Mitochondrial oxidative stress causes hyperphosphorylation of tau

Age-related neurodegenerative disease has been mechanistically linked with mitochondrial dysfunction via damage from reactive oxygen species produced within the cell. We determined whether increased mitochondrial oxidative stress could modulate or regulate two of the key neurochemical hallmarks of Alzheimer's disease (AD): tau phosphorylation, and beta-amyloid deposition. Mice lacking superoxide dismutase 2 (SOD2) die within the first week of life, and develop a complex heterogeneous phenotype arising from mitochondrial dysfunction and oxidative stress. Treatment of these mice with catalytic antioxidants increases their lifespan and rescues the peripheral phenotypes, while uncovering central nervous system pathology. We examined sod2 null mice differentially treated with high and low doses of a catalytic antioxidant and observed striking elevations in the levels of tau phosphorylation (at Ser-396 and other phospho-epitopes of tau) in the low-dose antioxidant treated mice at AD-associated residues. This hyperphosphorylation of tau was prevented with an increased dose of the antioxidant, previously reported to be sufficient to prevent neuropathology. We then genetically combined a well-characterized mouse model of AD (Tg2576) with heterozygous sod2 knockout mice to study the interactions between mitochondrial oxidative stress and cerebral Ass load. We found that mitochondrial SOD2 deficiency exacerbates amyloid burden and significantly reduces metal levels in the brain, while increasing levels of Ser-396 phosphorylated tau. These findings mechanistically link mitochondrial oxidative stress with the pathological features of AD.     

Media use and obesity in adolescent females

Objective: In the context of growing public health concern with the obesity rates among children and adolescents, much attention has focused on the role of television as a contributor to the problem. Less attention has been devoted to interactive media (internet surfing and video games), despite the fact that these forms of entertainment are fast gaining in popularity among youth. This study investigated the relative associations of TV viewing and interactive media use with body fat and BMI, controlling for both physical activity participation and cardiovascular fitness. Research Methods and Procedures: Female high‐school adolescents (N = 194) were assessed for cardiovascular fitness (cycle ergometer), percent body fat (DXA), and BMI. Time spent in moderate, vigorous, and sedentary activities was assessed with a 3‐day recall. Results: Multivariate regression analysis showed that only interactive media use was associated with percentage body fat and BMI, and the relationship remained strong even after controlling for physical activity participation and cardiovascular fitness. Discussion: It appears that, among this group of adolescent females, the association between interactive media use and obesity is not explained by a reduction in moderate or vigorous activity commensurate with media use.     

Membrane type-1 matrix metalloproteinases and tissue inhibitor of metalloproteinases-2 RNA levels mimic each other during Xenopus laevis metamorphosis

Matrix metalloproteinases (MMPs) and their endogenous inhibitors TIMPs (tissue inhibitors of MMPs), are two protein families that work together to remodel the extracellular matrix (ECM). TIMPs serve not only to inhibit MMP activity, but also aid in the activation of MMPs that are secreted as inactive zymogens. Xenopus laevis metamorphosis is an ideal model for studying MMP and TIMP expression levels because all tissues are remodeled under the control of one molecule, thyroid hormone. Here, using RT-PCR analysis, we examine the metamorphic RNA levels of two membrane-type MMPs (MT1-MMP, MT3-MMP), two TIMPs (TIMP-2, TIMP-3) and a potent gelatinase (Gel-A) that can be activated by the combinatory activity of a MT-MMP and a TIMP. In the metamorphic tail and intestine the RNA levels of TIMP-2 and MT1-MMP mirror each other, and closely resemble that of Gel-A as all three are elevated during periods of cell death and proliferation. Conversely, MT3-MMP and TIMP-3 do not have similar RNA level patterns nor do they mimic the RNA levels of the other genes examined. Intriguingly, TIMP-3, which has been shown to have anti-apoptotic activity, is found at low levels in tissues during periods of apoptosis.     

The tail of the Ordovician fish Sacabambaspis

The tail of the earliest known articulated fully skeletonized vertebrate, the arandaspid Sacabambaspis from the Ordovician of Bolivia, is redescribed on the basis of further preparation of the only specimen in which it is most extensively preserved. The first, but soon discarded, reconstruction, which assumed the presence of a long horizontal notochordal lobe separating equal sized dorsal and ventral fin webs, appears to have considerable merit. Although the ventral web is significantly smaller than the dorsal one, the presence of a very long notochordal lobe bearing a small terminal web is confirmed. The discrepancy in the size of the ventral and dorsal webs rather suggests that the tail was hypocercal, a condition that would better accord with the caudal morphology of the living agnathans and the other jawless stem gnathostomes.     

A comparative study of leptospirosis and dengue in Thai children

Background

Leptospirosis is an emerging zoonosis that is often under-recognized in children and commonly confused with dengue in tropical settings. An enhanced ability to distinguish leptospirosis from dengue in children would guide clinicians and public health personnel in the appropriate use of limited healthcare resources.

Methodology/Principal Findings

We conducted a prospective, hospital-based, study of children with acute febrile illnesses and dengue in Thailand. Among the children without dengue, we identified those with leptospirosis using anti-leptospira IgM and microscopic agglutination titers in paired acute and convalescent blood samples. We then performed a case-control comparison of symptoms, signs, and clinical laboratory values between children with leptospirosis and dengue.In a semi-rural region of Thailand, leptospirosis accounted for 19% of the non-dengue acute febrile illnesses among children presenting during the rainy season. None of the children with leptospirosis were correctly diagnosed at the time of hospital discharge, and one third (33%) were erroneously diagnosed as dengue or scrub typhus. A predictive model to distinguish pediatric leptospirosis from dengue was generated using three variables: the absolute neutrophil count, plasma albumin, and aspartate aminotransferase levels in the first 72 hours of illness.

Conclusions/Significance

Unrecognized leptospirosis can be a significant cause of “dengue-like” febrile illness in children. Increased awareness of pediatric leptospirosis, and an enhanced ability to discriminate between leptospirosis and dengue early in illness, will help guide the appropriate use of healthcare resources in often resource-limited settings.     

Mexican body mass index values in the late-19th-century American West

No research has been done on the body mass index values of the 19th-century Mexican population. This paper introduces a new data source of 19th-century Mexican male inmates in American prisons and finds that the majority of Mexican body mass was in the normal range (18.5-24.9). Few Mexicans were underweight or obese by modern standards. Body mass varied little (0-0.9 units) by occupations possibly because criminals probably came from the lower end of the socioeconomic distribution; however, it did vary with crimes for which inmates were incarcerated.