Adipose Tissue Dysregulation and Reduced Insulin Sensitivity in Non-Obese Individuals with Enlarged Abdominal Adipose Cells

Background: Obesity contributes to Type 2 diabetes by promoting systemic insulin resistance. Obesity causes features of metabolic dysfunction in the adipose tissue that may contribute to later impairments of insulin action in skeletal muscle and liver; these include reduced insulin-stimulated glucose transport, reduced expression of GLUT4, altered expression of adipokines, and adipocyte hypertrophy. Animal studies have shown that expansion of adipose tissue alone is not sufficient to cause systemic insulin resistance in the absence of adipose tissue metabolic dysfunction. To determine if this holds true for humans, we studied the relationship between insulin resistance and markers of adipose tissue dysfunction in non-obese individuals. Method 32 non-obese first-degree relatives of Type 2 diabetic patients were recruited. Glucose tolerance was determined by an oral glucose tolerance test and insulin sensitivity was measured with the hyperinsulinaemic-euglycaemic clamp. Blood samples were collected and subcutaneous abdominal adipose tissue biopsies obtained for gene/protein expression and adipocyte cell size measurements. Results: Our findings show that also in non-obese individuals low insulin sensitivity is associated with signs of adipose tissue metabolic dysfunction characterized by low expression of GLUT4, altered adipokine profile and enlarged adipocyte cell size. In this group, insulin sensitivity is positively correlated to GLUT4 mRNA (R = 0.49, p = 0.011) and protein (R = 0.51, p = 0.004) expression, as well as with circulating adiponectin levels (R = 0.46, 0 = 0.009). In addition, insulin sensitivity is inversely correlated to circulating RBP4 (R = −0.61, 0 = 0.003) and adipocyte cell size (R = −0.40, p = 0.022). Furthermore, these features are inter-correlated and also associated with other clinical features of the metabolic syndrome in the absence of obesity. No association could be found between the hypertrophy-associated adipocyte dysregulation and HIF-1alpha in this group of non-obese individuals. Conclusions: In conclusion, these findings support the concept that it is not obesity per se, but rather metabolic dysfunction of adipose tissue that is associated with systemic insulin resistance and the metabolic syndrome

Identification of a putative man-made object from an underwater crash site using CAD model superimposition

In order to identify an object in video, a comparison with an exemplar object is typically needed. In this paper, we discuss the methodology used to identify an object detected in underwater video that was recorded during an investigation into Amelia Earhart\u27s purported crash site. A computer aided design (CAD) model of the suspected aircraft component was created based on measurements made from orthogonally rectified images of a reference aircraft, and validated against historical photographs of the subject aircraft prior to the crash. The CAD model was then superimposed on the underwater video, and specific features on the object were geometrically compared between the CAD model and the video. This geometrical comparison was used to assess the goodness of fit between the purported object and the object identified in the underwater video

The normal ranges of cardiovascular parameters measured using the ultrasonic cardiac output monitor

The ultrasonic cardiac output monitor (USCOM) is a noninvasive transcutaneous continuous wave Doppler method for assessing hemodynamics. There are no published reference ranges for normal values in adults (aged 18– 60 years) for this device. This study aimed to (1) measure cardiovascular indices using USCOM in healthy adults aged 18–60 years; (2) combine these data with those for healthy children (aged 0–12), adolescents (aged 12–18), and the elderly (aged over 60) from our previously published studies in order to present normal ranges for all ages, and (3) establish normal ranges of USCOM-derived variables according to both weight and age. This was a population- based cross-sectional observational study of healthy Chinese subjects aged 0.5–89 years in Hong Kong. USCOM scans were performed on all subjects, to produce measurements including stroke volume, cardiac output, and systemic vascular resistance. Data from previously published studies (children, adolescents, and the elderly) were included. Normal ranges were defined as lying between the 2.5th and 97.5th percentiles. A total of 2218 subjects were studied (mean age = 16.4, range = 0.5–89; 52% male). From previous studies, 1197 children (aged 0–12, 55% male), 590 adolescents (aged 12–18, 49% male), and 77 elderly (aged 60–89, 55% male) were included. New data were collected from 354 adults aged 18–60 (47% male). Normal ranges are presented according to age and weight. We present comprehensive normal ranges for hemodynamic parameters obtained with USCOM in healthy subjects of all ages from infancy to the elderly

Modelling Immunological Systems using PEPA: a preliminary report

We present preliminary work on modelling aspects of the immune system using process algebra. The problem addressed is how T-helper cell populations respond to co-infections with parasites making conflicting immunological demands. Our goal is to build PEPA models of alternative hypotheses around T-helper cell behaviour and to evaluate those with respect to experimental data

Seismic evidence for shallow gas-escape features associated with a retreating gas hydrate zone offshore west Svalbard

Active gas venting occurs on the uppermost continental slope off west Svalbard, close to and upslope from the present-day intersection of the base of methane hydrate stability (BMHS) with the seabed in about 400 m water depth in the inter-fan region between the Kongsfjorden and Isfjorden cross-shelf troughs. From an integrated analysis of high-resolution, two-dimensional, pre-stack migrated seismic reflection profiles and multibeam bathymetric data, we map out a bottom simulating reflector (BSR) in the inter-fan region and analyze the subsurface gas migration and accumulation. Gas seeps mostly occur in the zone from which the BMHS at the seabed has retreated over the recent past (1975–2008) as a consequence of a bottom water temperature rise of 1°C. The overall margin-parallel alignment of the gas seeps is not related to fault-controlled gas migration, as seismic evidence of faults is absent. There is no evidence for a BSR close to the gas flare region in the upper slope but numerous gas pockets exist directly below the predicted BMHS. While the contour following trend of the gas seeps could be a consequence of retreat of the landward limit of the BMHS and gas hydrate dissociation, the scattered distribution of seeps within the probable hydrate dissociation corridor and the occurrence of a cluster of seeps outside the predicted BMHS limit and near the shelf break indicate the role of lithological heterogeneity in focusing gas migration

Inhibition of Toll-Like Receptor 4 Signaling Mitigates Microvascular Loss but Not Fibrosis in a Model of Ischemic Acute Kidney Injury

The development of chronic kidney disease (CKD) following an episode of acute kidney injury (AKI) is an increasingly recognized clinical problem. Inhibition of toll-like receptor 4 (TLR4) protects renal function in animal models of AKI and has become a viable therapeutic strategy in AKI. However, the impact of TLR4 inhibition on the chronic sequelae of AKI is unknown. Consequently, we examined the chronic effects of TLR4 inhibition in a model of ischemic AKI. Mice with a TLR4-deletion on a C57BL/6 background and wild-type (WT) background control mice (C57BL/6) were subjected to bilateral renal artery clamping for 19 min and reperfusion for up to 6 weeks. Despite the acute protective effect of TLR4 inhibition on renal function (serum creatinine 1.6 ± 0.4 mg/dL TLR4-deletion vs. 2.8 ± 0.3 mg/dL·WT) and rates of tubular apoptosis following ischemic AKI, we found no difference in neutrophil or macrophage infiltration. Furthermore, we observed significant protection from microvascular rarefaction at six weeks following injury with TLR4-deletion, but this did not alter development of fibrosis. In conclusion, we validate the acute protective effect of TLR4 signal inhibition in AKI but demonstrate that this protective effect does not mitigate the sequential fibrogenic response in this model of ischemic AKI