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AbstractBackground/Objectives There is a great unmet need for accessible adjunctive interventions to promote long-term recovery from substance use disorder (SUD). This study aimed to iteratively develop and test the initial feasibility and acceptability of Mindful Journey, a novel digital mindfulness-based intervention for promoting recovery among individuals with SUD.Patients/Materials Ten adults receiving outpatient treatment for SUD.Methods Phase 1 (n = 5) involved developing and testing a single introductory digital lesson. Phase 2 included a separate sample (n = 5) and involved testing all 15 digital lessons (each 30- to 45-minutes) over a 6-week period, while also receiving weekly brief phone coaching for motivational/technical support.Results Across both phases, quantitative ratings (rated on a 5-point scale) were all at or above a 4 (corresponding with ‘agree’) for key acceptability dimensions, such as usability, understandability, appeal of visual content, how engaging the content was, and helpfulness for recovery. Additionally, in both phases, qualitative feedback indicated that participants particularly appreciated the BOAT (Breath, Observe, Accept, Take a Moment) tool for breaking down mindfulness into steps. Qualitative feedback was used to iteratively refine the intervention. For example, based on feedback, we added a second core mindfulness tool, the SOAK (Stop, Observe, Appreciate, Keep Curious), and we added more example clients and group therapy videos. In Phase 2, 4 out of 5 participants completed all 15 lessons, providing initial evidence of feasibility. Participants reported that the phone coaching motivated them to use the app. The final version of Mindful Journey was a smartphone app with additional features, including brief on-the-go audio exercises and a library of mindfulness practices. Although, participants used these additional features infrequently.Conclusions Based on promising initial findings, future acceptability and feasibility testing in a larger sample is warranted. Future versions might include push notifications to facilitate engagement in the additional app features.

Introduction and Objectives: Different patterns of liver injury have been reported in association with the SARS-CoV-2 vaccines. The aim of this study was to describe a nationwide cohort of patients with SARS CoV-2 vaccine-induced liver injury, focusing on treatment and the evolution after further booster administration. Patients and Methods: multicentre, retrospective-prospective study, including subjects who developed abnormal liver tests within 90 days after administration of SARS-CoV-2 vaccination. Results: 47 cases were collected: 17 after prime dose and 30 after booster. Age was 57 years, 30 (63.8 %) were female, and 7 (14.9 %) had a history of prior autoimmune hepatitis (AIH). Most cases were non-severe, though 9 (19.1 %) developed acute liver injury or failure (ALF). Liver injury tended to be more severe in those presenting after a booster (p=0.084). Pattern of liver injury was hepatocellular (80.9 %), mixed (12.8 %) and 3 (6.4 %) cholestatic. Liver biopsy was performed on 33 patients; 29 showed findings of AIH. Forty-one (87.2 %) patients received immunosuppressants, mostly corticosteroids (35/41). One required liver transplantation and another died due to ALF. Immunosuppression was discontinued in 6/41 patients without later rebound. Twenty-five subjects received at least one booster and 7 (28.0 %) relapsed from the liver injury, but all were non-severe. Recurrence was less frequent among patients on immunosuppressants at booster administration (28.6 % vs. 88.9 %, p=0.007). Conclusions: SARS CoV-2 vaccine-induced liver injury is heterogeneous but mostly immune-mediated. Relapse of liver injury after re-exposure to vaccine is frequent (28.0 %) but mild. Immunosuppression at booster administration is associated with a lower risk of liver injury.

Background: Chronic hepatic inflammation leads to liver fibrosis, which may progress to cirrhosis, a condition with high morbidity. Our aim was to assess the as yet unknown role of innate immunity protein CD5L in liver fibrosis. Methods: CD5L was measured by ELISA in plasma samples from cirrhotic (n = 63) and hepatitis (n = 39) patients, and healthy controls (n = 7), by immunohistochemistry in cirrhotic tissue (n = 12), and by quantitative RT-PCR in mouse liver cell subsets isolated by cell sorting. Recombinant CD5L (rCD5L) was administered into a murine model of CCl4-induced fibrosis, and damage, fibrosis and hepatic immune cell infiltration, including the LyC6hi (pro-fibrotic)-LyC6low (pro-resolutive) monocyte ratio were determined. Moreover, rCD5L was added into primary human hepatic stellate cells to study transforming growth factor β (TGFβ) activation responses. Findings: Cirrhotic patients showed elevated plasma CD5L concentrations as compared to patients with hepatitis and healthy controls (Mann-Whitney test p

Background & Aims: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. Methods: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. Results: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). Conclusions: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. Lay summary: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.

Oxytocin is a neurotransmitter related to both feeding and social behavior; anorexia nervosa is a psychiatric illness defined by reduced food intake, weight loss, and problems in social perceptions. Oxytocin receptor single nucleotide polymorphisms rs2254298 or rs53576 and neural responses to social stimuli were evaluated in adult women with or recovered from anorexia nervosa using functional magnetic resonance imaging. Carriers of the A allele for OXTR rs2254298 (2 AA and 10 AG) showed significantly reduced activation of portions of the posterior cingulate cortex and medial prefrontal cortex for social stimuli as well as greater negative connectivity between the posterior cingulate and the occipital lobe relative to the GG subjects for rs2254298. Differences in the other OXTR SNP, rs53576, did not result in detectable neural differences in either whole brain or region of interest analyses. Development of a mechanistic, biological model of how social behavior is impacted by mental illness requires linking genes to functional brain activations in disease. This pilot study suggests that in anorexia nervosa, differences related to OXTR SNP rs2254298 may alter neural responses to social stimuli and disrupt the engagement and disengagement of the default mode network.

Abstract Betatectiviruses are prophages consisting of linear extrachromosomal genomes without obvious plasmid modules. It remains unclear how betatectiviruses are maintained in low-copy numbers in host cells and how they are vertically transmitted. Phage GIL01 is a model betatectivirus that infects the mosquito pathogen Bacillus thuringiensis serovar israelensis. Previous studies identified two closely spaced promoters, P1 and P2, responsible for the expression of GIL01 genes required for prophage replication and the switch from the lysogenic to lytic cycle. Here, we report that the GIL01-encoded 58-amino acid long gp1 protein forms a large nucleoprotein complex that represses its transcription from the strong promoter P2. Notably, ectopic expression of gp1 resulted in the loss of GIL01 in exponential cultures and immunized cells against infection with GIL01, indicating that gp1 plays a repressive role in the phage cycle. This finding is consistent with mutations in gp1 committing GIL01 to the lytic cycle and we show that maintenance of this phage variant in the bacterial population is contingent on the accumulation of deletions in the P1-P2 region. The fact that gp1 is conserved across most sequenced betatectiviruses suggests that the regulatory mechanism of gp1 that controls prophage maintenance is widespread among these bacteriophages.

Este artículo plantea las posibilidades de la literatura como fuente y modelo alternativo didáctico para la formación de escritores creativos. Para ello se examinan tres trabajos de minificción de José Juan Aboytia: Pretextos para una literatura inadjetiva (2015), ABC de la XYZ (2018) y Museo de nimiedades (2022). A partir del contenido y la articulación literaria de estas obras se destaca la potencialidad de la forma de la literatura breve, con recursos como las relaciones transtextuales, las variaciones y la metaficción, que desembocan en la creación con humor, y que permiten proponer nuevos modelos de enseñanza para la composición.

La Universidad Autónoma de Ciudad Juárez creó en 1998 el Programa de Literatura, el cual ha madurado y repercutido ineludiblemente en el ambiente cultural de la ciudad. Entre sus egresados, se distingue un grupo de jóvenes que nació a finales del siglo XX y que ha publicado obras en las que muestran los conocimientos adquiridos en los estudios formales. Se les puede considerar un movimiento de vanguardia en la región.

This review was conducted to assess the global incidence of transfusion-transmitted infections (TTIs) caused by contamination of blood components with the Burkholderia cepacia complex (Bcc). Our search encompassed various specialized databases such as Medline/PubMed, Web of Science, Scopus, Scielo, ScienceDirect, and ClinicalKey. An analysis of the literature revealed a total of eleven reported cases where blood components contaminated with Bcc had been transfused, resulting in sepsis among the affected patients. Of these cases, eight were documented in the literature, while the remaining three occurred within the institution involving the authors of this review. A comparative examination was conducted, considering factors such as primary diagnosis, transfused blood component, time elapsed between transfusion and manifestation of symptoms, administration of antibiotics, and final outcome. Interestingly, regardless of the storage temperature, all blood components were found to be susceptible to Bcc contamination. Furthermore, the cases investigated revealed diverse sources of contamination, and it was observed that all the affected patients had compromised immune systems due to underlying illnesses. Based on these findings, a series of preventive strategies were derived to mitigate and decrease the occurrence of similar cases.

Previous research has treated language as a reflection of modes of thought. There are ways to measure the use of words and, as results indicate, these help explain a community’s environment and social behavior. This work examines the use of the language from those who write in El Diario de Juárez, by analyzing three fragments relating to journalistic notes about the same subject and from different authors. Also, this article emphasizes the influence on speech that this newspaper, and mass media, exerts on the readers.

Bacillus thuringiensis is the most used biopesticide in agriculture. Its entomopathogenic capacity stems from the possession of plasmid-borne insecticidal crystal genes (cry), traditionally used as discriminant taxonomic feature for that species. As such, crystal and plasmid identification are key to the characterization of this species. To date, about 600 B. thuringiensis genomes have been reported, but less than 5% have been completed, while the other draft genomes are incomplete, hindering full plasmid delineation. Here we present the complete genome of Bacillus thuringiensis HER1410, a strain closely related to B. thuringiensis entomocidus and a known host for a variety of Bacillus phages. The combination of short and long-read techniques allowed fully resolving the genome and delineation of three plasmids. This enabled the accurate detection of an unusual location of a unique cry gene, cry1Ba4, located in a genomic island near the chromosome replication origin. Two megaplasmids, pLUSID1 and pLUSID2 could be delineated: pLUSID1 (368 kb), a likely conjugative plasmid involved in virulence, and pLUSID2 (156 kb) potentially related to the sporulation process. A smaller plasmidial prophage pLUSID3, with a dual lifestyle whose integration within the chromosome causes the disruption of a flagellar key component. Finally, phylogenetic analysis placed this strain within a clade comprising members from the B. thuringiensis serovar thuringiensis and other serovars and with B. cereus s. s. in agreement with the intermingled taxonomy of B. cereus sensu lato group.

Bam35 and related betatectiviruses are tail-less bacteriophages that prey on members of the Bacillus cereus group. These temperate viruses replicate their linear genome by a protein-primed mechanism. In this work, we have identified and characterized the product of the viral ORF2 as a single-stranded DNA binding protein (hereafter B35SSB). B35SSB binds ssDNA with great preference over dsDNA or RNA in a sequence-independent, highly cooperative manner that results in a non-specific stimulation of DNA replication. We have also identified several aromatic and basic residues, involved in base-stacking and electrostatic interactions, respectively, that are required for effective protein–ssDNA interaction. Although SSBs are essential for DNA replication in all domains of life as well as many viruses, they are very diverse proteins. However, most SSBs share a common structural domain, named OB-fold. Protein-primed viruses could constitute an exception, as no OB-fold DNA binding protein has been reported. Based on databases searches as well as phylogenetic and structural analyses, we showed that B35SSB belongs to a novel and independent group of SSBs. This group contains proteins encoded by protein-primed viral genomes from unrelated viruses, spanning betatectiviruses and Φ29 and close podoviruses, and they share a conserved pattern of secondary structure. Sensitive searches and structural predictions indicate that B35SSB contains a conserved domain resembling a divergent OB-fold, which would constitute the first occurrence of an OB-fold-like domain in a protein-primed genome.

In lieu of the growing relevance videogames have in how we spend our time off, those of us who seek de-constructing gender stereotypes in the direction of recognizing equal rights and opportunities for all, ask ourselves: which gender roles and representations are video games modeling? This paper aims to assess the Costarican reality related to the gender representations in the most popular videogames in Costa Rica. It develops an analysis of the content of the four most popular role-playing video games used through the mobile systems which have the largest penetration in the country: Android and Apple.

Replicating DNA and converting genetic information to protein is a feature of cellular life. Here the authors implement a coupled DNA replication and gene expression system inside vesicles.

Summary: Family B DNA polymerases (PolBs) play a central role during replication of viral and cellular chromosomes. Here, we report the discovery of a third major group of PolBs, which we denote primer-independent PolB (piPolB), that might be a link between the previously known protein-primed and RNA/DNA-primed PolBs. PiPolBs are encoded by highly diverse mobile genetic elements, pipolins, integrated in the genomes of diverse bacteria and also present as circular plasmids in mitochondria. Biochemical characterization showed that piPolB displays efficient DNA polymerization activity that can use undamaged and damaged templates and is endowed with proofreading and strand displacement capacities. Remarkably, the protein is also capable of template-dependent de novo DNA synthesis, i.e., DNA-priming activity, thereby breaking the long-standing dogma that replicative DNA polymerases require a pre-existing primer for DNA synthesis. We suggest that piPolBs are involved in self-replication of pipolins and may also contribute to bacterial DNA damage tolerance. : Redrejo-Rodríguez et al. report and characterize a DNA polymerase group (piPolB) from the B family that can perform primer-independent DNA replication. PiPolBs are encoded by Pipolins, diverse self-replicating genetic elements that are widespread among bacterial phyla and in mitochondria. Keywords: DNA replication, translesion synthesis, primer-independent DNA synthesis, de novo DNA synthesis, family B DNA polymerase, self-replicating mobile element, DNA damage

The genome of Bacillus subtilis phage ϕ29 consists of a linear double-stranded DNA with a terminal protein (TP) covalently linked to each 5' end (TP-DNA). ϕ29 DNA polymerase is the enzyme responsible for viral DNA replication, due to its distinctive properties: high processivity and strand displacement capacity, being able to replicate the entire genome without requiring the assistance of processivity or unwinding factors, unlike most replicases. ϕ29 single-stranded DNA binding protein (SSB) is encoded by the viral gene 5 and binds the ssDNA generated in the replication of the ϕ29 TP-DNA. It has been described to stimulate the DNA elongation rate during the DNA replication. Previous studies proposed residues Tyr50, Tyr57 and Tyr76 as ligands of ssDNA. The role of two of these residues has been determined in this work by site-directed mutagenesis. Our results showed that mutant derivative Y57A was unable to bind to ssDNA, to stimulate the DNA elongation and to displace oligonucleotides annealed to M13 ssDNA, whereas mutant Y50A behaved like the wild-type SSB.

This protocol analyzes the direct interaction between two DNA-binding proteins by pull-down co-immunoprecipitation. One of the proteins is overexpressed in E. coli as HA-tagged recombinant protein and cell-free extracts are immunoprecipitated in HA-affinity resin. Cell extracts are treated with nuclease to degrade DNA and RNA, which rules out nucleic acid-mediated indirect interaction. Then, a second immunoprecipitation step is performed using the purified putative partner protein. Co-immunoprecipitated proteins can be detected either by Coomassie Blue staining and/or Western blotting (WB) if a specific antibody is available. Moreover, many DNA/RNA binding proteins are highly electropositive, which can hinder WB under standard conditions, as has been shown in histones and histone-like proteins. In this case, we show that the high isoelectric point of the putative partner results in a poor transfer. Tips to troubleshot WB transfer of highly electropositive DNA-binding proteins are provided.

Durante la segunda mitad del siglo xx, en México no había trabajos de investigación tanto académica como independiente sobre la construcción del Estado y su relación estrecha con la violencia; apenas a finales del siglo y principios del actual han surgido. Sin embargo, el vínculo entre esa construcción del Estado y actos agresivos ha sido un tema constantemente tratado en la literatura. Tanto la zona gris expuesta por Wil G. Pansters como el sistema informal aparecen perfectamente retratados no únicamente en la literatura de los últimos sesenta años: dichos conceptos han estado presentes en la creación surgida en México desde su independencia en el siglo xix. Por supuesto, algunas de esas obras han tenido que esperar años para circular libremente, pues en su tiempo fueron vetadas o censuradas.

Bacteriophage Phi29 DNA polymerase belongs to the protein-primed subgroup of family B DNA polymerases that use a terminal protein (TP) as a primer to initiate genome replication. The resolution of the crystallographic structure showed that it consists of an N-terminal domain with the exonuclease activity and a C-terminal polymerization domain. It also has two subdomains specific of the protein-primed DNA polymerases; the TP Regions 1 (TPR1) that interacts with TP and DNA, and 2 (TPR2), that couples both processivity and strand displacement to the enzyme. The superimposition of the structures of the apo polymerase and the polymerase in the polymerase/TP heterodimer shows that the structural changes are restricted almost to the TPR1 loop (residues 304−314). In order to study the role of this loop in binding the DNA and the TP, we changed the residues Arg306, Arg308, Phe309, Tyr310, and Lys311 into alanine, and also made the deletion mutant Δ6 lacking residues Arg306−Lys311. The results show a defective TP binding capacity in mutants R306A, F309A, Y310A, and Δ6. The additional impaired primer-terminus stabilization at the polymerization active site in mutants Y310A and Δ6 allows us to propose a role for the Phi29 DNA polymerase TPR1 loop in the proper positioning of the DNA and TP-priming 3’-OH termini at the preinsertion site of the polymerase to enable efficient initiation and further elongation steps during Phi29 TP-DNA replication.

La literatura que habla de Ciudad Juárez ha sido producida tanto por los autores que radican en esta ciudad como por creadores foráneos. A la primera, Ricardo Vigueras- Fernández le ha llamado juarense, ya que -dice- los autores conocen bien su entorno; pero en el caso de la segunda, Vigueras-Fernández la denomina juarica, pues la fron - tera norte ha servido como fuente de inspiración para los escritores extranjeros ¿y fue - reños?, sin que estos estén muy bien enterados tanto del contexto como de los hechos acaecidos en la ciudad. En este trabajo analizaremos algunas obras de varios autores juarenses y veremos que, a grandes rasgos, se les puede calificar de realistas y de tener nexos estrechos con la historia reciente de Ciudad Juárez.

Bacillus subtilis phage Φ29 has a linear, double-stranded DNA 19 kb long with an inverted terminal repeat of 6 nucleotides and a protein covalently linked to the 5’ ends of the DNA. This protein, called terminal protein (TP), is the primer for the initiation of replication, a reaction catalyzed by the viral DNA polymerase at the two DNA ends. The DNA polymerase further elongates the nascent DNA chain in a processive manner, coupling strand displacement with elongation. The viral protein p5 is a single-stranded DNA binding protein (SSB) that binds to the single strands generated by strand displacement during the elongation process. Viral protein p6 is a double-stranded DNA binding protein (DBP) that preferentially binds to the origins of replication at the Φ29 DNA ends and is required for the initiation of replication. Both SSB and DBP are essential for Φ29 DNA amplification. This review focuses on the role of these phage DNA-binding proteins in Φ29 DNA replication both in vitro and in vivo, as well as on the implication of several B. subtilis DNA-binding proteins in different processes of the viral cycle. We will revise the enzymatic activities of the Φ29 DNA polymerase: TP-deoxynucleotidylation, processive DNA polymerization coupled to strand displacement, 3’-5’ exonucleolysis and pyrophosphorolysis. The resolution of the Φ29 DNA polymerase structure has shed light on the translocation mechanism and the determinants responsible for processivity and strand displacement. These two properties have made Φ29 DNA polymerase one of the main enzymes used in the current DNA amplification technologies. The determination of the structure of Φ29 TP revealed the existence of three domains: the priming domain, where the primer residue Ser232, as well as Phe230, involved in the determination of the initiating nucleotide, are located, the intermediate domain, involved in DNA polymerase binding, and the N-terminal domain, responsible for DNA binding and localization of the TP at the bacterial nucleoid, where viral DNA replication takes place. The biochemical properties of the Φ29 DBP and SSB and their function in the initiation and elongation of Φ29 DNA replication, respectively, will be described.

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Many different DNA delivery vehicles have been developed and tested, all with their advantages and disadvantages. The bacteriophage phi29 terminal protein (TP) is covalently linked to the 5' ends of the phage genome during the DNA replication process. Our approach is to utilize this TP as a platform to incorporate different protein or peptide modules that can target the DNA to the interior of the cell, to the nucleus, or even to subcellular compartments. In order to be able to insert different peptide modules on the TP sequence to endow it with desired functions and/or eliminate unwanted regions of the protein, we have carried out a transposition screening to detect insertion-permissive points on the sequence of the TP. We report the functional characterization of 12 insertion mutants of the TP, and the identification of one site at position 38 that allows the insertion of peptides up to 17 amino acids in length while maintaining the ability of the TP to support DNA amplification in vitro. A protein with one insertion at that position containing a cysteine residue, a linker, and a thrombin recognition site was purified and its amplification activity was optimized.

La Virología se ha desarrollado durante la última parte del siglo XX en paralelo con las nuevas técnicas de análisis y manipulación genética y con el auxilio de técnicas físicas e informáticas. En España se han formado núcleos activos tanto en genética viral como en virus patógenos de animales y plantas. Contrariamente a predicciones de hace tan solo tres décadas, las enfermedades víricas siguen siendo un importante problema en medicina, veterinaria y agricultura. Un gran número de enfermedades víricas emergentes constituyen un importante desafío para el siglo XXI.

OBJETIVO: Conocer la frecuencia, el tipo histológico y los cambios en cáncer pulmonar (CP) observados durante 40 años, en el Instituto Nacional de Enfermedades Respiratorias (INER). MATERIAL Y MÉTODOS: Estudio transversal realizado en el año de 1999. Se revisaron los informes de labores del INER, de 1983 a 1996, y los archivos de Patología Quirúrgica, de 1957 a 1996. Se obtuvieron los datos de 1 961 pacientes con los que se calcularon medidas de frecuencia acerca de: el lugar que ocupa el CP en los ingresos al Instituto, los estudios histológicos, edad, sexo, espécimen y diagnóstico. RESULTADOS: Entre 1983 y 1996, el CP ocupó del octavo al segundo lugar en los ingresos al INER. Los resultados se dividieron por décadas, en las dos primeras (1957-1976), 9% fueron mujeres; en la tercera (1977-1986), 32%, y en la última (1986-1996), 38%. El carcinoma epidermoide predominó en las dos primeras décadas (61%) y el adenocarcinoma en las dos últimas con 41 y 62%, respectivamente. CONCLUSIONES: Actualmente el cp es más frecuente en mujeres y predomina el adenocarcinoma.OBJECTIVE: To assess the frequency, histological type and the epidemiological pattern of lung cancer (LC), during a 40 year period, at the National Institute of Respiratory Diseases (iner). MATERIAL AND METHODS: This cross-sectional study was conducted in 1999. Data were abstracted from the INER's service reports for 1983-1996 and the surgical pathology archives for 1957-1996. Data from 1961 patients were analyzed, to obtain frequency measures on: the characteristics of INER LC patient admissions, age, sex, histological studies, specimens and diagnoses. RESULTS: Between 1983-1996, LC ranked eighth to second place in INER inpatient admissions. Results were grouped by decades. In the first two decades (1957-1976), 9% of patients were female; 32% in the third (1977-1986), and 38% in the last decade (1987-1996). Epidermoid cell carcinoma was more frequent in the two first decades (61%) and adenocarcinoma in the last two, (41% and 62%, respectively.) CONCLUSIONS: LC is currently more frequent in women, and adenocarcinoma is the most frequent neoplasia.

UnlabelledSpontaneously hypertensive rat (SHR) constitutes a genetic model widely used to study the natural evolution of hypertensive heart disease. Ca²⁺-handling alterations are known to occur in SHR. However, the putative modifications of Ca²⁺-handling proteins during the progression to heart failure (HF) are not well established. Moreover, the role of apoptosis in SHR is controversial. We investigated intracellular Ca²⁺, Ca²⁺-handling proteins and apoptosis in SHR vs. control Wistar rats (W) from 3 to 15 months (mo). Changes associated with the transition to HF (i.e. lung edema and decrease in midwall fractional shortening), occurred at 15 mo in 38% of SHR (SHRF). In SHRF, twitch and caffeine-induced Ca²⁺ transients, significantly decreased relative to 6/9 mo and 15 mo without HF signs. This decrease occurred in association with a decrease in the time constant of caffeine-Ca²⁺ transient decay and an increase in Na⁺/Ca²⁺ exchanger (NCX) abundance (pConclusions1. Apoptosis is an early and persistent event that may contribute to hypertrophic remodeling but would not participate in the contractile impairment of SHRF. 2. The increase in NCX expression/activity, associated with an increase in Ca²⁺ efflux from the cell, constitutes a primary alteration of Ca²⁺-handling proteins in the evolution to HF. 3. No changes in SERCA2a expression/activity are observed when HF signs become evident.

Resolution of the crystallographic structure of φ29 DNA polymerase binary and ternary complexes showed that residue Lys529, located at the C-terminus of the palm subdomain, establishes contacts with the 3' terminal phosphodiester bond. In this paper, site-directed mutants at this Lys residue were used to analyse its functional importance for the synthetic activities of φ29 DNA polymerase, an enzyme that starts linear φ29 DNA replication using a terminal protein (TP) as primer. Our results show that single replacement of φ29 DNA polymerase residue Lys529 by Ala or Glu decreases the stabilisation of the primer-terminus at the polymerisation active site, impairing both the insertion of the incoming nucleotide when DNA and TP are used as primers and the translocation step required for the next incoming nucleotide incorporation. In addition, combination of the DNA polymerase mutants with a TP derivative at residue Glu233, neighbour to the priming residue Ser232, leads us to infer a direct contact between Lys529 and Glu233 for initiation of TP-DNA replication. Altogether, the results are compatible with a sequential binding of φ29 DNA polymerase residue Lys529 with TP and DNA during replication of TP-DNA.

5-Fluorouracil (5FU) is a chemotherapeutic drug widely used in treating a range of advanced, solid tumours and, in particular, colorectal cancer. Here, we used high-density tiling DNA microarray technology to obtain the specific transcriptome-wide response induced by 5FU in the eukaryotic model Schizosaccharomyces pombe. This approach combined with real-time quantitative PCR analysis allowed us to detect splicing defects of a significant number of intron-containing mRNA, in addition to identify some rRNA and tRNA processing defects after 5FU treatment. Interestingly, our studies also revealed that 5FU specifically induced the expression of certain genes implicated in the processing of mRNA, tRNA and rRNA precursors, and in the post-transcriptional modification of uracil residues in RNA. The transcription of several tRNA genes was also significantly induced after drug exposure. These transcriptional changes might represent a cellular response mechanism to counteract 5FU damage since deletion strains for some of these up-regulated genes were hypersensitive to 5FU. Moreover, most of these RNA processing genes have human orthologs that participate in conserved pathways, suggesting that they could be novel targets to improve the efficacy of 5FU-based treatments.

Bacteriophages ϕ29 and Nf from Bacillus subtilis start replication of their linear genomes at both ends using a protein-primed mechanism by means of which the DNA polymerase initiates replication by adding dAMP to the terminal protein, this insertion being directed by the second and third 3' terminal thymine of the template strand, respectively. In this work, we have obtained evidences about the role of the 3' terminal base during the initiation steps of ϕ29 and Nf genome replication. The results indicate that the absence of the 3' terminal base modifies the initiation position carried out by ϕ29 DNA polymerase in such a way that now the third position of the template, instead of the second one, guides the incorporation of the initiating nucleotide. In the case of Nf, although the lack of the 3' terminal base has no effect on the initiation position, its absence impairs further elongation of the TP-dAMP initiation product. The results show the essential role of the 3' terminal base in guaranteeing the correct positioning of replication origins at the polymerization active site to allow accurate initiation of replication and further elongation.

La salud reproductiva es el estado de completo bienestar físico, psíquico y social de las parejas en su etapa reproductiva; está condicionada por factores de tipo social, político, cultural, religioso, demográfico, económico y por acciones provenientes de otros sectores como vivienda, educación, acceso a los servicios de salud y orientación, en aras de obtener un producto sano; por otro lado, se encuentra la violencia definida como cualquier relación, proceso o condición por la cual un individuo o grupo social viola la integridad física, psíquica, moral o social de otra persona; posee múltiples formas de expresión siendo la violencia doméstica la que trae implicaciones en la morbilidad y mortalidad de las mujeres y sus hijos. Ambos conceptos están muy interrelacionados, de modo que actúan afectando la célula fundamental de la sociedad: La Familia, por todo ello decidimos realizar una revisión y análisis de ambos temas. El problema de la violencia intrafamiliar (VIF) se ha convertido en la expresión más extrema y dolorosa de las relaciones de desigualdad de poder en la vida cotidiana entre hombres y mujeres. Una conclusión fundamental es que aún nos queda mucho por hacer en cuanto al conocimiento, reconocimiento y accionar en este tema. Palabras clave: salud reproductiva, violencia

Se realiza un estudio descriptivo y transversal de la totalidad de la población femenina del consultorio médico 870, del policlínico 13 de Marzo, comprendida en las edades de 40 a 59 años de edad. Se le aplicó un cuestionario anónimo donde se recogieron las siguientes variables: tenencia de pareja estable o no, síntomas psíquicos y físicos, erotismo en las parejas, vínculo afectivo y comunicación familiar. Se concluyó que la mayoría de las pacientes tenía pareja estable, la incidencia de síntomas síquicos fueron ansiedad, depresión e irritabilidad y los físicos: sofocos, cefaleas y dolores generalizados. El erotismo posee mejores indicadores en mujeres sin pareja estable. El vínculo afectivo y la comunicación familiar son deficientes.

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Los sistemas de enseñanza convencional y de instrucción personalizada son comparados en relación al nivel de dominio de aprendizaje y al número de alumnos aprobados al finalizar el curso. Se seleccionaron 120 estudiantes del V ciclo de Psicología. La instrucción se realizó durante un semestre académico alternado, en el mismo curso y con igual contenido; consistió en la aplicación de la enseñanza convencional (grupo control) a cargo de un profesor mediante objetivos conductuales y la instrucción personalizada (grupo experimental) a cargo de un profesor y monitores, mediante unidades instruccionales cancelatorias. Aprobaron el 91.6 % de alumnos del grupo control y el 88.3 % del grupo experimental; el porcentaje de alumnos que obtuvieron un excelente dominio de las unidades fue el 16.6 % en el grupo control y el 88.3 % en el grupo experimental. Lo que indica mejores resultados cualitativos en el curso dictado con el sistema de instrucción personalizada (SIP) en comparación con el sistema de enseñanza convencional (SIC).