Mobility assessment in people with Alzheimer disease using smartphone sensors

[EN] Background Understanding the functional status of people with Alzheimer Disease (AD), both in a single (ST) and cognitive dual task (DT) activities is essential for identifying signs of early-stage neurodegeneration. This study aims to compare the performance quality of several tasks using sensors embedded in an Android device, among people at different stages of Alzheimer and people without dementia. The secondary aim is to analyze the effect of cognitive task performance on mobility tasks. Methods This is a cross-sectional study including 22 participants in the control group (CG), 18 in the group with mild AD and 22 in the group with moderate AD. They performed two mobility tests, under ST and DT conditions, which were registered using an Android device. Postural control was measured by medial-lateral and anterior-posterior displacements of the COM (MLDisp and APDisp, respectively) and gait, with the vertical and medial-lateral range of the COM (Vrange and MLrange). Further, the sit-to-stand (PStand) and turning and sit power (PTurnSit), the total time required to complete the test and the reaction time were measured. Results There were no differences between the two AD stages either for ST or DT in any of the variables (p > 0.05). Nevertheless, people at both stages showed significantly lower values of PStand and PTurnSit and larger Total time and Reaction time compared to CG (p < 0.05). Further, Vrange is also lower in CDR1G than in CG (p < 0.05). The DT had a significant deleterious effect on MLDisp in all groups (p < 0.05) and on APDisp only in moderate AD for DT. Conclusions Our findings indicate that AD patients present impairments in some key functional abilities, such as gait, turning and sitting, sit to stand, and reaction time, both in mild and moderate AD. Nevertheless, an exclusively cognitive task only influences the postural control in people with AD.This work was funded by the Spanish Government, Secretaria de Estado de Investigacion, Desarrollo e Innovacion, and co-financed by EU FEDER funds (Grant DPI2013-44227-R). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Serra-Añó, P.; Pedrero, J.; Hurtado-Abellán, J.; Inglés, M.; Espí-López, G.; Lopez Pascual, J. (2019). Mobility assessment in people with Alzheimer disease using smartphone sensors. Journal of NeuroEngineering and Rehabilitation. 16(1). https://doi.org/10.1186/s12984-019-0576-yS161Association A. 2017 Alzheimer’s disease facts and figures. Alzheimers Dement. 2017;13(4):325–73.Harrington MG, Chiang J, Pogoda JM, Gomez M, Thomas K, Marion SD, et al. Executive function changes before memory in preclinical Alzheimer’s pathology: a prospective, cross-sectional, case control study. 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Structure and non-structure of centrosomal proteins

Here we perform a large-scale study of the structural properties and the expression of proteins that constitute the human Centrosome. Centrosomal proteins tend to be larger than generic human proteins (control set), since their genes contain in average more exons (20.3 versus 14.6). They are rich in predicted disordered regions, which cover 57% of their length, compared to 39% in the general human proteome. They also contain several regions that are dually predicted to be disordered and coiled-coil at the same time: 55 proteins (15%) contain disordered and coiled-coil fragments that cover more than 20% of their length. Helices prevail over strands in regions homologous to known structures (47% predicted helical residues against 17% predicted as strands), and even more in the whole centrosomal proteome (52% against 7%), while for control human proteins 34.5% of the residues are predicted as helical and 12.8% are predicted as strands. This difference is mainly due to residues predicted as disordered and helical (30% in centrosomal and 9.4% in control proteins), which may correspond to alpha-helix forming molecular recognition features (α-MoRFs). We performed expression assays for 120 full-length centrosomal proteins and 72 domain constructs that we have predicted to be globular. These full-length proteins are often insoluble: Only 39 out of 120 expressed proteins (32%) and 19 out of 72 domains (26%) were soluble. We built or retrieved structural models for 277 out of 361 human proteins whose centrosomal localization has been experimentally verified. We could not find any suitable structural template with more than 20% sequence identity for 84 centrosomal proteins (23%), for which around 74% of the residues are predicted to be disordered or coiled-coils. The three-dimensional models that we built are available at http://ub.cbm.uam.es/centrosome/models/index.php

Physical Activity Patterns of the Spanish Population Are Mostly Determined by Sex and Age: Findings in the ANIBES Study

Background Representative data for the Spanish population regarding physical activity (PA) behaviors are scarce and seldom comparable due to methodological inconsistencies. Aim Our objectives were to describe the PA behavior by means of the standardized self-reported International Physical Activity Questionnaire (IPAQ) and to know the proportion of the Spanish population meeting and not meeting international PA recommendations. Material and Methods PA was assessed using the IPAQ in a representative sample of 2285 individuals (males, 50.4%) aged 9–75 years and living in municipalities of at least 2,000 inhabitants. Data were analyzed according to: age groups 9–12, 13–17, 18–64, and 65–75 years; sex; geographical distribution; locality size and educational levels. Results Mean total PA was 868.8±660.9 min/wk, mean vigorous PA 146.4±254.1 min/wk, and mean moderate PA 398.1±408.0 min/wk, showing significant differences between sexes (p<0.05). Children performed higher moderate-vigorous PA than adolescents and seniors (p<0.05), and adults than adolescents and seniors (p<0.05). Compared to recommendations, 36.2%of adults performed <150 min/week of moderate PA, 65.4% <75 min/week of vigorous PA and 27.0%did not perform any PA at all, presenting significant differences between sexes (p<0.05). A total of 55.4%of children and adolescents performed less than 420 min/week of MVPA, being higher in the later (62.6%) than in the former (48.4%). Highest non-compliance was observed in adolescent females (86.5%). Conclusion Sex and age are the main influencing factors on PA in the Spanish population. Males engage in more vigorous and light PA overall, whereas females perform more moderate PA. PA behavior differs between age groups and no clear lineal increase with age could be observed. Twenty-seven percent of adults and 55.4% of children and adolescents do not meet international PA recommendations. Identified target groups should be addressed to increase PA in the Spanish populationCoca-Cola Iberia through Spanish Nutrition Foundation (FEN)Coca-Cola Iberi

XTACC3-XMAP215 association reveals an asymmetric interaction promoting microtubule elongation.

chTOG is a conserved microtubule polymerase that catalyses the addition of tubulin dimers to promote microtubule growth. chTOG interacts with TACC3, a member of the transforming acidic coiled-coil (TACC) family. Here we analyse their association using the Xenopus homologues, XTACC3 (TACC3) and XMAP215 (chTOG), dissecting the mechanism by which their interaction promotes microtubule elongation during spindle assembly. Using SAXS, we show that the TACC domain (TD) is an elongated structure that mediates the interaction with the C terminus of XMAP215. Our data suggest that one TD and two XMAP215 molecules associate to form a four-helix coiled-coil complex. A hybrid methods approach was used to define the precise regions of the TACC heptad repeat and the XMAP215 C terminus required for assembly and functioning of the complex. We show that XTACC3 can induce the recruitment of larger amounts of XMAP215 by increasing its local concentration, thereby promoting efficient microtubule elongation during mitosis.This work was supported by the Ministerio de Economia y Competitividad (BFU2011-23815/BMC and Consolider CSD2006-00023 to G.M., M.B. and I.V.; CTQ2011-22514 to M.B.); the Fundacion Ramon Areces and the Comunidad Autonoma de Madrid (CAMS-2010/BMD-2305 to G.M. and M.B.). G.B.M. is supported by a RyC grant RyC-2008-03366. T.C. is supported by a FPI fellowship BES-2010-031355. J.S.P. is supported by The Danish Research Council for Independent Research Natural Sciences. F.J.B. is supported by the MINECO CTQ2011-28680 grant. We would also like to thank Andrian Valazquez for his advice and usage of ITC200; Jaminka Boskovic for helping with the EM grids; Marco Marenchino for advice and assistance with the Biacore; and Blanca Lopez for helpful tips on MALS experiments.S

XTACC3-XMAP215 association reveals an asymmetric interaction promoting microtubule elongation

chTOG is a conserved microtubule polymerase that catalyses the addition of tubulin dimers to promote microtubule growth. chTOG interacts with TACC3, a member of the transforming acidic coiled-coil (TACC) family. Here we analyse their association using the Xenopus homologues, XTACC3 (TACC3) and XMAP215 (chTOG), dissecting the mechanism by which their interaction promotes microtubule elongation during spindle assembly. Using SAXS, we show that the TACC domain (TD) is an elongated structure that mediates the interaction with the C terminus of XMAP215. Our data suggest that one TD and two XMAP215 molecules associate to form a four-helix coiled-coil complex. A hybrid methods approach was used to define the precise regions of the TACC heptad repeat and the XMAP215 C terminus required for assembly and functioning of the complex. We show that XTACC3 can induce the recruitment of larger amounts of XMAP215 by increasing its local concentration, thereby promoting efficient microtubule elongation during mitosis

Empirical energy functions evaluated for each models and for the corresponding region of the template show that the predicted stability decrease is moderate.

<p>Empirical energy functions evaluated for each models and for the corresponding region of the template show that the predicted stability decrease is moderate.</p

Protein-protein interaction networks for interactions experimentally observed for human centrosomal proteins.

<p>The color code represents betweeness centrality, a graph theoretic measure of the centrality of a node in a network, red representing the most central node.</p

Assessment of Tissue Expression of the Oxytocin–Vasopressin Pathway in the Placenta of Women with a First-Episode Psychosis during Pregnancy

Psychosis refers to a mental health condition characterized by a loss of touch with reality, comprising delusions, hallucinations, disorganized thought, disorganized behavior, catatonia, and negative symptoms. A first-episode psychosis (FEP) is a rare condition that can trigger adverse outcomes both for the mother and newborn. Previously, we demonstrated the existence of histopathological changes in the placenta of pregnant women who suffer an FEP in pregnancy. Altered levels of oxytocin (OXT) and vasopressin (AVP) have been detected in patients who manifested an FEP, whereas abnormal placental expression of these hormones and their receptors (OXTR and AVPR1A) has been proven in different obstetric complications. However, the precise role and expression of these components in the placenta of women after an FEP have not been studied yet. Thus, the purpose of the present study was to analyze the gene and protein expression, using RT-qPCR and immunohistochemistry (IHC), of OXT, OXTR, AVP, and AVPR1a in the placental tissue of pregnant women after an FEP in comparison to pregnant women without any health complication (HC-PW). Our results showed increased gene and protein expression of OXT, AVP, OXTR, and AVPR1A in the placental tissue of pregnant women who suffer an FEP. Therefore, our study suggests that an FEP during pregnancy may be associated with an abnormal paracrine/endocrine activity of the placenta, which can negatively affect the maternofetal wellbeing. Nevertheless, additional research is required to validate our findings and ascertain any potential implications of the observed alterations

Fraction of protein length that is predicted to be disordered, coiled-coil, or modeled by homology.

<p>The plots represent the distribution of the percentage of protein length that has been (A) predicted to be disordered and coiled-coil at the same time; (B) Predicted to be disordered and not coiled-coil; (C) modeled; (D) Predicted to have regular secondary structure and not to be disordered neither coiled-coil, but not modeled.</p

Number of residues and number of models for each protein.

<p>The plots represent the distribution of the number of residues of the longest isoform of centrosomal genes (A) and the number of structural models obtained for each protein (B).</p