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El Rebolledo, en La Lora burgalesa, es un monumento funerario de avanzado el neolítico cuya excavación en 1992 mostró que, a diferencia de los dólmenes clásicos de la zona, era un túmulo sin cámara bien definida que cubría un osario depositado sobre un nivel arqueológico previo, probablemente doméstico. El estudio estratigráfico, antropológico y tafonómico del yacimiento permite reconstruir la siguiente secuencia de hechos: i) un conjunto de huesos humanos secos y descarnados, principalmente restos de cráneos y huesos largos, fueron sometidos a un fuego de unos 700 ºC; ii) finalizado éste, se añadieron al depósito una serie de microlitos, láminas, hachas pulimentadas y adornos; y iii) todo el conjunto fue recubierto con un túmulo de piedras calizas. Las dataciones radiocarbónicas sitúan la combustión del enterramiento en un momento antiguo del horizonte megalítico regional, dando pie a relacionar El Rebolledo con un fenómeno de tráfico, manipulación y monumentalización de reliquias procedentes de los dólmenes próximos de Fuente Pecina.

Analiza el fenómeno de reestructuración autoritaria y mercantil del espacio urbano y a la desaparición de los lugares públicos y de los intercambios directos entre los individuos que ocupan estos espacios. Fenómeno mundial que encuentra resistencias e intensas luchas locales donde la revuelta ha recuperado su pulso, revitalizando luchas y formas de luchar e inventando otras nuevas, con la asamblea y el diálogo libre como eje fundamental, la solidaridad y la espontaneidad. El caso de la revuelta del barrio burgalés de Gamonal, ubicado en la ciudad de Burgos en España, es uno de los ejemplos cuidadosamente tratado entre muchas revueltas urbanas alrededor del mundo.

Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/), The most vulnerable residential settings during the COVID-19 pandemic were older adult’s nursing homes, which experienced high rates of incidence and death from this cause. This paper aims to ascertain how institutionalized older people assessed their residential environment during the pandemic and to examine the differences according to personal and contextual characteristics. The COVID-19 Nursing Homes Survey (Madrid region, Spain) was used. The residential environment assessment scale (EVAER) and personal and contextual characteristics were selected. Descriptive and multivariate statistical analysis were applied. The sample consisted of 447 people (mean age = 83.8, 63.1% = women, 50.8% = widowed, 40% = less than primary studies). Four residential assessment subscales (relationships, mobility, residential aspects, privacy space) and three clusters according to residential rating (medium-high with everything = 71.5% of cases, low with mobility = 15.4%, low with everything = 13.1%) were obtained. The logistic regression models for each cluster category showed to be statistically significant. Showing a positive affect (OR = 1.08), fear of COVID-19 (OR = 1.06), high quality of life (OR = 1.05), not having suspicion of depression (OR = 0.75) and performing volunteer activities (OR = 3.67) were associated with the largest cluster. It is concluded that a better residential evaluation was related to more favourable personal and contextual conditions. These results can help in the design of nursing homes for older adults in need of accommodation and care to facilitate an age-friendly environment., This research was funded by (i) CSIC COVID-19 Research Fund (Urgent Measures to address the Economic and Social Impact of COVID-19, ref. 202010E158); this project was also supported with supplementary funding from the Spanish Radio and Television Corporation, as well as from the Fundación General CSIC, for aspects related to the social dissemination of the project. (ii) PTI+ Global Health, CSIC Next Generation Funding (REC_EU), ref. SGL2103055

We designed a clinical study to analyze patterns of adherence to obeticholic acid, factors influencing the adherence and potential correlation with treatment efficacy by using MEMS® cap in practice daily. Method: A multicenter prospective observational study of patients with primary biliary cholangitis. Adherence will be measured by MEMS® cap, pill count, and patient-reported outcomes during 3 months. The quality of life will be self- reported using the Chronic Liver Disease Questionnaire test, European Quality of Life 5-Dimension Questionnaire test and Itch Severity Scale.We expect to clarify if there is correlation between adherence with treatment efficacy and to identify causes for poor compliance and introduce measures to reduce its prevalence.Diseñamos un estudio clínico para analizar los patrones de adherencia al ácido obeticólico, los factores que influyen en la adherencia y la posible correlación con la eficacia del tratamiento mediante el uso de MEMS® cap en la práctica clínica diaria.Método: Estudio observacional prospectivo multicéntrico de pacientes con colangitis biliar primaria. La adherencia se medirá mediante MEMS® cap, el recuento de comprimidos y se registrarán los resultados comunicados por el paciente durante 3 meses. La calidad de vida será autoinformada utilizando el Cuestionario de Enfermedad Hepática Crónica, el Cuestionario Europeo de Calidad de Vida en cinco dimensiones y la Escala de Intensidad del Picor.Esperamos identificar si existe una relación entre la adherencia con la efectividad del tratamiento e identificar las causas de la falta de adherencia para poder introducir medidas para reducir su prevalencia.

We compared an ultra-minimally invasive ultrasound-guided percutaneous A1 pulley release and a classic open surgery for trigger digit.We designed a single-center randomized control trial. All cases had clinical signs of primary grade III trigger digit. Concealed allocation (1:1) was used for assigning patients to each group and data collectors were blinded. The Quick-Disabilities of the Arm, Shoulder, and Hand (Quick-DASH) questionnaire was our primary variable. Quick-DASH, two-point discrimination, grip strength, time until stopping analgesics, having full digital range of motion and restarting everyday activities were registered on the 1st, 3rd, and 6th weeks, 3rd and 6th months, and 1st year after the procedure.We randomized 84 patients to ultrasound-guided release and classic open surgery. Quick-DASH scores significantly favored the percutaneous technique until the 3rd month: 7.6 ± 1.2 versus 15.3 ± 2.4 (mean ± standard error of the mean). The percutaneous group obtained significantly better results in all the variables studied: time until stopping analgesics, achieving full range of motion and restarting everyday activities. Grip strength was significantly better in the percutaneous group for the 1st week only. Five cases of moderate local pain were observed in the open technique. There was one case of transient nerve numbness per group.The ultra-minimally invasive ultrasound-guided A1 pulley release was clinically superior to the classic open surgery in functional recovery with a lower complication rate.

Background: The primary validation of the Movement Disorder Society Non-Motor Rating Scale was recently published, but 2 important structural analyses were not included. The objective of this study was to examine the structural characteristics of the Movement Disorder Society Non-Motor Rating Scale by factor and cluster analyses. Methods: Data came from the validation study, an international multicenter cross-sectional study of 402 Parkinson's disease patients. Demographic and clinical data, the Movement Disorder Society Non-Motor Rating Scale, and Hoehn and Yahr staging were used. Exploratory and confirmatory factor analysis and nonhierarchical cluster analysis were performed. Results: The exploratory factor analysis showed that all 13 domains of the Movement Disorder Society Non-Motor Rating Scale, except 1, and the Non-Motor Fluctuations subscale performed as unidimensional (variance explained: 0.36, sleep and wakefulness; -0.82, orthostatic hypotension). The confirmatory factor analysis could be carried out in 9 domains and showed that 6 of them and the Non-Motor Fluctuations subscale adjusted to the model satisfactorily according to the root mean square error of approximation. Furthermore, all domains had comparative fit index values >0.95, except depression and pain (both, 0.94) and sleep and wakefulness (0.90). The Non-Motor Fluctuations subscale showed satisfactory root mean square error of approximation (0.07), but a low comparative fit index value (0.91). A 5-cluster solution, correctly classifying 96% of the cases, was found. Conclusions: Overall, most subscales of the Movement Disorder Society Non-Motor Rating Scale are unidimensional, and although each subscale is distinct in terms of content covered, factors and clusters that are of clinical relevance are discernible and contribute to our understanding of possible nonmotor subtypes in Parkinson's disease. The project was supported by a two-stage academic peer-reviewed grant from the International Parkinson’s and Movement Disorder’s Society (IPMDS) as well as Clinical Research Network (CRN), London South and London North Thames, National Institute of Health Research (for the UK sites). Sí

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/), Nursing homes for the elderly in Spain have experienced high rates of infection and mortality from COVID-19, although rates have varied from one region to another. Madrid is the region where most institutionalized older adults have died from the coronavirus. However, there is little known about the psychosocial and environmental factors involved in the high incidence of COVID-19 among the institutionalised population in this region. This article describes the protocol of a study on nursing homes during the SARS-CoV-2 pandemic in the Autonomous Community of Madrid (hereafter: Region of Madrid or Madrid Region) and provides information on the study design, measures used, and characteristics of the population studied. A questionnaire about life in nursing homes during the COVID-19 pandemic was designed and a total of 447 persons over 60 years of age without cognitive impairment—220 in private nursing homes and 227 in public nursing homes—participated by answering questions about different topics: personal situations during the pandemic, feelings and methods of coping, residential environment, health, quality of life, ageism, and self-perception of ageing. The institutionalised person profile discussed in this study was an old woman, widowed, without children, with a low level of education, with multimorbidity, and who perceived her health and quality of life positively. Most of the participants were very concerned about COVID-19 and its effects. In fact, 38% had been diagnosed with COVID-19, of whom 20% were admitted to hospital and 20% had suffered negative impacts, such as pain and neurological problems. In addition, 70% of the residents remained confined to their rooms, which increased their perceptions of loneliness and social isolation. The worst-rated aspects of the nursing home resulted from the restrictive measures imposed on nursing homes during the pandemic. This research offers useful material for understanding the pandemic and its consequences from the perspective of the older institutionalised population, which could provide insights for designing public policies., This research was funded by (i) CSIC COVID-19 Research Fund (Urgent Measures to address the Economic and Social Impact of COVID-19, ref. 202010E158); this project was also supported with supplementary funding from the Spanish Radio and Television Corporation, as well as from the Fundación General CSIC, for aspects related to the social dissemination of the project. (ii) PTI+ Global Health, CSIC Next Generation Funding (REC_EU), ref. SGL2103055

Background: Following the active ageing model based on the Health, Lifelong Learning, Participation and Security pillars, this research has a twofold objective: i) to classify older adults according to active ageing profiles, taking into account the four pillars, and ii) to ascertain the relationship between the profiles and personal and contextual factors, as well as well-being and quality of life in old age. Methods: A study sample of 5,566 Spanish older adults who participated in wave 6 of the Survey of Health, Ageing and Retirement in Europe (SHARE) was included. Data were analysed in different steps applying several statistical analyses (Principal Component, Cluster, Discriminant, Multiple Correspondence and bivariate analysis with Pearson chi-square and ANOVA). Results: Five older adult profiles were obtained (I: with moderate activity; II: quasi-dependents; III: with active ageing-limiting conditions; IV: with diverse and balanced activity; V: with excellent active ageing conditions). The first three profiles were characterised by subjects with a high average age, low educational level, who were retired or housewives, and who perceived a moderate level of loneliness, satisfaction with the social network and quality of life, as well as having a larger family network, but living in small households or alone. In contrast, the latter two profiles showed better personal and contextual conditions, well-being and quality of life. Discussion and conclusions: The multidimensional approach to active ageing followed in this article has revealed the presence of several older adult profiles, which are confined to groups with better or worse active ageing conditions. In this context, if ageing is a process that reflects the previous way of life, intervention priorities will have to consider actions that promote better conditions during the life cycle., Research of this paper is a part of i) the QASP research project, funded by the Institute of Health Carlos III, Intramural Strategical Action in Health AESI 2018 (PI18CIII/00046); ii) it has also been partially funded by REDISSEC (RD16/0005/0002 and RD16/0001/0005, co-funded by European Regional Development Fund/European Social Fund “A way to make Europe” / ”Investing in your future”) projects; iii) the R&D Activities Program ENCAGEn-CM (H2019/HUM-5698) funded by the Community of Madrid and co-funded by the European Social Fund; iv) the ENVACES R&D+i project (MINECO-FEDER, ref. CSO2015-64115-R). Authors acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).

Mitochondrial ATP-synthesis is catalyzed by a F1Fo-ATP synthase, an enzyme of dual genetic origin enriched at the edge of cristae where it plays a key role in their structure/stability. The enzyme’s biogenesis remains poorly understood, both from a mechanistic and a compartmentalization point of view. The present study provides novel molecular insights into this process through investigations on a human protein called TMEM70 with an unclear role in the assembly of ATP synthase. A recent study has revealed the existence of physical interactions between TMEM70 and the subunit c (Su.c), a protein present in 8 identical copies forming a transmembrane oligomeric ring (c-ring) within the ATP synthase proton translocating domain (FO). Herein we analyzed the ATP-synthase assembly in cells lacking TMEM70, mitochondrial DNA or F1 subunits and observe a reciprocal dependence of TMEM70 and Su.c levels, regardless of the status of other ATP synthase subunits or of mitochondrial bioenergetics. Immunoprecipitation and two-dimensional blue-native/SDS-PAGE reveal that TMEM70 forms large oligomers composed of 8 TMEM70 dimers and that TMEM70 oligomers interact with Su.c not yet incorporated into ATP synthase complexes. Moreover, discrete TMEM70-Su.c complexes with increasing Su.c contents can be detected, suggesting a role for TMEM70 oligomers in the gradual assembly of the c-ring. Furthermore, we demonstrate using expansion super-resolution microscopy the specific localization of TMEM70 at the inner cristae membrane, distinct from the MICOS component MIC60. Taken together, our results show that TMEM70 oligomers provide a scaffold for c-ring assembly and that mammalian ATP synthase is assembled within inner cristae membranes.

Sheep remains constitute the main archaeozoological evidence for the presence of Early Neolithic human groups in the highlands of the Southern Pyrenees but understanding the role of herding activities in the Neolithisation process of this mountain ecosystem calls for the analysis of large and well-dated faunal assemblages. Cova de Els Trocs (Bisaurri, Huesca, Spain), a cave located at 1564 m a.s.l on the southern slopes of the Central Pyrenees, is an excellent case study since it was seasonally occupied throughout the Neolithic (ca. 5312–2913 cal. BC) and more than 4000 caprine remains were recovered inside. The multi-proxy analytical approach here presented has allowed us to offer new data elaborating on vertical mobility practices and herd management dynamics as has not been attempted up until now within Neolithic high-mountain sites in the Iberian Peninsula. For the first time, δ18O and δ13C stable isotope analyses offer direct evidence on both the regular practice of altitudinal movements of sheep flocks and the extended breeding season of sheep. Autumn births are recorded from the second half of the fifth millennium cal. BC onwards. Age-at-death distributions illustrate the progressive decline in caprine perinatal mortality together with the rising survival rate of individuals older than six months of age and the larger frequency of adults. This trend alongside the ‘off-season’ lambing signal at the implementation of husbandry techniques over time, probably aiming to increase the size of the flocks and their productivity. Palaeoparasitological analyses of sediment samples document also the growing reliance on herding activities of the human groups visiting the Els Trocs cave throughout the Neolithic sequence. In sum, our work provides substantial arguments to conclude that the advanced herding management skills of the Early Neolithic communities arriving in Iberia facilitated the anthropisation process of the subalpine areas of the Central Pyrenees., This paper was supported by several projects awarded to MR-G: ‘Los Caminos del Neolítico’ (HAR2009-09027) and ‘Los Caminos del Neolítico II’ (HAR2013-46800 P) were granted by the National R&D&I Plan/Ministry of Economy, Industry and Competitiveness (https://www.ciencia.gob.es/portal/site/MICINN/) and co-financed by the Government of Aragón (https://www.aragon.es/), and ‘La Memoria del Camino: Ciencia y divulgación de las primeras rutas pecuarias neolíticas en el Pirineo-MEDELCA’ (FCT-2015-9947) was financed by the Spanish Foundation for Science and Technology (FECYT) (https://www.fecyt.es/). The archaeozoological research was carried out within the framework of the project awarded to MM-G ‘… y la oveja domesticó al pastor: Señales genómicas y arqueozoológicas de los primeros ovinos durante la neolitización de la península ibérica’ (HAR2016-75914-R) by the National R&D&I Plan/Ministry of Economy, Industry and Competitiveness (https://www.ciencia.gob.es/portal/site/MICINN/). AH was awarded a PhD grant by the Université Fédérale de Toulouse ANR-11-IDEX-0002-02 (https://www.univ-toulouse.fr/). Support of the publication fee was granted by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic., The research was funded by the Max Planck Society, the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (771234–PALEoRIDER, to W.H.; 805268–CoDisEASe to K. Bos; 834616–ARCHCAUCASUS to S.H.), the Slovak Academy of Sciences and the European Union’s Seventh Framework Programme and Marie Curie Actions under the Programme SASPRO (1340/03/03 to P.C.R.), the ERA.NET RUS Plus–S&T programm of the European Union’s Seventh Framework Programme (277–BIOARCCAUCASUS to S.Re. and S.H.), the Werner Siemens Stiftung (“Paleobiochemistry”, to CW), the Award Praemium Academiae of the Czech Academy of Sciences (to M.E.), the Institute of Archaeology of the Czech Academy of Sciences (RVO 67985912, to M.Dobe.), the Russian Foundation for Basic Research (19-09-00354a, to M.K.K. and V.V.K.; 19-78-10053 to SSh), the German Research Foundation (DFG-HA-5407/4-1–INTERACT to W.H. and RE2688/2 to S.Re.), the French National Research Agency (ANR-17-FRAL-0010–INTERACT, to M.F.D., M.Ri., S.Ro., S.Sai., D.Bi., and P.Le.), the Wenner-Gren Dissertation Fieldwork Grant (9558 to S.Sab.), and the Ministry of Education and Science of the Republic of Kazakhstan (AP08856654 to L.B.D., L.M., and E.Kh. and AP08857177 to A.Z.B.).

Although the frequency of pastoral activities involving vertical sheep mobility has decreased over the last century, this is a herding strategy still used in the Ebro basin, where animals move from overwintering valley locations up to the Pyrenees from late spring to early autumn. Such practice allows herders to avoid the worst climatic conditions, seasonally balancing the great contrast between ecological zones in this region, from dry lowland Mediterranean steppe to wet mountain subalpine grasslands. As recent regional archaeological works have suggested, the altitudinal movement of flocks may have begun with the first early Neolithic groups settled in this territory. Here we investigate through stable isotope analyses one of the last flocks that still performs this activity. Sheep specimens were analyzed by sequential analyses (δ13C and δ18O) in bioapatite of tooth enamel, allowing detection of seasonal changes. Tooth series are interpreted according to rainfall distribution, seasonal patterns in δ 18O of meteoric water, vegetation changes and δ13C values in pastures along the altitudinal gradient in the area. Vertical movements in sheep sequential series are recognized by an inverse relationship between δ13C and δ18O values. Monthly δ18O values in meteoric water obtained in valley and mountain locations describe the same type of seasonal oscillation, with high values during the warm months and low values during the cold months. Pastures analyzed along the altitudinal gradient showed a decrease in δ13C values with altitude, linked to the seasonal availability of precipitation and vegetation differences among locations. These results define a new analytical and conceptual framework for the interpretation of archaeological samples in this region., Dr Tornero is a Postdoctoral researcher funded by a Juan de la Cierva-Incorporación (nº: IJCI-2014-19909) grant from the Ministry of Economy and Competitiveness, Spanish Government. This paper was developed within the framework of the ‘Los Caminos del Neolítico’ (HAR2009-09027) and ‘Los Caminos del Neolítico II’ (HAR2013-46800 P) projects, both directed by Dr Manuel Rojo-Guerra, granted by the Subdirectorate General for Research Projects/General Directorate of Research and Management of the National Plan for R and D and Innovation/Secretary of State for Research of the Ministry of Science and Innovation of Spain, and co-financed by the Government of Aragon. Equally it is part of the ‘La Memoria del Camino: Ciencia y divulgación de las primeras rutas pecuarias neolíticas en el Pirineo - MEDELCA’ (FCT-2015-9947) project funded by the Spanish Foundation for Science and Technology (FECYT).

Background The impact of general surgeons (GS) taking trauma call on patient outcomes has been debated. Complex hepatopancreatobiliary (HPB) injuries present a particular challenge and often require specialized care. We predicted no difference in the initial management or outcomes of complex HPB trauma between GS and trauma/critical care (TCC) specialists. Materials and methods A retrospective review of patients who underwent operative intervention for complex HPB trauma from 2008 to 2015 at an ACS-verified level I trauma center was performed. Chart review was used to obtain variables pertaining to demographics, clinical presentation, operative management, and outcomes. Patients were grouped according to whether their index operation was performed by a GS or TCC provider and compared. Results 180 patients met inclusion criteria. The GS ( n = 43) and TCC ( n = 137) cohorts had comparable patient demographics and clinical presentations. Most injuries were hepatic (73.3% GS versus 72.6% TCC) and TCC treated more pancreas injuries (15.3% versus GS 13.3%; P = 0.914). No significant differences were found in HPB-directed interventions at the initial operation (41.9% GS versus 56.2% TCC; P = 0.100), damage control laparotomy with temporary abdominal closure (69.8% versus 69.3%; P = 0.861), LOS, septic complications or 30-day mortality (13.9% versus 10.2%; P = 0.497). TCC were more likely to place an intraabdominal drain than GS (52.6% versus 34.9%; P = 0.043). Conclusions We found no significant differences between GS and TCC specialists in initial operative management or clinical outcomes of complex HPB trauma. The frequent and proper use of damage control laparotomy likely contribute to these findings.

Background Parkinson's disease (PD) is characterized by motor and nonmotor symptoms that progress with time, causing disability. The performance of a disease-specific, self-applied tool for assessing disability, the MDS-UPDRS Part II, is tested against generic and rater-based rating scales. Methods An international, cross-sectional, observational study was performed. Patients were assessed with the Hoehn and Yahr (HY) and five disability measures: MDS-UPDRS Part II, Schwab and England Scale (S&E), Clinical Impression of Severity Index-PD (CISI-PD) Disability item, Barthel Index (BI), and Rapid Assessment of Disability Scale (RADS). Data analysis included correlation coefficients, Mann-Whitney and Kruskal-Wallis tests, and intraclass-correlation coefficient for concordance. Results The sample was composed of 451 patients, 55.2% men, with a mean age of 65.06 years (SD = 10.71). Disability rating scales correlated from |0.75| (CISI-PD Disability with BI) to 0.87 (MDS-UPDRS Part II with RADS). In general, MDS-UPDRS Part II showed high correlation coefficients with clinical variables and satisfactory concordance with the rest of disability measures, with ICC ranging from 0.83 (with BI) to 0.93 (with RADS). All disability rating scales showed statistical significant differences in the sample grouped by sex, age, disease duration, and severity level. Conclusions The MDS-UPDRS Part II showed an appropriate performance to assess disability in PD, even better than some rater-based, generic or specific, scales applied in this study.

Stable carbon and nitrogen isotope research on past populations in the Iberian Neolithic has emphasized the Atlantic and Mediterranean coasts. This study provides the first isotopic insights into the diet and subsistence economy of Early and Middle Neolithic populations from open-air sites in interior north-central Iberia. We present bone collagen carbon (?13C) and nitrogen (?15N) isotope ratios for 44 humans and 33 animals recovered from six cemeteries of the Ebro valley and the northern Iberian Plateau. The results obtained are consistent with the C3 terrestrial diets typical of other contemporary south-western European populations, but the spacing between human and herbivore values from Los Cascajos and Paternanbidea sites is higher than expected, and a significant positive correlation is identified between the ?13C and ?15N human values at both. Moreover, the results clearly differ from those of the Late Neolithic/Early Chalcolithic in the same region, which show significantly lower ?13C and ?15N values. These findings contribute to an understanding of the implementation of an agro-pastoral economy in interior Iberia, suggesting a stronger reliance on animal foods among the first Neolithic groups of inner Iberia than in subsequent periods as well as differential access to some resources (possibly suckling herbivores) in the diet, which may point to the existence of early social or economic inequalities that do not seem to be linked to age and sex parameters or to mortuary treatment. This research was funded by the Basque Government (POS_2013_1_147; POS_2014_2_24; POS_2015_2_ 0001) and the Spanish Ministry of Economy and Competitiveness (project ‘Coastal societies in a changing world: A diachronic and comparative approach to the Prehistory of SWEurope from the late Palaeolithic to the Neolithic (CoChange)’ (HAR2014-51830-P)). The study has also been supported by a Newton International Fellowship funded by the British Academy (NF170854); the Basque Government (IT542/10); the University of the Basque Country (UPV/EHU) (UFI11/09); and the Spanish Ministry of Science and Innovation (projects ‘Los Caminos del Neolítico’ (HAR2009-09027) and ‘Los Caminos del Neolítico II’ (HAR2013-46800-P)).

The Iberian Peninsula in southwestern Europe represents an important test case for the study of human population movements during prehistoric periods. During the Last Glacial Maximum (LGM), the peninsula formed a periglacial refugium [1] for hunter-gatherers (HGs) and thus served as a potential source for the re-peopling of northern latitudes [2]. The post-LGM genetic signature was previously described as a cline from Western HG (WHG) to Eastern HG (EHG), further shaped by later Holocene expansions from the Near East and the North Pontic steppes [3, 4, 5, 6, 7, 8, 9]. Western and central Europe were dominated by ancestry associated with the ∼14,000-year-old individual from Villabruna, Italy, which had largely replaced earlier genetic ancestry, represented by 19,000–15,000-year-old individuals associated with the Magdalenian culture [2]. However, little is known about the genetic diversity in southern European refugia, the presence of distinct genetic clusters, and correspondence with geography. Here, we report new genome-wide data from 11 HGs and Neolithic individuals that highlight the late survival of Paleolithic ancestry in Iberia, reported previously in Magdalenian-associated individuals. We show that all Iberian HGs, including the oldest, a ∼19,000-year-old individual from El Mirón in Spain, carry dual ancestry from both Villabruna and the Magdalenian-related individuals. Thus, our results suggest an early connection between two potential refugia, resulting in a genetic ancestry that survived in later Iberian HGs. Our new genomic data from Iberian Early and Middle Neolithic individuals show that the dual Iberian HG genomic legacy pertains in the peninsula, suggesting that expanding farmers mixed with local HGs., The genetic research was funded by the Max Planck Society and the European Research Council ERC-CoG 771234 PALEoRIDER (W.H.). V.V.-M. was funded by a predoctoral scholarship of the Gobierno de Aragon and the Fondo Social Europeo (BOA20150701025) and a 3-month research stay grant (CH 76/16) by Programa CAI-Ibercaja de Estancias de Investigacio´ n. V.V.-M. and P.U. are members of the Spanish project HAR2014-59042-P (Transiciones clima´ ticas y adaptaciones sociales en la prehistoria de la Cuenca del Ebro), and of the regional government of Aragon PPVE research group (H-07: Primeros Pobladores del Valle del Ebro). The Goyet project was funded by the Wenner-Gren Foundation (7837 to H.R.), the College of Social and Behavioral Sciences of CSUN, and the CSUN Competition for Research, Scholarship, and Creative Activity Awards.

Mitochondria are double membrane-bound organelles that possess their own genome encoding essential but minute part of mitochondrial proteome. The vast majority of mitochondrial proteins are nuclear-encoded and several complementary processes ensure proper targeting, import, processing, and assembly of these proteins into mitochondria. Coordination between the two genomes expression is essential for proper assembly and activity of the oxidative phosphorylation system, which play a key role in energy metabolism in the vast majority of eukaryotic cells. In vivo, mitochondria display a high degree of connectivity and mobility. Mitochondrial dynamics is an essential physiological process ensuring the proper localization of mitochondria at intracellular sites of high-energy demand. Beyond their role in energy metabolism, mitochondria are also involved in lipid, amino acid and nucleic acid syntheses and are essential for biosynthesis of iron-sulfur clusters, heme, and other prosthetic groups. Mitochondrial respiratory chain is an important site of ROS production and ROS level must be tightly controlled by various enzymes. Unbalance between ROS production and detoxification plays a key role in metabolic disorders. Mitochondrial activity is therefore essential to cell fate, and mitochondrial dysfunctions have been associated with metabolic disorders. This chapter gives a general introduction on mitochondrial properties and functions that will be developed further in subsequent specialized chapters.

The results of a multidisciplinary research Project about the neolithisation of Iberia are shown, which began in the 90’s in the inner lands of Soria, where we discovered the oldest proofs of farming in the interior highlands of Iberia. The dynamics of this project lead us to the neighbour Ebro valley, where we did fieldwork in several important sites such as the Artusia and Valmayor XI rock-shelters, but mainly in the Els Trocs cave, right in the central Pyrenees, with exceptional results that are changing the picture of the first Neolithic populations of the interior of the Iberian Peninsula. A synthesis of the main discoveries made in those excavations is offered, to finally conclude with a general outline of the most significant research lines that the investigations about the Iberian Neolithic has in the future agenda, part of which are also present in the projects we are currently developing, whose main provisional results are also shown.

The alteration of phonation modes may affect speaker identification, but it is not known to what extent changes in register can compromise discrimination in each case. To answer this question, specifically with respect to falsetto voice, a perception experiment was designed using disguised voice in order to analyze the listeners’ reaction to stimuli that differed only with respect to phonation modes. Results were significant, suggesting that falsetto voice does not compromise speaker recognition. In addition to the perception experiment, the chapter also provides a detailed analysis of the temporal aspects of each mode and the biomechanical behavior of the vocal folds. Connecting the perception experiment to the production analysis allows us, first, to know which parameters have been altered, and which have not, during the register shift to falsetto voice and, secondly, to discuss what perceptive weight such parameters may have on the recognition of individual voice quality.

Mitochondria are dynamic organelles that continually move, fuse and divide. The dynamic balance of fusion and fission of mitochondria determines their morphology and allows their immediate adaptation to energetic needs, keeps mitochondria in good health by restoring or removing damaged organelles or precipitates cells in apoptosis in cases of severe defects. Mitochondrial fusion and fission are essential in mammals and their disturbances are associated with several diseases. However, while mitochondrial fusion/fission dynamics, and the proteins that control these processes, are ubiquitous, associated diseases are primarily neurological disorders. Accordingly, inactivation of the main actors of mitochondrial fusion/fission dynamics is associated with defects in neuronal development, plasticity and functioning, both ex vivo and in vivo. Here, we present the central actors of mitochondrial fusion and fission and review the role of mitochondrial dynamics in neuronal physiology and pathophysiology. Particular emphasis is placed on the three main actors of these processes i.e. DRP1, MFN1-2, and OPA1 as well as on GDAP1, a protein of the mitochondrial outer membrane preferentially expressed in neurons. This article is part of a Special Issue entitled: Mitochondria & Brain.

Charcot-Marie-Tooth disease type 2A (CMT2A) is caused by dominant alleles of the mitochondrial pro-fusion factor Mitofusin 2 (MFN2). To address the consequences of these mutations on mitofusin activity and neuronal function, we generate Drosophila models expressing in neurons the two most frequent substitutions (R94Q and R364W, the latter never studied before) and two others localizing to similar domains (T105M and L76P). All alleles trigger locomotor deficits associated with mitochondrial depletion at neuromuscular junctions, decreased oxidative metabolism and increased mtDNA mutations, but they differently alter mitochondrial morphology and organization. Substitutions near or within the GTPase domain (R94Q, T105M) result in loss of function and provoke aggregation of unfused mitochondria. In contrast, mutations within helix bundle 1 (R364W, L76P) enhance mitochondrial fusion, as demonstrated by the rescue of mitochondrial alterations and locomotor deficits by over-expression of the fission factor DRP1. In conclusion, we show that both dominant negative and dominant active forms of mitofusin can cause CMT2A-associated defects and propose for the first time that excessive mitochondrial fusion drives CMT2A pathogenesis in a large number of patients.

Aims and objectives To identify the personal- and disease-related factors that are associated with living with Parkinson's disease. Background Living with Parkinson's disease affects the physical, psychological, social and spiritual areas of the person. Health professionals need to know which factors influence the daily living with Parkinson's disease, in order to facilitate a positive living. Design A multicentre cross-sectional study. Methods A total of 324 patients with Parkinson's disease diagnoses were included in the study through a consecutive case sampling. Data were collected from January-June 2015, in specialised units of movement disorders of public and private and community centres, from Spain, Argentina, Mexico, Ecuador and Cuba. Nine measures were applied to evaluate personal-related factors (age, gender, psychosocial function, satisfaction with life, social support, home economical situation) and Parkinson's disease-related factors (duration of disease, motor symptoms and non-motor symptoms). The STROBE checklist was used to ensure quality reporting during the study (see File S1). Multiple linear regression analysis was carried out. Results Results indicated that social support, followed by satisfaction with life and home economical situation are the only three factors that significantly influence in living with Parkinson's disease. The rest of the factors analysed did not present significant influence in the daily living with this neurodegenerative disease. Conclusion This study highlights the necessity to put more emphasis on the person and his/her daily living with the condition and less on symptoms and treatment. Health professionals need to develop person-centred interventions that also deal with other elements of the experience of living with a long-term condition like Parkinson's disease. Relevance to clinical practice Interventions to foster positive living with Parkinson's disease in clinical practice should integrate strategies to tackle and prevent loneliness and interagency elements to increase community resources and systems of support.

International audience; Mitochondria are double-membrane-bound organelles that constantly change shape through membrane fusion and fission. Outer mitochondrial membrane fusion is controlled by Mitofusin, whose molecular architecture consists of an N-terminal GTPase domain, a first heptad repeat domain (HR1), two transmembrane domains, and a second heptad repeat domain (HR2). The mode of action of Mitofusin and the specific roles played by each of these functional domains in mitochondrial fusion are not fully understood. Here, using a combination of in situ and in vitro fusion assays, we show that HR1 induces membrane fusion and possesses a conserved amphipathic helix that folds upon interaction with the lipid bilayer surface. Our results strongly suggest that HR1 facilitates membrane fusion by destabilizing the lipid bilayer structure, notably in membrane regions presenting lipid packing defects. This mechanism for fusion is thus distinct from that described for the heptad repeat domains of SNARE and viral proteins, which assemble as membrane-bridging complexes, triggering close membrane apposition and fusion, and is more closely related to that of the C-terminal amphipathic tail of the Atlastin protein.