Adipocyte mitochondrial genes and the forkhead factor FOXC2 are decreased in type 2 diabetes patients and normalized in response to rosiglitazone

<p>Abstract</p> <p>Background</p> <p>FOXC2 has lately been implicated in diabetes and obesity as well as mitochondrial function and biogenesis and also as a regulator of mtTFA/Tfam. In this study, the expression of FOXC2 and selected genes involved in mitochondrial function and biogenesis in healthy subjects and in a matched cohort with type 2 diabetes patients before and after treatment with rosiglitazone was determined. Quantitative real time PCR was used to analyze both RNA and DNA from biopsies from subcutaneous adipose tissue.</p> <p>Methods</p> <p>Blood samples and subcutaneous abdominal fat biopsies were collected from 12 T2D patients, of which 11 concluded the study, pre-treatment and 90 days after initiation of rosiglitazone treatment, and from 19 healthy control subjects on the first and only visit from healthy subjects. Clinical parameters were measured on the blood samples. RNA and DNA were prepared from the fat biopsies and gene expression was measured with real time PCR.</p> <p>Results</p> <p>The expression level of genes in the mitochondrial respiratory complexes I - IV were significantly downregulated in the diabetic patients and restored in response to rosiglitazone treatment. Rosiglitazone treatment also increased the relative number of mitochondria in diabetic patients compared with controls. Furthermore, the transcription factors FOXC2 and mtTFA/Tfam displayed a response pattern identical to the mitochondrial genes.</p> <p>Conclusions</p> <p>FOXC2, mtTFA/Tfam and subunits of the respiratory complexes I - IV show equivalent regulation in gene expression levels in response to TZD treatment. This, together with the knowledge that FOXC2 has a regulatory function of mtTFA/Tfam and mitochondrial biogenesis, suggests that FOXC2 has a possible functional role in the TZD activated mitochondrial response.</p

Allergy from infancy to adolescence. A population-based 18-year follow-up cohort

<p>Abstract</p> <p>Background</p> <p>Anxious parents have many concerns about the future health of their atopic infants. Paediatricians and primary care practitioners need to seek knowledge on long-term outcomes in order to cope with the increasing caseload of suspected allergy and the concerns of parents. The aim of the study was to assess suspected and diagnosed allergy in infancy as predictors of allergy and asthma in adolescence.</p> <p>Methods</p> <p>Families expecting their first baby and making their first visit to a maternity health care clinic in 1986 were selected as the study population in a random sample. There were 1278 eligible study families. The data were provided of the children at the ages of 9 and 18 months and 3, 5, 12, 15 and 18 years by health care professionals, parents, and adolescents (themselves).</p> <p>Results</p> <p>At the age of 9 months, the prevalence of allergy suspicions was distinctly higher than that of allergy diagnoses. At the age of five years suspected allergy approaches were nil, and the prevalence of diagnosed allergy was about 9%. During the adolescence, the prevalence of self-reported allergy increases steadily up to the age of 18 years, and that of asthma remains at approximately 5%. Suspected allergy at the age of 9 or 18 months and at the 5 years of age does not predict allergy at adolescence. Compared with non-allergic children, children with definite allergy at the age of 5 were over 8 times more likely to have allergy and nearly 7 times more likely to have asthma in adolescence.</p> <p>Conclusion</p> <p>An early ascertained diagnosis of allergy, but not suspicions of allergy, predicts prevailing allergy in adolescence. Efforts need to be focused on accurate diagnosis of early childhood allergies.</p

The New Legal Pluralism

Scholars studying interactions among multiple communities have often used the term legal pluralism to describe the inevitable intermingling of normative systems that results from these interactions. In recent years, a new application of pluralist insights has emerged in the international and transnational realm. This review aims to survey and help define this emerging field of global legal pluralism. I begin by briefly describing sites for pluralism research, both old and new. Then I discuss how pluralism has come to be seen as an attractive analytical framework for those interested in studying law on the world stage. Finally, I identify advantages of a pluralist approach and respond to criticisms, and I suggest ways in which pluralism can help both in reframing old conceptual debates and in generating useful normative insights for designing procedural mechanisms, institutions, and discursive practices for managing hybrid legal/cultural spaces

Small bowel MR enterography: problem solving in Crohn’s disease

Magnetic resonance enterography (MRE) is fast becoming the first-line radiological investigation to evaluate the small bowel in patients with Crohn’s disease. It can demonstrate both mural and extramural complications. The lack of ionizing radiation, together with high-contrast resolution, multiplanar capability and cine-imaging make it an attractive imaging modality in such patients who need prolonged follow-up. A key question in the management of such patients is the assessment of disease activity. Clinical indices, endoscopic and histological findings have traditionally been used as surrogate markers but all have limitations. MRE can help address this question. The purpose of this pictorial review is to (1) detail the MRE protocol used at our institution; (2) describe the rationale for the MR sequences used and their limitations; (3) compare MRE with other small bowel imaging techniques; (4) discuss how MRE can help distinguish between inflammatory, stricturing and penetrating disease, and thus facilitate management of this difficult condition

The environmental impact of fertilizer embodied in a wheat-to-bread supply chain

Food production and consumption cause approximately one-third of total greenhouse gas emissions, and therefore delivering food security challenges not only the capacity of our agricultural system, but also its environmental sustainability. Knowing where and at what level environmental impacts occur within particular food supply chains is necessary if farmers, agri-food industries and consumers are to share responsibility to mitigate these impacts. Here we present an analysis of a complete supply chain for a staple of the global diet, a loaf of bread. We obtained primary data for all the processes involved in the farming, production and transport systems that lead to the manufacture of a particular brand of 800 g loaf. The data were analysed using an advanced life cycle assessment (LCA) tool, yielding metrics of environmental impact, including greenhouse gas emissions. We show that more than half of the environmental impact of producing the loaf of bread arises directly from wheat cultivation, with the use of ammonium nitrate fertilizer alone accounting for around 40%. These findings reveal the dependency of bread production on the unsustainable use of fertilizer and illustrate the detail needed if the actors in the supply chain are to assume shared responsibility for achieving sustainable food production

Airflow Dynamics of Coughing in Healthy Human Volunteers by Shadowgraph Imaging: An Aid to Aerosol Infection Control

Cough airflow dynamics have been previously studied using a variety of experimental methods. In this study, real-time, non-invasive shadowgraph imaging was applied to obtain additional analyses of cough airflows produced by healthy volunteers. Twenty healthy volunteers (10 women, mean age 32.2±12.9 years; 10 men, mean age 25.3±2.5 years) were asked to cough freely, then into their sleeves (as per current US CDC recommendations) in this study to analyze cough airflow dynamics. For the 10 females (cases 1–10), their maximum detectable cough propagation distances ranged from 0.16–0.55 m, with maximum derived velocities of 2.2–5.0 m/s, and their maximum detectable 2-D projected areas ranged from 0.010–0.11 m2, with maximum derived expansion rates of 0.15–0.55 m2/s. For the 10 males (cases 11–20), their maximum detectable cough propagation distances ranged from 0.31–0.64 m, with maximum derived velocities of 3.2–14 m/s, and their maximum detectable 2-D projected areas ranged from 0.04–0.14 m2, with maximum derived expansion rates of 0.25–1.4 m2/s

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Cardio-Protection of Salvianolic Acid B through Inhibition of Apoptosis Network

Targeting cellular function as a system rather than on the level of the single target significantly increases therapeutic potency. In the present study, we detect the target pathway of salvianolic acid B (SalB) in vivo. Acute myocardial infarction (AMI) was induced in rats followed by the treatment with 10 mg/kg SalB. Hemodynamic detection and pathological stain, 2-dimensional electrophoresis, MALDI-TOF MS/MS, Western blot, pathway identification, apoptosis assay and transmission electron microscope were used to elucidate the effects and mechanism of SalB on cardioprotection. Higher SalB concentration was found in ischemic area compared to no-ischemic area of heart, correlating with improved heart function and histological structure. Thirty-three proteins regulated by SalB in AMI rats were identified by biochemical analysis and were classified as the components of metabolism and apoptosis networks. SalB protected cardiomyocytes from apoptosis, inhibited poly (ADP-ribose) polymerase-1 pathway, and improved the integrity of mitochondrial and nucleus of heart tissue during AMI. Furthermore, the protective effects of SalB against apoptosis were verified in H9c2 cells. Our results provide evidence that SalB regulates multi-targets involved in the apoptosis pathway during AMI and therefore may be a candidate for novel therapeutics of heart diseases