Miracle-dz/UniFAR-FTUs huggingface dataset:
The microbial metabolite urolithin A reduces Clostridioides difficile toxin expression and toxin-induced epithelial damage

ABSTRACT Clostridioides difficile is a Gram-positive, anaerobic, spore-forming bacterium responsible for antibiotic-associated pseudomembranous colitis. Clostridioides difficile infection (CDI) symptoms can range from diarrhea to life-threatening colon damage. Toxins produced by C. difficile (TcdA and TcdB) cause intestinal epithelial injury and lead to severe gut barrier dysfunction, stem cell damage, and impaired regeneration of the gut epithelium. Current treatment options for intestinal repair are limited. In this study, we demonstrate that treatment with the microbial metabolite urolithin A (UroA) attenuates CDI-induced adverse effects on the colon epithelium in a preclinical model of CDI-induced colitis. Moreover, our analysis suggests that UroA treatment protects against C. difficile-induced inflammation, disruption of gut barrier integrity, and intestinal tight junction proteins in the colon of CDI mice. Importantly, UroA treatment significantly reduced the expression and release of toxins from C. difficile without inducing bacterial cell death. These results indicate the direct regulatory effects of UroA on bacterial gene regulation. Overall, our findings reveal a novel aspect of UroA activity, as it appears to act at both the bacterial and host levels to protect against CDI-induced colitis pathogenesis. This research sheds light on a promising avenue for the development of novel treatments for C. difficile infection. IMPORTANCE Therapy for Clostridioides difficile infections includes the use of antibiotics, immunosuppressors, and fecal microbiota transplantation. However, these treatments have several drawbacks, including the loss of colonization resistance, the promotion of autoimmune disorders, and the potential for unknown pathogens in donor samples. To date, the potential benefits of microbial metabolites in CDI-induced colitis have not been fully investigated. Here, we report for the first time that the microbial metabolite urolithin A has the potential to block toxin production from C. difficile and enhance gut barrier function to mitigate CDI-induced colitis. Therapy for Clostridioides difficile infections includes the use of antibiotics, immunosuppressors, and fecal microbiota transplantation. However, these treatments have several drawbacks, including the loss of colonization resistance, the promotion of autoimmune disorders, and the potential for unknown pathogens in donor samples. To date, the potential benefits of microbial metabolites in CDI-induced colitis have not been fully investigated. Here, we report for the first time that the microbial metabolite urolithin A has the potential to block toxin production from C. difficile and enhance gut barrier function to mitigate CDI-induced colitis.
West Nile : Une arbovirose migrante d'actualité

Le virus West Nile est un arbovirus du genre flavivirus largement repandu en Afrique subsaharienne. Il est connu pour provoquer de temps a autre dans le bassin mediterraneen et en Europe du sud des epidemies ou des epizooties chez les chevaux. Le cycle de transmission fait intervenir des oiseaux et des moustiques essentiellement du genre Culex. La plupart des infections liees au virus West Nile sont inapparentes chez l'homme. Depuis quelques annees, le pouvoir pathogene du virus s'est modifie avec apparition de nombreuses atteintes nerveuses centrales et de deces observes principalement chez des personnes âgees en Algerie et en Roumanie mais aussi chez des oiseaux sauvages dans les zones d'emergence du virus. L'identification en 1999 du virus West Nile sur le continent americain en pleine zone urbaine a montre qu'un virus peut apparaitre brutalement la ou personne ne l'attendait. Seule la biologie moleculaire permet d'identifier avec precision le virus, les techniques serologiques ne pouvant distinguer une atteinte par le virus West Nile d'autres atteintes par flavivirus du groupe des encephalites comme l'encephalite japonaise presente en Asie ou l'encephalite de Saint-Louis en Amerique. Des etudes de veille microbiologique de reserves ornithologiques sentinelles devraient permettre de mieux comprendre l'epidemiologie et le pouvoir pathogene des souches circulantes.
Single intravitreal administration of a tetravalent siRNA exhibits robust and efficient gene silencing in rodent and swine photoreceptors

Inherited retinal dystrophies caused by dominant mutations in photoreceptor-expressed genes, are a major cause of irreversible vision loss. Oligonucleotide therapy has been of interest in diseases that conventional medicine cannot target. In the early days, small interfering RNAs (siRNAs) were explored in clinical trials for retinal disorders with limited success due to a lack of stability and efficient cellular delivery. Thus, an unmet need exists to identify siRNA chemistry that targets photoreceptor-expressed genes. Here we evaluated 12 different fully chemically modified siRNA configurations, where the valency and conjugate structure were systematically altered. The impact on retinal distribution following intravitreal delivery was examined. We found that the increase in valency (tetravalent siRNA) supports the best photoreceptor accumulation. A single intravitreal administration induces multi-months efficacy in rodent and porcine retinas while showing a good safety profile. The data suggest that this configuration can treat retinal diseases caused by photoreceptor-expressed genes with 1-2 intravitreal injections per year.
Host-microbe interactions at the blood-brain barrier through the lens of induced pluripotent stem cell-derived brain-like endothelial cells

ABSTRACT Microbe-induced meningoencephalitis/meningitis is a life-threatening infection of the central nervous system (CNS) that occurs when pathogens are able to cross the blood-brain barrier (BBB) and gain access to the CNS. The BBB consists of highly specialized brain endothelial cells that exhibit specific properties to allow tight regulation of CNS homeostasis and prevent pathogen crossing. However, during meningoencephalitis/meningitis, the BBB fails to protect the CNS. Modeling the BBB remains a challenge due to the specialized characteristics of these cells. In this review, we cover the induced pluripotent stem cell-derived, brain-like endothelial cell model during host-pathogen interaction, highlighting the strengths and recent work on various pathogens known to interact with the BBB. As stem cell technologies are becoming more prominent, the stem cell-derived, brain-like endothelial cell model has been able to reveal new insights in vitro, which remain challenging with other in vitro cell-based models consisting of primary human brain endothelial cells and immortalized human brain endothelial cell lines.
BRD4 isoforms have distinct roles in tumour progression and metastasis in rhabdomyosarcoma

BRD4, a bromodomain and extraterminal (BET) protein, is deregulated in multiple cancers and has emerged as a promising drug target. However, the function of the two main BRD4 isoforms (BRD4-L and BRD4-S) has not been analyzed in parallel in most cancers. This complicates determining therapeutic efficacy of pan-BET inhibitors. In this study, using functional and transcriptomic analysis, we show that BRD-L and BRD4-S isoforms play distinct roles in embryonal rhabdomyosarcoma. BRD4-L has an oncogenic role and inhibits myogenic differentiation, at least in part, by activating myostatin expression. Depletion of BRD4-L in vivo impairs tumor progression but does not impact metastasis. On the other hand, depletion of BRD4-S has no significant impact on tumor growth, but strikingly promotes metastasis in vivo. Interestingly, BRD4-S loss results in the enrichment of BRD4-L and RNA Polymerase II at integrin gene promoters resulting in their activation. Our work unveils isoform-specific functions of BRD4 and demonstrates that BRD4-S functions as a gatekeeper to constrain the full oncogenic potential of BRD4-L.
Wieloogniskowa neuropatia ruchowa

Wieloogniskowa neuropatia ruchowa z blokiem przewodzenia (MMN-CB, multifocal motor neuropathy with conduction block ) jest rzadką chorobą, najprawdopodobniej o podlozu immunologicznym, obejmującą wlokna ruchowe nerwow obwodowych. Klinicznie cechuje sie asymetrycznym niedowladem, zwykle przewazającym w konczynach gornych, z dolączającym sie po latach zanikiem mieśni w zakresie unerwienia poszczegolnych nerwow. Warunkiem rozpoznania choroby jest stwierdzenie bloku przewodzenia we wloknach ruchowych i prawidlowych wartości przewodzenia we wloknach czuciowych. W cześci przypadkow, po uplywie lat, blok przewodzenia moze ustąpic, co nasuwa pytanie o związek MMN-CB z MMN bez bloku przewodzenia. U niektorych pacjentow na początku choroby wystepują subiektywne zaburzenia czucia, a po latach obserwuje sie nieprawidlowe potencjaly czuciowe. W tych przypadkach roznicowanie z zespolem Lewisa-Sumnera wydaje sie istotne ze wzgledu na wybor leczenia. Uwzgledniając mozliwośc leczenia MMN-CB i MMN, nalezy potwierdzic lub wykluczyc te schorzenia u osob z podejrzeniem choroby dolnego neuronu ruchowego. W leczeniu MMN rutynowo stosuje sie wlewy immunoglobulin, podjeto rowniez proby leczenia rituksymabem.
Seasonal diet and habitat use in field roe deer (Capreolus capreolus) in the Picardie region

Le regime alimentaire de 85 chevreuils (25 femelles et 60 mâles) vivant en agroecosysteme en Picardie (nord de la France) a ete etudie par l'analyse des contenus du rumen, preleves durant les etes, les automnes et les hivers 1987-88 et 1988-89. Aucune difference liee au sexe n'est apparue. Les plantes cultivees, essentiellement les cereales et les betteraves sucrieres, representaient, en poids sec, 90% de la nourriture en ete et 77% en hiver. A l'automne, les plantes cultivees et les plantes non-cultivees representaient la meme biomasse dans la nourriture (respectivement 55% et 45%). Au cours des trois saisons, plus de 80% des rumens renfermaient des plantes non-cultivees. La variete du regime alimentaire a decru de neuf classes d'aliments consommes en ete a cinq classes d'aliments consommes en hiver. L'utilisation et le choix de l'habitat ont ete etudies grâce au radiopistage de trois mâles et deux femelles entre 1986 et 1987, et grâce a l'observation visuelle des chevreuils le long des transects routiers entre 1986 et 1988. Les secteurs non-cultives etaient selectionnes par les chevreuils (21,6% de localisations vs 5% de la surface totale, n=512, P<0,001), mais pas les secteurs cultives. Cependant, les animaux utilisaient intensivement les zones cultivees, a parts egales, pour se nourrir et se coucher. En hiver, les chaumes et les labours etaient plus frequemment utilises pour se coucher et pour se nourrir. L'importance relative des plantes non-cultivees (et en particulier les bois) jouent un role important dans l'ecologie du chevreuil de plaine
Explaining the Factors on Process of Academic Wikipedia Users Using Technology Acceptance Model Through the Structural Equation Model

As a teaching tool, Wikipedia is used by an increasing number of professors from many universities around the world. Wikipedia is very influential in allowing students and teachers to learn together and having various skills for students. In this chapter, the influenced main factors of the teaching uses of Wikipedia in higher education are determined and also the relationship between these factors are tried to be explained with the technology acceptance model (TAM) through the structural equation model (SEM). With this aim, teaching use of Wikipedia in all faculty members of the Universitat Oberta de Catalunya are used as data and the data is analyzed by LISREL software package. After the analysis, it is found that sharing attitude and use behaviour factors have important role in the model and there is a direct strong impact of sharing attitude on use behavior.
Intrinsic and extrinsic cues time somite progenitor contribution to the vertebrate primary body axis

During embryonic development, the timing of events at the cellular level must be coordinated across multiple length scales to ensure the formation of a well-proportioned body plan. This is clear during somitogenesis, where progenitors must be allocated to the axis over time whilst maintaining a progenitor population for continued elaboration of the body plan. However, the relative importance of intrinsic and extrinsic signals in timing progenitor addition at the single-cell level is not yet understood. Heterochronic grafts from older to younger embryos have suggested a level of intrinsic timing whereby later staged cells contribute to more posterior portions of the axis. To determine the precise step at which cells are delayed, we performed single-cell transcriptomic analysis on heterochronic grafts of somite progenitors in the chicken embryo. This revealed a previously undescribed cell state within which heterochronic grafted cells are stalled. The delayed exit of older cells from this state correlates with expression of posterior Hox genes. Using grafting and explant culture, we find that both Hox gene expression and the migratory capabilities of progenitor populations are intrinsically regulated at the population level. However, by grafting varied sizes of tissue, we find that small heterochronic grafts disperse more readily and contribute to more anterior portions of the body axis while still maintaining Hox gene expression. This enhanced dispersion is not replicated in explant culture, suggesting that it is a consequence of interaction between host and donor tissue and thus extrinsic to the donor tissue. Therefore, we demonstrate that the timing of cell dispersion and resulting axis contribution is impacted by a combination of both intrinsic and extrinsic cues.
A Freliminary Study of the Effects of Deferred Spring Grazing on the Pasture Vegetation

The effects of deferred spring grazing and continuous grazing on the vegetation characteristics of the natural pasture were studied during the ungraing persod of spring of 2002. The result shows that both the plant yield and coverage, and the plant height and density of the deferred spring grazing pasture far surpassed those of the continuous grazing pasture (P0.05). Deferred spring grazing contributes to the sustainable development of the pasture vegetation. Duration of ungrazing period in the spring affects the flourishing of the pasture vegetation, though not very vigorously.
Chronic Pulmonary Aspergillosis as a Considerable Complication in Post-Tuberculosis Lung Disease

Abstract Post-tuberculosis lung disease (PTLD) has only recently been put in the spotlight as a medical entity. Recent data suggest that up to 50% of tuberculosis (TB) patients are left with PTLD-related impairment after completion of TB treatment. The presence of residual cavities in the lung is the largest risk factor for the development of chronic pulmonary aspergillosis (CPA) globally. Diagnosis of CPA is based on four criteria including a typical radiological pattern, evidence of Aspergillus species, exclusion of alternative diagnosis, and a chronic course of disease. In this manuscript, we provide a narrative review on CPA as a serious complication for patients with PTLD.
Schwannoma of the Nose at the Keystone Area in Relation to the Dorsal Nasal Nerve

Schwannomas are well-circumscribed, solitary benign encapsulated tumors arising from Schwann cells, which originate from neural crest cells. 1 They constitute only 4% of the head and neck tumors and involve the paranasal sinuses and nasal cavities. 2 About 80% of cases involve the vestibulocochlear nerve, followed by the trigeminal nerve in this region. 3 A 27-year-old woman presented to us with complaints of swelling over the nose for the past 8 months. She was medically managed for associated tension headaches. She gave no history of nasal obstruction, trauma, epistaxis, localized facial numbness, anosmia, or other swellings. Clinical examination showed a hemispherical, ﬁ rm swelling of size 1.5 (cid:1) 1.0 (cid:1) 0.75cm over the rhinion and left keystone area in the subcutaneous plane, with side-to-side mobility and pinchable overlying skin. Deep palpation caused dyses-thesia at thetip of the nose.Anterior rhinoscopyexamination revealed no intranasal extension. High-de ﬁ nition ultrasonography (HD-USG) imaging showed no cystic degeneration. Computed tomography (CT) scan revealed a hyperintense lesion over the rhinion and left keystone area of the nose, with no bony or cartilaginous erosions. Contrast magnetic resonance imaging (MRI) showed the same with delayed centripetal ﬁ lling
Trans-dimensional Bayesian inversion of airborne electromagnetic data for 2D conductivity profiles

This paper presents the application of a novel trans-dimensional sampling approach to a time domain airborne electromagnetic (AEM) inverse problem to solve for plausible conductivities of the subsurface. Geophysical inverse field problems, such as time domain AEM, are well known to have a large degree of non-uniqueness. Common least-squares optimisation approaches fail to take this into account and provide a single solution with linearised estimates of uncertainty that can result in overly optimistic appraisal of the conductivity of the subsurface. In this new non-linear approach, the spatial complexity of a 2D profile is controlled directly by the data. By examining an ensemble of proposed conductivity profiles it accommodates non-uniqueness and provides more robust estimates of uncertainties. We apply a novel trans-dimensional Bayesian approach using a wavelet parameterisation to airborne electromagnetic (AEM) inversions using data from the Broken Hill region. This approach allows exploration of a range of plausible subsurface conductivity models and provides more robust uncertainty estimates while accounting for potential non-uniqueness.
Unravelling the origins of boldness behaviour: a common garden experiment with cavefish (Barbatula barbatula)

Many animals show an aversion to bright, open spaces, with significant variability seen across species, populations and individuals within populations. Although there is much interest in the underlying causes of this behaviour, few studies have been able to systematically isolate the role of heritable and environmental effects. Here, we addressed this gap using a common garden experiment with cavefish. Specifically, we bred and cross-bred cave loaches (Barbatula barbatula), Europe's only known cavefish, in the laboratory, raised the offspring in complete darkness or normal light conditions, and studied their light avoidance behaviour. Cavefish spent much more time in a light area and ventured further out, while surface fish spent considerable time in risk-assessment behaviour between the light and dark areas. Hybrids behaved most similarly to cavefish. Light treatment and eye quality and lens size only had a modest effect. Our results suggest light avoidance behaviour of cavefish has a heritable basis and is fundamentally linked to increased boldness rather than reduced vision, which is likely adaptive given the complete lack of macropredators in the cave environment. Our study provides novel experimental insights into the behavioural divergence of cavefish and contributes to our broader understanding of the evolution of boldness and behavioural adaptation.
Hummingbirds use distinct control strategies for forward and hovering flight

The detection of optic flow is important for generating optomotor responses to mediate retinal image stabilization, and it can also be used during ongoing locomotion for centring and velocity control. Previous work in hummingbirds has separately examined the roles of optic flow during hovering and when centring through a narrow passage during forward flight. To develop a hypothesis for the visual control of forward flight velocity, we examined the behaviour of hummingbirds in a flight tunnel where optic flow could be systematically manipulated. In all treatments, the animals exhibited periods of forward flight interspersed with bouts of spontaneous hovering. Hummingbirds flew fastest when they had a reliable signal of optic flow. All optic flow manipulations caused slower flight, suggesting that hummingbirds had an expected optic flow magnitude that was disrupted. In addition, upward and downward optic flow drove optomotor responses for maintaining altitude during forward flight. When hummingbirds made voluntary transitions to hovering, optomotor responses were observed to all directions. Collectively, these results are consistent with hummingbirds controlling flight speed via mechanisms that use an internal forward model to predict expected optic flow whereas flight altitude and hovering position are controlled more directly by sensory feedback from the environment.
A multi-criteria framework for disease surveillance site selection: case study for Plasmodium knowlesi malaria in Indonesia

Disease surveillance aims to collect data at different times or locations, to assist public health authorities to respond appropriately. Surveillance of the simian malaria parasite, Plasmodium knowlesi, is sparse in some endemic areas and the spatial extent of transmission is uncertain. Zoonotic transmission of Plasmodium knowlesi has been demonstrated throughout Southeast Asia and represents a major hurdle to regional malaria elimination efforts. Given an arbitrary spatial prediction of relative disease risk, we develop a flexible framework for surveillance site selection, drawing on principles from multi-criteria decision-making. To demonstrate the utility of our framework, we apply it to the case study of Plasmodium knowlesi malaria surveillance site selection in western Indonesia. We demonstrate how statistical predictions of relative disease risk can be quantitatively incorporated into public health decision-making, with specific application to active human surveillance of zoonotic malaria. This approach can be used in other contexts to extend the utility of modelling outputs.
TRILHAS INTERPRETATIVAS COMO INSTRUMENTO DE EDUCAÇÃO AMBIENTAL INTERPRETATIVE TRAILS AS A TOOL FOR ENVIRONMENTAL EDUCATION

The object of the present study is the interpretation of nature trails in a natural Park, to implement teaching practices through field studies. An Interpretation of trails is based on capture and translation of information concerning the environment for people who experiences it. Case studies, descriptive, with a quantitative approach, are the methodology applied in the present study. Excursions to the site were taken in order to to determine the path, following a action plan in terms of theoretical and practical, starting with the survey of resources for grants of themes. This study is justified by the importance of trails to encourage students about the preservation of nature, which should be providential in a country like Brazil, where there is a high biological diversity and a severe shortage of resources. The objective is to develop a practical lesson for Environmental Education, involving undergraduate students in Biological Sciences and Environmental Engineering.
The Parkland Mass Shooting and the Path to Intended Violence: A Case Study of Missed Opportunities and Avenues for Future Prevention

The 2018 mass shooting at Marjory Stoneman Douglas High School in Parkland, Florida reignited a discourse about safety and prevention that often follows such tragedies. Using a case study approach, we analyze the events leading up to the shooting (via official records from law enforcement and the shooting’s review commission) to identify missed opportunities for intervention, de-escalation, and ultimately prevention. The Path to Intended Violence model is employed to highlight the perpetrator’s escalating behaviors from grievance through the attack itself. The lessons learned then are utilized to offer recommendations for schools and communities seeking to prevent similar mass violence attacks.