A rat immobilization model based on cage volume reduction: a physiological model for bed rest?

Bed rest has been an established treatment in the past prescribed for critically illness or convalescing patients, in order to preserve their body metabolic resource, to prevent serious complications and to support their rapid path to recovery. However, it has been reported that prolonged bed rest can have detrimental consequences that may delay or prevent the recovery from clinical illness. In order to study disuse-induced changes in muscle and bone, as observed during prolonged bed rest in humans, an innovative new model of muscle disuse for rodents is presented. Basically, the animals are confined to a reduced space designed to restrict their locomotion movements and allow them to drink and eat easily, without generating physical stress. The animals were immobilized for either 7, 14, or 28 days. The immobilization procedure induced a significant decrease of food intake, both at 14 and 28 days of immobilization. The reduced food intake was not a consequence of a stress condition induced by the model since plasma corticosterone levels-an indicator of a stress response- were not altered following the immobilization period. The animals showed a significant decrease in soleus muscle mass, grip force and cross-sectional area (a measure of fiber size), together with a decrease in bone mineral density. The present model may potentially serve to investigate the effects of bed-rest in pathological states characterized by a catabolic condition, such as diabetes or cancer

La Cueva de El Sidrón (Piloña Asturias)

Estado de las excavaciones y estudios en la Cueva de El Sidrón (PIloña, Asturias)

Incidence, clinical characteristics and management of inflammatory bowel disease in Spain: large-scale epidemiological study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD—Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)—during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100, 000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31–56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

El grupu neandertal de la Cueva d' El Sidrón (Borines, Piloña)

El artículo está en la lengua asturianaPeer reviewe

El grupu neandertal de la Cueva d'El Sidrón (Borines, Piloña)

Na monografía clásica de Puig y Larraz (1896: 250-252) amiéntense delles cavidaes del Conceyu de Piloña, pero non la Cueva d’El Sidrón (Fig. 1). Esta conocíase, ensin dulda, dende la Guerra Civil y el maquis al servir d’abellugu a persiguíos políticos, y guarda una alcordanza imborrable nuna de les sos múltiples entraes, yá qu’ellí ta enterrada Olvido Otero González (1908-1938). Per El Sidrón pasaron munches persones a lo llargo de los años, pero en 1994 prodúxose’l descubrimientu per parte d’unos espeleólogos xixoneses d’unos güesos humanos que dieron un importante xiru a la conocencia de los nuesos antepasaos neandertales.Peer Reviewe

El Sidrón (Piloña, Asturias)

Los cazadores recolectores del Pleistoceno y del Holoceno en Iberia y el Estrecho de Gibraltar: estado actual del conocimiento del registro arqueológico, constituye una actualización del conocimiento de las sociedades con economía de predación que se asentaron en Iberia. El registro de esta región es esencial para la reconstrucción de la evolución humana biológica, comportamental y cultural en Europa ya que contiene los registros más primitivos y significativos de la humanización del continente y porque en ella se pueden trazar las grandes líneas explicativas del proceso. Ello es así por la gran riqueza de un registro muy amplio y completo, que abarca todas las etapas del desarrollo y las todas las formas adaptativas y culturales, cuyo descubrimiento ya se realizó en las primeras etapas de la disciplina en el siglo XIX. Este volumen pretende ser una presentación sistemática de datos empíricos realizada por los equipos de investigadores que están año tras año obteniendo y analizando ese registro. Se ha incluido en él los datos de los conjuntos arqueo-paleontológicos principales y con datos más significativos organizados en ocho grandes regiones fisiográficas y geológicas que buscan evidenciar la adaptación humana a entornos similares. Más allá de estas ocho regiones se ha creído conveniente presentar dos capítulos temáticos, dedicados a las regiones con registro de comportamiento simbólico rupestre más extenso: la región cantábrica y la levantina. Los registros rupestres externos a estas dos regiones se tratan cada uno dentro de las regiones correspondientes. Finalmente queremos señalar que, más allá de los datos empíricos, hemos querido poner de manifiesto las grandes líneas de investigación que la arqueología hispana moderna está desarrollando en este campo de investigación.Peer reviewe

The influence of schooling on the stability and mutability of gender attitudes: Findings from a longitudinal study of adolescent girls in Zambia

Purpose: Inequitable gender norms are thought to harm lifelong health and well-being. We explore the process of gender attitude change and the role of schooling in shifting or reinforcing gender norms among adolescent girls in Zambia. Methods: We used longitudinal data collected from unmarried, vulnerable girls (aged 10–19 years) as part of the Adolescent Girls Empowerment Program. We conducted random effects multinomial logistic regression to determine whether schooling-related factors were associated with shifts in adolescent girls\u27 gender attitudes across three survey rounds and explored whether these relationships varied by age. Results: Mean gender attitude scores at the aggregate level remained stable over time among rural girls and improved slightly for urban girls. At the individual level, about half the girls had relatively unchanged scores, whereas the other half shifted to higher or lower scores between rounds. Rural and urban girls currently attending school were more likely to have relatively stable equitable attitudes than stable, inequitable attitudes, or attitudes that shifted to inequitable. Educational attainment was not associated with shifts in gender attitudes among rural girls. Urban girls with higher educational attainment were more likely to have relatively stable equitable attitudes than stable, inequitable attitudes, or attitudes that shifted to inequitable or more equitable. Conclusions: Patterns of gender attitude stability and change differed more for urban girls than rural girls and varied by age and schooling-related factors. In general, schooling appears to be an institutional lever that holds promise for shifting gender attitudes toward greater equality. Our study highlights the importance of looking longitudinally at the effects of social context and reinforces calls for targeted, context-specific interventions for this age group

Electrostatic Binding and Hydrophobic Collapse of Peptide–Nucleic Acid Aggregates Quantified Using Force Spectroscopy

34 pages, 8 figures, Supplementary InformationKnowledge of the mechanisms of interaction between self-aggregating peptides and nucleic acids or other polyanions is key to the understanding of many aggregation processes underlying several human diseases (e.g., Alzheimer's and Parkinson's diseases). Determining the affinity and kinetic steps of such interactions is challenging due to the competition between hydrophobic self-aggregating forces and electrostatic binding forces. Kahalalide F (KF) is an anticancer hydrophobic peptide that contains a single positive charge that confers strong aggregative properties with polyanions. This makes KF an ideal model to elucidate the mechanisms by which self-aggregation competes with binding to a strongly charged polyelectrolyte such as DNA. We use optical tweezers to apply mechanical forces to single DNA molecules and show that KF and DNA interact in a two-step kinetic process promoted by the electrostatic binding of DNA to the aggregate surface followed by the stabilization of the complex due to hydrophobic interactions. From the measured pulling curves we determine the spectrum of binding affinities, kinetic barriers, and lengths of DNA segments sequestered within the KF-DNA complex. We find there is a capture distance beyond which the complex collapses into compact aggregates stabilized by strong hydrophobic forces and discuss how the bending rigidity of the nucleic acid affects this process. We hypothesize that within an in vivo context, the enhanced electrostatic interaction of KF due to its aggregation might mediate the binding to other polyanions. The proposed methodology should be useful to quantitatively characterize other compounds or proteins in which the formation of aggregates is relevant.J.C.S. acknowledges a grant associated with ICREA Academia 2008; F.R. is supported by the Human Frontier Science Program [Grant No. RGP55-2008], the Spanish Ministry of Economy and Competitiveness [Grant No. FIS2010-19342], and an ICREA Academia award; F.M.H. acknowledges a grant from the European Research Council [Starting Grant No. 206117] and the Spanish Ministry of Economy and Competitiveness [Grant No. FIS2011-24638]; M.E.F.P. was supported by a contract from CSIC [Contract No. 200920I123, associated with the ERC grant]. F.A. acknowledges CICYT [Grant No. CTQ2012-30930], and S.B.D. an invited professor position from AGAUR (Generalitat de Catalunya).Peer reviewe

Conditional ablation of neuroligin-1 in CA1 pyramidal neurons blocks LTP by a cell-autonomous NMDA receptor-independent mechanism

Neuroligins are postsynaptic cell-adhesion molecules implicated in autism and other neuropsychiatric disorders. Despite extensive work, the role of neuroligins in synapse function and plasticity, especially NMDA receptor (NMDAR)-dependent LTP, remains unclear. To establish which synaptic functions unequivocally require neuroligins, we analyzed single and triple conditional knockout (cKO) mice for all three major neuroligin isoforms (NL1-NL3). We inactivated neuroligins by stereotactic viral expression of Cre-recombinase in hippocampal CA1 region pyramidal neurons at postnatal day 0 (P0) or day 21 (P21), and measured synaptic function, synaptic plasticity, and spine numbers in acute hippocampal slices 2–3 weeks later. Surprisingly, we find that ablation of neuroligins in newborn or juvenile mice only modestly impaired basal synaptic function in hippocampus, and caused no alteration in postsynaptic spine numbers. However, triple cKO of NL1-NL3 or single cKO of NL1 impaired NMDAR-mediated excitatory postsynaptic currents (NMDAR EPSCs), and abolished NMDAR-dependent LTP. Strikingly, the NL1 cKO also abolished LTP elicited by activation of L-type Ca(2+)-channels during blockade of NMDARs. These findings demonstrate that neuroligins are generally not essential for synapse formation in CA1 pyramidal neurons but shape synaptic properties and that NL1 specifically is required for LTP induced by postsynaptic Ca(2+)-elevations, a function which may contribute to the pathophysiological role of neuroligins in brain disorders