Helical mutations in type I collagen that affect the processing of the amino-propeptide result in an Osteogenesis Imperfecta/Ehlers-Danlos Syndrome overlap syndrome

Background: Whereas mutations affecting the helical domain of type I procollagen classically cause Osteogenesis Imperfecta (OI), helical mutations near the amino (N)-proteinase cleavage site have been suggested to result in a mixed OI/Ehlers-Danlos syndrome (EDS)-phenotype. Methods: We performed biochemical and molecular analysis of type I (pro-) collagen in a cohort of seven patients referred with a clinical diagnosis of EDS and showing only subtle signs of OI. Transmission electron microscopy of the dermis was available for one patient. Results: All of these patients harboured a COL1A1 / COL1A2 mutation residing within the most N-terminal part of the type I collagen helix. These mutations affect the rate of type I collagen N-propeptide cleavage and disturb normal collagen fibrillogenesis. Importantly, patients with this type of mutation do not show a typical OI phenotype but mainly present as EDS patients displaying severe joint hyperlaxity, soft and hyperextensible skin, abnormal wound healing, easy bruising, and sometimes signs of arterial fragility. In addition, they show subtle signs of OI including blue sclerae, relatively short stature and osteopenia or fractures. Conclusion: Recognition of this distinct phenotype is important for accurate genetic counselling, clinical management and surveillance, particularly in relation to the potential risk for vascular rupture associated with these mutations. Because these patients present clinical overlap with other EDS subtypes, biochemical collagen analysis is necessary to establish the correct diagnosis

On the extraction of cellulose nanowhiskers from food by-products and their comparative reinforcing effect on a polyhydroxybutyrate-co-valerate polymer

The present work reports on the characterization of cellulose nanowhiskers (CNW) extracted from three different food by-products, i.e., wheat straw (WSCNW), Brewers spent grains (BGCNW) and olive pomace (OPCNW), by using an optimized hydrolysis method similar to that developed to extract bacterial cellulose nanowhiskers (BCNW). WSCNW and BGCNW were seen to present optimal properties, with aspect ratio, crystallinity and thermal stability values comparable to those of BCNW. Additionally, the optimized hydrolysis treatment led to extraction yields higher than those previously reported for food by-products. The CNW were subsequently incorporated into a commercial polyhydroxybutyrate-co-valerate polymer (PHBV) by solution casting, and the produced nanocomposites were characterized. Although the addition of BGCNW and WSCNW was advantageous in terms of mechanical performance in comparison with OPCNW, no significant enhancement of the pure PHBV mechanical properties was reported because of the low nanofiller loadings used and the inherent difficulty of achieving a high degree of dispersion by the casting method. Interestingly, BGCNW and WSCNW presented reduced moisture sensitivity as compared with BCNW, leading to greater barrier performance and resulting in oxygen permeability reductions up to 26 % with WSCNW and 44 % with BGCNW.Noelle Peutat, on leave from the University of Grenoble in France, is acknowledged for her great dedication and support in the experimental work. M. Martinez-Sanz would like to thank the Spanish Ministry of Education for FPU Grant 1484. The authors acknowledge financial support from the EU FP7 ECOBIOCAP Project. The Electronic Microscopy Department in the SCIE from the University of Valencia is acknowledged for the support with SEM and TEM analyses. The Portuguese authors also acknowledge support from the FCT (Portuguese Foundation for Science and Technology) through strategic project PEst-OE/EQB/LA0023/2013

A Cross-Sectional Study of Prisoners in Mexico City Comparing Prevalence of Transmissible Infections and Chronic Diseases with That in the General Population.

ObjectivesTo describe patterns of transmissible infections, chronic illnesses, socio-demographic characteristics and risk behaviors in Mexico City prisons, including in comparison to the general population, to identify those currently needing healthcare and inform policy.Materials and methodsA cross-sectional study among 17,000 prisoners at 4 Mexico City prisons (June to December 2010). Participation was voluntary, confidential and based on informed consent. Participants were tested for HIV, Hepatitis B & C, syphilis, hypertension, obesity, and, if at risk, glucose and cholesterol. A subset completed a questionnaire on socio-demographic characteristics and risk behaviors. Positive results were delivered with counseling and treatment or referral.Results76.8% (15,517/20,196) of men and 92.9% (1,779/1,914) of women participated. Complete data sets were available for 98.8%. The following prevalence data were established for transmissible infections: HIV 0.7%; syphilis: Anti-TP+/VDRL+ 2.0%; Hepatitis B: HBcAb 2.8%, HBsAg 0.15%; Anti-HCV 3.2%. Obesity: 9.5% men, 33.8% women. Compared with national age- and sex-matched data, the relative prevalence was greater for HIV and syphilis among women, HIV and Hepatitis C in men, and all infections in younger participants. Obesity prevalence was similar for women and lower among male participants. The prevalence of previously diagnosed diabetes and hypertension was lower. Questionnaire data (1,934 men, 520 women) demonstrated lower educational levels, increased smoking and substance use compared to national data. High levels of non-sterile tattooing, physical abuse and histories of sexual violence were found.ConclusionThe study identified that health screening is acceptable to Mexico City prisoners and feasible on a large-scale. It demonstrated higher prevalence of HIV and other infections compared to national data, though low rates compared to international data. Individual participants benefited from earlier diagnosis, treatment and support. The data collected will also enable the formulation of improved policy for this vulnerable group

Midbrain dopaminergic neurons generate calcium and sodium currents and release dopamine in the striatum of pups

Midbrain dopaminergic neurons (mDA neurons) are essential for the control of diverse motor and cognitive behaviors. However, our understanding of the activity of immature mDA neurons is rudimentary. Rodent mDA neurons migrate and differentiate early in embryonic life and dopaminergic axons enter the striatum and contact striatal neurons a few days before birth, but when these are functional is not known. Here, we recorded Ca2+ transients and Na+ spikes from embryonic (E16–E18) and early postnatal (P0–P7) mDA neurons with dynamic two-photon imaging and patch clamp techniques in slices from tyrosine hydroxylase-GFP mice, and measured evoked dopamine release in the striatum with amperometry. We show that half of identified E16–P0 mDA neurons spontaneously generate non-synaptic, intrinsically driven Ca2+ spikes and Ca2+ plateaus mediated by N- and L-type voltage-gated Ca2+ channels. Starting from E18–P0, half of the mDA neurons also reliably generate overshooting Na+ spikes with an abrupt maturation at birth (P0 = E19). At that stage (E18–P0), dopaminergic terminals release dopamine in a calcium-dependent manner in the striatum in response to local stimulation. This suggests that mouse striatal dopaminergic synapses are functional at birth

Marketing relacional y su influencia en la fidelización de los clientes de la empresa Repuestos Kevin Car, Trujillo 2021

El presente trabajo de investigación tiene como objetivo determinar cómo el marketing relacional influye en la fidelización de los clientes de la empresa Repuestos Kevin Car, Trujillo 2021. El estudio tuvo un enfoque cuantitativo, con diseño no experimental y correlacional, presentando una muestra de 164 clientes a quienes se les aplicó un cuestionario con 24 preguntas para la recolección de datos. En respuesta a los objetivos, se halló que la percepción de los clientes sobre el marketing relacional que aplica la empresa fue del 44.6% siendo de nivel regular; el nivel de fidelización de los clientes fue del 54.3% indicando un nivel bajo. La prueba de correlación de Rho del Spearman arrojó un valor de 0.713, aceptándose la hipótesis alterna del estudio; lo que significa que existe una relación positiva y moderada entre el marketing relacional y la fidelización de los clientes de la empresa Repuestos Kevin Car, Trujillo 2021.The present research work aims to determine how relationship marketing influences customer loyalty of the company Repuestos Kevin Car, Trujillo 2021. The study had a quantitative approach, with a non-experimental and correlational design, presenting a sample of 164 customers to whom a questionnaire with 24 questions was applied for data collection. In response to the objectives, it was found that the perception of clients about the relationship marketing applied by the company was 44.6%, being of a regular level; the level of customer loyalty was 54.3% indicating a low level. The Spearman Rho correlation test yielded a value of 0.713, accepting the alternative hypothesis of the study; which means that there is a positive and moderate relationship between relationship marketing and customer loyalty of the company Repuestos Kevin Car, Trujillo 2021

Structure of the intergenic spacers in chicken ribosomal DNA

International audienceAbstractBackgroundRibosomal DNA (rDNA) repeats are situated in the nucleolus organizer regions (NOR) of chromosomes and transcribed into rRNA for ribosome biogenesis. Thus, they are an essential component of eukaryotic genomes. rDNA repeat units consist of rRNA gene clusters that are transcribed into single pre-rRNA molecules, each separated by intergenic spacers (IGS) that contain regulatory elements for rRNA gene cluster transcription. Because of their high repeat content, rDNA sequences are usually absent from genome assemblies. In this work, we used the long-read sequencing technology to describe the chicken IGS and fill the knowledge gap on rDNA sequences of one of the key domesticated animals.MethodsWe used the long-read PacBio RSII technique to sequence the BAC clone WAG137G04 (Wageningen BAC library) known to contain chicken NOR elements and the HGAP workflow software suit to assemble the PacBio RSII reads. Whole-genome sequence contigs homologous to the chicken rDNA repetitive unit were identified based on the Gallus_gallus-5.0 assembly with BLAST. We used the Geneious 9.0.5 and Mega software, maximum likelihood method and Chickspress project for sequence evolution analysis, phylogenetic tree construction and analysis of the raw transcriptome data.ResultsThree complete IGS sequences in the White Leghorn chicken genome and one IGS sequence in the red junglefowl contig AADN04001305.1 (Gallus_gallus-5.0) were detected. They had various lengths and contained three groups of tandem repeats (some of them being very GC rich) that form highly organized arrays. Initiation and termination sites of rDNA transcription were located within small and large unique regions (SUR and LUR), respectively. No functionally significant sites were detected within the tandem repeat sequences.ConclusionsDue to the highly organized GC-rich repeats, the structure of the chicken IGS differs from that of IGS in human, apes, Xenopus or fish rDNA. However, the chicken IGS shares some molecular organization features with that of the turtles, which are other representatives of the Sauropsida clade that includes birds and reptiles. Our current results on the structure of chicken IGS together with the previously reported ribosomal gene cluster sequence provide sufficient data to consider that the complete chicken rDNA sequence is assembled with confidence in terms of molecular DNA organization

Subthalamic lesion or levodopa treatment rescues giant GABAergic currents of PINK1-deficient striatum

Cellular electrophysiological signatures of Parkinson's disease described in the pharmacological 6-hydroxydopamine (6-OHDA) animal models of Parkinson's disease include spontaneous repetitive giant GABAergic currents in a subpopulation of striatal medium spiny neurons (MSNs), and spontaneous rhythmic bursts of spikes generated by subthalamic nucleus (STN) neurons.Weinvestigated whether similar signatures are present in Pink1-/- mice, a genetic rodent model of the PARK6 variant of Parkinson's disease. Although 9- to 24-month-old Pink1-/-mice show reduced striatal dopamine content and release, and impaired spontaneous locomotion, the relevance of this model to Parkinson's disease has been questioned because mesencephalic dopaminergic neurons do not degenerate during the mouse lifespan. We show that 75% of the MSNs of 5- to 7-month-old Pink1-/- mice exhibit giant GABAergic currents, occurring either singly or in bursts (at 40 Hz), rather than the low-frequency (2 Hz), low-amplitude, tonic GABAergic drive common to wild-type MSNs of the same age. STN neurons from 5- to 7-month-old Pink1-/- mice spontaneously generated bursts of spikes instead of the control tonic drive. Chronic kainic acid lesion of the STN or chronic levodopa treatment reliably suppressed the giant GABAergic currents of MSNs after 1 month and replaced them with the control tonic activity. The similarity between the in vitro resting states of Pink1 MSNs and those of fully dopamine (DA)-depleted MSNs of 6-OHDA-treated mice, together with the beneficial effect of levodopa treatment, strongly suggest that dysfunction of mesencephalic dopaminergic neurons in Pink1-/-mice is more severe than expected. The beneficial effect of the STN lesion also suggests that pathological STN activity strongly influences striatal networks in Pink1-/- mic

El registro fósil de vertebrados y patrimonio paleontológico más representativo de los pirineos occidentales

Los Pirineos occidentales son un territorio con una notable diversidad geológica y un importante registro fósil, que constituye un gran archivo de paleobiodiversidad. En lo que respecta al registro fósil de vertebrados, los Pirineos occidentales (Región Vasco-Cantábrica, Cuenca de Pamplona y sector noroccidental de la Cuenca del Ebro) son relevantes tanto desde el punto de vista de los yacimientos paleontológicos como de las colecciones de fósiles procedentes de ellos. Varios yacimientos de vertebrados forman parte del Inventario de Lugares de Interés Geológico (LIG) con alto o muy alto interés paleontológico en la Comunidad Autónoma del País Vasco. Destacan los yacimientos de peces cretácicos de Zeanuri en Bizkaia, mamíferos eocenos de Zambrana e icnitas miocenas de Salinas de Añana en Álava/Araba y la asociación de vertebrados pleistocenos de Kiputz cerca de Mutriku, en Gipuzkoa. Otros yacimientos notables en el área de estudio deberían ser objeto de iniciativas de geoconservación: es el caso de la cantera de Laño (Condado de Treviño), con asociaciones fi nicretácicas de vertebrados continentales y marinos, los afloramientos con icnitas de aves y mamíferos del Eoceno al Mioceno inferior de Navarra/Nafarroa y la cueva vizcaína de Santa Isabel de Ranero (Pleistoceno), por citar únicamente los ejemplos más sobresalientes. Asimismo, existen colecciones de fósiles de vertebrados en los Pirineos occidentales que destacan por su elevado interés paleontológico, aunque algunos no provengan de LIG reconocidos. Estas colecciones están depositadas en diversos centros e instituciones de Bilbao, Irún, Leioa, Pamplona-Iruñea, y Vitoria-Gasteiz. La valoración de la paleobiodiversidad y el registro fósil es un paso importante para el conocimiento del patrimonio paleontológico de un territorio y la creación de fi guras de geoconservación (e.g., LIG, geosites). Sin embargo, la mera inclusión de los yacimientos paleontológicos en estas fi guras no garantiza su protección y conservación, ni la adecuada gestión de las colecciones de fósiles procedentes de ellos. Por lo tanto, es necesario diseñar estrategias de conservación transversales teniendo en cuenta las particularidades de cada yacimiento y/o colección. La divulgación científi ca y cultural del patrimonio paleontológico de un territorio, como el aquí estudiado, debe contar con una mayor colaboración entre los paleontólogos que han valorado los bienes paleontológicos y los técnicos que los gestionan. Para ello, es necesaria la disposición de partidas presupuestarias específicas que posibiliten el desarrollo de diferentes acciones encaminadas a la investigación, conservación y difusión social de este patrimonio.The western Pyrenees is a territory with a remarkable geodiversity and an important fossil record, which constitutes a large archive of palaeobiodiversity. With respect to the vertebrate fossil record, the western Pyrenees (Basque-Cantabrian Region, Pamplona Basin and the north-western sector of the Ebro Basin) are relevant both from the point of view of palaeontological sites and fossil collections. Several vertebrate fossil sites are integrated into the Inventory of Geological Interest Sites (LIG) with high to very high palaeontological interest of the Autonomous Community of the Basque Country. It is worth highlighting the Cretaceous fish sites of Zeanuri in Biscay, Eocene mammals of Zambrana and Miocene ichnites of Salinas de Añana in Araba, and the Pleistocene vertebrate fossil assemblage of Kiputz near Mutriku, in Gipuzkoa. Other highly significant sites in the study area should be subject to geoconservation initiatives. This is the case of the Laño quarry in the Condado de Treviño, which has provided continental and marine vertebrate fossil assemblages from the latest Cretaceous, Eocene to Early Miocene sites with bird and mammal tracks in Navarre, and the Pleistocene cave deposits of Santa Isabel de Ranero in Biscay, to mention only the most outstanding examples. There are also vertebrate fossil collections in the western Pyrenees that stand out for their high palaeontological interest, although some do not come from recognized LIG. These collections are deposited in several centres and institutions of Bilbao, Irun, Leioa, Pamplona-Iruñea and Vitoria-Gasteiz. The valuation of the palaeobiodiversity and fossil record is an important step for the study of palaeontological heritage of a territory and the set-up of geoconservation designations (e.g., LIG, geosites). However, the mere inclusion of the palaeontological assents in these geoconservation designations does not guarantee either their protection and conservation or the suitable management of the fossil collection. Therefore, it is necessary to design conservation strategies taking into account the particularities of each palaeontological site and/or fossil collection. The scientific and cultural dissemination of the palaeontological heritage of a territory like one studied here should have greater collaboration between the palaeontologists that have valued the palaeontological assets and the technicians and institutions that manage them. This requires the provision of specific budgetary items that enable the development of the different activities of research, conservation and social dissemination of this heritage.Fil: Badiola, Ainara. Universidad del País Vasco; EspañaFil: Arlegi, Mikel. Universidad del País Vasco; España. Université de Bordeaux; FranciaFil: Astibia, Humberto. Universidad del País Vasco; EspañaFil: Bardet, Nathalie. Centre National de la Recherche Scientifique; Francia. Muséum National d'Histoire Naturelle; Francia. Université Pierre et Marie Curie; FranciaFil: Berreteaga, Ana. Universidad del País Vasco; EspañaFil: Corral, J. Carmelo. Museo de Ciencias Naturales de Álava/; EspañaFil: Díaz Martínez, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro. Sede Alto Valle. Instituto de Investigaciones en Paleobiología y Geología; ArgentinaFil: Gómez Olivencia, Asier. Universidad del País Vasco; España. IKERBASQUE. Basque Foundation for Science; España. Universidad Carlos III de Madrid. Instituto de Salud; EspañaFil: Lopez Horgue, Mikel A.. Universidad del País Vasco; EspañaFil: Perales Gogenola, Leire. Universidad del País Vasco; EspañaFil: Pereda Suberbiola, Xabier. Universidad del País Vasco; Españ