Search

Pregnant women that are obese may develop gestational diabetes mellitus (GDM) configuring a new metabolic condition referred to as gestational diabesity. The metabolic alterations seen in gestational diabesity include a combination of an exacerbated pro-inflammatory state and fetoplacental endothelial dysfunction. Also, gestational diabesity associates with supra-physiological extracellular concentration of adenosine in the foetoplacental blood. Since adenosine plays a central role in the inflammatory response in GDM and obesity, it is likely that this nucleoside will play a similar role in gestational diabesity. However, the effect of adenosine in the foetoplacental vasculature in this condition is not yet addressed. Adenosine exerts its biological actions via four adenosine receptors. Activation of A2B adenosine receptors (A2BAR) subtype associates with an anti-inflammatory response in several tissue and diseases. In tissues from pregnant women with GDM, there is an overexpression of A2BAR, and higher mRNA expression of ADORA2B (for A2BAR) was shown to correlate with hyperglycaemia and oxidative stress. A2BAR shows low affinity for adenosine (micromolar) and its activation results in triggering intracellular signalling cascades lowering the inflammatory response. This phenomenon requires a high level of extracellular adenosine in diseases of pregnancy such as GDM or gestational diabesity. In this review, we focused on the role of A2BAR involvement in the biological actions of adenosine on inflammation in the foetoplacental vasculature in gestational diabesity. Some factors including oxidative stress and hypoxia in this phenomenon are discussed.

Diabesity is an abnormal metabolic condition shown by patients with obesity that develop type 2 diabetes mellitus. Patients with diabesity present with insulin resistance, reduced vascular response to insulin, and vascular endothelial dysfunction. Along with the several well-described mechanisms of insulin resistance, a state of endoplasmic reticulum (ER) stress, where the primary human targets are the adipose tissue, liver, skeletal muscle, and the foetoplacental vasculature, is apparent. ER stress characterises by the activation of the unfolded protein response via three canonical ER stress sensors, i.e., the protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6. Slightly different cell signalling mechanisms preferentially enable in diabesity in the ER stress-associated insulin resistance for adipose tissue (IRE1α/X-box binding protein 1 mRNA splicing/c-jun N-terminal kinase 1 activation), skeletal muscle (tribbles-like protein 3 (TRB3)/proinflammatory cytokines activation), and liver (PERK/activating transcription factor 4/TRB3 activation). There is no information in human subjects with diabesity in the foetoplacental vasculature. However, the available literature shows that pregnant women with pre-pregnancy obesity or overweight that develop gestational diabetes mellitus (GDM) and their newborn show insulin resistance. ER stress is recently reported to be triggered in endothelial cells from the human umbilical vein from mothers with pre-pregnancy obesity. However, whether a different metabolic alteration to obesity in pregnancy or GDM is present in women with pre-pregnancy obesity that develop GDM, is unknown. In this review, we summarised the findings on diabesity-associated mechanisms of insulin resistance with emphasis in the primary targets adipose, skeletal muscle, liver, and foetoplacental tissues. We also give evidence on the possibility of a new GDM-associated metabolic condition triggered in pregnancy by maternal obesity, i.e. gestational diabesity, leading to ER stress-associated insulin resistance in the human foetoplacental vasculature.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by severe and persistent fatigue. Along with clinical studies showing endothelial dysfunction (ED) in a subset of ME/CFS patients, we have recently reported altered ED-related microRNAs in plasma from affected individuals. Inadequate nitric oxide (NO), mainly produced by the endothelial isoform of nitric oxide synthase (eNOS) in endothelial cells (ECs), is a major cause of ED. In this study, we hypothesized that plasma from that cohort of ME/CFS patients induces eNOS-related ED in vitro. To test this, we cultured human umbilical vein endothelial cells (HUVECs) in the presence of plasma from either ME/CFS patients (ME/CFS-plasma, n = 11) or healthy controls (HC-plasma, n = 12). Then, we measured the NO production in the absence and presence of tyrosine kinase and G protein-coupled receptors agonists (TKRs and GPCRs, respectively), well-known to activate eNOS in ECs. Our data showed that HUVECs incubated with ME/CFS-plasma produced less NO either in the absence or presence of eNOS activators compared to ones in presence of HC-plasma. Also, the NO production elicited by bradykinin, histamine, and acetylcholine (GPCRs agonists) was more affected than the one triggered by insulin (TKR agonist). Finally, inhibitory eNOS phosphorylation at Thr

Sub-daily rainfall observations are vital to help us understand, model and adapt to changing climate extremes. However, gauge records often have quality issues, for example due to equipment malfunctions and recording errors. This paper presents a new, open-source quality control algorithm (GSDR-QC) to identify these issues in hourly rainfall data, along with an application of the algorithm to the Global Sub-Daily Rainfall (GSDR) observational dataset. The algorithm is based on 25 quality checks, which are combined into a simple rule base to remove suspicious data. The quality checks and rule base are adaptable to help incorporate local or regional information. Comparison with manually quality-controlled gauge data shows that the procedure results in an overall improvement to the quality of the GSDR dataset. A UK case study further demonstrates the performance of the GSDR-QC procedure, while showing how region-specific data and understanding can be incorporated into the quality control process.

A typical nucleolus structure is shaped by three components. A meshwork of fine fibers forming the fibrillar center (FC) is surrounded by densely packed fibers forming the dense fibrillar component (DFC). Meanwhile, wrapping the FC and DFC is the granular component (GC). During the mitotic prophase, the nucleolus undergoes disassembling of its components. On the contrary, throughout the first meiotic prophase that occurs in the cells of the germ line, small nucleoli are assembled into one nucleolus by the end of the prophase. These nucleoli are transcriptionally active, suggesting that they are fully functional. Electron microscopy analysis has suggested that these nucleoli display their three main components but a typical organization has not been observed. Here, by immunolabeling and electron microscopy, we show that the nucleolus has its three main components. The GC is interlaced with the DFC and is not as well defined as previously thought during leptotene and zygotene stage.

Leaf wetness duration (LWD) estimation models developed in the midwestern U.S. were assessed for portability to northwestern Costa Rica during wet and dry seasons. The CART/SLD/Wind (CART) model overestimated LWD by 5.4 h at five sites in northwestern Costa Rica during the 1999 wet season. The Fuzzy (FL) model, in contrast, estimated LWD at the same sites within 3 h. During the 2000–2001 and 2002–2003 dry seasons, both models underestimated LWD at most sites, probably due to the prevalence of less humid conditions than in the temperate climate of the midwestern U.S. However, accuracy of the FL model was substantially improved when a correction factor was utilized during the 2002–2003 dry season, indicating that this model could be adjusted to estimate LWD in a semi-arid climate with acceptable accuracy. The results suggested that the adjusted FL model could estimate LWD accurately in other tropical regions with climate regimes similar to northwestern Costa Rica.

Pathophysiological mechanisms involved in obesity include insulin resistance and endothelial dysfunction. It has been reported that endoplasmic reticulum stress (ERS) plays a key role in these mechanisms. Objective: To determine possible alterations in th