115 research outputs found

    Effect of betel and lemon aqueous extracts on clinical isolates of Escherichia coli

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    Escherichia coli causes a plethora of human infections and can be difficult to treat due to biofilm formation and high degree of antibiotic resistance. Hence, natural inhibitory compounds are being studied against this pathogen. Our study evaluated the inhibitory role of paan leaf and lemon on this pathogen. Both paan leaf and lemon juice showed inhibition of growth and virulence factors at 4 g% concentration. This can show the road for further studies to characterize these inhibitory natural moieties

    Cell models for Down syndrome-Alzheimer’s disease research

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    Down syndrome (DS) is the most common chromosomal abnormality and leads to intellectual disability, increased risk of cardiac defects, and an altered immune response. Individuals with DS have an extra full or partial copy of chromosome 21 (trisomy 21) and are more likely to develop early-onset Alzheimer’s disease (AD) than the general population. Changes in expression of human chromosome 21 (Hsa21)-encoded genes, such as APP, play an important role in the pathogenesis of AD in DS (DS-AD). However, the mechanisms of DS-AD remain poorly understood. To date, several mouse models with an extra copy of genes syntenic to Hsa21 have been developed to characterize DS-AD-related phenotypes. Nonetheless, due to genetic and physiological differences between mouse and human, mouse models cannot faithfully recapitulate all features of DS-AD. Cells differentiated from human induced pluripotent stem cells (iPSCs), isolated from individuals with genetic diseases, can be used to model disease-related cellular and molecular pathologies, including DS. In this review, we will discuss the limitations of mouse models of DS and how these can be addressed using recent advancements in modelling DS using human iPSCs and iPSC-mouse chimeras, and potential applications of iPSCs in preclinical studies for DS-AD

    Avant-propos

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    La chute des régimes communistes et l'instauration de démocraties pluralistes en Europe centrale et orientale, accompagnées de proclamations de rupture radicale avec le passé, ont engendré un bouleversement général des repères qui jusque-là permettaient les identifications individuelles et l'élaboration d'identités collectives dans toutes les sphères sociales. Le rejet obligé du passé a été décliné de différentes manières selon les pays, en fonction des diverses expériences du communisme (et de sa chute) dans chacune des sociétés concernées. Toutefois, si les modalités sont variables et les calendriers spécifiques, ces recompositions sociales et politiques se sont toutes inscrites dans un même cadre mental. La condamnation globale du communisme a favorisé des visions polarisées et simplifiées du passé, fondées sur des catégories binaires et des figures stéréotypées, plus ou moins marquées, de bourreaux et de victimes. Au-delà du consensus affiché dans le rejet et la condamnation du communisme, un examen plus fin du rapport au passé dans ces sociétés dites post-communistes souligne la difficulté d'élaborer un discours commun sur le passé (...)

    Aberrant Calcium Signaling in Astrocytes Inhibits Neuronal Excitability in a Human Down Syndrome Stem Cell Model.

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    Down syndrome (DS) is a genetic disorder that causes cognitive impairment. The staggering effects associated with an extra copy of human chromosome 21 (HSA21) complicates mechanistic understanding of DS pathophysiology. We examined the neuron-astrocyte interplay in a fully recapitulated HSA21 trisomy cellular model differentiated from DS-patient-derived induced pluripotent stem cells (iPSCs). By combining calcium imaging with genetic approaches, we discovered the functional defects of DS astroglia and their effects on neuronal excitability. Compared with control isogenic astroglia, DS astroglia exhibited more-frequent spontaneous calcium fluctuations, which reduced the excitability of co-cultured neurons. Furthermore, suppressed neuronal activity could be rescued by abolishing astrocytic spontaneous calcium activity either chemically by blocking adenosine-mediated signaling or genetically by knockdown of inositol triphosphate (IP3) receptors or S100B, a calcium binding protein coded on HSA21. Our results suggest a mechanism by which DS alters the function of astrocytes, which subsequently disturbs neuronal excitability

    Balancing serendipity and reproducibility: Pluripotent stem cells as experimental systems for intellectual and developmental disorders

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    Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) and their differentiation into neural lineages is a revolutionary experimental system for studying neurological disorders, including intellectual and developmental disabilities (IDDs). However, issues related to variability and reproducibility have hindered translating preclinical findings into drug discovery. Here, we identify areas for improvement by conducting a comprehensive review of 58 research articles that utilized iPSC-derived neural cells to investigate genetically defined IDDs. Based upon these findings, we propose recommendations for best practices that can be adopted by research scientists as well as journal editors

    Computed tomography measurements of different dimensions of maxillary and frontal sinuses

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    <p>Abstract</p> <p>Background</p> <p>We have previously proposed the use of Doppler ultrasound to non-invasively stage sinus infection, as we showed that acoustic streaming could be generated in nonpurulent sinus secretions and helped to distinguish it from mucopurulent sinus secretions. In order to continue this development of a clinically applicable Doppler equipment, we need to determine different dimensions of the paranasal sinuses, especially the thickness of the anterior wall of the maxillary sinus (at the canine fossa). To the best of our knowledge, this is the first report on the thickness of the canine fossa. This study aimed to (a) estimate different dimensions of the maxillary and frontal sinuses measured on computed tomography (CT) of the head, (b) define cut-off values for the normal upper and lower limits of the different measured structures, (c) determine differences in age, side and gender, (d) compare manually and automatically estimated maxillary sinuses volumes, and (e) present incidental findings in the paranasal sinuses among the study patients.</p> <p>Methods</p> <p>Dimensions of 120 maxillary and frontal sinuses from head CTs were measured independently by two radiologists.</p> <p>Results</p> <p>The mean value of the maxillary sinus volume was 15.7 ± 5.3 cm<sup>3 </sup>and significantly larger in males than in females (P = 0.004). There was no statistically significant correlation between the volume of maxillary sinuses with age or side. The mean value of the bone thickness at the canine fossa was 1.1 ± 0.4 mm. The automatically estimated volume of the maxillary sinuses was 14-17% higher than the calculated volume. There was high interobserver agreement with regard to the different measurements performed in this study. Different types of incidental findings of the paranasal sinuses were found in 35% of the patients.</p> <p>Conclusion</p> <p>We presented different dimensions of the maxillary and frontal sinuses on CTs. We believe that our data are necessary for further development of a clinically applicable Doppler equipment for staging rhinosinusitis.</p

    ISSCR standards for the use of human stem cells in basic research.

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    The laboratory culture of human stem cells seeks to capture a cellular state as an in vitro surrogate of a biological system. For the results and outputs from this research to be accurate, meaningful, and durable, standards that ensure reproducibility and reliability of the data should be applied. Although such standards have been previously proposed for repositories and distribution centers, no widely accepted best practices exist for laboratory research with human pluripotent and tissue stem cells. To fill that void, the International Society for Stem Cell Research has developed a set of recommendations, including reporting criteria, for scientists in basic research laboratories. These criteria are designed to be technically and financially feasible and, when implemented, enhance the reproducibility and rigor of stem cell research

    The Cyclic AMP Cascade Is Altered in the Fragile X Nervous System

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    Fragile X syndrome (FX), the most common heritable cause of mental retardation and autism, is a developmental disorder characterized by physical, cognitive, and behavioral deficits. FX results from a trinucleotide expansion mutation in the fmr1 gene that reduces levels of fragile X mental retardation protein (FMRP). Although research efforts have focused on FMRP's impact on mGluR signaling, how the loss of FMRP leads to the individual symptoms of FX is not known. Previous studies on human FX blood cells revealed alterations in the cyclic adenosine 3′, 5′-monophosphate (cAMP) cascade. We tested the hypothesis that cAMP signaling is altered in the FX nervous system using three different model systems. Induced levels of cAMP in platelets and in brains of fmr1 knockout mice are substantially reduced. Cyclic AMP induction is also significantly reduced in human FX neural cells. Furthermore, cAMP production is decreased in the heads of FX Drosophila and this defect can be rescued by reintroduction of the dfmr gene. Our results indicate that a robust defect in cAMP production in FX is conserved across species and suggest that cAMP metabolism may serve as a useful biomarker in the human disease population. Reduced cAMP induction has implications for the underlying causes of FX and autism spectrum disorders. Pharmacological agents known to modulate the cAMP cascade may be therapeutic in FX patients and can be tested in these models, thus supplementing current efforts centered on mGluR signaling

    (Re)theorising laddish masculinities in higher education

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    In the context of renewed debates and interest in this area, this paper reframes the theoretical agenda around laddish masculinities in UK higher education, and similar masculinities overseas. These can be contextualised within consumerist neoliberal rationalities, the neoconservative backlash against feminism and other social justice movements, and the postfeminist belief that women are winning the ‘battle of the sexes’. Contemporary discussions of ‘lad culture’ have rightly centred sexism and men¹s violence against women: however, we need a more intersectional analysis. In the UK a key intersecting category is social class, and there is evidence that while working class articulations of laddism proceed from being dominated within alienating education systems, middle class and elite versions are a reaction to feeling dominated due to a loss of gender, class and race privilege. These are important differences, and we need to know more about the conditions which shape and produce particular performances of laddism, in interaction with masculinities articulated by other social groups. It is perhaps unhelpful, therefore, to collapse these social positions and identities under the banner of ‘lad culture’, as has been done in the past

    Building the Future Therapies for Down Syndrome:The Third International Conference of the T21 Research Society

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    Research focused on Down syndrome has increased in the last several years to advance understanding of the consequences of trisomy 21 (T21) on molecular and cellular processes and, ultimately, on individuals with Down syndrome. The Trisomy 21 Research Society (T21RS) is the premier scientific organization for researchers and clinicians studying Down syndrome. The Third International Conference of T21RS, held June 6-9, 2019, in Barcelona, Spain, brought together 429 scientists, families, and industry representatives to share the latest discoveries on underlying cellular and molecular mechanisms of T21, define cognitive and behavioral challenges and better understand comorbidities associated with Down syndrome, including Alzheimer's disease and leukemia. Presentation of cutting-edge results in neuroscience, neurology, model systems, psychology, cancer, biomarkers and molecular and phar-ma-cological therapeutic approaches demonstrate the compelling interest and continuing advancement in all aspects of understanding and ameliorating conditions associated with T21
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