Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction of Signaling Lymphocytic Activation Molecule Family 1 (SLAMF1) receptor with Trypanosoma cruzi is strain-dependent and affects NADPH oxidase expression and activity

The receptor Signaling Lymphocyte-Activation Molecule Family 1 (SLAMF1) controls susceptibility to Infection by the lethal Trypanosoma cruzi Y strain. To elucidate whether genetic diversity of the parasite was related with disease susceptibility, we further analyzed the role of SLAMF1 using 6 different Trypanosoma cruzi strains including Y. The interaction of SLAMF1 receptor with T. cruzi was evidenced by fluorescence microscopy, flow cytometry and quantitative PCR. All the strains, except VFRA, showed a decrease in parasite load in infected macrophages in Slamf1-/- compared to BALB/c. In macrophages gene expression NADPH oxidase (NOX2), and reactive oxygen species (ROS) production increased in Slamf1-/- compared to BALB/c in 5 out of 6 strains. However, Slamf1-/-macrophages infected with VFRA strain exhibited a divergent behavior, with higher parasite load, lower NOX2 expression and ROS production compared to BALB/c. Parasitological and immunological studies in vivo with Y strain showed that in the absence of SLAMF1 the immune response protected mice from the otherwise lethal Y infection favoring a proinflammatory response likely involving CD4, CD8, dendritic cells and classically activated macrophages. In the case of VFRA, no major changes were observed in the absence of SLAMF1. Thus, the results suggest that the T. cruzi affects SLAMF1-dependent ROS production, controlling parasite replication in macrophages and affecting survival in mice in a strain-dependent manner. Further studies will focus in the identification of parasite molecules involved in SLAMF1 interaction to explain the immunopathogenesis of the disease.
New insights regarding SNARE proteins in autophagosome-lysosome fusion

ABSTRACT Macroautophagy/autophagy refers to the engulfment of cellular contents selected for lysosomal degradation. The final step in autophagy is the fusion of autophagosome with the lysosome, which is mediated by SNARE proteins. Of the SNAREs, autophagosome-localized Q-SNAREs, such as STX17 and SNAP29, and lysosome-localized R-SNAREs, such as VAMP8 or VAMP7, have been reported to be involved. Recent studies also reveal participation of the R-SNARE, YKT6, in autophagosome-lysosome fusion. These SNAREs, with the help of other regulatory factors, act coordinately to spatiotemporally control the fusion process. Besides regulating autophagosome-lysosome fusion, some SNAREs, such as STX17, also function in other autophagic processes, including autophagosome formation and mitophagy. A better understanding of the functions of SNAREs will shed light on the molecular mechanisms of autophagosome-lysosome fusion as well as on the mechanisms by which autophagy is globally regulated. Abbreviations: ATG: autophagy related; DNM1L: dynamin 1 like; ER: endoplasmic reticulum; GABARAP: GABA type A receptor-associated protein; GABARAPL1: GABA type A receptor associated protein like 1; IRGM: immunity related GTPase M; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; PIK3R4: phosphoinositide-3-kinase regulatory subunit 4; PLEKHM1: pleckstrin homology and RUN domain containing M1; PRKN: PRKN RBR E3 ubiquitin protein ligase; RAB2A: RAB2A, member RAS oncogene family; RAB33B: RAB33B, member RAS oncogene family; RAB7A: RAB7A, member RAS oncogene family; RB1CC1: RB1 inducible coiled-coil 1; RTN3: reticulon 3; RUBCNL: rubicon like autophagy enhancer; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SNAP29: synaptosomal associated protein 29; STX17: syntaxin 17; ULK1: unc-51 like autophagy activating kinase 1; VAMP7: vesicle associated membrane protein 7; VAMP8: vesicle associated membrane protein 8; YKT6: YKT6 v-SNARE homolog
In vivo synthesis of monolysocardiolipin and cardiolipin by Acinetobacter baumannii phospholipase D and effect on cationic antimicrobial peptide resistance.

Acinetobacter baumannii is an opportunistic pathogen which has become a rising threat in healthcare facilities worldwide due to increasing antibiotic resistances and optimal adaptation to clinical environments and the human host. We reported in a former publication on the identification of three phopholipases of the phospholipase D (PLD) superfamily in A. baumannii ATCC 19606T acting in concerted manner as virulence factors in Galleria mellonella infection and lung epithelial cell invasion. This study focussed on the function of the three PLDs. A Δpld1-3 mutant was defect in biosynthesis of the phospholipids cardiolipin (CL) and monolysocardiolipin (MLCL) whereas the deletion of pld2 and pld3 abolished the production of MLCL. Complementation of the Δpld1-3 mutant with pld1 restored CL biosynthesis demonstrating that the PLD1 is implicated in CL biosynthesis. Complementation of the Δpld1-3 mutant with either pld2 or pld3 restored MLCL and CL production leading to the conclusion that PLD2 and PLD3 are implicated in CL and MLCL production. Mutant studies revealed that two catalytic motifs are essential for the PLD3 mediated biosynthesis of CL and MLCL. The Δpld1-3 mutant exhibited a decreased colistin and polymyxin B resistance indicting a role of CL in cationic antimicrobial peptides (CAMPs) resistance. This article is protected by copyright. All rights reserved.
Multiobjective Particle Swarm Optimization for Feature Selection With Fuzzy Cost

Feature selection (FS) is an important data processing technique in the field of machine learning. There have been various FS methods, but all assume that the cost associated with a feature is precise, which restricts their real applications. Focusing on the FS problem with fuzzy cost, a fuzzy multiobjective FS method with particle swarm optimization, called PSOMOFS, is studied in this article. The proposed method develops a fuzzy dominance relationship to compare the goodness of candidate particles and defines a fuzzy crowding distance measure to prune the elitist archive and determine the global leader of particles. Also, a tolerance coefficient is introduced into the proposed method to ensure that the Pareto-optimal solutions obtained satisfy decision makers’ preferences. The developed method is used to tackle a series of the UCI datasets and is compared with three fuzzy multiobjective evolutionary methods and three typical multiobjective FS methods. Experimental results show that the proposed method can achieve feature sets with superior performances in approximation, diversity, and feature cost.
Dengue Virus Infection of Aedes aegypti Alters Extracellular Vesicle Protein Cargo to Enhance Virus Transmission

Dengue is the most burdensome vector-borne viral disease in the world. Dengue virus (DENV), the etiological cause of dengue, is transmitted primarily by the Aedes aegypti mosquito. Like any arbovirus, the transmission cycle of dengue involves the complex interactions of a multitude of human and mosquito factors. One point during this transmission cycle that is rich in these interactions is the biting event by the mosquito, upon which its saliva is injected into the host. A number of components in mosquito saliva have been shown to play a pivotal role in the transmission of dengue, however one such component that is not as well characterized is extracellular vesicles. Here, using high-performance liquid chromatography in tandem with mass spectrometry, we show that dengue infection altered the protein cargo of Aedes aegypti extracellular vesicles, resulting in the packaging of proteins with infection-enhancing ability. Our results support the presence of an infection-dependent pro-viral protein packaging strategy that uses the differential packaging of pro-viral proteins in extracellular vesicles of Ae. aegypti saliva to promote transmission. These studies represent the first investigation into the function of Ae. aegypti extracellular vesicle cargo during dengue infection.
A note on the iterative solution of weakly nonlinear elliptic control problems with control and state constraints

This work concerns with the solution of optimal control problems by means of nonlinear programming methods. The control problem is transcribed into a finite dimensional nonlinear programming problem by finite difference approximation. An iterative procedure for the solution of this nonlinear program is presented. An extensive numerical analysis of the behaviour of the method is reported on boundary control and distributed control problems with boundary conditions of Dirichlet or Neumann or mixed type. 1 Reaction-diffusion problems When the physical system under consideration involves a reaction process accompanied by diffusion, the physical principle of conservation leads to a set of partial differential equations for the unknown quantities of the system. These quantities may be mass concentration in chemical reaction processes, temperature in heat conduction, neutron flux in nuclear reactors, population density in population dynamics, and many others. In certain problems of physical and engineering sciences, a combination of these quantities is involved in a set of equations. The reaction–diffusion equation with convection has the form ∂φ ∂t − div(σgradφ) + v · gradφ+ αφ+ g(x, t, φ) = 0 (1) where φ = φ(x, t) is the density function at time t and position x in a diffusion medium R, σ = σ(x, t) is the diffusion coefficient, α = α(x, t) is the absorption term, v and is the velocity vector and −g(x, t, φ(x, t)) is the rate of change due to a reaction. When the physical system involves two or more density functions φ1, φ2, . , φr, the reaction–diffusion processes is described by a set of equations of the form ∂φi ∂t − div(σigradφi) + vi · gradφi + αiφi + gi(x, t, φ1, φ2, ., φr) = 0 i = 1, . , r (2) and σi(x, t), αi(x, t) and vi are the terms referred to φi(x, t). ∗This research was supported by the Italian Ministry of Education and Research (MIUR) project: PRIN–2006 n. 2006018748. This work was presented at 22nd Biennial Conference on Numerical Analysis ”NA07”, Dundee, June 26–29, 2007. 1 Quaderni del Dipartimento di Matematica, Università di Modena e Reggio Emilia, n. 79, October 2007. The multigroup diffusion approximation to the Boltzmann’s transport equation leads to the coupled system (2) with gi(x, t, φ1, ., φr) = r
TOWARDS WORD SENSE DISAMBIGUATION USING MULTIPLE KERNEL SUPPORT VECTOR MACHINE

Word sense disambiguation (WSD), the task of identifying the intended meanings (senses) of words in context, has been a long-standing research objective for natural language processing (NLP). In this paper, we investigate the problem of combining multiple feature channels using kernel methods for the purpose of eﬀective WSD. A straightforward method is to use a uniform combination of more adequate kernels, which are built from diﬀerent types of data representations or knowledge sources. Instead of using an equal weight for all kernels in the combination, we consider the problem of integrating multiple feature channels using the state-of-the-art multiple kernel learning (MKL) approach, which can learn diﬀerent weights that reﬂect the diﬀerent importance of the feature channels for disambiguation. This approach has the advantage of the possibility to combine and select the more relevant feature channels in an elegant way. Combined with the support vector machine (SVM), this approach is demonstrated with several Senseval/Semeval disambiguation tasks.
Impact of HVAC-Systems on the Dispersion of Infectious Aerosols in a Cardiac Intensive Care Unit

At the end of 2019, a variation of a coronavirus, named SARS-CoV-2, has been identified as being responsible for a respiratory illness disease (COVID-19). Since ventilation is an important factor that influences airborne transmission, we proposed to study the impact of heating, ventilation and air-conditioning (HVAC) with a variable air volume (VAV) primary air system, on the dispersion of infectious aerosols, in a cardiac intensive care unit, using a transient simulation with computational fluid dynamics (CFD), based on the finite element method (FEM). We analyzed three scenarios that followed the dispersion of pathogen carrying expiratory droplets particles from coughing, from patients possibly infected with COVID-19, depending on the location of the patients in the intensive care unit. Our study provides the mechanism for spread of infectious aerosols, and possibly of COVID-19 infection, by air conditioning systems and also highlights important recommendations for disease control and optimization of ventilation in intensive care units, by increasing the use of outdoor air and the rate of air change, decreasing the recirculation of air and using high-efficiency particulate air (HEPA) filters. The CFD-FEM simulation approach that was applied in our study could also be extended to other targets, such as public transport, theaters, philharmonics and amphitheaters from educational units.
A new malaria vector in Africa: Predicting the expansion range of Anopheles stephensi and identifying the urban populations at risk

Significance In 2012, an unusual outbreak of malaria occurred in Djibouti City followed by increasingly severe annual outbreaks. Investigations revealed the presence of an Asian mosquito species; Anopheles stephensi, which thrives in urban environments. An. stephensi has since been identified in Ethiopia and Sudan. By combining data for An. stephensi across its full range (Asia, Arabian Peninsula, Horn of Africa) with spatial models that identify the species’ preferred habitat, we provide evidence-based maps predicting the possible African locations where An. stephensi could establish if allowed to spread. Our results suggest over 126 million people in cities across Africa could be at risk. This supports the WHO’s call for targeted An. stephensi control and prioritized surveillance. In 2012, an unusual outbreak of urban malaria was reported from Djibouti City in the Horn of Africa and increasingly severe outbreaks have been reported annually ever since. Subsequent investigations discovered the presence of an Asian mosquito species; Anopheles stephensi, a species known to thrive in urban environments. Since that first report, An. stephensi has been identified in Ethiopia and Sudan, and this worrying development has prompted the World Health Organization (WHO) to publish a vector alert calling for active mosquito surveillance in the region. Using an up-to-date database of published locational records for An. stephensi across its full range (Asia, Arabian Peninsula, Horn of Africa) and a set of spatial models that identify the environmental conditions that characterize a species’ preferred habitat, we provide evidence-based maps predicting the possible locations across Africa where An. stephensi could establish if allowed to spread unchecked. Unsurprisingly, due to this species’ close association with man-made habitats, our maps predict a high probability of presence within many urban cities across Africa where our estimates suggest that over 126 million people reside. Our results strongly support the WHO’s call for surveillance and targeted vector control and provide a basis for the prioritization of surveillance.
TIRF Microscopy‐Based Monitoring of Drug Permeation Across a Lipid Membrane Supported on Mesoporous Silica

Abstract There is an urgent demand for analytic approaches that enable precise and representative quantification of the transport of biologically active compounds across cellular membranes. In this study, we established a new means to monitor membrane permeation kinetics, using total internal reflection fluorescence microscopy confined to a ≈500 nm thick mesoporous silica substrate, positioned underneath a planar supported cell membrane mimic. This way, we demonstrate spatiotemporally resolved membrane permeation kinetics of a small‐molecule model drug, felodipine, while simultaneously controlling the integrity of, and monitoring the drug binding to, the cell membrane mimic. By contrasting the permeation behaviour of pure felodipine with felodipine coupled to the permeability enhancer caprylate (C8), we provide evidence for C8‐facilitated transport across lipid membranes, thus validating the potential for this approach to successfully quantify carrier system‐induced changes to cellular membrane permeation.
Fluid Intake and Urinary Symptoms in Patients with Multiple Sclerosis.

PURPOSE The relationship between fluid intake and lower urinary tract symptoms (LUTS) in individuals with neurogenic bladder is unknown. We aimed to investigate the association between fluid intake and urinary symptoms in patients with multiple sclerosis (MS). MATERIALS AND METHODS A prospective cross-sectional study of patients with multiple sclerosis presenting to the neurology office was conducted. Fluid intake and LUTS were assessed by the Questionnaire Based Voiding Diary and the American Urological Association Symptom Score, respectively. The relationship between fluid intake and LUTS was assessed using univariate and multivariate analysis. RESULTS Among 200 individuals with multiple sclerosis, the mean total daily fluid intake was 2489 ml (SD 1883) and did not differ according to severity (i.e. mild, moderate, severe) of LUTS (F=0.30, p=0.74). Fluid restricting behavior to control urinary symptoms was reported by 47% of subjects. Subjects who reported fluid restricting were more likely to have worse urinary symptoms (OR 1.95, 95%CI 1.53-2.47, p<0.01). After accounting for fluid restricting behavior on multivariate analysis, there was a minimal relationship between caffeinated fluid intake and LUTS severity (OR 1.00 95%CI 1.00-1.01, p=0.01), and there was no relationship between total fluid intake and LUTS severity (OR 1.00 95%CI 1.00-1.00, p=0.07). CONCLUSIONS Caffeinated fluid intake has a minimal effect on LUTS in patients with MS. On average, patients with MS do not excessively hydrate, and a considerable proportion of patients with MS restrict fluid intake to control their urinary symptoms. Fluid intake may not considerably contribute to LUTS in patients with MS.
Using High-Content Screening to Generate Single-Cell Gene-Corrected Patient-Derived iPS Clones Reveals Excess Alpha-Synuclein with Familial Parkinson’s Disease Point Mutation A30P

The generation of isogenic induced pluripotent stem cell (iPSC) lines using CRISPR-Cas9 technology is a technically challenging, time-consuming process with variable efficiency. Here we use fluorescence-activated cell sorting (FACS) to sort biallelic CRISPR-Cas9 edited single-cell iPSC clones into high-throughput 96-well microtiter plates. We used high-content screening (HCS) technology and generated an in-house developed algorithm to select the correctly edited isogenic clones for continued expansion and validation. In our model we have gene-corrected the iPSCs of a Parkinson’s disease (PD) patient carrying the autosomal dominantly inherited heterozygous c.88G>C mutation in the SNCA gene, which leads to the pathogenic p.A30P form of the alpha-synuclein protein. Undertaking a PCR restriction-digest mediated clonal selection strategy prior to sequencing, we were able to post-sort validate each isogenic clone using a quadruple screening strategy prior to generating footprint-free isogenic iPSC lines, retaining a normal molecular karyotype, pluripotency and three germ-layer differentiation potential. Directed differentiation into midbrain dopaminergic neurons revealed that SNCA expression is reduced in the gene-corrected clones, which was validated by a reduction at the alpha-synuclein protein level. The generation of single-cell isogenic clones facilitates new insights in the role of alpha-synuclein in PD and furthermore is applicable across patient-derived disease models.
The effect of nicorandil in patients with cardiac syndrome X

Abstract Background: The prevalence of cardiac syndrome X (CSX) is considerable. Some patients show recurrent angina attacks and have a poor prognosis. However, the knowledge of CSX pathophysiological mechanism is still limited, and the treatment fails to achieve a satisfactory suppression of symptoms. Nicorandil has a beneficial effect on improving coronary microvascular dysfunction (CMD). This study aims to evaluate the clinical effects and safety of nicorandil on CSX patients. Methods: The Cochrane Library, Pubmed, EMBASE, ClinicalTrials.gov and 4 Chinese databases were searched to identify relevant studies. The Cochrane “Risk of bias” tool was used to assess the methodological quality of eligible studies. Meta-analysis was performed by RevMan 5.3 software. The Eggers test and meta-regression were performed by software Stata 14.0. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Twenty four randomized controlled trials (RCTs) involving 2323 patients were included. Most of the included studies were classified as having an unclear risk of bias because of poor reported methodology. The main outcomes are angina symptoms improvement, resting electrocardiogram (ECG) improvement, treadmill test result, and endothelial function. Meta-analysis showed that nicorandil had some benefit on improving angina symptoms (RR 1.24, 95% CI 1.19 to 1.29, I2 = 20%, P < .00001), resting ECG (RR = 1.24, 95% IC: 1.15 to 1.33, I2 = 0%, P < .00001), and prolonged the time to 1 mm ST-segment depression in treadmill test result (WMD = 38.41, 95% IC: 18.46 to 58.36, I2 = 0%, P = .0002). Besides nicorandil could reduce the level of endothelin-1 (ET-1) (SMD = −2.22, 95% IC: −2.61 to −1.83, I2 = 77%, P < .00001) and increase the level of nitric oxide (NO) (WMD = 27.45, 95% IC: 125.65 to 29.24, I2 = 81%, P < .00001). No serious adverse drug event was reported. The Eggers test showed that significant statistical publication bias was detected (Eggers test P = .000). The quality of evidence ranged from very low to low. Conclusions: Nicorandil shows the potential of improving angina symptoms, ECG, and endothelial dysfunction in patients with CSX. However, there is insufficient evidence for the clinical benefits of nicorandil due to the very low-quality evidence.