Bibliometric Overview on T-Cell Intracellular Antigens and Their Pathological Implications.

T-cell intracellular antigen 1 (TIA1) and TIA1-like/related protein (TIAL1/TIAR) are two members of the classical family of RNA binding proteins. Through their selective interactions with distinct RNAs and proteins, these multifunctional regulators are involved in chromatin remodeling, RNA splicing and processing and translation regulation, linking them to a wide range of diseases including neuronal disorders, cancer and other pathologies. From their discovery to the present day, many studies have focused on the behavior of these proteins in order to understand their impact on molecular and cellular processes and to understand their relationship to human pathologies. The volume of research on these proteins in various fields, including molecular biology, biochemistry, cell biology, immunology and cancer, has steadily increased, indicating a growing interest in these gene expression regulators among researchers. This information can be used to know the most productive institutions working in the field, understand the focus of research, identify key areas of involvement, delve deeper into their relationship and impact on different diseases, and to establish the level of study associated with them.

Chromatin-transcription interface: The secret of eternal youth?

In their recent study in Nature, Debès et al. report an increase in RNA polymerase II (Pol II)-mediated transcriptional elongation speed associated with chromatin remodeling during aging in four metazoan animals, two human cell lines, and human blood. Their findings might help us understand why we age through evolutionarily conserved essential processes, and open a window to the molecular and physiological mechanisms influencing healthspan, lifespan and/or longevity.

T-Cell Intracellular Antigen 1-Like Protein in Physiology and Pathology.

T-cell intracellular antigen 1 (TIA1)-related/like (TIAR/TIAL1) protein is a multifunctional RNA-binding protein (RBP) involved in regulating many aspects of gene expression, independently or in combination with its paralog TIA1. TIAR was first described in 1992 by Paul Anderson's lab in relation to the development of a cell death phenotype in immune system cells, as it possesses nucleolytic activity against cytotoxic lymphocyte target cells. Similar to TIA1, it is characterized by a subcellular nucleo-cytoplasmic localization and ubiquitous expression in the cells of different tissues of higher organisms. In this paper, we review the relevant structural and functional information available about TIAR from a triple perspective (molecular, cellular and pathophysiological), paying special attention to its expression and regulation in cellular events and processes linked to human pathophysiology.

Quantification of Pneumothorax Volume on Chest X-Ray: A More Accurate Index Based On Measurements Made With 3D-printed Models.

PURPOSE: Owing to the extent of lung collapse estimated on chest radiograph it is still the complementary test most commonly used in the management of patients with pneumothorax. There are several indices to assess the extent of lung collapse. The objective of this study was to develop a more accurate index, using the 3D printing technology. MATERIALS AND METHODS: We created physical hemithorax models using 3D printing. In this way, we obtained simple radiographs of models for which the lung volume was known accurately. In the first part of the study, we estimated the intraobserver and interobserver agreement as well as the agreement between methods. We created 2 new indices and the results obtained with these; the Light index and the Collins method were compared with data on real lung volume loss using linear regression analysis and by calculating the coefficient of determination (r2). In the second part of the study, we validated the 4 equations, comparing the Light index, the Collins method, and the 2 new indices using regression analysis. For this analysis, we used STATA V14. RESULTS: Both intraobserver and interobserver agreements were very high (<0.9). The agreement between the Collins method and the Light index was poor, with a mean difference of 18.6%. The equation that best represented real lung collapse was the new equation 2. CONCLUSIONS: This study demonstrates the poor agreement between the Light index and Collins method for measuring the extent of lung collapse in pneumothorax and proposes a more accurate equation for this measurement based on a simple chest radiograph.

Dynamics of T-Cell Intracellular Antigen 1-Dependent Stress Granules in Proteostasis and Welander Distal Myopathy under Oxidative Stress.

T-cell intracellular antigen 1 (TIA1) is an RNA-binding protein that is primarily involved in the post-transcriptional regulation of cellular RNAs. Furthermore, it is a key component of stress granules (SGs), RNA, and protein aggregates that are formed in response to stressful stimuli to reduce cellular activity as a survival mechanism. TIA1 p.E384K mutation is the genetic cause of Welander distal myopathy (WDM), a late-onset muscular dystrophy whose pathogenesis has been related to modifying SG dynamics. In this study, we present the results obtained by analyzing two specific aspects: (i) SGs properties and dynamics depending on the amino acid at position 384 of TIA1; and (ii) the formation/disassembly time-course of TIA1WT/WDM-dependent SGs under oxidative stress. The generation of TIA1 variants-in which the amino acid mutated in WDM and the adjacent ones were replaced by lysines, glutamic acids, or alanines-allowed us to verify that the inclusion of a single lysine is necessary and sufficient to alter SGs dynamics. Moreover, time-lapse microscopy analysis allowed us to establish in vivo the dynamics of TIA1WT/WDM-dependent SG formation and disassembly, after the elimination of the oxidizing agent, for 1 and 3 h, respectively. Our observations show distinct dynamics between the formation and disassembly of TIA1WT/WDM-dependent SGs. Taken together, this study has allowed us to expand the existing knowledge on the role of TIA1 and the WDM mutation in SG formation.

The Multifunctional Faces of T-Cell Intracellular Antigen 1 in Health and Disease.

T-cell intracellular antigen 1 (TIA1) is an RNA-binding protein that is expressed in many tissues and in the vast majority of species, although it was first discovered as a component of human cytotoxic T lymphocytes. TIA1 has a dual localization in the nucleus and cytoplasm, where it plays an important role as a regulator of gene-expression flux. As a multifunctional master modulator, TIA1 controls biological processes relevant to the physiological functioning of the organism and the development and/or progression of several human pathologies. This review summarizes our current knowledge of the molecular aspects and cellular processes involving TIA1, with relevance for human pathophysiology.

Deficiency of T-Cell Intracellular Antigen 1 in Murine Embryonic Fibroblasts Is Associated with Changes in Mitochondrial Morphology and Respiration.

T-cell intracellular antigen 1 (TIA1) is a multifunctional RNA-binding protein involved in regulating gene expression and splicing during development and in response to environmental stress, to maintain cell homeostasis and promote survival. Herein, we used TIA1-deficient murine embryonic fibroblasts (MEFs) to study their role in mitochondria homeostasis. We found that the loss of TIA1 was associated with changes in mitochondrial morphology, promoting the appearance of elongated mitochondria with heterogeneous cristae density and size. The proteomic patterns of TIA1-deficient MEFs were consistent with expression changes in molecular components related to mitochondrial dynamics/organization and respiration. Bioenergetics analysis illustrated that TIA1 deficiency enhances mitochondrial respiration. Overall, our findings shed light on the role of TIA1 in mitochondrial dynamics and highlight a point of crosstalk between potential pro-survival and pro-senescence pathways.

A novel bipartite antitermination system widespread in conjugative elements of Gram-positive bacteria.

Transcriptional regulation allows adaptive and coordinated gene expression, and is essential for life. Processive antitermination systems alter the transcription elongation complex to allow the RNA polymerase to read through multiple terminators in an operon. Here, we describe the discovery of a novel bipartite antitermination system that is widespread among conjugative elements from Gram-positive bacteria, which we named conAn. This system is composed of a large RNA element that exerts antitermination, and a protein that functions as a processivity factor. Besides allowing coordinated expression of very long operons, we show that these systems allow differential expression of genes within an operon, and probably contribute to strict regulation of the conjugation genes by minimizing the effects of spurious transcription. Mechanistic features of the conAn system are likely to decisively influence its host range, with important implications for the spread of antibiotic resistance and virulence genes.

Aspiración manual versus aspiración digital en el tratamiento inicial del neumotórax espontáneo primario: estudio AMVADI. Ensayo clínico aleatorizado / Manual versus digital aspiration for first-line treatment of primary spontaneous pneumothorax. The AMVADI study: a randomized clinical trial

INTRODUCCIÓN: La efectividad de la punción aspiración en el tratamiento inicial del neumotórax espontáneo primario ha sido ampliamente estudiada. El objetivo de este trabajo es comparar la aspiración digital frente a la manual en un ensayo clínico aleatorizado. MÉTODOS: Se ha diseñado un ensayo clínico aleatorizado paralelo con ratio 1:1 y evaluación ciega. El ensayo clínico se adapta al estándar del grupo CONSORT. El resultado primario se define como éxito inmediato e ingreso hospitalario, y los secundarios, como recidiva, reingreso, necesidad de cirugía y días de ingreso. Se realiza encuesta de satisfacción entre los profesionales que realizan los dos tipos de punción. RESULTADOS: Sesenta y siete pacientes han sido incluidos en el estudio (n = 36 grupo control, n = 31 grupo intervención) con un seguimiento del 100%. Ambos grupos presentan un éxito inmediato del 58%, evitándose el ingreso hospitalario. No se observan diferencias en cuanto a recidiva, reingreso, necesidad de cirugía o días de ingreso. El 80% del personal que realiza la técnica de punción prefiere la aspiración digital, siendo el 100% entre el personal que realiza más de 5 punciones al año. CONCLUSIONES: Tanto la punción aspiración manual como la digital ofrecen buenos resultados inmediatos que evitan ingresos hospitalarios; la aspiración digital es el método preferido por quienes realizan dicha técnica

INTRODUCTION: The effectiveness of needle aspiration in the initial treatment of primary spontaneous pneumothorax has been widely studied. The objective of this research was to compare digital with manual aspiration in a randomized clinical trial. METHODS: We designed a blinded parallel-group randomized clinical trial with a 1:1 allocation ratio. The clinical trial is reported in line with the guidelines of the CONSORT group. The primary outcome variables were immediate success and hospital admission, while the secondary outcome measures were relapse, re-admission and need for surgery, and length of hospital stay. A satisfaction survey was also carried out among clinicians who perform these 2 types of aspiration. RESULTS: A total of 67 patients were included in the study (n = 36, control group; n = 31, experimental group) with no losses to follow-up. In both groups, 58% of procedures were immediately successful, avoiding hospital admission. No differences were found in rates of relapse, re-admission, need for surgery, or length of hospital stay. Overall, 80% of clinicians who performed aspiration preferred the digital system, and this preference rose to 100% among clinicians who performed more than 5 procedures a year. CONCLUSIONS: Both manual and digital aspiration provide good immediate results avoiding hospital admission, while digital drainage is preferred by clinicians responsible for first-line treatment of pneumothorax

Ultrathin Washcoat and Very Low Loading Monolithic Catalyst with Outstanding Activity and Stability in Dry Reforming of Methane.

A Ni/CeO2/ZrO2 catalyst with improved redox properties has been washcoated onto a honeycomb cordierite monolith in the form of a nonconventional alumina-catalyst layer, just a few nanometers thick. In spite of the very low active phase loading, the monolith depicts outstanding performance in dry reforming of methane, both in terms of activity, with values reaching the thermodynamic limit already at 750 °C, even under extreme Weight Hourly Space Velocities (WHSV 115-346 L·g-1·h-1), as well as in terms of stability during prolonged Time on Stream (TOS 24-48 h).

Manual Versus Digital Aspiration for First-Line Treatment of Primary Spontaneous Pneumothorax. The AMVADI Study: A Randomized Clinical Trial. / Aspiración manual versus aspiración digital en el tratamiento inicial del neumotórax espontáneo primario: estudio AMVADI. Ensayo clínico aleatorizado.

INTRODUCTION: The effectiveness of needle aspiration in the initial treatment of primary spontaneous pneumothorax has been widely studied. The objective of this research was to compare digital with manual aspiration in a randomized clinical trial. METHODS: We designed a blinded parallel-group randomized clinical trial with a 1:1 allocation ratio. The clinical trial is reported in line with the guidelines of the CONSORT group. The primary outcome variables were immediate success and hospital admission, while the secondary outcome measures were relapse, re-admission and need for surgery, and length of hospital stay. A satisfaction survey was also carried out among clinicians who perform these 2 types of aspiration. RESULTS: A total of 67 patients were included in the study (n=36, control group; n=31, experimental group) with no losses to follow-up. In both groups, 58% of procedures were immediately successful, avoiding hospital admission. No differences were found in rates of relapse, re-admission, need for surgery, or length of hospital stay. Overall, 80% of clinicians who performed aspiration preferred the digital system, and this preference rose to 100% among clinicians who performed more than 5procedures a year. CONCLUSIONS: Both manual and digital aspiration provide good immediate results avoiding hospital admission, while digital drainage is preferred by clinicians responsible for first-line treatment of pneumothorax.

A Heterologous Cell Model for Studying the Role of T-Cell Intracellular Antigen 1 in Welander Distal Myopathy.

Welander distal myopathy (WDM) is a muscle dystrophy characterized by adult-onset distal muscle weakness, prevalently impacting the distal long extensors of the hands and feet. WDM is an autosomal dominant disorder caused by a missense mutation (c.1362G>A; p.E384K) in the TIA1 (T-cell intracellular antigen 1) gene, which encodes an RNA-binding protein basically required for the posttranscriptional regulation of RNAs. We have developed a heterologous cell model of WDM to study the molecular and cellular events associated with mutated TIA1 expression. Specifically, we analyzed how this mutation affects three regulatory functions mediated by TIA1: (i) control of alternative SMN2 (survival motor neuron 2) splicing; (ii) formation, assembly, and disassembly of stress granules; and (iii) mitochondrial dynamics and its consequences for mitophagy, autophagy, and apoptosis. Our results show that whereas WDM-associated TIA1 expression had only a mild effect on SMN2 splicing, it led to suboptimal adaptation to environmental stress, with exacerbated stress granule formation that was accompanied by mitochondrial dysfunction and autophagy. Overall, our observations indicate that some aspects of the cell phenotype seen in muscle of patients with WDM can be recapitulated by ectopic expression of WDM-TIA1 in embryonic kidney cells, highlighting the potential of this model to investigate the pathogenesis of this degenerative disease and possible therapeutics.