A missense mutation in Ehd1 associated with defective spermatogenesis and male infertility

Normal function of the C-terminal Eps15 homology domain-containing protein 1 (EHD1) has previously been associated with endocytic vesicle trafficking, shaping of intracellular membranes, and ciliogenesis. We recently identified an autosomal recessive missense mutation c.1192C>T (p.R398W) of EHD1 in patients who had low molecular weight proteinuria (0.7–2.1 g/d) and high-frequency hearing loss. It was already known from Ehd1 knockout mice that inactivation of Ehd1 can lead to male infertility. However, the exact role of the EHD1 protein and its p.R398W mutant during spermatogenesis remained still unclear. Here, we report the testicular phenotype of a knockin mouse model carrying the p.R398W mutation in the EHD1 protein. Male homozygous knockin mice were infertile, whereas the mutation had no effect on female fertility. Testes and epididymes were significantly reduced in size and weight. The testicular epithelium appeared profoundly damaged and had a disorganized architecture. The composition of developing cell types was altered. Malformed acrosomes covered underdeveloped and misshaped sperm heads. In the sperm tail, midpieces were largely missing indicating disturbed assembly of the sperm tail. Defective structures, i.e., nuclei, acrosomes, and sperm tail midpieces, were observed in large vacuoles scattered throughout the epithelium. Interestingly, cilia formation itself did not appear to be affected, as the axoneme and other parts of the sperm tails except the midpieces appeared to be intact. In wildtype mice, EHD1 co-localized with acrosomal granules on round spermatids, suggesting a role of the EHD1 protein during acrosomal development. Wildtype EHD1 also co-localized with the VPS35 component of the retromer complex, whereas the p.R398W mutant did not. The testicular pathologies appeared very early during the first spermatogenic wave in young mice (starting at 14 dpp) and tubular destruction worsened with age. Taken together, EHD1 plays an important and probably multifaceted role in spermatogenesis in mice. Therefore, EHD1 may also be a hitherto underestimated infertility gene in humans

Determination of zearalenone and its metabolites in endometrial cancer by coupled separation techniques

This study presents a selective method of isolation of zearalenone (ZON) and its metabolite, α-zearalenol (α-ZOL), in neoplastically changed human tissue by accelerated solvent and ultrasonic extractions using a mixture of acetonitrile/water (84/16% v/v) as the extraction solvent. Extraction effectiveness was determined through the selection of parameters (composition of the solvent mixture, temperature, pressure, number of cycles) with tissue contamination at the level of nanograms per gram. The produced acetonitrile/water extracts were purified, and analytes were enriched in columns packed with homemade molecularly imprinted polymers. Purified extracts were determined by liquid chromatography (LC) coupled with different detection systems (diode array detection - DAD and mass spectrometry - MS) involving the Ascentis RP-Amide as a stationary phase and gradient elution. The combination of UE-MISPE-LC (ultrasonic extraction - molecularly imprinted solid-phase extraction - liquid chromatography) produced high (R ≈ 95–98%) and repeatable (RSD < 3%) recovery values for ZON and α-ZOL

CLN7/MFSD8 may be an important factor for SARS-CoV-2 cell entry

The SARS-CoV-2 virus has triggered a worldwide pandemic. According to the BioGrid database, CLN7 (MFSD8) is thought to interact with several viral proteins. The aim of this work was to investigate a possible involvement of CLN7 in the infection process. Experiments on a CLN7-deficient HEK293T cell line exhibited a 90% reduced viral load compared to wild-type cells. This observation may be linked to the finding that CLN7 ko cells have a significantly reduced GM1 content in their cell membrane. GM1 is found highly enriched in lipid rafts, which are thought to play an important role in SARS-CoV-2 infection. In contrast, overexpression of CLN7 led to an increase in viral load. This study provides evidence that CLN7 is involved in SARS-CoV-2 infection. This makes it a potential pharmacological target for drug development against COVID-19. Furthermore, it provides insights into the physiological function of CLN7 where still only little is known about

Decreased glutathione levels and impaired antioxidant enzyme activities in drug-naive first-episode schizophrenic patients

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine glutathione levels and antioxidant enzyme activities in the drug-naive first-episode patients with schizophrenia in comparison with healthy control subjects.</p> <p>Methods</p> <p>It was a case-controlled study carried on twenty-three patients (20 men and 3 women, mean age = 29.3 ± 7.5 years) recruited in their first-episode of schizophrenia and 40 healthy control subjects (36 men and 9 women, mean age = 29.6 ± 6.2 years). In patients, the blood samples were obtained prior to the initiation of neuroleptic treatments. Glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr) and oxidized glutathione (GSSG) and antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) were determined by spectrophotometry.</p> <p>Results</p> <p>GSHt and reduced GSHr were significantly lower in patients than in controls, whereas GSSG was significantly higher in patients. GPx activity was significantly higher in patients compared to control subjects. CAT activity was significantly lower in patients, whereas the SOD activity was comparable to that of controls.</p> <p>Conclusion</p> <p>This is a report of decreased plasma levels of GSHt and GSHr, and impaired antioxidant enzyme activities in drug-naive first-episode patients with schizophrenia. The GSH deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in schizophrenia early in the course of illness. Finally, our results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies for schizophrenia from early stages.</p

A Survey on the Security and the Evolution of Osmotic and Catalytic Computing for 5G Networks

The 5G networks have the capability to provide high compatibility for the new applications, industries, and business models. These networks can tremendously improve the quality of life by enabling various use cases that require high data-rate, low latency, and continuous connectivity for applications pertaining to eHealth, automatic vehicles, smart cities, smart grid, and the Internet of Things (IoT). However, these applications need secure servicing as well as resource policing for effective network formations. There have been a lot of studies, which emphasized the security aspects of 5G networks while focusing only on the adaptability features of these networks. However, there is a gap in the literature which particularly needs to follow recent computing paradigms as alternative mechanisms for the enhancement of security. To cover this, a detailed description of the security for the 5G networks is presented in this article along with the discussions on the evolution of osmotic and catalytic computing-based security modules. The taxonomy on the basis of security requirements is presented, which also includes the comparison of the existing state-of-the-art solutions. This article also provides a security model, "CATMOSIS", which idealizes the incorporation of security features on the basis of catalytic and osmotic computing in the 5G networks. Finally, various security challenges and open issues are discussed to emphasize the works to follow in this direction of research.Comment: 34 pages, 7 tables, 7 figures, Published In 5G Enabled Secure Wireless Networks, pp. 69-102. Springer, Cham, 201

Mitochondrial and endoplasmic reticulum stress pathways cooperate in zearalenone-induced apoptosis of human leukemic cells

<p>Abstract</p> <p>Background</p> <p>Zearalenone (ZEA) is a phytoestrogen from <it>Fusarium </it>species. The aims of the study was to identify mode of human leukemic cell death induced by ZEA and the mechanisms involved.</p> <p>Methods</p> <p>Cell cytotoxicity of ZEA on human leukemic HL-60, U937 and peripheral blood mononuclear cells (PBMCs) was performed by using 3-(4,5-dimethyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Reactive oxygen species production, cell cycle analysis and mitochondrial transmembrane potential reduction was determined by employing 2',7'-dichlorofluorescein diacetate, propidium iodide and 3,3'-dihexyloxacarbocyanine iodide and flow cytometry, respectively. Caspase-3 and -8 activities were detected by using fluorogenic Asp-Glu-Val-Asp-7-amino-4-methylcoumarin (DEVD-AMC) and Ile-Glu-Thr-Asp-7-amino-4-methylcoumarin (IETD-AMC) substrates, respectively. Protein expression of cytochrome c, Bax, Bcl-2 and Bcl-xL was performed by Western blot. The expression of proteins was assessed by two-dimensional polyacrylamide gel-electrophoresis (PAGE) coupled with LC-MS2 analysis and real-time reverse transcription polymerase chain reaction (RT-PCR) approach.</p> <p>Results</p> <p>ZEA was cytotoxic to U937 > HL-60 > PBMCs and caused subdiploid peaks and G1 arrest in both cell lines. Apoptosis of human leukemic HL-60 and U937 cell apoptosis induced by ZEA was via an activation of mitochondrial release of cytochrome c through mitochondrial transmembrane potential reduction, activation of caspase-3 and -8, production of reactive oxygen species and induction of endoplasmic reticulum stress. Bax was up regulated in a time-dependent manner and there was down regulation of Bcl-xL expression. Two-dimensional PAGE coupled with LC-MS2 analysis showed that ZEA treatment of HL-60 cells produced differences in the levels of 22 membrane proteins such as apoptosis inducing factor and the ER stress proteins including endoplasmic reticulum protein 29 (ERp29), 78 kDa glucose-regulated protein, heat shock protein 90 and calreticulin, whereas only <it>ERp29 </it>mRNA transcript increased.</p> <p>Conclusion</p> <p>ZEA induced human leukemic cell apoptosis via endoplasmic stress and mitochondrial pathway.</p

Direct transfer and Raman characterization of twisted graphene bilayer

International audienc

Non délivrance et infécondité: intérêts de l’étiproston et du dosage de la PAGI (pregnancy-associated glycoprotein I) au cours du postpartum chez la vache.

peer reviewedaudience: researcher, professional, studentSixty Prim'holstein cows with retained placenta for more than 24 hours after parturition, were shared in three groups of 20 cows each. All cows were delivred manually 24 to 36 hours post partum and received local treatment with 1 g of oxytetracyclin. Cows in group 1 received two intra-muscular injections of 5 mg etiproston on day of manual delivery (D1) and 15 days after (D15). Cows on group II received only one etiproston administration (D1), and cows in group III remained untreated. Ratios of delayed uterine involution were respectively 20, 40 and 55 % in groupsI,II and III(I<0.05;II<0.005). PAGI concentrations were checked 15 days after parturition and were significantly higher in cows affected by delayed uterine involution (p < 0.05). V-IAF intervals were significantly (p < 0.05) different between groups I (58 days), II (102 days) and III(143 days).Soixante vaches de race Prim'holstein, ayant présenté une rétention placentaire 24 heures après le vêlage sont réparties en trois lots I, II et III (Témoin) de 20 vaches chacun. Toutes les vaches ont fait l'objet d'une délivrance manuelle 24 à 36 heures après le part, complétée d'un traitement antibiotique local à base d'oxytétracycline sous forme de 2 oblets gynécologiques dosés à 500 mg chacun. Les vaches du lot 1 ont reçu deux injections de 5 mg d'étiproston par la voie IM, le jour de la délivrance manuelle (J1) et 15 jours plus tard (J15). Les animaux du lot II sont traités par une seule injection du même produit àJ1 alors que les vaches du lot III n'ont rien reçu. Un retard de l'involution utérine (RIU) est enregistré dans 20, 40 et 55 p. cent des cas respectivement dans les lots I, II, III. La différence entre les lots let II et entre les lots I et III est significative (p < 0,05). La concentration moyenne de PAGI à 15 jours après le vêlage est plus éle'vée significativement chez les vaches ayant un RIU (p < 0,05). L'intervalle V- IAF est de 58, 102 et 143 jours respectivement dans les lots I, II et III. La différence est significative entre les lots pris deux à deux (p <0,05)

Iron addition induced tunable band gap and tetravalent Fe ion in hydrothermally prepared SnO₂ nanocrystals: Application in photocatalysis

Highly iron-doped tin dioxide nanoparticles (Sn1−xFexO2 NPs), with x varying from 0 to 0.2, were prepared by simple hydrothermal method. X-ray diffraction (XRD) patterns indicate that Sn1−xFexO2 NPs crystallize in the tetragonal rutile-like structure. High-resolution transmission electron microscopy (HRTEM) observations did not show any modification of the SnO2 lattice parameters with Fe addition. Mössbauer spectroscopy indicated Sn4+ substitution by Fe3+ and Fe4+ ions. It was found that iron addition induced high tunable band gap of SnO2 NPs. Photoluminescence (PL) spectra evidenced an improvement of SnO2 crystallinity after Fe introduction. All the results are consistent with the fact that Fe is strongly soluble in SnO2 host. Finally, the photocatalytic efficiency of Sn1−xFexO2 NPs was examined for the degradation of rhodamine B in aqueous solution under visible light irradiation. We show that Fe4+ and Fe3+ ions play a key role in the improvement of the photocatalytic efficiency