Is objective and accurate cognitive assessment across the menstrual cycle possible? A feasibility study

YesOBJECTIVES: Variation in plasma hormone levels influences the neurobiology of brain regions involved in cognition and emotion processing. Fluctuations in hormone levels across the menstrual cycle could therefore alter cognitive performance and wellbeing; reports have provided conflicting results, however. The aim of this study was to assess whether objective assessment of cognitive performance and self-reported wellbeing during the follicular and luteal phases of the menstrual cycle is feasible and investigate the possible reasons for variation in effects previously reported. METHODS: The Cambridge Neuropsychological Test Automated Battery and Edinburgh Postnatal Depression Scale were used to assess the cognitive performance and wellbeing of 12 women. Data were analysed by self-reported and hormone-estimated phases of the menstrual cycle. RESULTS: Recruitment to the study and assessment of cognition and wellbeing was without issue. Plasma hormone and peptide estimation showed substantial individual variation and suggests inaccuracy in self-reported menstrual phase estimation. CONCLUSION: Objective assessment of cognitive performance and self-assessed wellbeing across the menstrual cycle is feasible. Grouping data by hormonal profile rather by self-reported phase estimation may influence phase-mediated results. Future studies should use plasma hormone and peptide profiles to estimate cycle phase and group data for analyses

ZeroFL: Efficient On-Device Training for Federated Learning with Local Sparsity

When the available hardware cannot meet the memory and compute requirements to efficiently train high performing machine learning models, a compromise in either the training quality or the model complexity is needed. In Federated Learning (FL), nodes are orders of magnitude more constrained than traditional server-grade hardware and are often battery powered, severely limiting the sophistication of models that can be trained under this paradigm. While most research has focused on designing better aggregation strategies to improve convergence rates and in alleviating the communication costs of FL, fewer efforts have been devoted to accelerating on-device training. Such stage, which repeats hundreds of times (i.e. every round) and can involve thousands of devices, accounts for the majority of the time required to train federated models and, the totality of the energy consumption at the client side. In this work, we present the first study on the unique aspects that arise when introducing sparsity at training time in FL workloads. We then propose ZeroFL, a framework that relies on highly sparse operations to accelerate on-device training. Models trained with ZeroFL and 95% sparsity achieve up to 2.3% higher accuracy compared to competitive baselines obtained from adapting a state-of-the-art sparse training framework to the FL setting.Comment: Published as a conference paper at ICLR 202

A systematic review and meta-analysis of randomised controlled trials of treatments for clozapine-induced obesity and metabolic syndrome.

Metabolic complications are commonly found in people treated with clozapine. Reviews on the management of this problem have generally drawn conclusions by grouping different types of studies involving patients treated with various different antipsychotics. We carried out a systematic review and meta-analysis of pharmacological and non-pharmacological treatments for clozapine-induced obesity or metabolic syndrome. Two researchers independently searched PubMed and Embase for randomised controlled trials (RCTs) of treatments for clozapine-induced obesity or metabolic syndrome. All other types of studies were excluded. We only included RCTs where more than 50% of participants were taking clozapine. We identified 15 RCTs. Effective pharmacological treatments for clozapine-induced obesity and metabolic syndrome include metformin, aripiprazole, and Orlistat (in men only). Meta-analysis of three studies showed a robust effect of metformin in reducing body mass index and waist circumference but no effects on blood glucose, triglyceride levels, or HDL levels. In addition, there is limited evidence for combined calorie restriction and exercise as a non-pharmacological alternative for the treatment of clozapine-induced obesity, but only in an in-patient setting. Rosiglitazone, topiramate, sibutramine, phenylpropanolamine, modafinil, and atomoxetine have not shown to be beneficial, despite reports of efficacy in other populations treated with different antipsychotics. We conclude that randomised-controlled trial data support the use of metformin, aripiprazole, and Orlistat (in men only) for treating clozapine-induced obesity. Calorie restriction in combination with an exercise programme may be effective as a non-pharmacological alternative. Findings from trials in different populations should not be extrapolated to people being treated with clozapine.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.euroneuro.2016.07.01

Building Babies - Chapter 16

In contrast to birds, male mammals rarely help to raise the offspring. Of all mammals, only among rodents, carnivores, and primates, males are sometimes intensively engaged in providing infant care (Kleiman and Malcolm 1981). Male caretaking of infants has long been recognized in nonhuman primates (Itani 1959). Given that infant care behavior can have a positive effect on the infant’s development, growth, well-being, or survival, why are male mammals not more frequently involved in “building babies”? We begin the chapter defining a few relevant terms and introducing the theory and hypotheses that have historically addressed the evolution of paternal care. We then review empirical findings on male care among primate taxa, before focusing, in the final section, on our own work on paternal care in South American owl monkeys (Aotus spp.). We conclude the chapter with some suggestions for future studies.Deutsche Forschungsgemeinschaft (HU 1746/2-1) Wenner-Gren Foundation, the L.S.B. Leakey Foundation, the National Geographic Society, the National Science Foundation (BCS-0621020), the University of Pennsylvania Research Foundation, the Zoological Society of San Dieg

Architecture of Pol II(G) and molecular mechanism of transcription regulation by Gdown1.

Tight binding of Gdown1 represses RNA polymerase II (Pol II) function in a manner that is reversed by Mediator, but the structural basis of these processes is unclear. Although Gdown1 is intrinsically disordered, its Pol II interacting domains were localized and shown to occlude transcription factor IIF (TFIIF) and transcription factor IIB (TFIIB) binding by perfect positioning on their Pol II interaction sites. Robust binding of Gdown1 to Pol II is established by cooperative interactions of a strong Pol II binding region and two weaker binding modulatory regions, thus providing a mechanism both for tight Pol II binding and transcription inhibition and for its reversal. In support of a physiological function for Gdown1 in transcription repression, Gdown1 co-localizes with Pol II in transcriptionally silent nuclei of early Drosophila embryos but re-localizes to the cytoplasm during zygotic genome activation. Our study reveals a self-inactivation through Gdown1 binding as a unique mode of repression in Pol II function

Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models

The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example during chromosome organization. Describing phenomena that cover such diverse length, and also time scales, requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA, and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure

Nut production in Bertholletia excelsa across a logged forest mosaic: implications for multiple forest use

Although many examples of multiple-use forest management may be found in tropical smallholder systems, few studies provide empirical support for the integration of selective timber harvesting with non-timber forest product (NTFP) extraction. Brazil nut (Bertholletia excelsa, Lecythidaceae) is one of the world’s most economically-important NTFP species extracted almost entirely from natural forests across the Amazon Basin. An obligate out-crosser, Brazil nut flowers are pollinated by large-bodied bees, a process resulting in a hard round fruit that takes up to 14 months to mature. As many smallholders turn to the financial security provided by timber, Brazil nut fruits are increasingly being harvested in logged forests. We tested the influence of tree and stand-level covariates (distance to nearest cut stump and local logging intensity) on total nut production at the individual tree level in five recently logged Brazil nut concessions covering about 4000 ha of forest in Madre de Dios, Peru. Our field team accompanied Brazil nut harvesters during the traditional harvest period (January-April 2012 and January-April 2013) in order to collect data on fruit production. Three hundred and ninety-nine (approximately 80%) of the 499 trees included in this study were at least 100 m from the nearest cut stump, suggesting that concessionaires avoid logging near adult Brazil nut trees. Yet even for those trees on the edge of logging gaps, distance to nearest cut stump and local logging intensity did not have a statistically significant influence on Brazil nut production at the applied logging intensities (typically 1–2 timber trees removed per ha). In one concession where at least 4 trees ha-1 were removed, however, the logging intensity covariate resulted in a marginally significant (0.09) P value, highlighting a potential risk for a drop in nut production at higher intensities. While we do not suggest that logging activities should be completely avoided in Brazil nut rich forests, when a buffer zone cannot be observed, low logging intensities should be implemented. The sustainability of this integrated management system will ultimately depend on a complex series of socioeconomic and ecological interactions. Yet we submit that our study provides an important initial step in understanding the compatibility of timber harvesting with a high value NTFP, potentially allowing for diversification of forest use strategies in Amazonian Perù

Näyttöön perustuva tuki- ja liikuntaelinsairauksien kuntoutus

103 s.Kelan rahoittaman TULES- eli tuki- ja liikuntaelinsairauksien kuntoutuksen standardien kehittämistä tukevan tutkimuksen (11/2013–8/2014) yhtenä osatavoitteena oli kartoittaa keskeisin tutkimusnäyttö tuki- ja liikuntaelinsairauksien vaikuttavasta kuntoutuksesta. Tämän työpaperin tarkoitus on antaa kuntoutuksen suunnittelijoille ja käytännön työntekijöille tietoa tämänhetkisen TULES-kuntoutuksen tutkimuksen tuloksista. Järjestelmällinen kirjallisuuskatsaus tuo esille vaikuttavaksi osoitettuja kuntoutusmuotoja. Tähän kirjallisuuskatsaukseen on lisäksi kerätty tietoa eri maiden kuntoutussuosituksista alaselän, niskan, olkapään sekä polven ja lonkan TULE-sairauksien osalta sekä kuntouttavan liikuntaharjoittelun perusteista. Järjestelmällinen tiedonhaku suoritettiin viiden vuoden ajalta; vuoden 2009 alusta vuoden 2013 loppuun saakka. Järjestelmällisen katsauksen päätulokset osoittivat aktiiviseen terapeuttiseen harjoitteluun perustuvien ohjelmien olevan vaikuttavia kaikkien katsauksessa mukana olleiden TULE-sairauksien kuntoutuksessa. Lisäksi todettiin manuaalisen terapian olevan vaikuttavaa alaselän ja niskan kuntoutuksessa. Kohtalaista tutkimusnäyttöä löytyi tiettyjen fysikaalisten hoitojen, mm. akupunktion, laserterapian ja pulsoivan magneettiterapian vaikuttavuudesta jokaisessa tutkitussa TULE-sairaudessa. Ohjauksellisista interventioista ainoastaan behavioraalisen terapian vaikuttavuus on osoitettu kohtalaiseksi alaselän kuntoutuksessa. Eri maiden ja yhdistysten suositukset painottavat tutkimusnäytön mukaisesti aktiivista harjoittelua niin selkä-, niska- kuin nivelkuntoutuksessa

Scapinin, the Protein Phosphatase 1 Binding Protein, Enhances Cell Spreading and Motility by Interacting with the Actin Cytoskeleton

Copyright (c) 2009 Sagara et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Scapinin, also named phactr3, is an actin and protein phosphatase 1 (PP1) binding protein, which is expressed in the adult brain and some tumor cells. At present, the role(s) of scapinin in the brain and tumors are poorly understood. We show that the RPEL-repeat domain of scapinin, which is responsible for its direct interaction with actin, inhibits actin polymerization in vitro. Next, we established a Hela cell line, where scapinin expression was induced by tetracycline. In these cells, expression of scapinin stimulated cell spreading and motility. Scapinin was colocalized with actin at the edge of spreading cells. To explore the roles of the RPEL-repeat and PP1-binding domains, we expressed wild-type and mutant scapinins as fusion proteins with green fluorescence protein (GFP) in Cos7 cells. Expression of GFP-scapinin (wild type) also stimulated cell spreading, but mutation in the RPEL-repeat domain abolished both the actin binding and the cell spreading activity. PP1-binding deficient mutants strongly induced cell retraction. Long and branched cytoplasmic processes were developed during the cell retraction. These results suggest that scapinin enhances cell spreading and motility through direct interaction with actin and that PP1 plays a regulatory role in scapinin-induced morphological changes.ArticlePLOS ONE. 4(1):e4247 (2009)journal articl