Diminished dietary thermogenesis in exercise-trained human subjects

The influence of exercise-training on dietary-induced thermogenesis (DIT) was investigated in humans. The resting metabolic rate was identical in trained and non-trained subjects, but the response to a meal containing 1,636 kcal (6.9 MJ) was markedly lower in trained subjects. Mean dorsal skin temperature, as measured by thermography, was not influenced by training. A significant correlation was observed between postprandial RQ and DIT, which indicates that the reduced energy expenditure noted in trained subjects is related to a greater lipid oxidation. This sparing effect of exercise-training on energy utilization in the form of carbohydrate, is interpreted as adaptive in the sense that energy is preserved for the purpose of producing work.     

Biosynthesis of lysosomal hydrolases: their synthesis in bound polysomes and the role of co- and post-translational processing in determining their subcellular distribution

By in vitro translation of mRNA’s isolated from free and membrane-bound polysomes, direct evidence was obtained for the synthesis of two lysosomal hydrolases, β-glucuronidase of the rat preputial gland and cathespin D of mouse spleen, on polysomes bound to rough endoplasmic reticulum (ER) membranes. When the mRNA’s for these two proteins were translated in the presence of microsomal membranes, the in vitro synthesized polypeptides were cotranslationally glycosylated and transferred into the microsomal lumen. Polypeptides synthesized in the absence of microsomal membranes were approximately 2,000 daltons larger than the respective unglycosylated microsomal polypeptides found after short times of labeling in cultured rat liver cells treated with tunicamycin. This strongly suggests that nascent chains of the lysosomal enzymes bear transient amino terminal signals which determine synthesis on bound polysomes and are removed during the cotranslational insertion of the polypeptides into the ER membranes. In the line of cultured rat liver cells used for this work, newly synthesized lysosomal hydrolases showed a dual destination; approximately 60 percent of the microsomal polypeptides detected after short times of labeling were subsequently processed proteolytically to lower molecular weight forms characteristic of the mature enzymes. The remainder was secreted from the cells without further proteolytic processing. As previously observed by other investigations in cultured fibroblasts (A. Gonzalez-Noriega, J.H. Grubbs, V. Talkad, and W.S. Sly, 1980, J Cell Biol. 85: 839-852; A. Hasilik and E.F. Neufeld, 1980, J. Biol. Chem., 255:4937-4945.) the lysosomotropic amine chloroquine prevented the proteolytic maturation of newly synthesized hydrolases and enhanced their section. In addition, unglycosylated hydrolases synthesized in cells treated with tunicamycin were exclusively exported from the cells without undergoing proteolytic processing. These results support the notions that modified sugar residues serve as sorting out signals which address the hydrolases to their lysosomal destination and that final proteolytic cleavage of hydrolase precursors take place within lysosome itself. Structural differences in the carbohydrate chains of intracellular and secreted precursors of cathespin D were detected from their differential sensitivity to digestion with endoglycosidases H and D. These observations suggest that the hydrolases exported into the medium follow the normal secretory route and that some of their oligosaccharides are subject to modifications known to affect many secretory glycoproteins during their passage through the Golgi apparatus.     

Adiposity and eating behaviors in patients under second generation antipsychotics

Background: Second generation antipsychotics (SGA) induce substantial weight gain but the mechanisms responsible for this phenomenon remain speculative. Objective: To explore eating behaviors among SGA‐treated patients and compare them with nonschizophrenic healthy sedentary individuals (controls). Methods and Procedures: Appetite sensations were recorded before and after a standardized breakfast using visual analog scales. Three hours after breakfast, a buffet‐type meal was offered to participants to document spontaneous food intake and food preferences. Satiety quotients (SQs) were calculated to determine the satiation of both meals and the Three‐Factor Eating Questionnaire (TFEQ) was used to document eating behaviors. Body composition and abdominal fat distribution were assessed. Results: Compared with controls (n = 20), SGA‐treated patients (n = 18) showed greater adiposity indices (P ≤ 0.04). Patients' degree of hunger was also higher following the standardized breakfast (P = 0.03). Moreover, patients had significantly higher cognitive dietary restraint, disinhibition, and susceptibility to hunger scores than the reference group (P ≤ 0.05). Disinhibition in the reference group was positively associated with hunger triggered by external cues (r = 0.48, P = 0.03) whereas internal cues seem to mainly regulate emotional susceptibility to disinhibition in patients (r = 0.56, P = 0.02). Higher strategic restraint behavior in patients was associated with decreased satiation right after the buffet‐type meal (r = ?0.56, P = 0.02). Discussion: These exploratory findings suggest that patients under SGA seem to develop disordered eating behaviors in response to altered appetite sensations and increased susceptibility to hunger, a factor which may influence the extent of body weight gain triggered by these drugs.     

Investing in early human development: Timing and economic efficiency

Policy discussions to ameliorate socioeconomic (SES) inequalities are increasingly focused on investments in early childhood. Yet such interventions are costly to implement, and clear evidence on the optimal time to intervene to yield a high economic and social return in the future is meagre. The majority of successful early childhood interventions start in the preschool years. However socioeconomic gradients in cognitive skills, socio-emotional functioning and health can be observed by age three, suggesting that preventative programmes starting earlier in childhood may be even more effective. We discuss the optimal timing of early childhood intervention with reference to recent research in developmental neuroscience. We motivate the need for early intervention by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life. We provide a brief review of the economic rationale for investing early in life and propose the “antenatal investment hypothesis”. We conclude by discussing a suite of new European interventions that will inform this optimal timing debate.     

Performances of a full-scale novel multiplate anaerobic reactor treating cheese whey effluent

A 450-m(3) multiplate anaerobic reactor (MPAR) has been started-up in April 1992 for treating wastewater (whey permeate and domestic wastewater) at the Nutrinor (Lactel) cheese factory in Chambord (Québec, Canada). The MPAR consists of four superimposed sections. The liquid flows upwards from one section to the next, while the gas is collected below each plate and evacuated through side-outlets. The wastewater is concurrently distributed at the bottom of the first, second, and third sections, as 50%, 33%, and 17% of the total influent stream, respectively. Granular anaerobic sludge at an initial concentration of 30 kg of volatile suspended solids (VSS) per cubic meter of reactor liquid volume was used to inoculate the reactor. Under normal operation of the factory, the chemical oxygen demand (COD) concentration of the influent ranged from 20 to 37 kg COD m(-3). The reactor organic loading rate (OLR) fluctuated between 9 and 14.7 kg COD m(-3) d(-1) for hydraulic retention times (HRT) maintained between 55 and 68 h. At the highest OLR, the MPAR showed an efficiency of 98% and 92% for soluble and total COD removal, respectively, and a methane production rate averaging around 4 m(3) m(-3) d(-1).Biomass-specific activities ranged between 7 and 51, 1.3 and 8.5, 5.3 and 12.2, 60 and 119, and 119 and 211 mmol g(-1) VSS d(-1) for glucose, propionate, acetate, formate, and hydrogen, respectively. Average equivalent-diameter of the granules was around 0.65 mm. The MPAR reactor generally showed a large capacity for solid retention with a biomass content between 32 and 37 kg VSS m(-3). (c) 1995 John Wiley & Sons, Inc.     

Statin compounds reduce human immunodeficiency virus type 1 replication by preventing the interaction between virion-associated host intercellular adhesion molecule 1 and its natural cell surface ligand LFA-1

A variety of host factors, including membrane proteins acquired by human immunodeficiency virus type 1 (HIV-1), play a dominant role in HIV-1 adsorption onto host cells. Examples include the integrin intercellular adhesion molecule 1 (ICAM-1), which, once acquired by HIV-1, promotes virus infectivity via ligation to LFA-1. We tested the ability of statins to diminish HIV-1 replication, based on the idea that these compounds have been shown to block ICAM-1-LFA-1 interactions. Our data indicate that statins diminish HIV-1 attachment to target cells by suppressing ICAM-1-LFA-1 interactions. The capacity of statins to limit the initial steps in virus replication could represent an interesting approach for the treatment of HIV-1 infection.     

High sero-prevalence of caseous lymphadenitis identified in slaughterhouse samples as a consequence of deficiencies in sheep farm management in the state of Minas Gerais, Brazil

Background

Multiple congenital ocular anomalies (MCOA) syndrome is a hereditary congenital eye defect that was first described in Silver colored Rocky Mountain horses. The mutation causing this disease is located within a defined chromosomal interval, which also contains the gene and mutation that is associated with the Silver coat color (PMEL17, exon 11). Horses that are homozygous for the disease-causing allele have multiple defects (MCOA-phenotype), whilst the heterozygous horses predominantly have cysts of the iris, ciliary body or retina (Cyst-phenotype). It has been argued that these ocular defects are caused by a recent mutation that is restricted to horses that are related to the Rocky Mountain Horse breed. For that reason we have examined another horse breed, the Icelandic horse, which is historically quite divergent from Rocky Mountain horses.

Results

We examined 24 Icelandic horses and established that the MCOA syndrome is present in this breed. Four of these horses were categorised as having the MCOA-phenotype and were genotyped as being homozygous for the PMEL17 mutation. The most common clinical signs included megaloglobus, iris stromal hypoplasia, abnormal pectinate ligaments, iridociliary cysts occasionally extending into the peripheral retina and cataracts. The cysts and pectinate ligament abnormalities were observed in the temporal quadrant of the eyes. Fourteen horses were heterozygous for the PMEL17 mutation and were characterized as having the Cyst-phenotype with cysts and occasionally curvilinear streaks in the peripheral retina. Three additional horses were genotyped as PMEL17 heterozygotes, but in these horses we were unable to detect cysts or other forms of anomalies. One eye of a severely vision-impaired 18 month-old stallion, homozygous for the PMEL17 mutation was examined by light microscopy. Redundant duplication of non-pigmented ciliary body epithelium, sometimes forming cysts bulging into the posterior chamber and localized areas of atrophy in the peripheral retina were seen.

Conclusions

The MCOA syndrome is segregating with the PMEL17 mutation in the Icelandic Horse population. This needs to be taken into consideration in breeding decisions and highlights the fact that MCOA syndrome is present in a breed that are more ancient and not closely related to the Rocky Mountain Horse breed.     

Protein-tyrosine phosphatase 1B potentiates IRE1 signaling during endoplasmic reticulum stress

Protein-tyrosine phosphatase 1B (PTP-1B) is the prototypic tyrosine phosphatase whose function in insulin signaling and metabolism is well established. Although the role of PTP-1B in dephosphorylating various cell surface receptor tyrosine kinases is clear, the mechanisms by which it modulates receptor function from the endoplasmic reticulum (ER) remains an enigma. Here, we provide evidence that PTP-1B has an essential function in regulating the unfolded protein response in the ER compartment. The absence of PTP-1B caused impaired ER stress-induced IRE1 signaling. More specifically, JNK activation, XBP-1 splicing, and EDEM (ER degradation-enhancing alpha-mannosidase-like protein) gene induction, as well as ER stress-induced apoptosis, were attenuated in PTP-1B knock-out mouse embryonic fibroblasts in response to two ER stressors, tunicamycin and azetidine-2 carboxylic acid. We demonstrate that PTP-1B is not just a passive resident of the ER but on the contrary has an essential role in potentiating IRE1-mediated ER stress signaling pathways.