Miracle-dz/UniFAR-FTUs huggingface dataset:
UNC-45a promotes myosin folding and stress fiber assembly

Contractile actomyosin bundles, stress fibers, are crucial for adhesion, morphogenesis, and mechanosensing in nonmuscle cells. However, the mechanisms by which nonmuscle myosin II (NM-II) is recruited to those structures and assembled into functional bipolar filaments have remained elusive. We report that UNC-45a is a dynamic component of actin stress fibers and functions as a myosin chaperone in vivo. UNC-45a knockout cells display severe defects in stress fiber assembly and consequent abnormalities in cell morphogenesis, polarity, and migration. Experiments combining structured-illumination microscopy, gradient centrifugation, and proteasome inhibition approaches revealed that a large fraction of NM-II and myosin-1c molecules fail to fold in the absence of UNC-45a. The remaining properly folded NM-II molecules display defects in forming functional bipolar filaments. The C-terminal UNC-45/Cro1/She4p domain of UNC-45a is critical for NM-II folding, whereas the N-terminal tetratricopeptide repeat domain contributes to the assembly of functional stress fibers. Thus, UNC-45a promotes generation of contractile actomyosin bundles through synchronized NM-II folding and filament-assembly activities.
How Fast Does a Signal Propagate through Proteins?

As the molecular basis of signal propagation in the cell, proteins are regulated by perturbations, such as mechanical forces or ligand binding. The question arises how fast such a signal propagates through the protein molecular scaffold. As a first step, we have investigated numerically the dynamics of force propagation through a single (Ala) protein following a sudden increase in the stretching forces applied to its end termini. The force propagates along the backbone into the center of the chain on the picosecond scale. Both conformational and tension dynamics are found in good agreement with a coarse-grained theory of force propagation through semiflexible polymers. The speed of force propagation of 50Å ps−1 derived from these simulations is likely to determine an upper speed limit of mechanical signal transfer in allosteric proteins or molecular machines.
Hyperbaric Oxygen Reduces Aspergillus fumigatus Proliferation In Vitro and Influences In Vivo Disease Outcomes

ABSTRACT Recent estimates suggest that more than 3 million people have chronic or invasive fungal infections, causing more than 600,000 deaths every year. Aspergillus fumigatus causes invasive pulmonary aspergillosis (IPA) in patients with compromised immune systems and is a primary contributor to increases in human fungal infections. Thus, the development of new clinical modalities as stand-alone or adjunctive therapy for improving IPA patient outcomes is critically needed. Here we tested the in vitro and in vivo impacts of hyperbaric oxygen (HBO) (100% oxygen, >1 atmosphere absolute [ATA]) on A. fumigatus proliferation and murine IPA outcomes. Our findings indicate that HBO reduces established fungal biofilm proliferation in vitro by over 50%. The effect of HBO under the treatment conditions was transient and fungistatic, with A. fumigatus metabolic activity rebounding within 6 h of HBO treatment being removed. In vivo, daily HBO provides a dose-dependent but modest improvement in murine IPA disease outcomes as measured by survival analysis. Intriguingly, no synergy was observed between subtherapeutic voriconazole or amphotericin B and HBO in vitro or in vivo with daily HBO dosing, though the loss of fungal superoxide dismutase genes enhanced HBO antifungal activity. Further studies are needed to optimize the HBO treatment regimen and better understand the effects of HBO on both the host and the pathogen during a pulmonary invasive fungal infection.
Deletion of ADA2 Increases Antifungal Drug Susceptibility and Virulence in Candida glabrata

ABSTRACT Candida glabrata, the second most frequent cause of candidiasis after Candida albicans, is an emerging human fungal pathogen that is intrinsically drug tolerant. Currently, studies of C. glabrata genes involved in drug tolerance are limited. Ada2, a component serving as a transcription adaptor of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, is required for antifungal drug tolerance and virulence in C. albicans. However, its roles in C. glabrata remain elusive. In this study, we found that ada2 mutants demonstrated severe growth defects at 40°C but only mild defects at 37°C or 25°C. In addition, C. glabrata ada2 mutants exhibited pleiotropic phenotypes, including susceptibility to three classes of antifungal drugs (i.e., azoles, echinocandins, and polyenes) and cell wall-perturbing agents but resistance to the endoplasmic reticulum stressor tunicamycin. According to RNA sequence analysis, the expression of 43 genes was downregulated and the expression of 442 genes was upregulated in the ada2 mutant compared to their expression in the wild type. C. glabrata ADA2, along with its downstream target ERG6, controls antifungal drug tolerance and cell wall integrity. Surprisingly, ada2 mutants were hypervirulent in a murine model of systemic infection, possibly due to the upregulation of multiple adhesin-like genes, increased agar invasion, and overstimulation of murine tumor necrosis factor alpha production.
An effective microphone array post-filter in arbitrary environments

The theoretic foundation of traditional microphone array post-filters is the signal model in which the noise between sensors is assumed to be uncorrelated. However, this model is inaccurate in real environments since the correlated noise exists. In this paper, a more generalized signal model which considers both the correlated and uncorrelated noise is introduced. A general expression of the microphone array post-filter is proposed for this model. For better residual noise shaping, the human auditory property is incorporated into the post-filter estimation process. In experiments with real noise microphone array recordings, the proposed technique has shown to produce impressive results in terms of quality measures of the enhanced speech.
Development of a Novel Helper-Dependent Adenovirus-Epstein-Barr Virus Hybrid System for the Stable Transformation of Mammalian Cells

ABSTRACT Epstein-Barr virus (EBV) episomes are stably maintained in permissive proliferating cell lines due to EBV nuclear antigen 1 (EBNA-1) protein-mediated replication and segregation. Previous studies showed the ability of EBV episomes to confer long-term transgene expression and correct genetic defects in deficient cells. To achieve quantitative delivery of EBV episomes in vitro and in vivo, we developed a binary helper-dependent adenovirus (HDA)-EBV hybrid system that consists of one HDA vector for the expression of Cre recombinase and a second HDA vector that contains all of the sequences for the EBV episome flanked by loxP sites. Upon coinfection of cells, Cre expressed from the first vector recombined loxP sites on the second vector. The resulting circular EBV episomes expressed a transgene and contained the EBV-derived family of repeats, an EBNA-1 expression cassette, and 19 kb of human DNA that functions as a replication origin in mammalian cells. This HDA-EBV hybrid system transformed 40% of cultured cells. Transgene expression in proliferating cells was observed for over 20 weeks under conditions that selected for the expression of the transgene. In the absence of selection, EBV episomes were lost at a rate of 8 to 10% per cell division. Successful delivery of EBV episomes in vivo was demonstrated in the liver of transgenic mice expressing Cre from the albumin promoter. This novel gene transfer system has the potential to confer long-term episomal transgene expression and therefore to correct genetic defects with reduced vector-related toxicity and without insertional mutagenesis.
Valorization of chestnut manufacture process residues

alcohols) allows to obtain high added value biomolecules from the solid manufacture wastes. Table 1 reports the chestnut wastewater chemical/physical parameters and Table 2 the energy potential of chestnut wastewaters. The extraction methods for shells residues were compared considering the biomolecules contents (data not showed). The best result was obtained utilizing hot water at 100 °C in as solid/liquid ratio of 1:40 (data not showed). The ortho-diphenol fraction, provided with the highest antioxidant power among the phenolic molecules, corresponded to 80% of the total phenols. Some interesting phenolic compounds (as Rutin, Gallic, Ellagic, p-Coumaric and Ferulic acid) with antiradical activity were identified in the extracts. The chestnut shells extracts showing highest phenolic amount were also tested for antioxidant properties and their activity was evaluated through DPPH assay (Table 3). Poster number
Preparation and Efficacy of a Live Newcastle Disease Virus Vaccine Encapsulated in Chitosan Nanoparticles

Background Newcastle disease (ND) is a highly contagious viral disease of poultry caused by pathogenic strains of the Newcastle disease virus (NDV). Live NDV vaccines are administered by drinking water, eyedrops or coarse aerosol spray. To further enhance mucosal immune responses, chitosan nanoparticles were developed for the mucosal delivery of a live NDV vaccine. Methodology/Principal Findings A lentogenic live-virus vaccine (strain LaSota) against NDV encapsulated in chitosan nanoparticles were developed using an ionic crosslinking method. Chitosan nanoparticles containing the lentogenic live-virus vaccine against NDV (NDV-CS-NPs) were produced with good morphology, high stability, a mean diameter of 371.1 nm, an encapsulation rate of 77% and a zeta potential of +2.84 mV. The Western blotting analysis showed that NDV structural proteins were detected in NDV-CS-NPs. The virus release assay results of NDV-CS-NPs indicated that NDV was released from NDV-CS-NPs. Chickens immunized orally or intranasally with NDV-CS-NPs were fully protected whereas one out of five chickens immunized with the LaSota live NDV vaccine and three out of five chickens immunized with the inactivated NDV vaccine were dead after challenge with the highly virulent NDV strain F48E9. Conclusions/Significance NDV-CS-NPs induced better protection of immunized specific pathogen free chickens compared to the live NDV vaccine strain LaSota and the inactivated NDV vaccine. This study lays a foundation for the further development of mucosal vaccines and drugs encapsulated in chitosan nanoparticles.
Development and numerical validation of a 2-scale computational model to study the mechanical behavior of nanocrystalline metals

Devant un jury compose de : Mme J. LECOMTE-BECKERS, Professeur a l'Universite de Liege, Presidente; M. L. NOELS, Charge de cours a l'Universite de Liege, Promoteur; Mme A. HABRAKEN, Directeur de recherches FNRS a l'Universite de Liege; MM P. GHOSEZ, Professeur a l'Universite de Liege; A. JERUSALEM, Professeur a la University of Oxford (Royaume-Uni); F. SANSOZ, Professeur a la University of Vermont (USA); L. STAINIER, Professeur a l'Ecole Centrale de Nantes (France).
Primary Open-Angle Glaucoma Risk Factors

Purpose: The objective of this study was to identify possible risk factors associated with primary open-angle glaucoma (POAG). Methods: A case-control study included patients seen at Rasoul-Akram Hospital ophthalmology clinic. Cases were consecutive patients with confirmed unilateral or bilateral POAG presented during the study period. Controls were a random sample of all other patients aged 30 or more, seen in the same department in the same period who were randomly selected if they fulfilled the inclusion criteria and then matched with the cases by age and sex. Data on demographic, anthropometric as well as medical characteristics were collected from 191 subjects, by interview and medical examination. Results: Sixty consecutive patients with POAG and 131 controls were chosen. Odds ratios (OR) are calculated for the relation between POAG and family history of glaucoma, body mass index, hypertension, diabetes mellitus, cigarette smoking, migraine, and refractive error. Chi-square and student t tests were used. Results indicated the following: family history of glaucoma: OR: 35, 95% CI: 4.57-282.43, P<0.0001, hyperopia: OR: 0.432, 95% CI: 0.209-0.893, P=0.021, hypertension: OR: 1.46, 95% CI: 0.78-2.73, P=0.223, body mass index: P=0.378 (student t test) , migraine: OR: 0.46, 95% CI: 0.098-2.23, P=0.507, and cigarette smoking: OR, 1.81; 95% CI, 0.747-4.41; P= 0.184. Conclusion: This study replicated the finding that family history is a major risk factor for POAG (when adjusting for age and sex), while it failed to show that hypertension, diabetes mellitus, myopia, cigarette smoking, migraine, and body mass index to be associated with POAG. It also suggested a protective role for hyperopia in POAG.
Factor structure and measurement invariance across various demographic groups and over time for the PHQ-9 in primary care patients in Spain

The Patient Health Questionnaire (PHQ-9) is a widely-used screening tool for depression in primary care settings. The purpose of the present study is to identify the factor structure of the PHQ-9 and to examine the measurement invariance of this instrument across different sociodemographic groups and over time in a sample of primary care patients in Spain. Data came from 836 primary care patients enrolled in a randomized controlled trial (PsicAP study) and a subsample of 218 patients who participated in a follow-up assessment at 3 months. Confirmatory factor analysis (CFA) was used to test one- and two-factor structures identified in previous studies. Analyses of multiple-group invariance were conducted to determine the extent to which the factor structure is comparable across various demographic groups (i.e., gender, age, marital status, level of education, and employment situation) and over time. Both one-factor and two-factor re-specified models met all the pre-established fit criteria. However, because the factors identified in the two-factor model were highly correlated (r = .86), the one-factor model was preferred for its parsimony. Multi-group CFA indicated measurement invariance across different demographic groups and across time. The present findings suggest that physicians in Spain can use the PHQ-9 to obtain a global score for depression severity in different demographic groups and to reliably monitor changes over time in the primary care setting.
Optimizing the underlying parameters for protein-nanoparticle interaction: advancement in theoretical simulation

Abstract The interaction of nanosized materials with living organisms is the central concern in the key applications of nanotechnology. In particular, the protein adsorption to nanomaterial surface has been a major focus of study in the past decade. Unfortunately, the underlying principles and molecular mechanisms are still not well understood, and there have been various approaches to address the issue. Bottom-up approaches like computational simulations at the atomistic level have already proved their potential. Several force fields and models have been developed to simulate realistic dynamics to mimic the interaction of solid surfaces and peptides, even in some cases, the whole protein. However, there are a few major limitations and bottlenecks of these studies, which remain mostly ignored and unexplored. Here, we review the studies that have been the major contributors to our present understanding of the nanoparticle (NP)-protein interaction. As the complexity of this phenomenon arises from different stages, the study of protein-NP interactions from multiple directions is necessary. In the perspective of bioapplications, we discuss the major challenges of this field and future scopes of research that can be designed rationally, sometimes coupled with numerous available experimental techniques to understand NP-protein docking in a more realistic manner.
Kobe University, NICT and University of Siegen at TRECVID 2017 AVS Task

—This paper presents the result of the TRECVID 2017 AVS task by kobe nict siegen team. Consisting of three research institutes Kobe University, NICT and University of Siegen. We submitted the following three runs. 1) kobe nict siegen D M 1: This run uses feature vectors extracted by a pre-trained convolutional neural network (CNN) as input for a small-scale multi-layer neural network called micro neural network (microNN). The microNN is a lightweight detector ﬁne-tuned to a target concept using a balanced set of positive and negative data from ImageNet and IACC video datasets. Finally, the results of several microNNs are combined to generate the ranked result. 2) kobe nict siegen D M 2: This run is basically identical to kobe nict siegen D M 1, but applys additional motion features. The motion features are extracted by a motion CNN which involves biologically-inspired motion thresh-olding and competitive learning. 3) kobe nict siegen D M 3: This run is a degraded version of kobe nict siegen D M 1, and apply fully averaged pooling to feature vectors extracted with CNN, the dimention of the vector is reduced from 3 × 3 × 2048 to 2048 . We also use a word2vec model to ﬁnd synonyms of concepts in order to improve the performance.
CCLPA: A clustering coefficient based label propagation algorithm for unfolding communities in complex networks

Identifying interconnected groups in complex networks such as social networks, biological networks, and communication networks is an ever important task in data analysis. These interconnected groups are termed as communities in social network analysis and plays an important role in understanding the structural and behavioral properties of complex networks. In this paper, we propose a novel label propagation algorithm, called CCLPA (A Clustering Coefficient based Label Propagation Algorithm) to address the randomness issue of label propagation algorithm. Our algorithm defines the function, clustering coefficient, to measure the neighborhood connectivity between nodes quantitatively without any contact with the user. Based on the clustering coefficient, we present a new label propagation algorithm with explicit node update sequence to uncover communities in complex networks. Experiments on real-world network datasets demonstrate that it overcomes the random initial label selection and random label update order of underlying label propagation algorithm. Our algorithm identifies stable communities and becomes more robust and efficient. Wide experiments show the better-quality and effectiveness of the proposed algorithm.
Ephrin-A/EphA specific co-adaptation as a novel mechanism in topographic axon guidance

Genetic hardwiring during brain development provides computational architectures for innate neuronal processing. Thus, the paradigmatic chick retinotectal projection, due to its neighborhood preserving, topographic organization, establishes millions of parallel channels for incremental visual field analysis. Retinal axons receive targeting information from quantitative guidance cue gradients. Surprisingly, novel adaptation assays demonstrate that retinal growth cones robustly adapt towards ephrin-A/EphA forward and reverse signals, which provide the major mapping cues. Computational modeling suggests that topographic accuracy and adaptability, though seemingly incompatible, could be reconciled by a novel mechanism of coupled adaptation of signaling channels. Experimentally, we find such ‘co-adaptation’ in retinal growth cones specifically for ephrin-A/EphA signaling. Co-adaptation involves trafficking of unliganded sensors between the surface membrane and recycling endosomes, and is presumably triggered by changes in the lipid composition of membrane microdomains. We propose that co-adaptative desensitization eventually relies on guidance sensor translocation into cis-signaling endosomes to outbalance repulsive trans-signaling. DOI: http://dx.doi. org/10.7554/eLife.25533. 001
Universität Des Saarlandes Fachrichtung 6.1 – Mathematik Diffusion-inspired Shrinkage Functions and Stability Results for Wavelet Denoising Diffusion-inspired Shrinkage Functions and Stability Results for Wavelet Denoising

We study the connections between discrete 1-D schemes for non-linear diffusion and shift-invariant Haar wavelet shrinkage. We show that one step of a (stabilised) explicit discretisation of nonlinear diffusion can be expressed in terms of wavelet shrinkage on a single spatial level. This equivalence allows a fruitful exchange of ideas between the two fields. In this paper we derive new wavelet shrinkage functions from existing diffusivity functions, and identify some previously used shrinkage functions as corresponding to well known diffusivities. We demonstrate experimentally that some of the diffusion-inspired shrinkage functions are among the best for translation-invariant multiscale wavelet denoising. Moreover, by transferring stability notions from diffusion filtering to wavelet shrinkage, we derive conditions on the shrinkage function that ensure that shift invariant single-level Haar wavelet shrinkage is maximum-minimum stable, monotonicity preserving , and variation diminishing.
DNA as a Versatile Building-Block for Bioanalytical and Therapeutic Applications

Deoxyribonucleic acid (DNA) as the genetic material of the living organisms has been extensively exploited since past decades. In recent years, chemists have begun to engineer DNA for bioanalytical and therapeutic applications. In bioanalytical application, molecular beacons and aptamers are widely used. Molecular beacons are hairpinshaped oligonucleotides that contain both fluorophore and quencher moieties. They are normally in a turned-off state when the fluorophore and the quencher are brought together; when loop of the molecular beacon hybridize to a nucleic acid strand containing a target sequence they undergo a conformational change that separates the fluorophore and quencher, and in consequence fluorescence is turned ‘‘on. ’’ Please see review [1] for more details on molecular beacons. Aptamers are single-stranded DNAs or RNAs that have high affinity to their target molecules. Aptamers are selected via a process called Systematic Evolution of Ligands by Exponential Enrichment (SELEX) [2,3]. Application of DNA aptamers in analytical and biomedical sciences was well summarized in the review of You et al. [4]. Molecular beacons and DNA aptamers have been widely used in chemistry, biology, and medical sciences for biomolecular recognition.
Compact coherence enhancement by subharmonic self-seeding in X-ray free-electron laser facilities

A simple method to significantly enhance the coherence of X-ray free-electron laser (FEL) pulses by combining self-seeding and the harmonic generation mechanism is presented. This work is a fundamental step towards obtaining fully coherent FEL pulses, solving in this way a critical problem in the FEL field and its multidisciplinary scientific applications. In particular, the coherence improvement will be extremely beneficial for many photon science applications requiring a small bandwidth such as resonant inelastic X-ray scattering, therefore opening new areas of research and playing a crucial role in the future of all scientific users of the FEL facilities.