A high percentage of women having polycystic ovarian syndrome (PCOS) exhibit hyperinsulinemia and obesity. Transforming necrosis factor-α (TNF-α) is an adipokine that increases in obesity and ...negatively affects insulin action in several tissues, including the endometrium. In fact, it has been reported that insulin signaling is altered in the endometrium of PCOS women, affecting its reproductive function. The aim of this study was to determine the proinflammatory environment and TNF-α signaling in endometrium from obese women with PCOS, and also to evaluate the effect of TNF-α on endometrial cell energy homeostasis.
Serum and endometrial tissues were obtained from four study groups: normal-weight, normal-weight-PCOS, obese and obese-PCOS (hyperandrogenemia/hyperinsulinemia) (n=7 per group). Serum TNF-α level was assayed by enzyme-linked immunosorbent assay (ELISA); endometrial TNF-α level and its receptors (TNFR1/TNFR2) as well as nuclear factor (NF)-κB content were determined by immunohistochemistry. Finally, we evaluated TNF-α effect on glucose uptake in cultured human endometrial stromal cells (T-HESC) treated or not with testosterone/insulin resembling partially the PCOS condition.
TNF-α plasma levels were similar between groups, whereas cytokine levels and macrophage number increased in endometrium from obese-PCOS women (P<0.001). Both receptor types were higher in obese vs normal-weight women, particularly TNFR2 content in the obese-PCOS group (P<0.001). Furthermore, an increased NF-κB nuclear content in endometrium from obese-PCOS was observed (P<0.001). Finally, TNF-α treatment of T-HESC cultures exhibited a decrease of glucose uptake (P<0.05), although similar to cells treated with testosterone or testosterone/insulin/TNF-α.
These results suggest that the PCOS condition induces an inflammatory state exacerbated when obesity is present, where a higher TNF-α signaling is observed, all of which could affect glucose uptake in the tissue and may cause fertility failures in these women.
The neonatal mammal faces an array of sensory stimuli when diverse neuronal types have yet to form sensory maps. How these inputs interact with intrinsic neuronal activity to facilitate circuit ...assembly is not well understood. By using longitudinal calcium imaging in unanesthetized mouse pups, we show that layer I (LI) interneurons, delineated by co-expression of the 5HT3a serotonin receptor (5HT3aR) and reelin (Re), display spontaneous calcium transients with the highest degree of synchrony among cell types present in the superficial barrel cortex at postnatal day 6 (P6). 5HT3aR Re interneurons are activated by whisker stimulation during this period, and sensory deprivation induces decorrelation of their activity. Moreover, attenuation of thalamic inputs through knockdown of NMDA receptors (NMDARs) in these interneurons results in expansion of whisker responses, aberrant barrel map formation, and deficits in whisker-dependent behavior. These results indicate that recruitment of specific interneuron types during development is critical for adult somatosensory function.
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•5HT3aR Re interneurons in LI barrel cortex desynchronize by the second postnatal week•Whisker stimulation recruits 5HT3aR Re interneurons in the first postnatal week•Sensory deprivation and NMDAR knockdown in 5HT3aR Re interneurons disrupt synchrony•5HT3aR Re interneurons constrain pyramidal cell activation and barrel size
Che et al. combine genetic tools and longitudinal in vivo calcium imaging in young mouse pups to show that superficial interneurons participate in a transient thalamocortical circuit. Their recruitment is critical for the emergence of sensory maps and sensory discrimination.
A hallmark of multiple sclerosis (MS) is the formation of multiple focal demyelinating lesions within the central nervous system (CNS). These lesions mainly consist of phagocytes that play a key role ...in lesion progression and remyelination, and therefore represent a promising therapeutic target in MS. We recently showed that unsaturated fatty acids produced by stearoyl-CoA desaturase-1 induce inflammatory foam cell formation during demyelination. These fatty acids are elongated by the "elongation of very long chain fatty acids" proteins (ELOVLs), generating a series of functionally distinct lipids. Here, we show that the expression and activity of ELOVLs are altered in myelin-induced foam cells. Especially ELOVL6, an enzyme responsible for converting saturated and monounsaturated C16 fatty acids into C18 species, was found to be up-regulated in myelin phagocytosing phagocytes in vitro and in MS lesions. Depletion of
induced a repair-promoting phagocyte phenotype through activation of the S1P/PPARγ pathway.
-deficient foamy macrophages showed enhanced ABCA1-mediated lipid efflux, increased production of neurotrophic factors, and reduced expression of inflammatory mediators. Moreover, our data show that ELOVL6 hampers CNS repair, as
deficiency prevented demyelination and boosted remyelination in organotypic brain slice cultures and the mouse cuprizone model. These findings indicate that targeting ELOVL6 activity may be an effective strategy to stimulate CNS repair in MS and other neurodegenerative diseases.
The control of optical fields is usually achieved through the electro-optic or acousto-optic effect in single-crystal ferroelectric or polar compounds such as LiNbO3 or quartz. In recent years, ...tremendous progress has been made in ferroelectric oxide thin film technology-a field which is now a strong driving force in areas such as electronics, spintronics and photovoltaics. Here, we apply epitaxial strain engineering to tune the optical response of BiFeO3 thin films, and find a very large variation of the optical index with strain, corresponding to an effective elasto-optic coefficient larger than that of quartz. We observe a concomitant strain-driven variation in light absorption--reminiscent of piezochromism--which we show can be manipulated by an electric field. This constitutes an electrochromic effect that is reversible, remanent and not driven by defects. These findings broaden the potential of multiferroics towards photonics and thin film acousto-optic devices, and suggest exciting device opportunities arising from the coupling of ferroic, piezoelectric and optical responses.
Epidemiological research on the relationship between diet and asthma has increased in the last decade. Several components found in foods have been proposed to have a series of antioxidant, ...anti‐allergic and anti‐inflammatory properties, which can have a protective effect against asthma risk. Several literature reviews and critical appraisals have been published to summarize the existing evidence in this field. In the context of this EAACI Lifestyle and asthma Task Force, we summarize the evidence from existing systematic reviews on dietary intake and asthma, using the PRISMA guidelines. We therefore report the quality of eligible systematic reviews and summarize the results of those with an AMSTAR score ≥32. The GRADE approach is used to assess the overall quality of the existing evidence. This overview is centred on systematic reviews of nutritional components provided in the diet only, as a way to establish what type of advice can be given in clinical practice and to the general population on dietary habits and asthma.
Natural ventilation and balconies are two of the most desirable features of a living space in subtropical climates. The aim of this paper is to investigate the effect of balconies on natural ...ventilation performance and thermal comfort of residential buildings. To this end, in-situ full-scale measurements were carried out for Computational Fluid Dynamics (CFD) model validation and further analysis. A number of parameters such as balcony type, balcony depth, ventilation mode, and wind angle were used in developing case studies. Once validated, the CFD model was used for investigation of air movement inside each case study. Combined and separate effects of the defined parameters on natural ventilation performance were evaluated using air velocity and Standard Effective Temperature (SET*) as criteria. The results indicate that the addition of a balcony to a building with single-sided ventilation can improve the ventilation performance. In contrast, indoor air velocity was reduced as a result of balcony addition when the case study was operated in cross ventilation mode. Furthermore, ventilation performance of single-sided ventilation was found to be more sensitive to the change of parameters compared to that of the cross ventilation. It has also been found that among the investigated parameters, incident wind angle affects the ventilation performance most for both natural ventilation modes.
•The effect of balcony type, depth, ventilation mode, and wind direction on ventilation performance was investigated.•The addition of balcony to cross ventilation reduces the indoor air velocity.•Provision of an open balcony to single-sided ventilation improves the ventilation performance.•Ventilation performance of single-sided ventilation is mostly affected by the prevailing wind direction.
► Positive effect of R&D intensity on sales growth in European firms. ► Investment in R&D makes a bigger contribution to the rates of growth of high-growth firms. ► The positive effect of R&D ...intensity on sales growth is notably significant in high-technology sectors.
Following recent literature, we present a model of endogenous firm growth with R&D investment as one of the main mechanisms of growth. Our study evidences a positive effect of R&D intensity on the sales growth by using OLS, quantile regressions, and GMM system estimators for a sample of 754 European firms for the 2003–2007 period. We also find this association is more intense in high-growth firms and is especially significant when referring to high-technology sectors. This paper gives empirical support to those recommendations from policy makers and business leaders for maintaining the R&D expenditures especially in high-technology sectors even when facing a recession.
Recipients of extended criteria donor (ECD) kidneys are at increased risk for graft dysfunction/loss, and may benefit from immunosuppression that avoids calcineurin inhibitor (CNI) nephrotoxicity. ...Belatacept, a selective costimulation blocker, may preserve renal function and improve long‐term outcomes versus CNIs. BENEFIT‐EXT (Belatacept Evaluation of Nephroprotection and Efficacy as First‐line Immunosuppression Trial—EXTended criteria donors) is a 3‐year, Phase III study that assessed a more (MI) or less intensive (LI) regimen of belatacept versus cyclosporine in adult ECD kidney transplant recipients. The coprimary endpoints at 12 months were composite patient/graft survival and a composite renal impairment endpoint. Patient/graft survival with belatacept was similar to cyclosporine (86% MI, 89% LI, 85% cyclosporine) at 12 months. Fewer belatacept patients reached the composite renal impairment endpoint versus cyclosporine (71% MI, 77% LI, 85% cyclosporine; p = 0.002 MI vs. cyclosporine; p = 0.06 LI vs. cyclosporine). The mean measured glomerular filtration rate was 4–7 mL/min higher on belatacept versus cyclosporine (p = 0.008 MI vs. cyclosporine; p = 0.1039 LI vs. cyclosporine), and the overall cardiovascular/metabolic profile was better on belatacept versus cyclosporine. The incidence of acute rejection was similar across groups (18% MI; 18% LI; 14% cyclosporine). Overall rates of infection and malignancy were similar between groups; however, more cases of posttransplant lymphoproliferative disorder (PTLD) occurred in the CNS on belatacept. ECD kidney transplant recipients treated with belatacept‐based immunosuppression achieved similar patient/graft survival, better renal function, had an increased incidence of PTLD, and exhibited improvement in the cardiovascular/metabolic risk profile versus cyclosporine‐treated patients.
In a Phase III trial in recipients of extended criteria donor kidneys, patients treated with belatacept‐based immunosuppression achieved similar patient/graft survival, better renal function, and a better cardiovascular/metabolic profile but with a higher incidence of PTLD as compared to treatment with cyclosporine. See editorial by Kaplan on page 441.
Fatty Acid Synthesis in Glial Cells of the CNS Garcia Corrales, Aida V.; Haidar, Mansour; Bogie, Jeroen F. J. ...
International journal of molecular sciences,
08/2021, Letnik:
22, Številka:
15
Journal Article
Recenzirano
Odprti dostop
Fatty acids (FAs) are of crucial importance for brain homeostasis and neural function. Glia cells support the high demand of FAs that the central nervous system (CNS) needs for its proper ...functioning. Additionally, FAs can modulate inflammation and direct CNS repair, thereby contributing to brain pathologies such Alzheimer’s disease or multiple sclerosis. Intervention strategies targeting FA synthesis in glia represents a potential therapeutic opportunity for several CNS diseases.
The clinical profile of belatacept in kidney transplant recipients was evaluated to determine if earlier results in the BENEFIT study were sustained at 3 years. BENEFIT is a randomized 3 year, phase ...III study in adults receiving a kidney transplant from a living or standard criteria deceased donor. Patients were randomized to a more (MI) or less intensive (LI) regimen of belatacept, or cyclosporine. 471/666 patients completed ≥3 years of therapy. A total of 92% (MI), 92% (LI), and 89% (cyclosporine) of patients survived with a functioning graft. The mean calculated GFR (cGFR) was ∼21 mL/min/1.73 m2 higher in the belatacept groups versus cyclosporine at year 3. From month 3 to month 36, the mean cGFR increased in the belatacept groups by +1.0 mL/min/1.73 m2/year (MI) and +1.2 mL/min/1.73 m2/year (LI) versus a decline of −2.0 mL/min/1.73 m2/year (cyclosporine). One cyclosporine‐treated patient experienced acute rejection between year 2 and year 3. There were no new safety signals and no new posttransplant lymphoproliferative disorder (PTLD) cases after month 18. Belatacept‐treated patients maintained a high rate of patient and graft survival that was comparable to cyclosporine‐treated patients, despite an early increased occurrence of acute rejection and PTLD.
Three‐year results from the BENEFIT study confirm the durability of the renal function benefits of belatacept over time compared to cyclosporine, balancing the early risks (acute rejection, posttransplant lymphoproliferative disorder) associated with belatacept.
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