to become useful targets for the diagnosis and treatment of breast cancer.
Optimizing insect metabarcoding using replicated mock communities

Metabarcoding (high-throughput sequencing of marker gene amplicons) has emerged as a promising and cost-effective method for characterizing insect community samples. Yet, the methodology varies greatly among studies and its performance has not been systematically evaluated to date. In particular, it is unclear how accurately metabarcoding can resolve species communities in terms of presence-absence, abundances, and biomass. Here we use mock community experiments and a simple probabilistic model to evaluate the performance of different metabarcoding protocols. Specifically, we ask four questions: (Q1) How consistent are the recovered community profiles across replicate mock communities? ; (Q2) How does the choice of lysis buffer affect the recovery of the original community? ; (Q3) How are community estimates affected by differing lysis times and homogenization? ; and (Q4) Is it possible to obtain adequate species abundance estimates through the use of biological spike-ins? We show that estimates are quite variable across community replicates. In general, a mild lysis protocol is better at reconstructing species lists and approximate counts, while homogenization is better at retrieving biomass composition. Tiny insects are more likely to be detected in lysates, while some tough species require homogenization to be detected. Results are less consistent across biological replicates for lysates than for homogenates. Some species are associated with strong PCR amplification bias, which complicates the reconstruction of species counts. Yet, with adequate spike-in data, species abundance can be determined with roughly 40% standard error for homogenates, and with roughly 50% standard error for lysates, under ideal conditions. In the latter case, however, this often requires species-specific reference data, while spike-in data generalizes better across species for homogenates. We conclude that a non-destructive, mild lysis approach shows the highest promise for presence/absence description of the community, while also allowing future morphological or molecular work on the material. However, homogenization protocols perform better for characterizing community composition, in particular in terms of biomass.
Improved Outcomes in Patients Hospitalised with Community Associated Pneumonia: Can Established Warfarin Therapy Play a Role?

Community-Acquired Pneumonia (CAP) remains a common and serious infection in all developed countries. CAP remains associated with significant mortality. It has been suggested that adjunctive therapy, given in combination with antimicrobials, may improve CAP treatment outcomes. This observational study sought to identify factors associated with improved short-term outcome in adult patients hospitalised with radiologically-confirmed CAP in Malta. The influence of established warfarin treatment on outcome in this cohort of patients was also assessed. We retrospectively studied patients with radiologically diagnosed CAP requiring admission to the only tertiary care hospital in Malta over between 2011 and 2013. Ethical clearance was obtained. The radiological diagnosis was validated by the investigators using the hospital Picture Archiving and Communication System (PACS) system. Eligible patients needed to be at least 16 years old. Through logistic regression analysis, increased 30-day mortality was positively associated with increased CURB-65 scores between two and four, radiologically severe pneumonia, and increasing age. However, mortality was significantly reduced in patients taking warfarin on admission, independent of INR levels (OR 0.24, 95%CI: 0.11-0.52). This seemingly protective effect of warfarin, hypothetically through its influence on disturbed thrombin formation and alveolar fibrin deposition, merits further investigation in larger populations.
Critical Thinking and Clinical Judgment Skills for baccalaureate Nursing Students in EL-Minia University

, Abstract: Background: Critical thinking and clinical judgment in nursing has been accentuated in response to the rapidly changing health care environment. Nurses must think critically and clinically judgment to provide quality of care and coping with the expansion in role associated with the complexities of current health care systems. Aim of the study: to assess critical thinking and clinical judgment skills for baccalaureate nursing students in EL-Minia University. Methodology: The study was developed within descriptive approach. Setting: The study was carried out at Faculty of Nursing in EL-Minia University. Subject: All Baccalaureate nursing students at Faculty of Nursing in EL-Minia University in the academic year 2010/2011 with total number (n=105). Tools of study : The study tools were two the first tool for critical thinking consisted of two parts 1st part related to socio demographic characteristics sheet &2ndpart was the California Critical Thinking Disposition Inventory (CCTDI), Second tool for clinical judgment. Results: There were no statistically significant differences between demographic characteristics (sex& residence) with critical thinking and clinical judgment items . Conclusions: The rate of urban and male student nurses were had high level in the total score of critical thinking. Moreover , rate of rural and female student nurses were had middle to high level in the total score of clinical judgment. Recommendations: Attending of nursing teachers a training program about how to identifying teaching strategies needed and how to use these strategies in effective ways for the development of critical thinking and clinical judgment skills for nursing students.
Associação das sub-escalas de Braden com o risco do desenvolvimento de úlcera por pressão

Ulceras por pressao (UP) podem aumentar a incidencia de complicacoes hospitalares, devendo-se prevenir este dano. A Escala de Braden destaca-se como instrumento para avaliar o risco de UP. O estudo objetivou identificar quais alteracoes, na pontuacao das subescalas de Braden, estao associadas com o risco do desenvolvimento de UP. Empregou-se regressao logistica em uma coorte retrospectiva realizada no Hospital de Clinicas de Porto Alegre, em adultos hospitalizados em unidades clinicas e cirurgicas, de outubro de 2005 a junho de 2006. Foram avaliados os registros de banco de dados de 1503 pacientes, com idade de 55,5±16 anos, sendo 52,7% do sexo feminino. A incidencia de UP foi de 1,8%, e foi associada com diabetes e insuficiencia cardiaca. Houve mais UP em pacientes com pior percepcao sensorial, mobilidade, atividade e na presenca de umidade. Nao houve associacao entre nutricao e UP. Exceto nutricao, as demais subescalas de Braden mostraram-se preditivas de UP.
ON EQUITABLE ROUND-ROBIN TOURNAMENTS WITH MAXIMAL BREAK INTERVAL GREATER THAN OR EQUAL TO 5

In our earlier paper, we studied the mathematical structure of equitable round-robin tournaments with home-away assignments, and gave some necessary conditions for their feasibility in terms of friend-enemy tables and break interval sequences. We also enumerated all the feasible home-away tables of such tournaments satisfying both the opening and the closing conditions, up to 26 teams. In this paper, we study the maximal break interval of such tournaments. From this point of view, the tournaments satisfying both the opening and the closing conditions correspond to the case where the maximal break interval is greater than or equal to 4. The aim of this paper is to examine the case where the maximal break interval is greater than or equal to 5. We enumerate all the feasible cyclic break interval sequences of such tournaments, up to 42
The Causes of the Rentier State: A Comparative Study of Bolivia and Venezuela

2 TABLE OF CONTENTS.3 LIST OF TABLES AND FIGURES.5 CHAPTER ONE – INTRODUCTION.7 Background.7 Objective.9 Research question(s). 10 Introduction to methodology.11 Relevance.12 Overview of the thesis structure.13 CHAPTER TWO – LITERATURE REVIEW. 14 1. The definitions.14 2. The economic dimension.16 3. The political dimension.20 4. Empirical studies.28 5. Remarks.31 CHAPER THREE – THEORY.32 1. Features of a rentier state. 32 2. Factors causing a rentier state. 34 3. Remarks.36 4. Propositions.37 CHAPTER FOUR – METHODOLOGY.3 9 1. Research method.39 2. Case description.40
Uterine NK cells Unique Receptor Repertoire in Mouse

Uterine NK (uNK) cells are a prominent feature of the uterine mucosa and regulate placentation. NK cell activity is regulated by a balance of activating and inhibitory receptors, however the receptor repertoire of mouse uNK cells is unknown. We describe herein two distinct subsets of CD3 (cid:1) CD122 (cid:2) NK cells in the mouse uterus (comprising decidua and mesometrial lymphoid aggregate of pregnancy) at mid-gestation: a small subset indistinguishable from peripheral NK cells, and a larger subset that expresses NKp46 and Ly49 receptors, but not NK1.1 or DX5. This larger subset reacts with Dolichus biﬂores agglutinin, a marker of uNK cells in the mouse, and is adjacent to the invading trophoblast. By multiparametric analysis we show that the phenotype of uNK cells is unique and unprecedented in terms of adhesion, activation, and MHC binding potential. Thus, the Ly49 repertoire and the expression of other differentiation markers strikingly distinguish uNK cells from peripheral NK cells, suggesting that a selection process shapes the receptor repertoire of mouse uNK cells. The Journal of Immunology, 2008, 181: 6140–6147. early of pregnancy
14-3-3 Proteins Are Constituents of the Insoluble Glycoprotein Framework of the Chlamydomonas Cell Wall

The cell wall of the unicellular green alga Chlamydomonas reinhardtii consists predominantly of Hyp-rich glycoproteins, which also occur in the extracellular matrix of multicellular green algae and higher plants. In addition to the Hyp-rich polypeptides, the insoluble glycoprotein framework of the Chlamydomonas cell wall contains minor amounts of 14-3-3 proteins, as revealed by immunochemical studies and mass spectroscopic analysis of tryptic peptides. Polypeptides immunologically related to the 14-3-3 proteins also were found in the culture medium of Chlamydomonas. The levels of two of these 14-3-3–related polypeptides were decreased in the culture medium of the wall-deficient mutant cw-15 . These findings indicate that 14-3-3 proteins are involved in the cross-linking of Hyp-rich glycoproteins in the Chlamydomonas cell wall. mass spectrometer (Micromass, Manchester, UK) equipped with a nanoflow electrospray ionization source. Gold-coated glass capillary nanoflow needles were obtained from Protana (type Medium NanoES spray capillaries; Odense, Denmark). Database searches (NCBInr, non- redundant protein database) were performed using MASCOT software from Matrix Science (London, UK) (Perkins et al., 1999). Upon request, all novel materials described in this article will be made available in a timely manner for noncommercial research purposes.