The influence of shc proteins on the whole body energetic response to calorie restriction initiated in 3-month-old mice.

There is increasing evidence that Shc proteins play a role in energy metabolism, and we have previously reported that knockdown of Shc proteins influences the energetic response to acute (3 days) calorie restriction (CR) in 18-month-old mice. Whether Shc proteins play a role in the metabolic response to CR in younger mice has yet to be elucidated. Hence, we sought to determine the impact of 3 days and longer term (2 months) CR on energy expenditure (EE) and respiratory quotient (RQ) in 3 month-old Shc knockout (ShcKO) and wild-type (WT) mice. ShcKO mice decreased (P < 0.001) EE normalized for body weight (EEBW) by 3 days of CR, while no such change was observed in WT animals. However, both ShcKO and WT mice decreased (P < 0.001) EEBW at 2 months of CR and there were no differences in body weight between the ShcKO and WT mice at either 3 days or 2 months of CR. Consistent with increased fatty acid oxidation, only ShcKO mice maintained decreased (P < 0.001) 24 h RQ through 2 months of CR, suggesting that they were able to maintain increased fatty acid oxidation for a longer period of time than WT mice. These results indicate that Shc proteins may contribute to some of the acute energetic responses to CR

The influence of shc proteins and aging on whole body energy expenditure and substrate utilization in mice.

While it has been proposed that Shc family of adaptor proteins may influence aging by regulating insulin signaling and energy metabolism, the overall impact of Shc proteins on whole body energy metabolism has yet to be elucidated. Thus, the purpose of this study was to determine the influence of Shc proteins and aging on whole body energy metabolism in a mouse model under ambient conditions (22°C) and acute cold exposure (12°C for 24 hours). Using indirect respiration calorimetry, we investigated the impact of Shc proteins and aging on EE and substrate utilization (RQ) in p66 Shc-/- (ShcKO) and wild-type (WT) mice. Calorimetry measurements were completed in 3, 15, and 27 mo mice at 22°C and 12°C. At both temperatures and when analyzed across all age groups, ShcKO mice demonstrated lower 24 h total EE values than that of WT mice when EE data was expressed as either kJ per mouse, or adjusted by body weight or crude organ mass (ORGAN) (P≤0.01 for all). The ShcKO mice also had higher (P<0.05) fed state RQ values than WT animals at 22°C, consistent with an increase in glucose utilization. However, Shc proteins did not influence age-related changes in energy expenditure or RQ. Age had a significant impact on EE at 22°C, regardless of how EE data was expressed (P<0.05), demonstrating a pattern of increase in EE from age 3 to 15 mo, followed by a decrease in EE at 27 mo. These results indicate a decline in whole body EE with advanced age in mice, independent of changes in body weight (BW) or fat free mass (FFM). The results of this study indicate that both Shc proteins and aging should be considered as factors that influence energy expenditure in mice

Sources of Errors on Visuoperceptual Tasks: Role of Education, Literacy, and Search Strategy

The current study explored possible sources of demographic effects through analyses of errors from modified formats of the Benton Visual Retention Test (BVRT) completed by African American elders. Results indicate that: (1) reading level was a stronger predictor of BVRT performance than years of education; (2) on the single-item matching format of the task, individuals with lower reading levels disproportionately produced errors on items that differed in geometric, rather than spatial features; and (3) on a multiple-choice matching format, individuals with lower reading levels committed more errors on items where the target was located in the lower half of a 2 × 2 matrix

Aqueous Processes and Microbial Habitability of Gale Crater Sediments from the Blunts Point to the Glenn Torridon Clay Unit

A driving factor for sending the Mars Science Laboratory, Curiosity rover to Gale Crater was the orbital detection of clay minerals in the Glen Torridon (GT) clay unit. Clay mineral detections in GT suggested a past aqueous environment that was habitable, and could contain organic evidence of past microbiology. The mission of the Sample Analysis at Mars (SAM) instrument onboard Curiosity was to detect organic evidence of past microbiology and to detect volatile bearing mineralogy that can inform on whether past geochemical conditions would have supported microbiological activity. The objective of this work was to 1) evaluate the depositional/alteration conditions of Blunts Point (BP) to GT sediments 2) search for evidence of organics, and 3) evaluate microbial habitability in the BP, Vera Rubin Ridge (VRR), and GT sedimentary rock

Biofluorescence in Catsharks (Scyliorhinidae): Fundamental Description and Relevance for Elasmobranch Visual Ecology

Biofluorescence has recently been found to be widespread in marine fishes, including sharks. Catsharks, such as the Swell Shark (Cephaloscyllium ventriosum) from the eastern Pacific and the Chain Catshark (Scyliorhinus retifer) from the western Atlantic, are known to exhibit bright green fluorescence. We examined the spectral sensitivity and visual characteristics of these reclusive sharks, while also considering the fluorescent properties of their skin. Spectral absorbance of the photoreceptor cells in these sharks revealed the presence of a single visual pigment in each species. Cephaloscyllium ventriosum exhibited a maximum absorbance of 484 ± 3 nm and an absorbance range at half maximum (λ1/2max) of 440–540 nm, whereas for S. retifer maximum absorbance was 488 ± 3 nm with the same absorbance range. Using the photoreceptor properties derived here, a “shark eye” camera was designed and developed that yielded contrast information on areas where fluorescence is anatomically distributed on the shark, as seen from other sharks’ eyes of these two species. Phylogenetic investigations indicate that biofluorescence has evolved at least three times in cartilaginous fishes. The repeated evolution of biofluorescence in elasmobranchs, coupled with a visual adaptation to detect it; and evidence that biofluorescence creates greater luminosity contrast with the surrounding background, highlights the potential importance of biofluorescence in elasmobranch behavior and biology

Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football

IMPORTANCE: Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE). OBJECTIVE: To determine the neuropathological and clinical features of deceased football players with CTE. DESIGN, SETTING, AND PARTICIPANTS: Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history. EXPOSURES: Participation in American football at any level of play. MAIN OUTCOMES AND MEASURES: Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia. RESULTS: Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre–high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia. CONCLUSIONS AND RELEVANCE: In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.This study received support from NINDS (grants U01 NS086659, R01 NS078337, R56 NS078337, U01 NS093334, and F32 NS096803), the National Institute on Aging (grants K23 AG046377, P30AG13846 and supplement 0572063345-5, R01 AG1649), the US Department of Defense (grant W81XWH-13-2-0064), the US Department of Veterans Affairs (I01 CX001038), the Veterans Affairs Biorepository (CSP 501), the Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (grant B6796-C), the Department of Defense Peer Reviewed Alzheimer’s Research Program (grant 13267017), the National Operating Committee on Standards for Athletic Equipment, the Alzheimer’s Association (grants NIRG-15-362697 and NIRG-305779), the Concussion Legacy Foundation, the Andlinger Family Foundation, the WWE, and the NFL

Isotopes of nitrogen on Mars: Atmospheric measurements by Curiosity's mass spectrometer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102173/1/wong_readme.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102173/2/wong2013_SM_v4b.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102173/3/grl51166.pd

Silent progression in disease activity-free relapsing multiple sclerosis.

ObjectiveRates of worsening and evolution to secondary progressive multiple sclerosis (MS) may be substantially lower in actively treated patients compared to natural history studies from the pretreatment era. Nonetheless, in our recently reported prospective cohort, more than half of patients with relapsing MS accumulated significant new disability by the 10th year of follow-up. Notably, "no evidence of disease activity" at 2 years did not predict long-term stability. Here, we determined to what extent clinical relapses and radiographic evidence of disease activity contribute to long-term disability accumulation.MethodsDisability progression was defined as an increase in Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 (or greater) from baseline EDSS = 0, 1.0-5.0, and 5.5 or higher, respectively, assessed from baseline to year 5 (±1 year) and sustained to year 10 (±1 year). Longitudinal analysis of relative brain volume loss used a linear mixed model with sex, age, disease duration, and HLA-DRB1*15:01 as covariates.ResultsRelapses were associated with a transient increase in disability over 1-year intervals (p = 0.012) but not with confirmed disability progression (p = 0.551). Relative brain volume declined at a greater rate among individuals with disability progression compared to those who remained stable (p < 0.05).InterpretationLong-term worsening is common in relapsing MS patients, is largely independent of relapse activity, and is associated with accelerated brain atrophy. We propose the term silent progression to describe the insidious disability that accrues in many patients who satisfy traditional criteria for relapsing-remitting MS. Ann Neurol 2019;85:653-666

Functional magnetic resonance imaging in primary hyperparathyroidism

Objective: The neurophysiological mechanisms underlying cognitive dysfunction in primary hyperparathyroidism (PHPT) and the brain regions affected are not clear. We assessed neural activation during cognitive testing (matrix reasoning, paired associates, and logical memory) using functional MRI (fMRI) in 23 patients with PHPT and 23 healthy controls. A subset with PHPT was re-assessed 6 months post-parathyroidectomy (PTX). Design: This is an observational study comparing neural activation by fMRI in patients with PHPT to normative controls. Postmenopausal women were studied at a tertiary referral center. Results: There were no between-group differences in cognitive task performance. Patients with PHPT had lower neural activation vs controls (max Z = 4.02, all P < 0.01) during matrix reasoning in brain regions involved in executive function (left frontal lobe (k = 57) and right medial frontal gyrus (k = 72)) and motor function (right precentral gyrus (k = 51)). During paired associates (verbal memory), those with PHPT had greater activation in the right inferior parietal lobule (language/mathematical operations; k = 65, P < 0.01). Greater activation in this region bilaterally correlated with higher PTH (k = 96, P < 0.01). Post-PTX, activation decreased during matrix reasoning, but in different regions than those affected pre-PTX. Conclusions: PHPT is associated with differences in task-related neural activation patterns, but no difference in cognitive performance. While this may indicate compensation to maintain the same cognitive function, there was no clear improvement in neural activation after PTX. Larger, longitudinal studies that include PHPT patients followed without surgery are needed to determine if PTX could prevent worsening of altered neural activation patterns in PHPT

Fine Mapping of 10q and 18q for Familial Alzheimer's Disease in Caribbean Hispanics

Familial Alzheimer's disease (AD [MIM 104300]) has been a focus of intense investigation, primarily in Caucasian families from Europe and North America families. Although the late-onset form of familial AD, beginning after age 65 years, has been linked to regions on chromosomes 10q and 12p, the specific genetic variants have not yet been consistently identified. Using a unique cohort of families of Caribbean Hispanics ancestry, we screened the genome using 340 markers on 490 family members from 96 families with predominantly late-onset AD. We observed the strongest support for linkage on 18q (LOD=3.14). However, 17 additional markers (chromosomes 1-6, 8, 10, 12, and 14) exceeded a two-point LOD score of 1.0 under the affecteds-only autosomal dominant model or affected sibpair model. As we previously reported the fine-mapping effort on 12p showing modest evidence of linkage, we focused our fine-mapping efforts on two other candidate regions in the current report, namely 10q and 18q. We added 31 family members and eight additional Caribbean Hispanic families to fine map 10q and 18q. With additional microsatellite markers, the evidence for linkage for 18q strengthened near 112 cM, where the two-point LOD score for D18S541 was 3.37 and the highest NPL score in that region was 3.65 (P=0.000177). This narrow region contains a small number of genes expressed in the brain. However, at 10q (134-138 cM), the NPL score decreased from 3.15 (P=0.000486) to 2.1 (P=0.0218), but two broad peaks remained overlapping with previously reported peaks. Our results provide modest support for linkage on 10q and 12p in this cohort of Caribbean Hispanic families with familial Alzheimer's disease, and strong evidence for a new locus on 18