Bullardlorentzen8409

Seventeen species of fungi belonging to thirteen genera were screened for the ability to carry out the transformation of 7-oxo-DHEA (7-oxo-dehydroepiandrosterone). Some strains expressed new patterns of catalytic activity towards the substrate, namely 16β-hydroxylation (Laetiporus sulphureus AM498), Baeyer-Villiger oxidation of ketone in D-ring to lactone (Fusicoccum amygdali AM258) and esterification of the 3β-hydroxy group (Spicaria divaricata AM423). The majority of examined strains were able to reduce the 17-oxo group of the substrate to form 3β,17β-dihydroxy-androst-5-en-7-one. The highest activity was reached with Armillaria mellea AM296 and Ascosphaera apis AM496 for which complete conversion of the starting material was achieved, and the resulting 17β-alcohol was the sole reaction product. Two strains of tested fungi were also capable of stereospecific reduction of the conjugated 7-keto group leading to 7β-hydroxy-DHEA (Inonotus radiatus AM70) or a mixture of 3β,7α,17β-trihydroxy-androst-5-ene and 3β,7β,17β-trihydroxy-androst-5-ene (Piptoporus betulinus AM39). The structures of new metabolites were confirmed by MS and NMR analysis. They were also examined for their cholinesterase inhibitory activity in an enzymatic-based assay in vitro test.Currently over 30 000 allogeneic hematopoietic stem cell (HSC) transplantations have been performed for the treatment of hematological and nonhematological diseases using HSC from umbilical cord blood (CB). However, the wide utilization of CB as a source of HSC is limited by the low number of cells recovered. Immunology inhibitor One strategy to expand ex vivo CB-HSC is represented by the use of bone marrow mesenchymal stromal cells (BM-MSCs) as a feeder to enhance HSC proliferation while maintaining HSC stemness. Indeed, BM-MSCs have been recognized as one of the most relevant players in the HSC niche. Thus, it has been hypothesized that they can support the ex vivo expansion of HSC by mimicking the physiological microenvironment present in the hematopoietic niche. Due to the role of placenta in supporting fetal hematopoiesis, MSC derived from the amniotic membrane (hAMSC) of human term placenta could represent an interesting alternative to BM-MSC as a feeder layer to enhance the proliferation and maintain HSC stemness. Therefore, in this study we investigated if hAMSC could support the ex vivo expansion of HSC and progenitor cells. The capacity of hAMSCs to support the ex vivo expansion of CB-HSC was evaluated in comparison to the control condition represented by the CB-CD34+ cells without a feeder layer. The coculture was performed at two different CD34+ MSC ratios (12 and 18) in both cell-to-cell contact and transwell setting. After 7 days, the cells were collected and analyzed for phenotype and functionality. Our results suggest that hAMSCs represent a valuable alternative to BM-MSC to support (a) the ex vivo expansion of CB-HSC in both contact and transwell systems, (b) the colony forming unit ability, and (c) long-term culture initiating cells ability. Overall, these findings may contribute to address the unmet need of high HSC content in CB units available for transplantation.There are several examples of single mutations that lead to a well-defined disease through a well-known mechanism. In other cases, a collection of mutations of the same protein produces a pathology with different degrees of severity. The accompanying work by Uusitalo et al. studies several mutants of the fatty acid binding protein P2 of the peripheral nervous system myelin. They conserve the native tertiary structure but a remarkable difference in the capacity to interact with lipids. This could be a clue to unravel the complex way in which these mutations affect myelin structure and function in a variant of Charcot-Marie-Tooth disease. Comment on https//doi.org/10.1111/febs.16079.Lymphocytes require of constant and dynamic changes in their transcriptome for timely activation and production of effector molecules to combat external pathogens. Synthesis and translation of messenger (m)RNAs into these effector proteins is controlled both quantitatively and qualitatively by RNA binding proteins (RBPs). RBP-dependent regulation of RNA editing, subcellular location, stability, and translation shapes immune cell development and immunity. Extensive evidences have now been gathered from few model RBPs, HuR, PTBP1, ZFP36, and Roquin. However, recently developed methodologies for global characterization of proteinRNA interactions suggest the existence of complex RNA regulatory networks in which RBPs co-ordinately regulate the fate of sets of RNAs controlling cellular pathways and functions. In turn, RNA can also act as scaffolding of functionally related proteins modulating their activation and function. Here we review current knowledge about how RBP-dependent regulation of RNA shapes our immune system and discuss about the existence of a hidden immune cell epitranscriptome. This article is categorized under RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions Functional Implications.

Metabolomic analysis is commonly used to understand the biological underpinning of diseases such as obesity. However, our knowledge of gut metabolites related to weight outcomes in young children is currently limited.

To (1) explore the relationships between metabolites and child weight outcomes, (2) determine the potential effect of covariates (e.g., child's diet, maternal health/habits during pregnancy, etc.) in the relationship between metabolites and child weight outcomes, and (3) explore the relationship between selected gut metabolites and gut microbiota abundance.

Using

H-NMR, we quantified 30 metabolites from stool samples of 170 two-year-old children. To identify metabolites and covariates associated with children's weight outcomes (BMI [weight/height

], BMI z-score [BMI adjusted for age and sex], and growth index [weight/height]), we analysed the

H-NMR data, along with 20 covariates recorded on children and mothers, using LASSO and best subset selection regression techniques. Previously characterized microbiota community information from the same stool samples was used to determine associations between selected gut metabolites and gut microbiota.

At age 2 years, stool butyrate concentration had a significant positive association with child BMI (p-value=3.58 × 10

), BMI z-score (p-value=3.47 × 10

), and growth index (p-value=7.73 × 10

). Covariates such as maternal smoking during pregnancy are important to consider. Butyrate concentration was positively associated with the abundance of the bacterial genus Faecalibacterium (p-value=9.61 × 10

).

Stool butyrate concentration is positively associated with increased child weight outcomes and should be investigated further as a factor affecting childhood obesity.

Stool butyrate concentration is positively associated with increased child weight outcomes and should be investigated further as a factor affecting childhood obesity.Growth in pork production during the last decade in South Africa has escalated the risk of zoonotic pathogen emergence. This cross-sectional study was conducted to evaluate evidence for transmission of influenza A virus between pigs and swine workers. Between February and October 2018, samples from swine workers and pigs were collected from three farms in KwaZulu-Natal Province, South Africa. Workers nasal washes and serum samples, and swine oral secretion samples (rope sampling method) were studied for evidence of swine influenza A virus infection using molecular and serological methods. Among 84 human nasal washes and 51 swine oral secretion specimens, 44 (52.4%) and 6 (11.8%) had molecular evidence of influenza A virus. Microneutralization assays with workers' enrolment sera against swine H1N1 and H3N2 viruses revealed a high prevalence of elevated antibodies. Multivariate risk factor analysis showed that male workers from the age-group quartile 23-32 years, who self-reported a recent history of exposure to someone with influenza disease and seldom use of personal protective equipment were at highest risk of molecular detection of influenza A virus. These pilot study data suggest that influenza A viruses are likely highly prevalent in South African swine farms. South Africa would benefit from periodic surveillance for novel influenza viruses in swine farms as well as education and seasonal influenza vaccine programmes for swine workers.Here, we present the case of an 81-year-old male patient, who was hospitalized for a severe form of COVID-19. Transthoracic echocardiogram (TTE) performed 1 month after symptom onset was normal. Respiratory evolution was favourable, and the patient was discharged at Day 78. At 6 months, despite a good functional recovery, he presented pulmonary sequelae, and the TTE revealed a clear reduction of left ventricular ejection fraction (LVEF) and mild LV dilatation without cardiac symptoms. The cardiac magnetic resonance (CMR) using Lake Louise Criteria (LLC), T1 and T2 mapping showed focal infero-basal LV wall oedema, elevated T1 and T2 myocardial relaxation times especially in basal inferior and infero-lateral LV walls, and sub-epicardial late gadolinium enhancement in those LV walls. The diagnosis of active myocarditis was raised especially based on TTE abnormalities and CMR LLC, T1 and T2 mapping. Currently, we are not aware of published reports of a 6 month post-COVID-19 active myocarditis.Standard meta-analysis methods are vulnerable to bias from incomplete reporting of results (both publication and outcome reporting bias) and poor study quality. Several alternative methods have been proposed as being less vulnerable to such biases. To evaluate these claims independently we simulated study results under a broad range of conditions first with no bias, then introducing simulated publication bias, outcome reporting bias, and bias from poor study quality. We then implemented common and the proposed bias robust meta-analysis methods and compared the mean bias and mean squared error (MSE) for four estimates of effect and the coverage probability of seven confidence intervals. We found that no methods perform well in the presence of any substantial bias. A regression based extension to Egger's test gave an estimate of effect with lower mean bias than standard methods in the presence of publication bias or poor study quality, but had a substantially worse MSE except in very specific conditions. Coverage of all 95% confidence intervals was very poor with increasing numbers of studies in biased conditions, often falling below 50%. The Knapp-Hartung interval performed closest to nominal coverage with fewer than 10 studies in most conditions, and the Henmi-Copas interval generally performed best with more than 10 studies. There was no evidence that a multiplicative term for heterogeneity improved coverage. Multiple forms of bias remain problematic for all meta-analysis methods, with very poor performance under conceivable conditions.

Oxidative stress plays an important role in the development and progression of heart failure (HF). Although exercise and oxidative stress are closely related, the effect of acute exercise on reactive oxygen species production and the fluctuation on prognosis are unclear.

We enrolled 94 patients who were hospitalized for worsening HF (mean age 68.0±14.5years old, 63.8% male). The changes in diacron-reactive oxygen metabolites (d-ROM) values, a marker of oxidative stress, before and after a cardiopulmonary exercise test were considered as Δd-ROM. The mean follow-up period was 24±13months, during which 15 patients had all-cause death or left ventricular assist system implantation. Kaplan-Meier analysis demonstrated that all-cause death or left ventricular assist system implantation was significantly higher in the Δd-ROM-positive group than in the Δd-ROM-negative group (log-rank P=0.047). Elevated Δd-ROM levels were associated with increased mortality risk. Multivariate analysis adjusted for body mass index and peak oxygen uptake revealed that Δd-ROM was an independent prognostic factor of adverse events (Tertile 3 vs.