Activiteit

Pregnancy induces a deep modification of women’s gut microbiota composition. These changes may influence hormonal and metabolic factors, increasing insulin resistance and leading to hyperglycaemia in susceptible women. Data on 29 women in pregnancy showed insignificant reductions in the Bacteroidetes/ Firmicutes ratio in women with (n. 14) and without (n. 15) gestational diabetes (GDM). Gut microbiota compositions at the genera and species level were further analysed in ten pregnant women with and ten without GDM (9 samples were excluded due to low DNA quality/quantity), showing differences in functionally specific patterns affecting host energy dietary polysaccharide metabolism pathways. According to our results, gut microbiome alteration may play a role in GDM pathogenesis through an increase of gut permeability and higher intestinal energetic balance.

Low back pain is responsible for more global disability than any other condition. Its incidence is closely related to intervertebral disc (IVD) failure, which is likely caused by an accumulation of microtrauma within the IVD. Crucial factors in microtrauma development are not entirely known yet, probably because their exploration in vivo or in vitro remains tremendously challenging. In-silico modelling is, therefore, definitively appealing, and shall include approaches to integrate influences of multiple cell stimuli at the microscale. Accordingly, this study introduces a hybrid Agent-based (AB) model in IVD research and exploits network modelling solutions in systems biology to mimic the cellular behaviour of Nucleus Pulposus cells exposed to a 3 D multifactorial biochemical environment, based on mathematical integrations of existing experimental knowledge. Bimiralisib research buy Cellular activity reflected by mRNA expression of Aggrecan, Collagen type I, Collagen type II, MMP-3 and ADAMTS were calculated for inflamed and non-in through referenced, published papers.

laura.baumgartner@upf.edu.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.

Empagliflozin (EMPA) is a potent inhibitor of the renal sodium-glucose cotransporter 2 (SGLT2) and an effective treatment for type-2 diabetes. In patients with diabetes and heart failure, EMPA has cardioprotective effects independent of improved glycaemic control, despite SGLT2 not being expressed in the heart. A number of non-canonical mechanisms have been proposed to explain these cardiac effects, most notably an inhibitory action on cardiac Na+/H+ exchanger 1 (NHE1), causing a reduction in intracellular [Na+] ([Na+]i). However, at resting intracellular pH (pHi), NHE1 activity is very low and its pharmacological inhibition is not expected to meaningfully alter steady-state [Na+]i. We re-evaluate this putative EMPA target by measuring cardiac NHE1 activity.

The effect of EMPA on NHE1 activity was tested in isolated rat ventricular cardiomyocytes from measurements of pHi recovery following an ammonium pre-pulse manoeuvre, using cSNARF1 fluorescence imaging. Whereas 10 µM cariporide produced near-complete unknown. Understanding this mechanism is clearly essential as the use of SGLT2 inhibitors in non-diabetics is increasing and a better understanding may allow refinement of therapeutic approaches in both HFpEF and HFrEF. One suggested mechanism that has received significant attention, inhibition of cardiac Na+/H+ exchanger, is investigated here.

The activity of a transcription factor (TF) in a sample of cells is the extent to which it is exerting its regulatory potential. Many methods of inferring TF activity from gene expression data have been described, but due to the lack of appropriate large-scale datasets, systematic and objective validation has not been possible until now.

We systematically evaluate and optimize the approach to TF activity inference in which a gene expression matrix is factored into a condition-independent matrix of control strengths and a condition-dependent matrix of TF activity levels. We find that expression data in which the activities of individual TFs have been perturbed are both necessary and sufficient for obtaining good performance. To a considerable extent, control strengths inferred using expression data from one growth condition carry over to other conditions, so the control strength matrices derived here can be used others. Finally, we apply these methods to gain insight into the upstream factors that regulate the activities of yeast TFs Gcr2, Gln3, Gcn4, and Msn2.

When a high-quality network map and TF perturbation-response data are available, inferring TF activity levels by factoring gene expression matrices is effective. Furthermore, it can provide insight into regulators of TF activity.

Evaluation code and data available at https//doi.org/10.5281/zenodo.4050573.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.Schizophrenia (SCZ) is a highly heterogeneous disorder with remarkable intersubject variability in clinical presentations. Previous neuroimaging studies in SCZ have primarily focused on identifying group-averaged differences in the brain connectome between patients and healthy controls (HCs), largely neglecting the intersubject differences among patients. We acquired whole-brain resting-state functional MRI data from 121 SCZ patients and 183 HCs and examined the intersubject variability of the functional connectome (IVFC) in SCZ patients and HCs. Between-group differences were determined using permutation analysis. Then, we evaluated the relationship between IVFC and clinical variables in SCZ. Finally, we used datasets of patients with bipolar disorder (BD) and major depressive disorder (MDD) to assess the specificity of IVFC alteration in SCZ. The whole-brain IVFC pattern in the SCZ group was generally similar to that in HCs. Compared with the HC group, the SCZ group exhibited higher IVFC in the bilateral sensorimotor, visual, auditory, and subcortical regions. Moreover, altered IVFC was negatively correlated with age of onset, illness duration, and Brief Psychiatric Rating Scale scores and positively correlated with clinical heterogeneity. Although the SCZ shared altered IVFC in the visual cortex with BD and MDD, the alterations of IVFC in the sensorimotor, auditory, and subcortical cortices were specific to SCZ. The alterations of whole-brain IVFC in SCZ have potential implications for the understanding of the high clinical heterogeneity of SCZ and the future individualized clinical diagnosis and treatment of this disease.