Molecular convergence of hexosamine biosynthetic pathway and ER stress leading to insulin resistance in L6 skeletal muscle cells

Augmentation of hexosamine biosynthetic pathway (HBP) and endoplasmic reticulum (ER) stress were independently related to be the underlying causes of insulin resistance. We hypothesized that there might be a molecular convergence of activated HBP and ER stress pathways leading to insulin resistance. Augmentation of HBP in L6 skeletal muscle cells either by pharmacological (glucosamine) or physiological (high-glucose) means, resulted in increased protein expression of ER chaperones (viz., Grp78, Calreticulin, and Calnexin), UDP-GlcNAc levels and impaired insulin-stimulated glucose uptake. Cells silenced for O-glycosyl transferase (OGT) showed improved insulin-stimulated glucose uptake (P < 0.05) but without any effect on ER chaperone upregulation. While cells treated with either glucosamine or high-glucose exhibited increased JNK activity, silencing of OGT resulted in inhibition of JNK and normalization of glucose uptake. Our study for the first time, demonstrates a molecular convergence of O-glycosylation processes and ER stress signals at the cross-road of insulin resistance in skeletal muscle.

Real-time wide-area loading margin sensitivity (WALMS) in power systems

Loading margin sensitivity (LMS) has been widely used in applications in the realm of voltage stability assessment and control. Typically, LMS is derived based on system equilibrium equations near bifurcation and therefore requires full detailed system model and significant computation effort. Availability of phasor measurement units (PMUs) due to the recent development of wide-area monitoring system (WAMS) provides an alternative computation-friendly approach for calculating LMS. With such motivation, this work proposes measurement-based wide-area loading margin sensitivity (WALMS) in bulk power systems. The proposed sensitivity, with its simplicity, has great potential to be embedded in real-time applications. Moreover, the calculation of the WALMS is not limited to low voltage near bifurcation point. A case study on IEEE 39-bus system verifies the proposed sensitivity. Finally, a voltage control scenario demonstrates the potential application of the WALMS.

Resolution and sensitivity of the eyes of the Asian honeybees Apis florea, Apis cerana and Apis dorsata

Bees of the genus Apis are important foragers of nectar and pollen resources. Although the European honeybee, Apis mellifera, has been well studied with respect to its sensory abilities, learning behaviour and role as pollinators, much less is known about the other Apis species. We studied the anatomical spatial resolution and absolute sensitivity of the eyes of three sympatric species of Asian honeybees, Apis cerana, Apis florea and Apis dorsata and compared them with the eyes of A. mellifera. Of these four species, the giant honeybee A. dorsata (which forages during moonlit nights) has the lowest spatial resolution and the most sensitive eyes, followed by A. mellifera, A. cerana and the dwarf honeybee, A. florea (which has the smallest acceptance angles and the least sensitive eyes). Moreover, unlike the strictly diurnal A. cerana and A. florea, A. dorsata possess large ocelli, a feature that it shares with all dim-light bees. However, the eyes of the facultatively nocturnal A. dorsata are much less sensitive than those of known obligately nocturnal bees such as Megalopta genalis in Panama and Xylocopa tranquebarica in India. The differences in sensitivity between the eyes of A. dorsata and other strictly diurnal Apis species cannot alone explain why the former is able to fly, orient and forage at half-moon light levels. We assume that additional neuronal adaptations, as has been proposed for A. mellifera, M. genalis and X. tranquebarica, might exist in A. dorsata.

Antibiotic Sensitivity Testing

Respiratory bacterial pathogens in pigs are currently treated with antibiotics. Intervet - Schering Plough markets an antibiotic called Nurflor (Florfenicol) targeting respiratory pathogens. This project tests the effectiveness of this antibiotic against a series of respiratory pathogens. 6 isolates will be tested per serovar/strain and the isolates will be from 4 different farms using MIC testing. The sensitivity of Florfenicol will be compared to sensitivity of the organisms to Tilmicosin and Amoxicillin. Development of resistance to certain antibiotics have been reported, so it is important to have alternative antibiotics available to treat the respiratory pathogens on farms.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Physical activity, fitness, abdominal obesity, and cardiovascular risk factors in Finnish men and women : The National FINRISK 2002 Study

Physical inactivity, low cardiorespiratory fitness, and abdominal obesity are direct and mediating risk factors for cardiovascular disease (CVD). The results of recent studies suggest that individuals with higher levels of physical activity or cardiorespiratory fitness have lower CVD and all-cause mortality than those with lower activity or fitness levels regardless of their level of obesity. The interrelationships of physical activity, fitness, and abdominal obesity with cardiovascular risk factors have not been studied in detail. The aim of this study was to investigate the associations of different types of leisure time physical activity and aerobic fitness with cardiovascular risk factors in a large population of Finnish adults. In addition, a novel aerobic fitness test was implemented and the distribution of aerobic fitness was explored in men and women across age groups. The interrelationships of physical activity, aerobic fitness and abdominal obesity were examined in relation to cardiovascular risk factors. This study was part of the National FINRISK Study 2002, which monitors cardiovascular risk factors in a Finnish adult population. The sample comprised 13 437 men and women aged 25 to 74 years and was drawn from the Population Register as a stratified random sample according to 10-year age groups, gender and area. A separate physical activity study included 9179 subjects, of whom 5 980 participated (65%) in the study. At the study site, weight, height, waist and hip circumferences, and blood pressure were measured, a blood sample was drawn, and an aerobic fitness test was performed. The fitness test estimated maximal oxygen uptake (VO2max) and was based on a non-exercise method by using a heart rate monitor at rest. Waist-to-hip ratio (WHR) was calculated by dividing waist circumference with hip circumference and was used as a measure of abdominal obesity. Participants filled in a questionnaire on health behavior, a history of diseases, and current health status, and a detailed 12-month leisure time physical activity recall. Based on the recall data, relative energy expenditure was calculated using metabolic equivalents, and physical activity was divided into conditioning, non-conditioning, and commuting physical activity. Participants aged 45 to 74 years were later invited to take part in a 2-hour oral glucose tolerance test with fasting insulin and glucose measurements. Based on the oral glucose tolerance test, undiagnosed impaired glucose tolerance and type 2 diabetes were defined. The estimated aerobic fitness was lower among women and decreased with age. A higher estimated aerobic fitness and a lower WHR were independently associated with lower systolic and diastolic blood pressure, lower total cholesterol and triglyceride levels, and with higher high-density lipoprotein (HDL) cholesterol and HDL to total cholesterol ratio. The associations of the estimated aerobic fitness with diastolic blood pressure, triglycerides, and HDL to total cholesterol ratio were stronger in men with a higher WHR. High levels of conditioning and non-conditioning physical activity were associated with lower high-sensitivity C-reactive protein (CRP) levels. High levels of conditioning and overall physical activities were associated with lower insulin and glucose levels. The associations were stronger among women than men. A better self-rated physical fitness was associated with a higher estimated aerobic fitness, lower CRP levels, and lower insulin and glucose levels in men and women. In each WHR third, the risk of impaired glucose tolerance and type 2 diabetes was higher among physically inactive individuals who did not undertake at least 30 minutes of moderate-intensity physical activity on five days per week. These cross-sectional data show that higher levels of estimated aerobic fitness and regular leisure time physical activity are associated with a favorable cardiovascular risk factor profile and that these associations are present at all levels of abdominal obesity. Most of the associations followed a dose-response manner, suggesting that already low levels of physical activity or fitness are beneficial to health and that larger improvements in risk factor levels may be gained from higher activity and fitness levels. The present findings support the recommendation to engage regularly in leisure time physical activity, to pursue a high level of aerobic fitness, and to prevent abdominal obesity.

Noise sensitivity medical, psychological and genetic aspects

Noise can be defined as unwanted sound. It may adversely affect the health and well-being of individuals. Noise sensitivity is a personality trait covering attitudes towards noise in general and a predictor of noise annoyance. Noise sensitive individuals are more affected by noise than less sensitive individuals. The determinants and characteristics related to noise sensitivity are rather poorly known. The risk of health effects caused by noise can be hypothesized to be higher for noise sensitive individuals compared to those who are not noise sensitive. A cardiovascular disease may be an example of outcomes. The general aim of the present study was to investigate the association of noise sensitivity with specific somatic and psychological factors, including the genetic component of noise sensitivity, and the association of noise sensitivity with mortality. The study was based on the Finnish Twin Cohort of same-sex twin pairs born before 1958. In 1988 a questionnaire was sent to twin pairs discordant for hypertension. 1495 individuals (688 men, 807 women) aged 31 88 years replied, including 573 twin pairs. 218 of the subjects lived in the Helsinki Metropolitan Area. Self-reported noise sensitivity, lifetime noise exposure and hypertension were obtained from the questionnaire study in 1988 and other somatic and psychological factors from the questionnaire study in 1981 for the same individuals. In addition, noise map information (1988 1992) from the Helsinki Metropolitan Area and mortality follow-up 1989 2003 were used. To evaluate the stability and validity of noise sensitivity, a new questionnaire was sent in 2002 to a sample of the subjects who had replied to the 1988 questionnaire. Of all subjects who had answered the question on noise sensitivity, 38 % were noise sensitive. Noise sensitivity was independent of noise exposure levels indicated in noise maps. Subjects with high noise sensitivity reported more transportation noise exposure than subjects with low noise sensitivity. Noise sensitive subjects reported transportation noise exposure outside the environmental noise map areas almost twice as often as non-sensitive subjects. Noise sensitivity was associated with hypertension, emphysema, use of psychotropic drugs, smoking, stress and hostility, even when lifetime noise exposure was adjusted for. Monozygotic twin pairs were more similar with regards noise sensitivity than dizygotic twin pairs, and quantitative genetic modelling indicated significant familiality. The best fitting genetic model provided an estimate of heritability of 36 %. Follow-up of subjects in the case-control study showed that cardiovascular mortality was significantly increased among noise sensitive women, but not among men. For coronary heart mortality the interaction of noise sensitivity and lifetime noise exposure was statistically significant in women. In conclusion, noise sensitivity has both somatic and psychological components. It does aggregate in families and probably has a genetic component. Noise sensitivity may be a risk factor for cardiovascular mortality in women.

Temperature sensitivity of soil organic matter decomposition in boreal soils

The temperature sensitivity of decomposition of different soil organic matter (SOM) fractions was studied with laboratory incubations using 13C and 14C isotopes to differentiate between SOM of different age. The quality of SOM and the functionality and composition of microbial communities in soils formed under different climatic conditions were also studied. Transferring of organic layers from a colder to a warmer climate was used to assess how changing climate, litter input and soil biology will affect soil respiration and its temperature sensitivity. Together, these studies gave a consistent picture on how warming climate will affect the decomposition of different SOM fractions in Finnish forest soils: the most labile C was least temperature sensitive, indicating that it is utilized irrespective of temperature. The decomposition of intermediate C, with mean residence times from some years to decades, was found to be highly temperature sensitive. Even older, centennially cycling C was again less temperature sensitive, indicating that different stabilizing mechanisms were limiting its decomposition even at higher temperatures. Because the highly temperature sensitive, decadally cycling C, forms a major part of SOM stock in the organic layers of the studied forest soils, these results mean that these soils could lose more carbon during the coming years and decades than estimated earlier. SOM decomposition in boreal forest soils is likely to increase more in response to climate warming, compared to temperate or tropical soils, also because the Q10 is temperature dependent. In the northern soils the warming will occur at a lower temperature range, where Q10 is higher, and a similar increase in temperature causes a higher relative increase in respiration rates. The Q10 at low temperatures was found to be inversely related to SOM quality. At higher temperatures respiration was increasingly limited by low substrate availability.

Interacting effects of vegetation, soils and management on the sensitivity of Australian savanna rangelands to climate change

There is an increasing need to understand what makes vegetation at some locations more sensitive to climate change than others. For savanna rangelands, this requires building knowledge of how forage production in different land types will respond to climate change, and identifying how location-specific land type characteristics, climate and land management control the magnitude and direction of its responses to change. Here, a simulation analysis is used to explore how forage production in 14 land types of the north-eastern Australian rangelands responds to three climate change scenarios of +3A degrees C, +17% rainfall; +2A degrees C, -7% rainfall; and +3A degrees C, -46% rainfall. Our results demonstrate that the controls on forage production responses are complex, with functional characteristics of land types interacting to determine the magnitude and direction of change. Forage production may increase by up to 60% or decrease by up to 90% in response to the extreme scenarios of change. The magnitude of these responses is dependent on whether forage production is water or nitrogen (N) limited, and how climate changes influence these limiting conditions. Forage production responds most to changes in temperature and moisture availability in land types that are water-limited, and shows the least amount of change when growth is restricted by N availability. The fertilisation effects of doubled atmospheric CO2 were found to offset declines in forage production under 2A degrees C warming and a 7% reduction in rainfall. However, rising tree densities and declining land condition are shown to reduce potential opportunities from increases in forage production and raise the sensitivity of pastures to climate-induced water stress. Knowledge of these interactions can be applied in engaging with stakeholders to identify adaptation options.

The sensitivity of the northern hemisphere summer mean meridional circulation to changes in the large scale eddy forcing

A zonally averaged version of the Goddard Laboratory for Atmospheric Sciences (GLAS) climate model is used to study the sensitivity of the northern hemisphere (NH) summer mean meridional circulation to changes in the large scale eddy forcing. A standard solution is obtained by prescribing the latent heating field and climatological horizontal transports of heat and momentum by the eddies. The radiative heating and surface fluxes are calculated by model parameterizations. This standard solution is compared with the results of several sensitivity studies. When the eddy forcing is reduced to 0.5 times or increased to 1.5 times the climatological values, the strength of the Ferrel cells decrease or increase proportionally. It is also seen that such changes in the eddy forcing can influence the strength of theNH Hadley cell significantly. Possible impact of such changes in the large scale eddy forcing on the monsoon circulation via changes in the Hadley circulation is discussed. Sensitivity experiments including only one component of eddy forcing at a time show that the eddy momentum fluxes seem to be more important in maintaining the Ferrel cells than the eddy heat fluxes. In the absence of the eddy heat fluxes, the observed eddy momentum fluxes alone produce subtropical westerly jets which are weaker than those in the standard solution. On the other hand, the observed eddy heat fluxes alone produce subtropical westerly jets which are stronger than those in the standard solution.

Explosive sensitivity of methylammonium perchlorates

The explosive sensitivity of methylammonium perchlorates has been investigated by differential thermal analysis, thermogravimetric analysis, mass spectrometry and explosion delay experiments. The decomposition temperature of these compounds increases in the order CH3NH3ClO4>(CH3)2NH2ClO4>(CH3)3NHClO4. The activation energy shows the reverse order, indicating thereby that the stability increases with increasing substitution. Mass spectrometric investigation, however, suggests an increasing reactivity with increasing substitution. A possible explanation for such behaviour is proposed. It appears that explosion delay is correlated with thermal decomposition and impact sensitivity.

Relative sensitivity of the corpus luteum of different days of pregnancy to LH-deprivation in the rat and hamster

Deprivation of endogenous LH by LH antiserum (LH A/S) in 6-day pregnant rats did not affect the luteal or serum progesterone within 24 h. LH A/S treatment on day 7 or 8 of pregnancy, however, caused a 70 and 92% reduction in luteal progesterone, respectively, within 24 h. Serum levels of progesterone showed a similar reduction. In the case of pregnant hamster, unlike the rat, there was a significant decrease in progesterone in the serum, luteal and non-luteal compartments whether the A/S was administered on day 4, 5 or 6. There was more than a 10-fold increase in the luteal cholesterol esters within 24 h whether the A/S was given on day 6, 7 or 8 of pregnancy in the rat. Rat corpora lutea of days 6 and 8 of pregnancy reacted in a like manner to LH-deprivation, showing an increased utilization of [U-14C]glucose to form 14CO2 in vitro. In the rat, LH (25 μg NIH-S19) administration in vivo either on day 6 or day 8 of pregnancy, caused within 2 h an increase in serum and non-luteal progesterone, but luteal progesterone was unchanged. On the other hand, LH administration to hamsters on day 8 of pregnancy caused an increase in progesterone levels in serum, luteal and non-luteal tissue. Incubation of corpora lutea isolated from untreated 6- and 8-day pregnant rats with LH brought about an increase in progesterone secretion into the medium in both cases. The results show that, even though LH-deprivation does not apparently affect progesterone concentration in the corpus luteum of 6-day pregnant rats, it does affect other metabolic parameters such as glucose utilization and cholesterol turnover, suggesting that the corpus luteum of early pregnancy exhibits a continuous dependency on LH for the maintainence of metabolic functions.

An approach for sensitivity-reduced design of linear regulators

A now procedure for the design of sensitivity-reduced control for linear regulators is described. The control is easily computable and implementable since it requires neither the solution of an increased-order augmented system nor the generation and feedback of a trajectory sensitivity vector. The method provides a trade-off between reduction in sensitivity measure and increase in performance index.