β-Secretases, Alzheimer's Disease, and Down Syndrome

Individuals with Down Syndrome (DS), or trisomy 21, develop Alzheimer's disease (AD) pathology by approximately 40 years of age. Chromosome 21 harbors several genes implicated in AD, including the amyloid precursor protein and one homologue of the β-site APP cleaving enzyme, BACE2. Processing of the amyloid precursor protein by β-secretase (BACE) is the rate-limiting step in the production of the pathogenic Aβ peptide. Increased amounts of APP in the DS brain result in increased amounts of Aβ and extracellular plaque formation beginning early in life. BACE dysregulation potentially represents an overlapping biological mechanism with sporadic AD and a common therapeutic target. As the lifespan for those with DS continues to increase, age-related concerns such as obesity, depression, and AD are of growing concern. The ability to prevent or delay the progression of neurodegenerative diseases will promote healthy aging and improve quality of life for those with DS

β-Secretases, Alzheimer\u27s Disease, and Down Syndrome

Individuals with Down Syndrome (DS), or trisomy 21, develop Alzheimer\u27s disease (AD) pathology by approximately 40 years of age. Chromosome 21 harbors several genes implicated in AD, including the amyloid precursor protein and one homologue of the β-site APP cleaving enzyme, BACE2. Processing of the amyloid precursor protein by β-secretase (BACE) is the rate-limiting step in the production of the pathogenic Aβ peptide. Increased amounts of APP in the DS brain result in increased amounts of Aβ and extracellular plaque formation beginning early in life. BACE dysregulation potentially represents an overlapping biological mechanism with sporadic AD and a common therapeutic target. As the lifespan for those with DS continues to increase, age-related concerns such as obesity, depression, and AD are of growing concern. The ability to prevent or delay the progression of neurodegenerative diseases will promote healthy aging and improve quality of life for those with DS

Efficient Activation of Reconstructed Rat Embryos by Cyclin-Dependent Kinase Inhibitors

This Article is brought to you for free and open access by the Molecular and Cellular Biochemistry at UKnowledge. It has been accepted for inclusion in Molecular and Cellular Biochemistry Faculty Publication by an authorized administrator of UKnowledge. For more information, please contac

Language aptitude in the visuospatial modality: L2 British Sign Language acquisition and cognitive skills in British Sign Language-English interpreting students

© 2022 The Authors. Published by Frontiers Media. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3389/fpsyg.2022.932370Sign language interpreting (SLI) is a cognitively challenging task performed mostly by second language learners (i.e., not raised using a sign language as a home language). SLI students must first gain language fluency in a new visuospatial modality and then move between spoken and signed modalities as they interpret. As a result, many students plateau before reaching working fluency, and SLI training program drop-out rates are high. However, we know little about the requisite skills to become a successful interpreter: the few existing studies investigating SLI aptitude in terms of linguistic and cognitive skills lack baseline measures. Here we report a 3-year exploratory longitudinal skills assessments study with British Sign Language (BSL)-English SLI students at two universities (n = 33). Our aims were two-fold: first, to better understand the prerequisite skills that lead to successful SLI outcomes; second, to better understand how signing and interpreting skills impact other aspects of cognition. A battery of tasks was completed at four time points to assess skills, including but not limited to: multimodal and unimodal working memory, 2-dimensional and 3-dimensional mental rotation (MR), and English comprehension. Dependent measures were BSL and SLI course grades, BSL reproduction tests, and consecutive SLI tasks. Results reveal that initial BSL proficiency and 2D-MR were associated with selection for the degree program, while visuospatial working memory was linked to continuing with the program. 3D-MR improved throughout the degree, alongside some limited gains in auditory, visuospatial, and multimodal working memory tasks. Visuospatial working memory and MR were the skills closest associated with BSL and SLI outcomes, particularly those tasks involving sign language production, thus, highlighting the importance of cognition related to the visuospatial modality. These preliminary data will inform SLI training programs, from applicant selection to curriculum design.This work was supported by an Economic and Social Research Council of Great Britain 1 + 3 doctoral studentship awarded to FW (ES/J50001X/1) and a British Academy/Leverhulme Trust Small Research Grant awarded to RT, SW, and CS (SRG19\191348).Published onlin

Grassroots Leadership Development

Over a four-year period, the W.K. Kellogg Foundation invested more than $20 million in grants to 23 local, regional, and national organizations involved in grassroots leadership development. Dr. Jeanne Campbell, a Minnesota-based research consultant, was retained to lead the research on this project. Her charge was to visit these 23 organizations and capture what they had learned about grassroots leadership. Largely based on the Campbell Report, this workbook provides new insights for aspiring or current grassroots leaders to sharpen and clarify assumptions about grassroots leadership and its power.Healthy communities need involved citizens. A civil society depends on citizen concern and citizen action as its lifeblood. How we sustain and strengthen communities is an enduring question. The examples in this workbook offer practical, proven suggestions on how to strengthen and build healthy communities.Whether you are interested in solving a problem in your community or involving more of your neighbors in your cause, you'll find something of value to your work in these findings. Some of the findings give weight and credibility to the obvious or assumed. Others break new ground and point to approaches that can help all of us get more results from grassroots leadership efforts.What follows are the five main findings from this research and related work by the W.K. Kellogg Foundation

Protected areas support more species than unprotected areas in Great Britain, but lose them equally rapidly

Protected areas are a key conservation tool, yet their effectiveness at maintaining biodiversity through time is rarely quantified. Here, we assess protected area effectiveness across sampled portions of Great Britain (primarily England) using regionalized (protected vs unprotected areas) Bayesian occupancy-detection models for 1238 invertebrate species at 1 km resolution, based on ~1 million occurrence records between 1990 and 2018. We quantified species richness, species trends, and compositional change (temporal beta diversity; decomposed into losses and gains). We report results overall, for two functional groups (pollinators and predators), and for rare and common species. Whilst we found that protected areas have 15 % more species on average than unprotected ones, declines in occupancy are of similar magnitude and species composition has changed 27 % across protected and unprotected areas, with losses dominating gains. Pollinators have suffered particularly severe declines. Still, protected areas are colonized by more locally-novel pollinator species than unprotected areas, suggesting that they might act as ‘landing pads’ for range-shifting pollinators. We find almost double the number of rare species in protected areas (although rare species trends are similar in protected and unprotected areas); whereas we uncover disproportionately steep declines for common species within protected areas. Our results highlight strong invertebrate reorganization and loss across both protected and unprotected areas. We therefore call for more effective protected areas, in combination with wider action, to bend the curve of biodiversity loss – where we provide a toolkit to quantify effectiveness. We must grasp the opportunity to effectively conserve biodiversity through time

Energy expenditure during sleep, sleep deprivation and sleep following sleep deprivation in adult humans

Sleep has been proposed to be a physiological adaptation to conserve energy, but little research has examined this proposed function of sleep in humans. We quantified effects of sleep, sleep deprivation and recovery sleep on whole-body total daily energy expenditure (EE) and on EE during the habitual day and nighttime. We also determined effects of sleep stage during baseline and recovery sleep on EE. Seven healthy participants aged 22 ± 5 years (mean ± s.d.) maintained ∼8 h per night sleep schedules for 1 week before the study and consumed a weight-maintenance diet for 3 days prior to and during the laboratory protocol. Following a habituation night, subjects lived in a whole-room indirect calorimeter for 3 days. The first 24 h served as baseline – 16 h wakefulness, 8 h scheduled sleep – and this was followed by 40 h sleep deprivation and 8 h scheduled recovery sleep. Findings show that, compared to baseline, 24 h EE was significantly increased by ∼7% during the first 24 h of sleep deprivation and was significantly decreased by ∼5% during recovery, which included hours awake 25–40 and 8 h recovery sleep. During the night time, EE was significantly increased by ∼32% on the sleep deprivation night and significantly decreased by ∼4% during recovery sleep compared to baseline. Small differences in EE were observed among sleep stages, but wakefulness during the sleep episode was associated with increased energy expenditure. These findings provide support for the hypothesis that sleep conserves energy and that sleep deprivation increases total daily EE in humans

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for direct stau production in events with two hadronic tau-leptons in root s=13 TeV pp collisions with the ATLAS detector

A search for the direct production of the supersymmetric partners ofτ-leptons (staus) in final stateswith two hadronically decayingτ-leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of139fb−1, recorded with the ATLAS detector at the LargeHadron Collider at a center-of-mass energy of 13 TeV. No significant deviation from the expected StandardModel background is observed. Limits are derived in scenarios of direct production of stau pairs with eachstau decaying into the stable lightest neutralino and oneτ-lepton in simplified models where the two staumass eigenstates are degenerate. Stau masses from 120 GeV to 390 GeV are excluded at 95% confidencelevel for a massless lightest neutralino