SHORT Syndrome with Partial Lipodystrophy Due to Impaired Phosphatidylinositol 3 Kinase Signaling

The phosphatidylinositol 3 kinase (PI3K) pathway regulates fundamental cellular processes such as metabolism, proliferation, and survival. A central component in this pathway is the p85α regulatory subunit, encoded by PIK3R1. Using whole-exome sequencing, we identified a heterozygous PIK3R1 mutation (c.1945C>T [p.Arg649Trp]) in two unrelated families affected by partial lipodystrophy, low body mass index, short stature, progeroid face, and Rieger anomaly (SHORT syndrome). This mutation led to impaired interaction between p85α and IRS-1 and reduced AKT-mediated insulin signaling in fibroblasts from affected subjects and in reconstituted Pik3r1-knockout preadipocytes. Normal PI3K activity is critical for adipose differentiation and insulin signaling; the mutated PIK3R1 therefore provides a unique link among lipodystrophy, growth, and insulin signaling.     

Insomnia,Excessive Sleepiness,Excessive Fatigue,Anxiety, Depression and Shift Work Disorder in Nurses Having Less than 11 Hours in-Between Shifts

Study objective

To assess if less than 11 hours off work between work shifts (quick returns) was related to insomnia, sleepiness, fatigue, anxiety, depression and shift work disorder among nurses.

Methods

A questionnaire including established instruments measuring insomnia (Bergen Insomnia Scale), sleepiness (Epworth Sleepiness Scale), fatigue (Fatigue Questionnaire), anxiety/depression (Hospital Anxiety and Depression Scale) and shift work disorder was administered. Among the 1990 Norwegian nurses who participated in the study; 264 nurses had no quick returns, 724 had 1–30 quick returns and 892 had more than 30 quick returns during the past year. 110 nurses did not report the number of quick returns during the past year. The prevalence of insomnia, excessive sleepiness, excessive fatigue, anxiety, depression and shift work disorder was calculated within the three groups of nurses. Crude and adjusted logistic regression analyses were performed to assess the relation between quick returns and such complaints.

Results

We found a significant positive association between quick returns and insomnia, excessive sleepiness, excessive fatigue and shift work disorder. Anxiety and depression were not related to working quick returns.

Conclusions

There is a health hazard associated with quick returns. Further research should aim to investigate if workplace strategies aimed at reducing the number of quick returns may reduce complaints among workers.     

Mechanisms Preserving Insulin Action during High Dietary Fat Intake

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Role of myokines in exercise and metabolism.

During the past 20 yr, it has been well documented that exercise has a profound effect on the immune system. With the discovery that exercise provokes an increase in a number of cytokines, a possible link between skeletal muscle contractile activity and immune changes was established. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an "exercise factor," which could mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We suggest that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either paracrine or endocrine effects should be classified as "myokines." Since the discovery of interleukin (IL)-6 release from contracting skeletal muscle, evidence has accumulated that supports an effect of IL-6 on metabolism. We suggested that muscle-derived IL-6 fulfils the criteria of an exercise factor and that such classes of cytokines should be named "myokines." Interestingly, recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. Thus skeletal muscle has the capacity to express several myokines. To date the list includes IL-6, IL-8, and IL-15, and contractile activity plays a role in regulating the expression of these cytokines in skeletal muscle. The present review focuses on muscle-derived cytokines, their regulation by exercise, and their possible roles in metabolism and skeletal muscle function and it discusses which cytokines should be classified as true myokines.     

Shoulder muscle load and muscle fatigue among industrial sewing-machine operators

Physiological responses to physical work were assessed for 29 female industrial sewing-machine operators during an 8-h working day under ordinary working conditions. During sewing-machine work, the average (left and right) static load in the trapezius muscle was 9% of the maximal electromyogram (EMG) amplitude (% EMG_max), while the average mean load was 15% EMG_max, and the average peak load was 23% EMG_max. The static load level was unrelated to the muscle strength of the sewing-machine operators, which for the group as a whole was within the normal range. The load levels remained unchanged during the working day, while changes in the EMG mean power frequency and zero crossing frequency rate occurred, both indicating the development of muscle fatigue in left and right trapezius muscle during the working day. In line with this, the rating of perceived exertion in the shoulder and neck region increased during. the working day. Dividing the group of sewing-machine operators into two groups, those with the highest frequency and those with the lowest frequency of shoulder/neck troubles showed that the former group had significantly lower muscle strength, despite the fact that no differences in the surface EMG during sewing were found between the two groups. It was concluded that industrial sewing-machine work involves a pattern of shoulder muscle activity which induces fatiguing processes in the shoulder and neck regions. Furthermore, since the static shoulder muscle load was independent of muscle strength, factors other than working posture may be of significance for the static shoulder muscle load.     

The impact of forest continuity and management on forest floor vegetation evaluated by species traits

The distribution of the flora with different species attributes are investigated in two studies of forest ecosystems in Denmark, One study compared 17 forests with different degrees of management, the other study compared the flora of 25 old forests with that of 6 new forests. No effect of forest management could be detected in the distribution of species attributes in the flora, whereas the forest continuity was correlated with almost all of the 14 traits investigated. Species with heavy seeds, transient seedbanks, ant dispersed seeds, early and short flowering time, low stature and high extent of lateral spread were more common in old forests, while the proportion of species with small, short-lived seeds, epizoochorous dispersal, little lateral spread and later and longer flowering period was higher in new forests. In particular, Raunkiaers therophyles, and ruderal species were more common in new forests than in old.
Differences in the effects of the two types of disturbance - forest management, and breaks in forest eontinuity - are discussed in relation to survival strategies of the forest flora. The importanee of persistence ability in contrast to colonisation ability is stressed for many forest plants.     

Competitive sustained exercise in humans, lymphokine activated killer cell activity, and glutamine – an intervention study

This study examined whether oral glutamine supplementation abolishes some of the exercise-induced changes in lymphocyte functions following long-term intense exercise. A group of 16 marathon runners participating in The Copenhagen Marathon 1996 were placed randomly in either a placebo (n = 7) or a glutamine receiving group (n = 9). Each subject received four doses of either placebo or glutamine (100 mg · kg⁻¹) administered at 0, 30, 60, and 90-min post-race. In the placebo group the plasma glutamine concentrations were lower than pre-race values during the post-exercise period [mean 647 (SEM 32) compared to 470 (SEM 22) μmol · l⁻¹ 90-min post-race, P < 0.05] whereas glutamine supplementation maintained the plasma glutamine concentration (at ∼750 μmol · l⁻¹). Glutamine supplementation in vivo had no effect on the lymphokine activated killer (LAK) cell activity, the proliferative responses or the exercise-induced changes in concentrations or percentages of any of the leucocyte subpopulations examined. Glutamine addition in in vitro studies enhanced the proliferative response in both groups. These data would suggest that decreased plasma glutamine concentrations post-exercise are not responsible for exercise-induced decrease in LAK activity and that the influence of glutamine in vitro is not dependent on the plasma glutamine concentration at the time of sampling. Accepted: 23 April 1998     

Functional consequences of alterations to amino acids located in the hinge domain of the Ca(2+)-ATPase of sarcoplasmic reticulum.

Site-specific mutagenesis of the sarcoplasmic reticulum Ca(2+)-ATPase was used to investigate the functional roles of 18 amino acid residues located at or near the "hinge-domain," a highly conserved region of the cation-transporting ATPases. Mutation of Lys684 to arginine, alanine, histidine, and glutamine resulted in complete loss of calcium transport function and ATPase activity. For the Lys684----Ala, histidine, and glutamine mutants, this coincided with a loss of the ability to form a phosphorylated intermediate from ATP or Pi. The Lys684----Arg mutant retained the ability to phorphorylate from ATP with normal apparent affinity, demonstrating the importance of the positive charge. On the other hand, no phosphorylation was observed with Pi as substrate in this mutant. Examination of the partial reactions after phosphorylation from ATP in the Lys684----Arg mutant demonstrated a reduction of the rate of transformation of the ADP-sensitive phosphoenzyme intermediate (E1P) to the ADP-insensitive phosphoenzyme intermediate (E2P), which could account for the loss of transport function. Once accumulated, the E2P intermediate was able to decompose rapidly in the presence of K+ at neutral pH. These results may be interpreted in terms of a preferential destabilization of protein phosphate interactions in the E2P form of this mutant. The Asp703----Ala and Asn-Asp707----Ala-Ala mutants were completely inactive and unable to form phosphoenzyme intermediates from ATP or Pi. In these mutants as well as in the Lys684----Ala mutant, nucleotides were found to protect with normal affinity against intramolecular cross-linking induced with glutaraldehyde, indicating that the nucleotide binding site was intact. Mutation of Glu646, Glu647, Asp659, Asp660, Glu689, Asp695, Glu696, Glu715, and Glu732 to alanine did not affect the maximum rates of calcium transport and ATP hydrolysis or the apparent affinities for calcium and ATP. Mutation of the 2 highly conserved proline residues, Pro681 and Pro709, as well as Lys728, to alanine resulted in partially inhibited Ca(2+)-ATPase enzymes with retention of the ability to form a phosphoenzyme intermediate from ATP or Pi and with normal apparent affinities for ATP and calcium. The proline mutants retained the biphasic ATP concentration dependence of ATPase activity, characteristic of the wild-type, and therefore the partial inhibition of turnover could not be ascribed to a disruption of the low affinity modulatory ATP site.(ABSTRACT TRUNCATED AT 400 WORDS)