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The description of the skin reactions produced by the different vaccines against SARS-CoV-2 has focused on the symptoms reported by the general population. There are few studies with very different measurement methods focused on healthcare workers. A longitudinal observational study was conducted on all the healthcare workers from the Hospital Universitario San Cecilio that received vaccination against COVID-19 with BNT162b2. The recruitment period was from December 2020 to September 2021. The recommended regimen was double, with a minimum interval of 21 days between doses. All dermatological reactions reported as adverse effects of the vaccine were evaluated by the Staff of the Dermatology Unit of our center. A total of 3969 healthcare workers of our center were followed. Only 0.7% of them reported dermatological adverse reactions. The most frequently reported reactions were morbilliform rash and COVID arm. In the multivariate analysis, the vaccination regimen (one dose) and the history of COVID-19 infection remained the main factors associated with the report of dermatological adverse reactions. The rate of dermatological adverse reactions after vaccination with BNT162b2 (Pfizer-BioNTech) is extraordinarily low. No patient required hospitalization, which supports the safety of this vaccination in a population of healthcare workers.

Post-traumatic stress disorder (PTSD) is a common and debilitating psychiatric disorder that may occur in individuals exposed to traumatic events such as accidents, interpersonal violence, war, combat, or natural disasters. Additionally, PTSD has been implicated in the development of a variety of chronic conditions including cardiovascular and metabolic diseases, suggesting that the biological alterations of the disorder can manifest themselves as chronic diseases in those suffering from PTSD. The biological underpinnings of the disorder are not well understood. Gene expression studies can illuminate the complex physiology of PTSD reflecting the embodiment of trauma, i.e. the process in which traumatic experiences in our social environments are manifested in our body by genomic mechanisms. To date, gene expression studies that examine the whole transcriptome are scarce and limited to single-timepoint assessments. Here we applied a transcriptome-wide gene expression screen with RNA-sequencing to whole blood samples to elucidate the gene expression signatures associated with the development of PTSD. The study participants (N=72, of whom 21 eventually developed PTSD) are a trauma exposed subsample of participants enrolled in a longitudinal and prospective cohort study of adults living in Detroit, Michigan. PTSD was assessed in a structured telephone interview and whole blood samples were taken both before and after trauma exposure. We found 45 differentially expressed genes associated with PTSD development with an estimated log2fold change > 1.5 at a nominal p value (pPAX6,TSPAN7,PXDN,VWC2,SULF1andNFATC4were also ubiquitously expressed in all brain regions examined. Subsequent gene set enrichment analysis identified several pathways relating to brain and immune functioning to be enriched in individuals developing PTSD. Longitudinal sampling provides a promising mean to elucidate the pathophysiology underlying the embodiment of trauma.

The influence of emotions is very significant in PSIT, since these professionals usually find themselves interpreting in communicative situations in which the people that they provide a service to suffer some kind of emotional distress. This can be particularly challenging for interpreters, since many codes of conduct on the ethics of the profession highlight neutrality as one of the main features that they must respect. In the case of empathy, a value expected to be offered by public workers, many studies have highlighted the importance it has to improve interactions. However, this topic has not been developed in depth in many research studies up to date. Therefore, the aim of this article is to conduct a systematic review of the studies published in the field of PSIT with relation to empathy and how it affects the profession. We will limit the review to studies published from 2000 to 2020. In the conclusions we will reflect on the importance of conducting this kind of studies to review current research needs and establish future directions., La influencia de las emociones es muy significativa en la TISP, ya que estos profesionales suelen encontrarse interpretando en situaciones comunicativas en las que las personas a las que prestan un servicio sufren algún tipo de estrés emocional. Esto puede ser problemático para los intérpretes, ya que los códigos éticos de la profesión destacan la neutralidad como una de las principales características que deben respetar. En el caso de la empatía, valor que se espera que ofrezcan los trabajadores públicos, numerosos estudios han destacado la importancia que tiene para mejorar las interacciones. Sin embargo, este tema no ha sido desarrollado en profundidad en los estudios de investigación publicados hasta la fecha. Por tanto, el objetivo de este artículo es llevar a cabo una revisión sistemática de los estudios publicados en el campo de la TISP en relación con la empatía y cómo afecta a la profesión. Limitaremos la revisión a los estudios publicados entre 2000 y 2020. En las conclusiones reflexionaremos sobre la importancia de realizar este tipo de estudios para revisar las necesidades de investigación actuales y establecer direcciones futuras.

Anabolic resistance to a mechanical stimulus may contribute to the loss of skeletal muscle mass observed with age. In this study, young and aged mice were injected with saline or human LM-111 (1 mg/kg). One week later, the myotendinous junction of the gastrocnemius muscle was removed via myotenectomy (MTE), thus placing a chronic mechanical stimulus on the remaining plantaris muscle for 2 weeks. LM-111 increased α7B integrin protein expression and clustering of the α7B integrin near DAPI+ nuclei in aged muscle in response to MTE. LM-111 reduced CD11b+ immune cells, enhanced repair, and improved the growth response to loading in aged plantaris muscle. These results suggest that LM-111 may represent a novel therapeutic approach to prevent and/or treat sarcopenia.

The complete 16,345-bp mitochondrial genome of the agriculturally destructive pod sucking pest, the giant coreid bug, Anoplocnemis curvipes (Hemiptera: Coreidae), was assembled from paired-end Illumina HiSeq 2500 reads. The A. curvipes mitochondrial genome consists of 13 protein coding genes (PCGs), 22 tRNAs, 2 rRNAs and a control region in the order and orientation typical among insects. PCG initiation codons (ATG, ATC, ATT and ATA) with termination codon (TAA) are used with the exception of TAG stop codons by Cytb and ND3. All tRNA genes fold into predicted cloverleaf secondary structures having requisite triplets on the anticodon loop, apart from tRNA-Ser1 (AGN) whose dihydrouridine (DHU) arm forms a simple loop. The phylogenetic analysis of hemipteran mitogenomes clusters to the family level and supports the monophyly of the five superfamilies in Pentatomomorpha of Hemiptera. The Coreoidea and Pyrrhocoroidea are sister groups, while Coreidae and Alydidae are sister groups to Rhopalidae. These analyses provide insight to mitogenomics and evolutionary relationships among pentatomoid insects.

The brown pod-sucking bug, Clavigralla tomentosicollis Stal (Hemiptera: Coreidae), causes significant damage to cultivated cowpea, Vigna unguiculata Walp, a staple crop in sub-Saharan Africa. C. tomentosicollis pierce and suck sap from cowpea pods, resulting in reduced grain yield and quality. The complete, 16,089 bp mitogenome of C. tomentosicollis encodes 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs) and an A + T rich control region, with gene order and orientation identical to that of the insect ancestral gene order. The initiation and termination codons for the PCGs used standard ATN codons and TAA or TAG codons respectively. All predicted tRNAs fold into a clover-leaf secondary structures with the exception of tRNA-Ser (AGN) with a semi-loop dihydrouridine arm. The 1509 bps A + T rich region contains a single 89 bp tandem repeat unit duplicated 3.7 times. When compared with other published Coreoidea mitogenomes, C. tomentosicollis was also highly A − T skewed, and similar in both size and A − T%; however, its longer tandem repeat within the A + T rich region was unique. The C. tomentosicollis mitogenome can serve as a foundation to combine molecular marker data with pest monitoring strategies to better understand the population dynamics of this species.

Complete mitochondrial genome sequences were assembled for the rice weevil, Sitophilus oryzae (17,602 bp) and the maize weevil, S. zeamais (18,105 bp; Coleoptera: Curculionidae: Dryophthorinae), which encode 13 protein coding genes (PCGs), 22 transfer RNAs, and 2 ribosomal RNAs that is typical among Animalia. The A + T-rich control regions of S. oryzae (2818 bp) and S. zeamais (2832 bp) are the longest described to date among curculionoidea (weevils). Additionally, non-coding intergenic regions have increased in size due to expansion of tandem repeat arrays, but is more pronounced in S. zeamais (606 bp) compared to S. oryzae (109 bp). A total of 69 and 22 substitution mutations were found among reads from S. oryzae and S. zeamais, out of which 68 and 2 were predicted in the PCGs respectively, with a majority in NADH Dehydrogenase subunit I. Phylogenetic analyses of coleopteran insects based upon full mitogenomes PCG sequence supported the existence of Curculionoidea and Tenebrionoidea as a monophyletic group, whereas the Cucujoidea and Elateroidea remain paraphyletic. The mitogenomes of these two Sitophilus species provide insight into short-term evolutionary relationships among curculionid beetles, and provide resources for the potential deciphering of more broad systematic questions in the Order Coleoptera.

Resumen Introduccion La diarrea por Clostridium difficile constituye un importante problema de salud que parece incrementarse. En nuestro estudio analizamos los cambios en la incidencia de esta infeccion en los ultimos 11 anos. Material y metodos Estudio retrospectivo de los pacientes hospitalizados con diarrea por Clostridium difficile diagnosticados en el Hospital Universitario Marques de Valdecilla (Santander) desde el ano 2004 hasta el 2014. Resultados Se estudio a 244 pacientes (53% varones) de 66 (DE 15) anos. Los casos de adquisicion hospitalaria (80%) tenian, respecto a los de adquisicion comunitaria, mayor edad [67 (DE 15) vs. 63 (DE 19) anos; p = 0,01], comorbilidad alta (86% hospitalarios y 75% comunitarios; p = 0,01), uso de antibioticos (95 vs. 75%; p Clostridium difficile en los ultimos 11 anos. Conclusion El perfil clinico de los pacientes con diarrea por C lostridium difficile varia segun el lugar de adquisicion de la infeccion. Aumenta la prevalencia de esta enfermedad.

Introduction Clostridium difficile associated diarrhoea is a major health problem that seems to be on the increase. In our study, we analyse the changes in the incidence of this infection over the last 11 years. Methods A descriptive study in hospitalised patients with C. difficile associated diarrhoea in University Hospital Marques de Valdecilla (Santander, Spain) from 2004 to 2014. Results A total of 244 adults were identified [53% men; 66 (SD 15) years]. The cases of nosocomial acquisition (80%), with respect to community acquired C. difficile infection, were older [67 (SD 15) years vs. 63 (19) years; p = 0.01], high comorbidity (86% vs. 75%; p = 0.01), use of antibiotics (95% vs. 75%; p p C. difficile associated diarrhoea in our hospital over an 11-year period. Conclusion The clinical profile of patients with C. difficile diarrhoea varies by place of acquisition of infection. The prevalence of this disease is increasing.

The organochloride insecticide dichlorodiphenyltrichloroethane (DDT) and its metabolites can increase cellular levels of reactive oxygen species (ROS), cause mitochondrial dysfunction, and induce apoptosis. The highly DDT-resistant Drosophila melanogaster Meigen 1830 (Drosophila) strain, 91-R, and its susceptible control, 91-C, were used to investigate functional and structural changes among mitochondrial-derived pathways. Resequencing of mitochondrial genomes (mitogenomes) detected no structural differences between 91-R and 91-C, whereas RNA-seq suggested the differential expression of 221 mitochondrial-associated genes. Reverse transcriptase-quantitative PCR validation of 33 candidates confirmed that transcripts for six genes (Cyp12d1-p, Cyp12a4, cyt-c-d, COX5BL, COX7AL, CG17140) were significantly upregulated and two genes (Dif, Rel) were significantly downregulated in 91-R. Among the upregulated genes, four genes are duplicated within the reference genome (cyt-c-d, CG17140, COX5BL, and COX7AL). The predicted functions of the differentially expressed genes, or known functions of closely related genes, suggest that 91-R utilizes existing ROS regulation pathways of the mitochondria to combat increased ROS levels from exposure to DDT. This study represents, to our knowledge, the initial investigation of mitochondrial genome sequence variants and functional adaptations in responses to intense DDT selection and provides insights into potential adaptations of ROS management associated with DDT selection in Drosophila.

AB Purpose: The [alpha]7[beta]1 integrin is a transmembrane protein expressed in the skeletal muscle that can link the actin cytoskeleton to the surrounding basal lamina. We have previously demonstrated that transgenic mice overexpressing the [alpha]7B integrin in the skeletal muscle (MCK:[alpha]7B; [alpha]7Tg) mount an enhanced satellite cell and growth response to single or multiple bouts of eccentric exercise. In addition, interstitial stem cells characterized as mesenchymal stem cells (MSCs) accumulate in [alpha]7Tg muscle (mMSCs) in the sedentary state and after exercise. The results from these studies prompted us to determine the extent to which mMSC underlie the beneficial adaptive responses observed in [alpha]7Tg skeletal muscle after exercise. Methods: mMSCs (Sca-1+CD45-) were isolated from [alpha]7Tg mice, dye-labeled, and intramuscularly injected into adult wild type recipient mice. After injection of mMSCs or saline, mice remained sedentary (SED) or were subjected to eccentric exercise training (TR) (downhill running) on a treadmill (three times per week) for 2 or 4 wk. Gastrocnemius-soleus complexes were collected 24 h after the last bout of exercise. Results: mMSCs did not directly fuse with existing fibers; however, mMSCs injection enhanced Pax7+ satellite cell number and myonuclear content compared with all other groups at 2 wk after exercise. Mean CSA, percentage of larger caliber fibers (>3000 [mu]m2), and grip strength were increased in mMSCs/TR compared with saline/SED and mMSCs/SED at 4 wk. mMSC transplantation did not enhance repair or growth in the absence of exercise. Conclusions: The results from this study demonstrate that mMSCs contribute to beneficial changes in satellite cell expansion and growth in [alpha]7Tg muscle after eccentric exercise. Thus, MSCs that naturally accumulate in the muscle after eccentric contractions may enhance the adaptive response to exercise.

A major challenge for translating cell-based therapies is understanding the dynamics of cells and cell populations in complex in vivo environments. Intravital microscopy has shown great promise for directly visualizing cell behavior in vivo. However, current methods are limited to relatively short imaging times (hours), by ways to track cell and cell population dynamics over extended time-lapse periods (days to weeks to months), and by relatively few imaging contrast mechanisms that persist over extended investigations. We present technology to visualize and quantify complex, multifaceted dynamic changes in natural deformable skin over long time periods using novel multimodal imaging and a non-rigid image registration method. These are demonstrated in green fluorescent protein (GFP) bone marrow (BM) transplanted mice to study dynamic skin regeneration. This technology provides a novel perspective for studying dynamic biological processes and will enable future studies of stem, immune, and tumor cell biology in vivo.

The α7β1-integrin is an adhesion molecule highly expressed in skeletal muscle that can enhance regeneration in response to eccentric exercise. We have demonstrated that mesenchymal stem cells (MSCs), predominantly pericytes, accumulate in muscle (mMSCs) overexpressing the α7B-integrin (MCK:α7B; α7Tg) and contribute to new fiber formation following exercise. Since vascularization is a common event that supports tissue remodeling, we hypothesized that the α7-integrin and/or mMSCs may stimulate vessel growth following eccentric exercise. Wild-type (WT) and α7Tg mice were subjected to single or multiple (3 times/wk, 4 wk) bouts of downhill running exercise. Additionally, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) -labeled mMSCs were intramuscularly injected into WT recipients. A subset of recipient mice were run downhill before injection to recapitulate the exercised microenvironment. While total number of CD31+ vessels declined in both WT and α7Tg muscle following a single bout of exercise, the number of larger CD31+ vessels with a visible lumen was preferentially increased in α7Tg mice following eccentric exercise training ( P < 0.05). mMSC transplantation similarly increased vessel diameter and the total number of neuron-glial antigen-2 (NG2+) arterioles postexercise. Secretion of arteriogenic factors from mMSCs in response to mechanical strain, including epidermal growth factor and granulocyte macrophage-colony stimulating factor, may account for vessel remodeling. In conclusion, this study demonstrates that the α7-integrin and mMSCs contribute to increased vessel diameter size and arteriolar density in muscle in response to eccentric exercise. The information in this study has implications for the therapeutic treatment of injured muscle and disorders that result in vessel occlusion, including peripheral artery disease.

Clostridium difficile associated diarrhoea is a major health problem that seems to be on the increase. In our study, we analyse the changes in the incidence of this infection over the last 11 years.A descriptive study in hospitalised patients with Clostridium difficile associated diarrhoea in University Hospital Marqués de Valdecilla (Santander, Spain) from 2004 to 2014.A total of 244 adults were identified [53% men; 66 (SD 15) years]. The cases of nosocomial acquisition (80%), with respect to community acquired Clostridium difficile infection, were older [67 (SD 15) years vs. 63 (19) years; P=.01), high comorbidity (86% vs. 75%; P=.01), use of antibiotics (95% vs. 75%; P.001) and proton pump inhibitors (87% vs. 48% P.001). There has been an increasing incidence of Clostridium difficile associated diarrhoea in our hospital over an 11-year period.The clinical profile of patients with Clostridium difficile diarrhoea varies by place of acquisition of infection. The prevalence of this disease is increasing.

Mechanical stimuli increase skeletal muscle growth in a mammalian target of rapamycin (mTOR)- and p70S6K-dependent manner. It has been proposed that costameric proteins at Z bands may sense and transfer tension to these initiators of protein translation, but few candidates have been identified. The purpose of this study was to determine whether a role exists for the α7-integrin in the activation of hypertrophic signaling and growth following eccentric exercise training. Five-week-old, wild-type (WT) and α7BX2-integrin transgenic (α7Tg) mice were randomly assigned to one of two groups: 1) sedentary (SED), or 2) exercise training (EX). Exercise training consisted of downhill running 3 sessions/wk for 4 wk (−20°, 17 m/min, 30 min). Downhill running was used to induce physiological mechanical strain. Twenty-four hours following the final training session, maximal isometric hindlimb plantar flexor force was measured. Gastrocnemius-soleus complexes were collected for further analysis of signaling changes, which included AKT, mTOR and p70S6K, and muscle growth. Despite increased p70S6Kactivity in WT/EX, no significant changes in cross-sectional area or force were observed in WT/EX compared with WT/SED. AKT, mTOR, and p70S6Kactivation was higher, and whole muscle hypertrophy, relative muscle weight, myofibrillar protein, and force were significantly elevated in α7Tg/EX compared with α7Tg/SED. A marked increase in average myofiber cross-sectional area was observed in α7Tg/EX compared with all groups. Our findings demonstrate that the α7β1-integrin sensitizes skeletal muscle to mechanical strain and subsequent growth. Thus the α7β1-integrin may represent a novel molecular therapy for the treatment of disuse muscle atrophy.

Dentro de los Estudios de Traducción, la Traducción e Interpretación en los Servicios Públicos (TISP) es un área relativamente reciente (Critical Link 1995) en lucha todavía por conseguir el reconocimiento académico y profesional que se merece dentro y fuera de los límites que marca dicha disciplina. Gran parte de las dificultades para conseguir esa aceptación y reconocimiento se halla en la controversia que envuelve el papel del traductor e intérprete en sus actuaciones en los servicios públicos. En un intento por explicar la actuación de estos intérpretes, que con frecuencia va más allá de la invisibilidad y del mero trasvase lingüístico, y siguiendo la influencia que la teoría social de Bourdieu está teniendo en otras áreas de los Estudios de Traducción (Simeoni 1998; Heilbron y Sapiro 2002; Inghilleri 2003, 2005), es nuestra intención tratar de aplicar los conceptos fundamentales (habitus, campo, illusio y capital simbólico) de las teorías bourdianas a la TISP y analizar el papel del intérprete desde sus presupuestos, así como sugerir nuevas vías de investigación para el desarrollo de un teoría sociológica de la TISP. Within Translation Studies (TS), Public Service Interpreting and Translation (PSIT) is a relatively recent area (Critical Link 1995) still fighting for academic and professional recognition inside and outside the limits of that discipline. The growing interest in PSIT is undoubtedly linked to the migration phenomenon and the intervention of intermediaries (interpreters and translators) who make communication possible is generally recognised. But the controversy about the role(s) these intermediaries have to perform in public services seems to be one of the main difficulties to obtain academic and institutional acceptance and recognition. Following the influence of Bourdieu's social theory in certain areas of TS (Simeoni 1998; Heilbron and Sapiro 2002; Inghilleri 2003, 2005), it is our intention to apply the basic concepts of his theory (habitus, field, illusion and symbolic capital) to PSIT in an attempt to explain the performance of these ‘visible’ interpreters. New areas of research in the development of a sociological theory of PSIT will also be suggested.

Neurofibromatosis type 1 (NF1) is a common genetic disease caused by haploinsufficiency of the NF1 tumor-suppressor gene. Different pathogenetic mechanisms have been identified, with the majority (95%) causing intragenic lesions. Single or multiexon NF1 copy number changes occur in about 2% of patients, but little is known about the molecular mechanisms behind these intragenic deletions. We report here on the molecular characterization of a novel NF1 multiexonic deletion. The application of a multidisciplinary approach including multiplex ligation-dependent probe amplification, allelic segregation analysis, and fluorescent in situ hybridization allowed us to map the breakpoints in IVS27b and IVS48. Furthermore, the breakpoint junction was characterized by sequencing. Using bioinformatic analysis, we identified some recombinogenic motifs in close proximity to the centromeric and telomeric breakpoints and predicted the presence of a mutated messenger ribonucleic acid, which was deleted between exons 28 and 48 and encodes a neurofibromin that lacks some domains essential for its function. Through reverse transcriptase-polymerase chain reaction, the expression of the mutated allele was verified, showing the junction between exons 27b and 49 and, as expected, was not subjected to nonsense-mediated decay. Multiexonic deletions represent 2% of NF1 mutations, and until now, the breakpoint has been identified in only a few cases. The fine characterization of multiexonic deletions broadens the mutational repertoire of the NF1 gene, allowing for the identification of different pathogenetic mechanisms causing NF1.

The Drosophila melanogaster 91-R and 91-C strains are of common origin, however, 91-R has been intensely selected for dichlorodiphenyltrichloroethane (DDT) resistance over six decades while 91-C has been maintained as the non-selected control strain. These fly strains represent a unique genetic resource to understand the accumulation and fixation of mutations under laboratory conditions over decades of pesticide selection. Considerable research has been done to investigate the differential expression of genes associated with the highly DDT resistant strain 91-R, however, with the advent of whole genome sequencing we can now begin to develop an in depth understanding of the genomic changes associated with this intense decades-long xenobiotic selection pressure. Here we present the first whole genome sequencing analysis of the 91-R and 91-C fly strains to identify genome-wide structural changes within the open reading frames. Between-strain changes in allele frequencies revealed a higher percent of new alleles going to fixation for the 91-R strain, as compared to 91-C (P

Mechanical stimuli increase skeletal muscle growth in a mammalian target of rapamycin (mTOR)- and p70(S6K)-dependent manner. It has been proposed that costameric proteins at Z bands may sense and transfer tension to these initiators of protein translation, but few candidates have been identified. The purpose of this study was to determine whether a role exists for the α(7)-integrin in the activation of hypertrophic signaling and growth following eccentric exercise training. Five-week-old, wild-type (WT) and α(7)BX2-integrin transgenic (α(7)Tg) mice were randomly assigned to one of two groups: 1) sedentary (SED), or 2) exercise training (EX). Exercise training consisted of downhill running 3 sessions/wk for 4 wk (-20°, 17 m/min, 30 min). Downhill running was used to induce physiological mechanical strain. Twenty-four hours following the final training session, maximal isometric hindlimb plantar flexor force was measured. Gastrocnemius-soleus complexes were collected for further analysis of signaling changes, which included AKT, mTOR and p70(S6K), and muscle growth. Despite increased p70(S6K) activity in WT/EX, no significant changes in cross-sectional area or force were observed in WT/EX compared with WT/SED. AKT, mTOR, and p70(S6K) activation was higher, and whole muscle hypertrophy, relative muscle weight, myofibrillar protein, and force were significantly elevated in α(7)Tg/EX compared with α(7)Tg/SED. A marked increase in average myofiber cross-sectional area was observed in α(7)Tg/EX compared with all groups. Our findings demonstrate that the α(7)β(1)-integrin sensitizes skeletal muscle to mechanical strain and subsequent growth. Thus the α(7)β(1)-integrin may represent a novel molecular therapy for the treatment of disuse muscle atrophy.

The α7β1-integrin is a heterodimeric transmembrane protein that adheres to laminin in the extracellular matrix, representing a critical link that maintains structure in skeletal muscle. In addition to preventing exercise-induced skeletal muscle injury, the α7-integrin has been proposed to act as an intrinsic mechanosensor, initiating cellular growth in response to mechanical strain. The purpose of this study was to determine the extent to which the α7-integrin regulates muscle hypertrophy following eccentric exercise. Wild-type (WT) and α7-integrin transgenic (α7Tg) mice completed a single bout of downhill running exercise (−20°, 17 m/min, 60 min), and gastrocnemius-soleus complexes were collected 1, 2, 4, and 7 days (D) postexercise (PE). Maximal isometric force was maintained and macrophage accumulation was suppressed in α7Tg muscle 1D PE. Mean fiber cross-sectional area was unaltered in WT mice but increased 40% in α7Tg mice 7D PE. In addition, a rapid and striking fivefold increase in embryonic myosin heavy chain-positive fibers appeared in α7Tg mice 2D PE. Although Pax7-positive satellite cells were increased in α7Tg muscle 1D PE, the number of nuclei per myofiber was not altered 7D PE. Phosphorylation of mammalian target of rapamycin (mTOR) was significantly elevated in α7Tg 1D PE. This study provides the first demonstration that the presence of the α7β1-integrin in skeletal muscle increases fiber hypertrophy and new fiber synthesis in the early time course following a single bout of eccentric exercise. Further studies are necessary to elucidate the precise mechanism by which the α7-integrin can enhance muscle hypertrophy following exercise.

Walker-Warburg syndrome (WWS) is the most severe of a group of congenital disorders that have in common defects in the O-glycosylation of α-dystroglycan. WWS is characterized by congenital muscular dystrophy coupled with severe ocular and brain malformations. Moreover, in at least one-fifth of the reported cases, mutations in the POMT1 gene are responsible for this disease. During embryonic development (E8.5 to E1.5), the mouse Pomt1 gene is expressed in the tissues most severely affected in WWS, the muscle, eye, and brain. In this study, we show that mPomt1 expression is maintained in the muscle and eye in later developmental stages and, notably, that its expression is particularly strong in regions of brain and cerebellum that, when affected, could generate the defects observed in patients with WWS. We show that the Pomt1 protein is localized to the sarcoplasmic reticulum of muscle tissue cells in adult mice, where α-dystroglycan is O-glycosylated. Furthermore, the Pomt1 protein is localized to the acrosome of maturing spermatids, where α-dystroglycan is not glycosylated, so that Pomt1 might have a different target for O-mannosylation in the testes. This expression pattern in the testes could also be related to the gonadal anomalies observed in some patients with WWS. Copyright © American Society for Investigative Pathology., Supported by the Spanish Comisio´n Interministerial de Ciencia y TecnologÍa (SAF03-01619) and Fondo de Investigaciones Sanitarias (PI02/0715).

Insecticide-resistant Drosophila melanogaster strains represent a resource for the discovery of the underlying molecular mechanisms of cytochrome P450 constitutive over-expression, even if some of these P450s are not directly involved in the resistance phenotype. For example, in select 4,4’-dichlorodiphenyltrichloroethane (DDT) resistant strains the glucocorticoid receptor-like (GR-like) potential transcription factor binding motifs (TFBMs) have previously been shown to be associated with constitutively differentially-expressed cytochrome P450s, Cyp12d1, Cyp6g2 and Cyp9c1. However, insects are not known to have glucocorticoids. The only ortholog to the mammalian glucocorticoid receptor (GR) in D. melanogaster is an estrogen-related receptor (ERR) gene, which has two predicted alternative splice isoforms (ERRa and ERRb). Sequencing of ERRa and ERRb in select DDT susceptible and resistant D. melanogaster strains has revealed a glycine (G) codon insertion which was only observed in the ligand binding domain of ERR from the resistant strains tested (ERR-G). Transgenic flies, expressing the ERRa-G allele, constitutively over-expressed Cyp12d1, Cyp6g2 and Cyp9c1. Only Cyp12d1 and Cyp6g2 were over-expressed in the ERRb-G transgenic flies. Phylogenetic studies show that the G-insertion appeared to be located in a less conserved domain in ERR and this insertion is found in multiple species across the Sophophora subgenera.

O-mannosylation is an important protein modification in eukaryotes that is initiated by an evolutionarily conserved family of protein O -mannosyltransferases. The first mammalian protein O -mannosyltransferase gene described was the human POMT1 . Mutations in the hPOMT1 gene are responsible for Walker–Warburg syndrome (WWS), a severe recessive congenital muscular dystrophy associated with defects in neuronal migration that produce complex brain and eye abnormalities. During embryogenesis, the murine Pomt1 gene is prominently expressed in the neural tube, the developing eye, and the mesenchyme. These sites of expression correlate with those in which the main tissue alterations are observed in WWS patients. We have inactivated a Pomt1 allele by gene targeting in embryonic stem cells and produced chimeras transmitting the defect allele to offspring. Although heterozygous mice were viable and fertile, the total absence of Pomt1 – / – pups in the progeny of heterozygous intercrosses indicated that this genotype is embryonic lethal. An analysis of the mutant phenotype revealed that homozygous Pomt1 – / – mice suffer developmental arrest around embryonic day (E) 7.5 and die between E7.5 and E9.5. The Pomt1 – / – embryos present defects in the formation of Reichert's membrane, the first basement membrane to form in the embryo. The failure of this membrane to form appears to be the result of abnormal glycosylation and maturation of dystroglycan that may impair recruitment of laminin, a structural component required for the formation of Reichert's membrane in rodents. The targeted disruption of mPomt1 represents an example of an engineered deletion of a known glycosyltransferase involved in O -mannosyl glycan synthesis.

In yeasts and other fungi, O-mannosyl glycans constitute a major protein modification that is essential for cell viability. For several decades, protein O-mannosylation was considered a yeast-specific modification. Thus, it was especially interesting when it became evident that O-mannosyl glycans in mammals are not as rare as previously thought. O-mannosyl glycans are abundant in the mammalian brain and are also an abundant modification of alpha-dystroglycan, a component of the dystrophin-glycoprotein complex. Recently, mutations in genes that are or might be involved in the glycosylation of alpha-dystroglycan have been identified. Their association with neuromuscular diseases has focused the attention of different research areas on protein O-mannosylation.