136 research outputs found

    Reynolds number and Shallow Depth Sloshing

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    The dependence on the Reynolds number of shallow depth sloshing flows inside rectangular tanks subjected to forced harmonic motion is studied in this paper with weakly compressible SPH. We are interested in assessing the in fluenceof viscous effects on the dynamics of shallow depth sloshing flows by using an SPH solver and by comparing with a Navier-Stokes level-set solver results. The goal of trying to model these viscous flows is compromised by the resolution requested due to their Reynolds number, if boundary layer effects are to be modeled. The convenience and feasibility of the implementation of free-slip and no-slip boundary conditions is also discusse

    Diffraction microtomography with sample rotation: influence of a missing apple core in the recorded frequency space

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    Diffraction microtomography in coherent light is foreseen as a promising technique to image transparent living samples in three dimensions without staining. Contrary to conventional microscopy with incoherent light, which gives morphological information only, diffraction microtomography makes it possible to obtain the complex optical refractive index of the observed sample by mapping a three-dimensional support in the spatial frequency domain. The technique can be implemented in two configurations, namely, by varying the sample illumination with a fixed sample or by rotating the sample using a fixed illumination. In the literature, only the former method was described in detail. In this report, we precisely derive the three-dimensional frequency support that can be mapped by the sample rotation configuration. We found that, within the first-order Born approximation, the volume of the frequency domain that can be mapped exhibits a missing part, the shape of which resembles that of an apple core. The projection of the diffracted waves in the frequency space onto the set of sphere caps covered by the sample rotation does not allow for a complete mapping of the frequency along the axis of rotation due to the finite radius of the sphere caps. We present simulations of the effects of this missing information on the reconstruction of ideal objects.Comment: 7 pages, 11 figures, presented at Focus On Microscopy 200

    piRNAs Are Associated with Diverse Transgenerational Effects on Gene and Transposon Expression in a Hybrid Dysgenic Syndrome of D. virilis

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    Sexual reproduction allows transposable elements (TEs) to proliferate, leading to rapid divergence between populations and species. A significant outcome of divergence in the TE landscape is evident in hybrid dysgenic syndromes, a strong form of genomic incompatibility that can arise when (TE) family abundance differs between two parents. When TEs inherited from the father are absent in the mother's genome, TEs can become activated in the progeny, causing germline damage and sterility. Studies in Drosophila indicate that dysgenesis can occur when TEs inherited paternally are not matched with a pool of corresponding TE silencing PIWI-interacting RNAs (piRNAs) provisioned by the female germline. Using the D. virilis syndrome of hybrid dysgenesis as a model, we characterize the effects that divergence in TE profile between parents has on offspring. Overall, we show that divergence in the TE landscape is associated with persisting differences in germline TE expression when comparing genetically identical females of reciprocal crosses and these differences are transmitted to the next generation. Moreover, chronic and persisting TE expression coincides with increased levels of genic piRNAs associated with reduced gene expression. Combined with these effects, we further demonstrate that gene expression is idiosyncratically influenced by differences in the genic piRNA profile of the parents that arise though polymorphic TE insertions. Overall, these results support a model in which early germline events in dysgenesis establish a chronic, stable state of both TE and gene expression in the germline that is maintained through adulthood and transmitted to the next generation. This work demonstrates that divergence in the TE profile is associated with diverse piRNA-mediated transgenerational effects on gene expression within populations

    Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort study

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    Background: While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking. Methods: A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1–365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021. Findings: Advanced age (HR 2.77, 95%CI 2.53–3.04, p < 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03–4.17, p < 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55–5.00, p < 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14–1.39, p < 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37–0.46, p < 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17–1.54, p < 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20–1.58, p < 0.0001), male sex (HR 1.67, 95%CI 1.45–1.93, p < 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80–13.91, p < 0.0001), and hypertension (HR 1.22, 95%CI 1.10–1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32–1.67) and 365 days (RR 1.54, 95%CI 1.21–1.96) compared to COVID-19 patients with no AKI. Interpretation: COVID-19-associated AKI was associated with higher mortality, and severe COVID-19-associated AKI was associated with worse long-term post-AKI kidney function recovery. Funding: Authors are supported by various funders, with full details stated in the acknowledgement section

    Impairment of circulating endothelial progenitors in Down syndrome

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    <p>Abstract</p> <p>Background</p> <p>Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome.</p> <p>Methods</p> <p>Circulating endothelial progenitors of Down syndrome affected individuals were isolated, <it>in vitro </it>cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1Îą plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of <it>CXCL12 </it>gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis.</p> <p>Results</p> <p>We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1Îą plasma levels and their progenitors had a reduced expression of SDF-1Îą encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells.</p> <p>Conclusions</p> <p>Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.</p

    Transcriptome Analysis of Neisseria meningitidis in Human Whole Blood and Mutagenesis Studies Identify Virulence Factors Involved in Blood Survival

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    During infection Neisseria meningitidis (Nm) encounters multiple environments within the host, which makes rapid adaptation a crucial factor for meningococcal survival. Despite the importance of invasion into the bloodstream in the meningococcal disease process, little is known about how Nm adapts to permit survival and growth in blood. To address this, we performed a time-course transcriptome analysis using an ex vivo model of human whole blood infection. We observed that Nm alters the expression of ≈30% of ORFs of the genome and major dynamic changes were observed in the expression of transcriptional regulators, transport and binding proteins, energy metabolism, and surface-exposed virulence factors. In particular, we found that the gene encoding the regulator Fur, as well as all genes encoding iron uptake systems, were significantly up-regulated. Analysis of regulated genes encoding for surface-exposed proteins involved in Nm pathogenesis allowed us to better understand mechanisms used to circumvent host defenses. During blood infection, Nm activates genes encoding for the factor H binding proteins, fHbp and NspA, genes encoding for detoxifying enzymes such as SodC, Kat and AniA, as well as several less characterized surface-exposed proteins that might have a role in blood survival. Through mutagenesis studies of a subset of up-regulated genes we were able to identify new proteins important for survival in human blood and also to identify additional roles of previously known virulence factors in aiding survival in blood. Nm mutant strains lacking the genes encoding the hypothetical protein NMB1483 and the surface-exposed proteins NalP, Mip and NspA, the Fur regulator, the transferrin binding protein TbpB, and the L-lactate permease LctP were sensitive to killing by human blood. This increased knowledge of how Nm responds to adaptation in blood could also be helpful to develop diagnostic and therapeutic strategies to control the devastating disease cause by this microorganism

    [Research on the epileptogenic complex]

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    The great importance of a correct definition of the lesional-functional epileptogenic complex for the surgical treatment of the epileptic patient is stressed. The means utilizable to reach the knowledge of the topographic organizatif the latters are descri0ed and discussed in detail: the scalp EEG, the examinations based on the EEG effects of endocarotid injection of barbiturates and convulsants, the EEG during nocturnal sleep, the direct recording of electrocerebral activity from the cortical surface (electro-corticography) and from deep cerebral structures (stereoelectro-encephalography). The relative importance of the informations provided by the electrical activity of "lesional" type, by the interictal epileptic activity and by the ictal one is analyzed. The utilization of methodologies of automatic elaboration of the electrocerebral signals is reminded. Finally, the different modes of application of the means of analysis mentioned above in the different epileptic patients are discussed and exemplified

    Discussion on the causes of failure of surgical treatment of partial epilepsies

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    Despite continuous improvement in diagnosis and surgery, persistence of seizures following surgical treatment of partial epilepsies still occurs in a relevant number of cases (30--40%). The analysis of personal material and of data from the literature appears to indicate that relevant causes of surgical failure are difficulties in delimitation of the epileptogenic zone and therefore of complete surgical removal. These difficulties are illustrated and discussed
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