Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of Mph1 kinase and its substrates in spindle checkpoint signalling

VI Chapter 1: Introduction 1 1.1 General Introduction 1 1.2 Fission yeast 2 1.3 The cell cycle 2 1.3.1 Fission yeast cell cycle 4 1.4 Mitosis 7 1.5 Regulation of the cell cycle by controlled proteolysis 7 1.5.1 The proteasome 7 1.5.2 E3 ubiquitin ligases 8 1.5.2.1 SCF complex 8 1.5.2.2 Anaphase promoting complex 9 1.5.2.2.1 Overview 9 1.5.2.2.2 Composition of the APC 10 1.5.2.2. 3 APC activators 12 1.5.2.2. 4 Substrate recognition by the APC 13 1.5.2.2. 5 Regulation of the APC 14 1.5.2.2. 5.1 Phosphorylation of the APC 14 1.6 Cell cycle checkpoints 15 1.6. 1 DNA damage checkpoint 15 1.6. 2 Mitotic Checkpoints 16 1.6. 2.1 The spindle checkpoint 16 1.6. 2.1.1 Overview 16 1.6. 2.1.2 The spindle checkpoint and disease 18 1.6. 2.1.3 The core spindle checkpoint components 19 1.6. 2.1.3.1 The kinase Mps1 19 1.6. 2.1.3.2 Mad1 24 1.6. 2.1.3.3 Mad2 25 1.6. 2.1.3.4 Mad3/BubR1 28 1.6. 2.1.3.5 The kinase Bub1 31 1.6. 2.1.3.6 Bub3 34 1.6. 2.1.4 Additional checkpoint proteins 35 1.6. 2.1.4.1 Rod, Zw10 and Zwilch 35 1.6. 2.1.4.2 Aurora kinase 35 1.6. 2.1.5 APC inhibition upon activation of the spindle checkpoint 37 1.6. 2.1.5.1 Phosphorylation of Cdc20 38 1.6. 2.1.5.2 Cdc20 ubiquitination 39 1.6. 2.1.5.3 Cdc20 sequestration and MCC binding to the APC 40 1.6. 2.1.6 The role of the kinetochores in spindle checkpoint signalling 42 1.6. 2.1. 7 Spindle checkpoint silencing 44
Structure and function of the olfactory bulb microcircuit

The aim of this study is to contribute to understand the physiology of the Olfactory System through detailed microcircuit investigation, adopting advanced electrophysiological and anatomical techniques. Multiple patch clamp recordings allow understanding the structural foundations supporting the network architecture, the biophysical rules adopted by the microcircuit connectivity and the fine dynamic of the synaptic transmission. The study focuses on the Olfactory Bulb microcircuit as a first neuronal processor of sensory inputs. The excitatory elements of the Olfactory Bulb microcircuit are anatomically defined by affiliation to the same receptive field: the Glomerulus. A correlated subthreshold activity between microcircuit elements defines the physiological signature of the microcircuit. We experimentally addressed three fundamental issues: origin of the correlated subthreshold activity, connectivity rules and dynamic of the synaptic transmission. In the first study we attribute the origin of correlated subthreshold activity to a class of pacemaker cells responsible for the synchronization of the population onset and acting therefore as a timer of the microcircuit response. In the second study we investigated the connectivity rules supporting the interaction between excitatory cells. The tight apposition between gap junctions and chemical synapses on the excitatory cells dendrites allows gap junctions to propagate postsynaptic potentials toward surrounding compartments. The result of the propagation is represented by an enhancement in the amplification of the sensory information and an increase in the speed of the reaction time. In the third study we extensively analyzed the mechanisms of the synaptic transmission and the activity dependent properties of synapses, revealing a potential role for the short-term plasticity in the development of the sensory processing. The results of our investigation are going to constitute the foundation of a database available for high definition multi-compartmental modeling of the Olfactory Bulb network.
Photosynthetic response of three aquatic species of Schoenoplectus (Reichenb.) Palla under salt stress

The experiment was conducted to evaluate physiological and anatomical modification in response to sat tolerance three halophytic species of Schoenoplectus (Reichenb.) Palla. Plants were collected from three different sites were grown in non-aerated hydroponic conditions. Four levels of NaCl, 0, 100, 200 and 300 mM, were maintained in solution culture to investigate the response of growth and photosynthesis to salt stress. Schoenoplectus triqueter showed optimal growth at 100 mM NaCl and better photosynthetic response to salt stress than that recorded in the other two species (S. lacustris and S. juncoides). Net CO2 assimilation rate (A) of S. juncoides remained unaffected up to 200 mM NaCl, but thereafter at 300 mM NaCl it decreased drastically. In contrast, in S. triqueter, CO2 assimilation was found to be stimulated at 100 and 200 mM NaCl, whereas such stimulation in net CO2 assimilation in S. lacustris was found only at 100 mM NaCl. Transpiration rate decreased in S. lacustris and S. triqueter with increasing salt stress, whereas in S. juncoides it increased at all salt levels. Stomatal conductance decreased in all three species at 300 mM in. Water use efficiency (WUE=A/E) in S. triqueter increased with increase in external salt concentration of the three Schoenoplectus species. Schoenoplectus triqueter was more efficient in controlling stomatal movement. The dominant anatomical traits related to S. triqueter (the most tolerant among all species) were found to be stomatal size, shape, and density, high water use efficiency, low transpiration rate, and low reduction in photosynthetic rate and chlorophyll pigments. Moreover, stomata were oriented in distinct grooves.
An introduction to domain decomposition methods - algorithms, theory, and parallel implementation

The purpose of this book is to offer an overview of the most popular domain decomposition methods for partial differential equations (PDEs). These methods are widely used for numerical simulations in solid mechanics, electromagnetism, flow in porous media, etc., on parallel machines from tens to hundreds of thousands of cores. The appealing feature of domain decomposition methods is that, contrary to direct methods, they are naturally parallel. The authors focus on parallel linear solvers. The authors present all popular algorithms, both at the PDE level and at the discrete level in terms of matrices, along with systematic scripts for sequential implementation in a free open-source finite element package as well as some parallel scripts. Also included is a new coarse space construction (two-level method) that adapts to highly heterogeneous problems. Audience: This book is intended for those working in domain decomposition methods, parallel computing, and iterative methods, in particular those who need to implement parallel solvers for PDEs. It will also be of interest to mechanical, civil, and aeronautical engineers, physical and environmental scientists, and physicists in need of parallel PDE solvers.
Epidemiology of human intestinal parasites in Qwa-Qwa, South Africa.

This study investigated the prevalences and intensity of intestinal parasites and aspects of their epidemiology among children in the Qwa-Qwa region of the eastern Free St~te. Faecal samples of 1180 children differing socio-economic status from nine schools at altitudes varying from 1660m to 2200m were examined quantitatively by means of the formol-ether sedimentation technique. Socio-economic, and demographic characteristics for the communities served by the schools were obtained from the literature and from a questionnaire. The study showed that, the area supports a markedly low diversity of parasite infections, and at lower intensities, than lowaltitude areas such as the coastal plain of KwaZulu-Natal and Eastern Cape, the Northern Province, Mpumalanga and the Western Cape. The intestinal parasite fauna affecting children in Qwa-Qwa is dominated by protozoans with only few helminths and no hookworm or bilharzia. The results indicated that factors which influence the transmission of intestinal parasites in Qwa-Qwa appear to be related primarily to social, economic and cultural aspects of the peoples' lifestyles. Climatic factors were not found important. There was a significant seasonal effect on the intensities of all parasite infection, except two protozoans, Entamoeba coli and Endolimax nana.
Diurnal defecation rate of moose in southwest Finland.

An accurate measure of defecation rate is essential for application of pellet group counts in moose (Alces alces) population estimates. We measured the wintertime, diurnal defecation rate of moose by tracking 7 GPS-collared and 22 uncollared moose in southwest Finland. The mean defeca- tion rate was 23.5 ± 4.2 pellet groups/d, one of the highest values reported. The mean defecation rate did not differ between the tracking methods (GPS vs. uncollared moose); limited sample size pre- cluded conclusions about sex and age differences. The defecation rate was not correlated with calendar week, length of accumulation period, or number of diurnal beds. Our results are appropriate for use in southwest Finland when using the pellet group method to assess moose population density. ALCES VOL. 49: 155-161 (2013)
Judgments of marital rape as a function of honor culture, masculine reputation threat, and observer gender: A cross‐cultural comparison between Turkey, Germany, and the UK

Abstract Previous research has shown that there is higher tolerance of violence against women in cultures with salient gender‐specific honor norms, especially when the violence occurs in intimate relationships and in response to threat to male honor. The present cross‐cultural study (N = 398) extended these findings to sexual aggression (i.e., marital rape) by comparing participants from a culture that emphasizes honor (Turkey) and participants from cultures without strong honor traditions (Germany and Britain). Turkish participants blamed the victim and exonerated the perpetrator more than did German and British participants. In all cultural groups, participants blamed the victim and exonerated the perpetrator more when the husband's reputation was threatened than in the absence of such threat, and in all cultural groups, men blamed the victim and exonerated the perpetrator more than women. Yet, the effect of masculine reputation threat and this pattern of gender differences were somewhat more pronounced among Turkish than German or British participants. Results exploring the predictive role of honor norms at the individual level beyond rape myth acceptance and traditional gender role attitudes revealed that honor norms were the primary predictor of rape perceptions and blame attributions in Turkey (an honor culture), but not in Germany and Britain (dignity cultures) where rape myth acceptance was the strongest predictor. These results provide insights into the cultural factors influencing marital rape judgments in ways that may undermine victim's well‐being and fair handling of rape cases, and highlight the domains most urgently in need of potential intervention.
Microsatellite analysis of population structure in Slovak Pinzgau cattle

The aim of the study was improve knowledge about population structure of Slovak Pinzgau cattle using genetic markers. Observed population structure was characterized by use of eight microsatellites. Each locus was tested for deviations from the Hardy-Weinberg Equilibrium (HWE). In general, breed was in genetic equilibrium, only locus BM1824 deviated from HWE. Cluster algorithms identify groups of related individuals without reference to prior information of the genetic subdivision. We considered 3 clusters that capture the major structure of the data (representative K value) and most likely reflect genealogical structuring. The chosen set of microsatellites confirmed the suitability for genetic structure assessment and its usefulness in determination of the subpopulations for Pinzgau cattle in Slovakia.
Analysis of Feature Extraction Methods for Prediction of 30-Day Hospital Readmissions

Abstract Objectives This article aims to determine possible improvements made by feature extraction methods to the machine learning prediction methods for predicting 30-day hospital readmissions. Methods The study evaluates five feature extraction methods including principal component analysis (PCA), kernel principal component analysis (KPCA), isomap, Laplacian eigenmaps, and locality preserving projections (LPPs) for improving the accuracy of nine machine learning prediction methods in predicting 30-day hospital readmissions. The specific prediction methods considered include logistic regression, Cox regression, linear discriminant analysis, k-nearest neighbor (KNN), support vector machines (SVMs), bagged trees, boosted trees, random forest, and artificial neural networks. All models are developed in MATLAB and validated using area under the curve based on two population-based data sets from partner hospitals. Results Laplacian eigenmaps and isomap feature extraction provide the most improvement to the readmission predictive accuracy of KNN, SVM, bagged trees, boosted trees, and linear discriminant analysis methods. The results for artificial neural networks, random forest, Cox regression, and logistic regression show improvement for only one of the data sets. Also, PCA and LPP provided the best computation efficiency followed by KPCA, Laplacian eigenmaps, and isomap. Conclusion Feature extraction methods can improve the predictive performance of machine learning methods for predicting readmissions. However, the improvement depended on the specific choice of the prediction method, feature extraction method, and the complexity of the data set features.
The Transcriptional Regulation of Stem Cell Differentiation Programs by Hedgehog Signalling

The Hedgehog (Hh) signalling pathway is one of the key signalling pathways orchestrating intricate organogenesis, including the development of neural tube, heart and skeletal muscle. Yet, insufficient mechanistic understanding of its diverse roles is available. Here, we show the molecular mechanisms regulating the neurogenic, cardiogenic and myogenic properties of Hh signalling, via effector protein Gli2, in embryonic and adult stem cells. In Chapter 2, we show that Gli2 induces neurogenesis, whereas a dominant-negative form of Gli2 delays neurogenesis in P19 embryonal carcinoma (EC) cells, a mouse embryonic stem (ES) cell model. Furthermore, we demonstrate that Gli2 associates with Ascl1/Mash1 gene elements in differentiating P19 cells and activates the Ascl1/Mash1 promoter in vitro. Thus, Gli2 mediates neurogenesis in P19 cells at least in part by directly regulating Ascl1/Mash1 expression. In Chapter 3, we demonstrate that Gli2 and MEF2C bind each other’s regulatory elements and regulate each other’s expression while enhancing cardiomyogenesis in P19 cells. Furthermore, dominant-negative Gli2 and MEF2C proteins downregulate each other’s expression while imparing cardiomyogenesis. Lastly, we show that Gli2 and MEF2C form a protein complex, which synergistically activates cardiac muscle related promoters. In Chapter 4, we illustrate that Gli2 associates with MyoD gene elements while enhancing skeletal myogenesis in P19 cells and activates the MyoD promoter in vitro. Furthermore, inhibition of Hh signalling in muscle satellite cells and in proliferating myoblasts leads to reduction in MyoD and MEF2C expression. Finally, we demonstrate that endogenous Hh signalling is important for MyoD transcriptional activity and that Gli2, MEF2C and MyoD form a protein complex capable of inducing skeletal muscle-specific gene expression. Thus, Gli2, MEF2C and MyoD participate in a regulatory loop and form a protein complex capable of inducing skeletal muscle-specific gene expression. Our results provide a link between the regulation of tissue-restricted factors like Mash1, MEF2C and MyoD, and a general signal-regulated Gli2 transcription factor. We therefore provide novel mechanistic insights into the neurogenic, cardiogenic and myogenic properties of Gli2 in vitro, and offer novel plausible explanations for its in vivo functions. These results may also be important for the development of stem cell therapy strategies.
Mixed convection in a lid-driven cavity : Appearance of bifurcation, periodicity and hysteresis

Mixed convection in a rectangular parallelepiped has been studied by solving the Navier-Stokes and the energy equations. The convective motion may show a time periodic behaviour for certain combinations of the parameters, even though the boundary conditions are steady. Further, certain features of dynamical systems like bifurcation, hysteresis and period doubling are also seen
The relationship between pancreas steatosis and the risk of metabolic syndrome and insulin resistance in Chinese adolescents with concurrent obesity and non‐alcoholic fatty liver disease

Summary Background The incidence of childhood obesity and associated comorbidities are on an increasing trend worldwide. More than 340 million children and adolescents aged between 5 and 19 years old were overweight or had obesity in 2016, from which over 124 million children and adolescents (6% of girls and 8% of boys) had obesity. Objective To describe the relationship between pancreas steatosis, body fat and the risk of metabolic syndrome, insulin resistance in Hong Kong Chinese adolescents with both obesity and non‐alcoholic fatty liver disease (NAFLD). Methods Fifty two adolescents with obesity and NAFLD were analysed (14‐18 years), stratified into fatty and non‐fatty pancreas groups using chemical shift encoded MRI‐pancreas proton density fat fraction ≥5%. Pancreatic, abdominal subcutaneous adipose tissue (SAT)/visceral adipose tissue (VAT) volumes, biochemical and anthropometric parameters were measured. Mann‐Whitney U test, multiple linear/binary logistic regression analyses and odds ratios were used. Results Fifty percent had fatty pancreas, 38% had metabolic syndrome and 81% had insulin resistance. Liver proton density fat fraction (PDFF) and VAT were independent predictors of insulin resistance (P = .006, .016). Pancreas and liver PDFF were both independent predictors of beta cells dysfunction (P = .015, .050) and metabolic syndrome (P = .021, .041). Presence of fatty pancreas in obesity was associated with insulin resistance (OR = 1.58, 95% CI = 0.39‐6.4) and metabolic syndrome (OR = 1.70, 95% CI = 0.53‐5.5). Conclusion A significant causal relationship exists between fatty pancreas, fatty liver, body fat and the risk of developing metabolic syndrome and insulin resistance. Key Points Fatty pancreas is a common finding in adolescents with obesity, with a prevalence rate of 50% in this study cohort. Liver PDFF and VAT are independent predictors of insulin resistance while pancreas PDFF and liver PDFF are independent predictors of both beta cells dysfunction and metabolic syndrome. Presence of fatty pancreas at imaging should not be considered as a benign finding but rather as an imaging biomarker of emerging pancreatic metabolic and endocrine dysfunction.
Functional Proteomics: Mapping Lipid-Protein Interactomes

Cell function is dependent upon the co-ordinated and dynamic formation of complex interaction networks between molecules of diverse biochemical properties. These networks, or interactomes, are comprised of macromolecular biopolymers; proteins, DNA, RNA and polysaccharides, in addition to non-polymer compounds such as small molecular metabolites. This myriad of interactions is highly regulated and any perturbation or alteration has potential to result in disease. Profiling protein-protein interactions has been the major focus of interactomics in the past few years (Charbonnier et al. 2008) largely due to the advances in technological platforms that have the capacity to probe globally. Early efforts have included two-hybrid screens to identify binary binding interactions; more recent studies have used a range of mass spectrometry based methods to identify protein complexes that are a better reflection of multi-interactive nature of such complexes. Protein/small molecule interactions are equally important in modulating the function of their target proteins but few studies have analyzed these interactions on a large scale. The field is indeed still in its infancy due to difficulties in identifying metabolites but has recently benefitted from technological advances in mass spectrometry, data analysis software and metabolites database development for the measurement and identification of metabolites. The next step is to integrate metabolomic profiling to functional characterization of metabolic pathways by identifying systematically metabolite-protein interactions. Research efforts have in general been more focused on lipid-mediated interactions and this chapter reviews the global methods as well as their applications used to map lipid-protein interactomes based on mass spectrometry or arrays. The potential of these studies to deepen our understanding on the biological function of metabolites as protein effectors is also discussed.
Denver and Marshall scores successfully predict susceptibility to multiple independent infections in trauma patients

Trauma patients are at risk of repeated hospital-acquired infections, however predictive scores aiming to identify susceptibility to such infections are lacking. The objective of this study was to investigate whether commonly employed disease-severity scores can successfully predict susceptibility to multiple independent infectious episodes (MIIEs) among trauma patients. A secondary analysis of data derived from the prospective, longitudinal study “Inflammation and the Host Response to Injury” (“Glue Grant”) was performed. 1,665 trauma patients, older than 16, were included. Patients who died within seven days from the time of injury were excluded. Five commonly used disease-severity scores [Denver, Marshall, Acute Physiology and Chronic Health Evaluation II (APACHE II), Injury Severity Score (ISS), and New Injury Severity Score (NISS)] were examined as independent predictors of susceptibility to MIIEs. The latter was defined as two or more independent infectious episodes during the index hospital stay. Multivariable logistic regression was used for the statistical analysis. 22.58% of the population was found to be susceptible to MIIEs. Denver and Marshall scores were highly predictive of the MIIE status. For every 1-unit increase in the Denver or the Marshall score, there was a respective 15% (Odds Ratio:1.15; 95% CI: 1.07–1.24; p < 0.001) or 16% (Odds Ratio:1.16; 95% CI: 1.09–1.24; p < 0.001) increase in the odds of MIIE occurrence. APACHE II, ISS, and NISS were not independent predictors of susceptibility to MIIEs. In conclusion, the Denver and Marshall scores can reliably predict which trauma patients are prone to MIIEs, prior to any clinical sign of infection. Early identification of these individuals would potentially allow the implementation of rapid, personalized, preventative measures, thus improving patient outcomes and reducing healthcare costs.
Determinants of Active and Healthy Ageing in Sub-Saharan Africa: Evidence from Cameroon

This paper examines the determinants and policy implications of active and healthy ageing in Sub-Saharan Africa, taking the case of Bamenda, in Cameroon. Specifically, the study sought to identify and explore the determinants of active and healthy ageing using a mixed-methods approach involving qualitative and quantitative data collection and analysis. Focus group discussions were conducted complemented by a survey (random and snowball sampling) using a structured questionnaire. Narratives and thematic analysis were used to analyze the data generated from the focus group discussion and Tobit regression was employed to analyze the multiple determinants of active ageing by dimensions and on a global scale in Cameroon. Results identified three key dimensions of active and healthy ageing: employment/livelihood options (EL), community support and health (CH) and housing and living in Bamenda (HL). The regression results reveal gender bias in active ageing, a non-effect of education and health on active ageing, and a positive effect of income on active and healthy ageing. This study contributes, among others, to the competence–environmental press theory on active ageing with regards to unbundling context specific determinants of active and healthy ageing. It equally derives policy considerations with regards to gender mainstreaming and the identification of age friendly income earning options to enhance the active and healthy ageing process.