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Insights from a proteomic atlas of human Alzheimer's disease brain tissue

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Neural Regeneration Research 2025年第3期20卷 799-800页

作者： Tomas Kavanagh eleanor.dr.mmond Brain and Mind Centre and School of Medical Sciences University of SydneyCamperdownNSWAustralia

There is an urgent need to identify new drug targets for Alzheimer's disease(AD). While new immunotherapies show promise, clinical benefit appears low, and side effects are high. A greater understanding of the disease mechanisms driving AD is an essential factor that will facilitate the identification of new, effective drug targets.

关键词： Alzheimer clinical driving

Development,validation,and transportability of several machine-learned,non-exercise-based VO_(2max)prediction models for older adults

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Journal of Sport and Health Science 2024年第5期13卷 611-620页

作者： Benjamin T.Schumacher Michael J.LaMonte Andrea Z.LaCroix eleanor M.Simonsick Steven P.Hooker Humberto Parada Jr. John Bellettiere Arun Kumar Herbert Wertheim School of Public Health and Human Longevity Science University of California San DiegoLa JollaCA 92093USA Department of Epidemiology and Environmental Health School of Public Health and Health ProfessionsUniversity at BuffaloState University of New YorkBuffaloNY 14214USA Translational Gerontology Branch Intramural Research ProgramNational Institute on AgingNational Institutes of HealthBaltimoreMD 21225USA College of Health and Human Services San Diego State UniversitySan DiegoCA 92182USA Division of Epidemiology and Biostatistics School of Public HealthSan Diego State UniversitySan DiegoCA 92182USA University of California San Diego Moores Cancer Center La JollaCA 92093USA Computer Science and Engineering and Halicioglu Data Science Institute University of California San DiegoLa JollaCA 92093USA

Background:There exist few maximal oxygen uptake(VO_(2max))non-exercise-based prediction equations,fewer using machine learning(ML),and none specifically for older *** direct measurement of VO_(2max)is infeasible in large epidemiologic cohort studies,we sought to develop,validate,compare,and assess the transportability of several ML VO_(2max)prediction ***:The Baltimore Longitudinal Study of Aging(BLSA)participants with valid VO2_(max)tests were included(n=1080).Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine(SVM)algorithms were trained to predict VO_(2max)*** developed these algorithms for:(a)the overall BLSA,(b)by sex,(c)using all BLSA variables,and(d)variables common in aging ***,we quantified the associations between measured and predicted VO_(2max)and ***:The age was 69.0±10.4 years(mean±SD)and the measured VO_(2max)was 21.6±5.9 mL/kg/*** absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine yielded root mean squared errors of 3.4 mL/kg/min,3.6 mL/kg/min,3.4 mL/kg/min,3.6 mL/kg/min,and 3.5 mL/kg/min,*** quartiles of measured VO_(2max)showed an inverse gradient in mortality *** VO_(2max)variables yielded similar effect estimates but were not robust to ***:Measured VO_(2max)is a strong predictor of *** ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to *** studies should seek to reproduce these results so that VO_(2max),an important vital sign,can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.

关键词： Cardiorespiratory fitness Prediction algorithms Epidemiology Mortality

Vertical Distribution of Soil Pyrogenic Matter: A Review

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Pedosphere 2019年第2期29卷 137-149页

作者： eleanor HOBLEY Soil Science Technical University of Munich

Alteration of terrestrial biomass during fire produces pyrogenic matter, a large quantity of which is deposited on and may enter soils. The amount of annual burning around the globe implies greater production and storage of carbon in soil pyrogenic organic matter(pyrOM) than is regularly found in investigations of soil pyrogenic matter. A portion of this unaccounted for pyrogenic material may be translocated to subsurface soil depths, which is frequently excluded from soil investigations, and the presence of subsoil charcoal helps to partially fill this pyrOM gap. In this paper, I discuss the mechanisms for vertical redistribution of pyrogenic matter in soils and develop conceptual models to describe the depth, particle size, and age distribution of pyrogenic matter resulting from different translocation mechanisms. Based on the relationships between pyrogenic matter turnover and translocation, the suitability of pyrogenic matter in soils as an indicator for soil processes is discussed. Deciphering the relationships between pyrogenic matter depth, particle size, and age distribution yields valuable insights into the dynamics of soil forming processes as well as soil pyrogenic matter turnover,which should therefore, be a focus of future studies.

关键词： age black carbon charcoal mobility organic matter particle size subsoil translocation

It takes more than tau to tangle:using proteomics to determine how phosphorylated tau mediates toxicity in neurodegenerative diseases

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Neural Regeneration Research 2021年第11期16卷 2211-2212页

作者： Geoffrey Pires eleanor.dr.mmond Center for Cognitive Neurology Department of NeurologyNew York University School of MedicineNew YorkNYUSA Alzheimer’s and Prion Diseases Team Paris Brain InstituteCNRSUMR 7225INSERM 1127Sorbonne University UM75ParisFrance

Two of the most common causes of dementia are Alzheimer’s disease(AD)and frontotemporal dementia(FTD).AD is an irreversible,progressive neurodegenerative disorder that is clinically characterized by severe memory loss and behavioral impairment that eventually interferes with everyday *** is neuropathologically defined by the presence of extracellularβ-amyloid plaques and intracellular accumulation of neurofibrillary tangles(NFTs)that primarily contain aggregated,hyperphosphorylated tau(pTau).Intriguingly,pTau is also the central protein in multiple subtypes of FTD(*** degeneration,progressive supranuclear palsy,Pick’s disease).FTD is an umbrella term for a group of neurological conditions that primarily affect the temporal and frontal regions of the *** in the tau gene(MAPT)can cause familial FTD,providing further evidence of the integral role of tau in ***,tau regulates microtubule structure and dynamics,as well as axonal transport through interaction with *** is also involved in neuronal development and *** AD and FTD,tau becomes hyperphosphorylated and undergoes major conformational changes,causing it to aggregate into the characteristic neuropathological lesions that define AD and *** the known involvement of tau in these diseases,exactly how tau mediates toxicity is still unclear.

关键词： tau involvement media

The use of localized proteomics to identify the drivers of Alzheimer's disease pathogenesis

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Neural Regeneration Research 2017年第6期12卷 912-913页

作者： eleanor.dr.mmond Thomas Wisniewski Center for Cognitive Neurology Department of Neurology New York University School of Medicine Departments of Neurology Pathology and Psychiatry New York University School of Medicine

Alzheimer’s disease（AD）is broadly defined by dementia and the presence of specific neuropathological features in the brain（amyloid plaques,neurofibrillary tangles（NFTs）and congophilic amyloid angiopathy）.However,the rate of disease progression,type of cognitive impairment,and extent of neuropathology vary widely in patients with AD（Murray et al.,2011）.

关键词： amyloid pathogenesis proteomics localized impairment plaques Murray targeted progression brains

Bottom Simulating Reflector and Gas Seepage in Okinawa Trough:Evidence of Gas Hydrate in an Active Back-Arc Basin

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Journal of China University of Geosciences 2008年第2期19卷 152-161页

作者：栾锡武 Kelin Wang Roy Hyndman eleanor Willoughby Key Laboratory of Marine Geology and Environment Institute of Oceanology Chinese Academy of Sciences （IOCAS） Qingdao 266071 China Pacific Geoscience Centre （PGC） Geological Survey of Canada Sidney V8L4B2 Canada

To look for gas hydrate, 22 multi-channel and 3 single-channel seismic lines on the East China Sea （ECS） shelf slope and at the bottom of the Okinawa Trough were examined. It was found that there was indeed bottom simulating reflector （BSR） occurrence, but it is very rare. Besides several BSRs, a gas seepage was also found. As shown by the data, both the BSR and gas seepage are all related with local geological structures, such as mud diapir, anticline, and fault-controlled graben-like structure. However, similar structural ＂anomalies＂ are quite common in the tectonically very active Okinawa Trough region, but very few of them have developed BSR or gas seepage. The article points out that the main reason is probably the low concentration of organic carbon of the sediment in this area. It was speculated that the rare occurrence of gas hydrates in this region is governed by structure-controlled fluid flow. Numerous faults and fractures form a network of high-permeability channels in the sediment and highly fractured igneous basement to allow fluid circulation and ventilation. Fluid flow in this tectonic environment is driven primarily by thermal buoyancy and takes place on a wide range of spatial scales. The fluid flow may play two roles to facilitate hydrate formation： to help gather enough methane into a small area and to modulate the thermal regime.

关键词： gas hydrate BSR gas seepage back-arc basin formation mechanism.

Rectal biopsy for Hirschsprung's disease:a review of techniques,pathology,and complications

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世界儿科杂志:英文版 2016年第2期12卷 135-141页

作者： eleanor Dorothy Muise Robert Anthony Cowles Section of Pediatric Surgery Department of SurgeryYale University School of MedicineNew HavenCTUSA

Background:Hirschsprung's disease(HD)is one of the most common congenital anomalies of colorectal function,affecting approximately 1 in 5000 live births,with a 4:1 male *** is characterized by aganglionosis that is most often limited to the rectosigmoid,but can extend proximally along the colon and,in rare instances,reach into the small intestine.A clinical history of delayed passage of meconium beyond 48 hours after birth,physical exam findings of abdominal distention and vomiting,and a contrast enema demonstrating a transition zone are highly suggestive of *** sources:We searched databases including PubMed,Google Scholar,and Scopus for the following key words:Hirschsprung's disease,rectal biopsy,pathology,ganglion cell,nerve trunk hypertrophy,pediatric constipation,and selected publications written in English that were relevant to the scope of this ***:Based on the data presented in the literature,we reviewed 1)biopsy techniques for the diagnosis of Hirschsprung's disease,addressed inadequate biopsies,and complications from rectal biopsy,and 2)pathologic and histologic interpretation of biopsy specimens for the diagnosis of Hirschsprung's ***:A well-executed rectal biopsy with expert pathologic evaluation of the specimen remains the gold standard for the diagnosis of Hirschsprung's disease and is the subject of this review.

关键词： ganglion cell Hirschsprung's disease nerve trunk hypertrophy pediatric constipation rectal biopsy

Use of Ribavirin for Hepatitis C Treatment in the Modern Direct-acting Antiviral Era

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Journal of Clinical and Translational Hepatology 2018年第4期6卷 431-437页

作者： Poonam Mathur Shyamasundaran Kottilil eleanor Wilson Division of Clinical Care and Research Institute of Human VirologyUniversity of Maryland School of MedicineBaltimoreMDUSA

Ribavirin,once a staple of hepatitis C treatment,has significant drawbacks,including treatment-limiting side effects,the requirement for intensive laboratory monitoring,the need for frequent dose adjustments,and *** factors make it difficult to escalate ribavirin-based HCV treatment to most infected patients *** studies have shown comparable response rates between ribavirin-inclusive and ribavirin-sparing regimens in uncomplicated patient ***,ribavirin is still used in the management of patients who have failed previous therapy as well as those with decompensated liver *** this review,we explore the evidence supporting the use of ribavirin in the current climate of hepatitis C treatment with oral combination direct-acting antiviral agents.

关键词： Chronic hepatitis C Direct-acting antivirals Ribavirin

Carbon storage in a wolfberry plantation chronosequence established on a secondary saline land in an arid irrigated area of Gansu Province,China

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Journal of Arid Land 2018年第2期10卷 202-216页

作者： MA Quanlin WANG Yaolin LI Yinke SUN Tao eleanor MILNE State Key Laboratory of Desertification and Aeolian Sand Disaster Combating Gansu Desert Control Research InstituteLanzhou 730070China Natural Resource Ecology Laboratory Colorado State UniversityFort Collins CO 80523-1499USA

Carbon（C） storage has received significant attention for its relevance to agricultural security and climate change. Afforestation can increase C storage in terrestrial ecosystems, and has been recognized as an important measure to offset CO_2 emissions. In order to analyze the C benefits of planting wolfberry（Lycium barbarum L.） on the secondary saline lands in arid areas, we conducted a case study on the dynamics of biomass carbon（BC） storage and soil organic carbon（SOC） storage in different-aged wolfberry plantations（4-, 7-and 11-year-old） established on a secondary saline land as well as on the influence of wolfberry plantations on C storage in the plant-soil system in an arid irrigated area（Jingtai County） of Gansu Province, China. The C sequestration and its potential in the wolfberry plantations of Gansu Province were also evaluated. An intact secondary saline land was selected as control. Results show that wolfberry planting could decrease soil salinity, and increase BC, SOC and litter C storage of the secondary saline land significantly, especially in the first 4 years after planting. The aboveground and belowground BC storage values in the intact secondary saline land（control） accounted for only 1.0% and 1.2% of those in the wolfberry plantations, respectively. Compared to the intact secondary saline land, the SOC storage values in the 4-, 7-and 11-year-old wolfberry plantations increased by 36.4%, 37.3% and 43.3%, respectively, and the SOC storage in the wolfberry plantations occupied more than 92% of the ecosystem C storage. The average BC and SOC sequestration rates of the wolfberry plantations for the age group of 0–11 years were 0.73 and 3.30 Mg C/（hm^2·a）, respectively. There were no significant difference in BC and SOC storage between the 7-year-old and 11-year-old wolfberry plantations, which may be due in part to the large amounts of C offtakes in new branches and fruits. In Gansu Province, the C storage in the wolfberry plantations has reached up

关键词： Lycium barbaum biomass carbon soil organic carbon carbon sequestration potential secondary saline land wolfberry plantation carbon dynamics