Identification of BC005512 as a DNA Damage Responsive Murine Endogenous Retrovirus of GLN Family Involved in Cell Growth Regulation

Genotoxicity assessment is of great significance in drug safety evaluation, and microarray is a useful tool widely used to identify genotoxic stress responsive genes. In the present work, by using oligonucleotide microarray in an in vivo model, we identified an unknown gene BC005512 (abbreviated as BC, official full name: cDNA sequence BC005512), whose expression in mouse liver was specifically induced by seven well-known genotoxins (GTXs), but not by non-genotoxins (NGTXs). Bioinformatics revealed that BC was a member of the GLN family of murine endogenous retrovirus (ERV). However, the relationship to genotoxicity and the cellular function of GLN are largely unknown. Using NIH/3T3 cells as an in vitro model system and quantitative real-time PCR, BC expression was specifically induced by another seven GTXs, covering diverse genotoxicity mechanisms. Additionally, dose-response and linear regression analysis showed that expression level of BC in NIH/3T3 cells strongly correlated with DNA damage, measured using the alkaline comet assay,. While in p53 deficient L5178Y cells, GTXs could not induce BC expression. Further functional studies using RNA interference revealed that down-regulation of BC expression induced G1/S phase arrest, inhibited cell proliferation and thus suppressed cell growth in NIH/3T3 cells. Together, our results provide the first evidence that BC005512, a member from GLN family of murine ERV, was responsive to DNA damage and involved in cell growth regulation. These findings could be of great value in genotoxicity predictions and contribute to a deeper understanding of GLN biological functions

Evolution after Anti-TNF Discontinuation in Patients with Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study

OBJECTIVES:The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed.METHODS:This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included.RESULTS:A total of 1, 055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn''s disease and ulcerative colitis patients, respectively. In both Crohn''s disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn''s disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe.CONCLUSIONS:The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe

The Progeny of Arabidopsis thaliana Plants Exposed to Salt Exhibit Changes in DNA Methylation, Histone Modifications and Gene Expression

Plants are able to acclimate to new growth conditions on a relatively short time-scale. Recently, we showed that the progeny of plants exposed to various abiotic stresses exhibited changes in genome stability, methylation patterns and stress tolerance. Here, we performed a more detailed analysis of methylation patterns in the progeny of Arabidopsis thaliana (Arabidopsis) plants exposed to 25 and 75 mM sodium chloride. We found that the majority of gene promoters exhibiting changes in methylation were hypermethylated, and this group was overrepresented by regulators of the chromatin structure. The analysis of DNA methylation at gene bodies showed that hypermethylation in the progeny of stressed plants was primarily due to changes in the 5′ and 3′ ends as well as in exons rather than introns. All but one hypermethylated gene tested had lower gene expression. The analysis of histone modifications in the promoters and coding sequences showed that hypermethylation and lower gene expression correlated with the enrichment of H3K9me2 and depletion of H3K9ac histones. Thus, our work demonstrated a high degree of correlation between changes in DNA methylation, histone modifications and gene expression in the progeny of salt-stressed plants

The Gene Ontology knowledgebase in 2023

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project

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

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

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

The Gene Ontology knowledgebase in 2023

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project

Interacción de la oxitetraciclina con la seroalbumina ovina

The interaction of oxytetracycline with ovine serum albumin was studied. The apparent association constants, the number of binding sites and the thermodynamic parameters of the interaction were established using the equilibrium dialysis technique at 15, 20 and 25" C. At the three temperatures, one binding site was found for the ovine serum albumin.The apparent association constants ranged from 11845.54 to 13361.10 M-1 .The decrease in the constants, due to the decrease in temperature, suggests a loss of affinity between the oxytetracycline and the ovine serum albumin. The spontaneity of the interaction was established, based on the negative value of the standard free energy (AG). The decrease of spontaneity when the temperature drops was demonstrated by the variation of AG at the different temperatures. This fact arises from the loss of affinity between the oxytetracycline and the ovine serum albumin. Furihermore, the interaction was found to occur endothermically (standard enthalpy (AH >O), with stability (standard entropy (AS >O) and is regulated. fundamentally by electrostatic attraction.En el presente trabajo se ha estudiado la interacción de la oxitetraciclina con la seroalbúmina ovina, estableciéndose las constantes de asociación aparente, el número de sitios de unión y los parámetros termodinámicos de la interacción utilizando la técnica de la diálisis de equilibrio a 15, 20 y 25°C. A las tres temperaturas se encontró un sitio de unión para la seroalbúmina ovina, mientras que las constantes de asociación aparentes halladas oscilaron entre 11845.54 y 13361.10 M-1. La disminución del valor de las constantes con la temperatura sugiere una pérdida de afinidad entre la oxitetraciclina y la seroalbúmina ovina. Se estableció la espontaneidad de la reacción. en base al valor negativo de AG. La variación del valor de AG a las distintas temperaturas del ensayo nos indica que la espontaneidad disminuye con la temperatura, hecho que se deriva del descenso de afinidad de la oxitetraciclina por la proteína. La interacción se produce además de manera endotérmica (AH>O) y estable (AS>O), estando regulada fundamentalmente por fuerzas de atracción electrostática

Los trastornos temporomandibulares en pacientes esquizofrenicos: un estudio de casos-controles.

El objetivo del presente trabajo era valorar la prevalencia de trastornos témporomandibulares(TTM) en pacientes esquizofrénicos comparados con pacientes control. Diseño del estudio. El estudio se realizó en 50 pacientes esquizofrénicos ingresados en la Unidad de Psiquiatría del Hospital Universitario Virgen Macarena de Sevilla y se compararon con 50 pacientes adultos de los que acuden a recepción de la Facultad de Odontología de la Universidad de Sevilla, excluyendo de este último grupo aquellos pacientes que presentaban alguna patología sistémica en el momento de la exploración o en los seis meses previos a ésta. En ambos grupos se valoró la presencia de trastornos témporomandibulares según el protocolo de la OMS. Resultados y Discusión. Entre los pacientes esquizofrénicos, el 32% presentaban síntomas de trastornos témporomandibulares, sobre todo chasquidos o ruidos articulares (24%) y autocorreción de la dislocación (8%); mientras que en los pacientes control, la frecuencia era del 8%, que se correspondía con ruidos articulares. Estas diferencias eran significativas, lo que confirma que los TTM son más prevalentes entre los pacientes que sufren trastornos mentales. El estudio demuestra que el estado de la ATM era independiente de la edad de los pacientes. Los hombres presentaban mayor frecuencia de TTM en ambos grupos. No existía relación entre la presencia de TTM y el estado prostodóncico de los pacientes. Los hallazgos del presente trabajo demuestran una tendencia significativa entre un mayor número medio de dientes perdidos y la frecuencia de TTM en los pacientes sanos control. Conclusiones. Los pacientes esquizofrénicos constituyen una población de riesgo para los TTM porque presentan una mayor prevalencia y severidad de los mismos.The aim of this study was to assess the prevalence of temporomandibular disorders (tmd) in schizophrenic patients compared with control patients. Patients and methods. 50 schizophrenic patients attended in the Psychiatric Unit at the Virgen Macarena Universitary Hospital of Seville were compared with 50 control patients (without systemic diseases, and drugs) attended in the School of Dentistry of Seville. TMD were assessed according to the WHO criteria. Results and Discusion. 32% of schizophrenic patients showed symptoms of TMD, clicking (24%) and self-correcting blocking (8%); compared with 8% (sounds) of control patients. Significantly, these differences support that TMD are most prevalent in patients with mental disorders. Prevalence of TMD are not related with age of patients.TMD are more frequent among male patients in both groups. There are not relationship between TMD and prosthodontic status. Clinical findings of this study showed a significantly tendency between TMD with a highest number of missing teeth in control patients. Conclusions. Schizophrenic patients constitute a high risk population for TMD because showed a more prevalence and severity of TMD