A major T cell antigen of Mycobacterium leprae is a 10-kD heat-shock cognate protein.

Several mycobacterial antigens, identified by monoclonal antibodies and patient sera, have been found to be homologous to stress or heat-shock proteins (hsp) defined in Escherichia coli and yeast. A major antigen recognized by most Mycobacterium leprae-reactive human T cell lines and cell wall-reactive T cell clones is a 10-kD protein that has now been cloned and sequenced. The predicted amino acid sequence of this protein is 44% homologous to the hsp 10 (GroES) of E. coli. The purified native and recombinant 10-kD protein was found to be a stronger stimulator of peripheral blood T cell proliferation than other native and recombinant M. leprae proteins tested. The degree of reactivity paralleled the response to intact M. leprae throughout the spectrum of leprosy. Limiting-dilution analysis of peripheral blood lymphocytes from a patient contact and a tuberculoid patient indicated that approximately one third of M. leprae-reactive T cell precursors responded to the 10-kD antigen. T cell lines derived from lepromin skin tests were strongly responsive to the 10-kD protein. T cell clones reactive to both the purified native and recombinant 10-kD antigens recognized M. leprae-specific epitopes as well as epitopes crossreactive with the cognate antigen of M. tuberculosis. Further, the purified hsp 10 elicited strong delayed-type hypersensitivity reactions in guinea pigs sensitized to M. leprae. The strong T cell responses against the M. leprae 10-kD protein suggest a role for this heat-shock cognate protein in the protective/resistant responses to infection

Protein Requirements of Pre-Menopausal Female Athletes: Systematic Literature Review

This systematic literature review aimed to determine the protein requirements of pre-menopausal (e.g., 18–45 years) female athletes and identify if the menstrual cycle phase and/or hormonal contraceptive use influence protein requirements. Four databases were searched for original research containing pre-menopausal female athletes that ingested protein alongside exercise. The Academy of Nutrition and Dietetics Quality Criteria Checklist was used to determine study quality. Fourteen studies, which included 204 recreationally active or competitive females, met the eligibility criteria for inclusion in this review, and all were assessed as positive quality. The estimated average requirement (EAR) for protein intake of pre-menopausal recreational and/or competitive female athletes is similar for those undertaking aerobic endurance (1.28–1.63 g/kg/day), resistance (1.49 g/kg/day) and intermittent exercise (1.41 g/kg/day) of ~60–90 min duration. The optimal acute protein intake and influence of menstrual cycle phase or hormonal contraceptive use on protein requirements could not be determined. However, pre- and post-exercise protein intakes of 0.32–0.38 g/kg have demonstrated beneficial physiological responses in recreational and competitive female athletes completing resistance and intermittent exercise. The protein requirements outlined in this review can be used for planning and assessing protein intakes of recreational and competitive pre-menopausal female athletes

Association of Obesity-Mediated Insulin Resistance and Hypothalamic Volumes: Possible Sex Differences

The hypothalamus is important in hunger and metabolism. Although a lot is known about the basic role of the human hypothalamus, less is known about how the in vivo volume is affected in obesity, particularly among adolescents. Based on pediatric body mass index percentiles, 95 participants were assigned to lean or obese groups. All subjects had medical evaluations, including fasting blood tests, to assess insulin sensitivity and circulating CRP and neurotrophins (NGF and BDNF) and an MRI of the brain. Hypothalamic volumes were measured by a segmentation method combining manual and automated steps. Overall, obese participants had descriptively smaller hypothalamic volumes, although this difference did not reach statistical significance; however, among obese participants, females had significantly smaller hypothalamic volumes than their male counterparts. There was a significant interaction between insulin resistance and sex on hypothalamus volume; obese females with significant insulin resistance have smaller hypothalamic volumes than obese males. Obese adolescents had higher circulating CRP and neurotrophin levels. Furthermore, among obese females, BDNF concentrations were inversely associated with hypothalamus volumes ( = −0.48). Given this negative association between BDNF and hypothalamus volumes among obese insulin-resistant females, elevated neurotrophin levels may suggest an attempt at protective compensation

Cerebral White Matter and Retinal Arterial Health in Hypertension and Type 2 Diabetes Mellitus

We examined 33 hypertensive (22 with comorbid type 2 diabetes mellitus (T2DM)) and 29 normotensive (8 with T2DM) middle-aged and elderly adults, comparable in age and education. Relative to normotensive participants, those with hypertension, in addition to a higher prevalence of periventricular white matter (WM) lesions, had significantly lower WM microstructural integrity of major fiber tracts as seen with MRI-based diffusion tensor imaging. Among participants with hypertension, those with co-morbid T2DM (n=22) had more widespread WM pathology than those without T2DM (n=11). Furthermore and consistent with previous research, both hypertension and T2DM were related to decreased retinal arterial diameter. Further exploratory analysis demonstrated that the observed retinal arteriolar narrowing among individual with hypertension was associated with widespread subclinical losses in WM microstructural integrity and these associations were present predominantly in the frontal lobe. We found that T2DM adds to the damaging effects of hypertension on cerebral WM, and notably these effects were independent of age and body mass index. Given that the decrease in retinal arteriolar diameter may be a biomarker for parallel pathology in cerebral arterioles, our data suggest that the frontal lobe may be particularly vulnerable to microvascular damage in the presence of hypertension and T2DM

Forebrain-specific transgene rescue of 11β-HSD1 associates with impaired spatial memory and reduced hippocampal BDNF mRNA levels in aged 11β-HSD1 deficient mice

Mice lacking the intracellular glucocorticoid‐regenerating enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) are protected from age‐related spatial memory deficits. 11β‐HSD1 is expressed predominantly in the brain, liver and adipose tissue. Reduced glucocorticoid levels in the brain in the absence of 11β‐HSD1 may underlie the improved memory in aged 11β‐HSD1 deficient mice. However, the improved glucose tolerance, insulin sensitisation and cardioprotective lipid profile associated with reduced peripheral glucocorticoid regeneration may potentially contribute to the cognitive phenotype of aged 11β‐HSD1 deficient mice. In the present study, transgenic mice with forebrain‐specific overexpression of 11β‐HSD1 (Tg) were intercrossed with global 11β‐HSD1 knockout mice (HSD1KO) to examine the influence of forebrain and peripheral 11β‐HSD1 activity on spatial memory in aged mice. Transgene‐mediated delivery of 11β‐HSD1 to the hippocampus and cortex of aged HSD1KO mice reversed the improved spatial memory retention in the Y‐maze but not spatial learning in the watermaze. Brain‐derived neurotrophic factor (BDNF) mRNA levels in the hippocampus of aged HSD1KO mice were increased compared to aged wild‐type mice. Rescue of forebrain 11β‐HSD1 reduced BDNF mRNA in aged HSD1KO mice to levels comparable to aged wild‐type mice. These findings indicate that 11β‐HSD1 regenerated glucocorticoids in the forebrain and decreased levels of BDNF mRNA in the hippocampus play a role in spatial memory deficits in aged wild‐type mice, although 11β‐HSD1 activity in peripheral tissues may also contribute to spatial learning impairments in aged mice