RESUMEN
Core promoters are sites where transcriptional regulatory inputs of a gene are integrated to direct the assembly of the preinitiation complex (PIC) and RNA polymerase II (Pol II) transcription output. Until now, core promoter functions have been investigated by distinct methods, including Pol II transcription initiation site mappings and structural characterization of PICs on distinct promoters. Here, we bring together these previously unconnected observations and hypothesize how, on metazoan TATA promoters, the precisely structured building up of transcription factor (TF) IID-based PICs results in sharp transcription start site (TSS) selection; or, in contrast, how the less strictly controlled positioning of the TATA-less promoter DNA relative to TFIID-core PIC components results in alternative broad TSS selections by Pol II.
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Factor de Transcripción TFIID , Transcripción Genética , Animales , Factor de Transcripción TFIID/genética , Factor de Transcripción TFIID/metabolismo , TATA Box , Regiones Promotoras Genéticas , ARN Polimerasa II/metabolismoRESUMEN
NF-Y is a Transcription Factor that regulates transcription through binding to the CCAAT-box. To understand its strategy, we analyzed 16 ChIP-seq datasets from human and mouse cells. Shared loci, mostly located in promoters of expressed genes of cell cycle, metabolism and gene expression pathways, are associated with histone marks of active chromatin and specific modules of TFs. Other peaks are in enhancers and Transposable Elements -TE- of retroviral origin in human and mouse. We evaluated the relationship with USF1, a common synergistic partner in promoters and MLT1 TEs, upon NF-YB inactivation: USF1 binding decreases in promoters, modestly in MLT1, suggesting a pioneering role of NF-Y in formers, not in the latters. These data define a common set of NF-Y functional targets across different mammalian cell types, suggesting a pioneering role in promoters with respect to TEs.
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Brain microstructure plays a key role in driving the transport of drug molecules directly administered to the brain tissue, as in Convection-Enhanced Delivery procedures. The proposed research analyzes the hydraulic permeability of two white matter (WM) areas (corpus callosum and fornix) whose three-dimensional microstructure was reconstructed starting from the acquisition of electron microscopy images. We cut the two volumes with 20 equally spaced planes distributed along two perpendicular directions, and, on each plane, we computed the corresponding permeability vector. Then, we considered that the WM structure is mainly composed of elongated and parallel axons, and, using a principal component analysis, we defined two principal directions, parallel and perpendicular, with respect to the axons' main direction. The latter were used to define a reference frame onto which the permeability vectors were projected to finally obtain the permeability along the parallel and perpendicular directions. The results show a statistically significant difference between parallel and perpendicular permeability, with a ratio of about two in both the WM structures analyzed, thus demonstrating their anisotropic behavior. Moreover, we find a significant difference between permeability in corpus callosum and fornix, which suggests that the WM heterogeneity should also be considered when modeling drug transport in the brain. Our findings, which demonstrate and quantify the anisotropic and heterogeneous character of the WM, represent a fundamental contribution not only for drug-delivery modeling, but also for shedding light on the interstitial transport mechanisms in the extracellular space.
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Sustancia Blanca/metabolismo , Humanos , Microscopía Electrónica , Permeabilidad , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/ultraestructuraRESUMEN
The standard 12-lead electrocardiogram (ECG) represents a cornerstone for the diagnosis and evaluation of hypertrophic cardiomyopathy (HCM), the most common genetically determined heart muscle disease, due to its cost-effectiveness and wide availability. The ECG may surprisingly look normal in 4-6% of adult patients, and in less than 3% of paediatric patients, but it is abnormal in the vast majority of the remaining patients. 'Specific' features comprise pathological Q-waves, deep S-waves in V1-V3, or high R-waves in V4-V6 due to left ventricular hypertrophy with T-wave (TW) depression or negative TWs. Negative giant TWs are often found in apical HCM. However, in many patients, the ECG may only show non-specific ST-T changes with diphasic or flat TWs. An isolated inverted TW in lateral leads (usually aVL) may be the only marker for HCM in some patients. Electrocardiogram helps to diagnose sarcomeric HCM and distinguish it from different phenocopies, such as cardiac amyloidosis, glycogen storage, or Fabry disease. Electrocardiogram may also have a prognostic role, identifying high-risk features that could impact the clinical outcome.
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NF-Y is a trimeric pioneer Transcription Factor (TF) whose target sequence -the CCAAT box- is present in ~25% of mammalian promoters. We reconstruct the phylogenetic history of the regulatory NF-YA subunit in vertebrates. We find that in addition to the remarkable conservation of the subunits-interaction and DNA-binding parts, the Transcriptional Activation Domain (TAD) is also conserved (>90% identity among bony vertebrates). We infer the phylogeny of the alternatively spliced exon-3 and partial splicing events of exon-7 -7N and 7C- revealing independent clade-specific losses of these regions. These isoforms shape the TAD. Absence of exon-3 in basal deuterostomes, cartilaginous fishes and hagfish, but not in lampreys, suggests that the "short" isoform is primordial, with emergence of exon-3 in chordates. Exon 7N was present in the vertebrate common ancestor, while 7C is a molecular innovation of teleost fishes. RNA-seq analysis in several species confirms expression of all these isoforms. We identify 3 blocks of amino acids in the TAD shared across deuterostomes, yet structural predictions and sequence analyses suggest an evolutionary drive for maintenance of an Intrinsically Disordered Region -IDR- within the TAD. Overall, these data help reconstruct the logic for alternative splicing of this essential eukaryotic TF.
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Factores de Transcripción , Vertebrados , Empalme Alternativo , Animales , Evolución Molecular , Peces/metabolismo , Mamíferos , Filogenia , Regiones Promotoras Genéticas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Factores de Transcripción/genética , Vertebrados/genéticaRESUMEN
The human general transcription factor TFIID is composed of the TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs). In eukaryotic cells, TFIID is thought to nucleate RNA polymerase II (Pol II) preinitiation complex formation on all protein coding gene promoters and thus, be crucial for Pol II transcription. TFIID is composed of three lobes, named A, B, and C. A 5TAF core complex can be assembled in vitro constituting a building block for the further assembly of either lobe A or B in TFIID. Structural studies showed that TAF8 forms a histone fold pair with TAF10 in lobe B and participates in connecting lobe B to lobe C. To better understand the role of TAF8 in TFIID, we have investigated the requirement of the different regions of TAF8 for the in vitro assembly of lobe B and C and the importance of certain TAF8 regions for mouse embryonic stem cell (ESC) viability. We have identified a region of TAF8 distinct from the histone fold domain important for assembling with the 5TAF core complex in lobe B. We also delineated four more regions of TAF8 each individually required for interacting with TAF2 in lobe C. Moreover, CRISPR/Cas9-mediated gene editing indicated that the 5TAF core-interacting TAF8 domain and the proline-rich domain of TAF8 that interacts with TAF2 are both required for mouse embryonic stem cell survival. Thus, our study defines distinct TAF8 regions involved in connecting TFIID lobe B to lobe C that appear crucial for TFIID function and consequent ESC survival.
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Células Madre Embrionarias de Ratones/metabolismo , Pliegue de Proteína , Factores Asociados con la Proteína de Unión a TATA/metabolismo , Factor de Transcripción TFIID/metabolismo , Factores de Transcripción/metabolismo , Animales , Línea Celular , Supervivencia Celular , Humanos , Ratones , Dominios Proteicos , Factores Asociados con la Proteína de Unión a TATA/química , Factores Asociados con la Proteína de Unión a TATA/genética , Factor de Transcripción TFIID/química , Factor de Transcripción TFIID/genética , Factores de Transcripción/química , Factores de Transcripción/genéticaRESUMEN
NF-Y transcription factor comprises three subunits: NF-YA, NF-YB and NF-YC. NF-YB and NF-YC dimerize through their histone fold domain (HFD), which can bind DNA in a non-sequence-specific fashion while serving as a scaffold for NF-YA trimerization. Upon trimerization, NF-YA specifically recognizes the CCAAT box sequence on promoters and enhancers. In plants, each NF-Y subunit is encoded by several genes giving rise to hundreds of potential heterotrimeric combinations. In addition, plant NF-YBs and NF-YCs interact with other protein partners to recognize a plethora of genomic motifs, as the CCT protein family that binds CORE sites. The NF-Y subunit organization and its DNA-binding properties, together with the NF-Y HFD capacity to adapt different protein modules, represent plant-specific features that play a key role in development, growth and reproduction. Despite their relevance, these features are still poorly understood at the molecular level. Here, we present the structures of Arabidopsis and rice NF-YB/NF-YC dimers, and of an Arabidopsis NF-Y trimer in complex with the FT CCAAT box, together with biochemical data on NF-Y mutants. The dimeric structures identify the key residues for NF-Y HFD stabilization. The NF-Y/DNA structure and the mutation experiments shed light on HFD trimerization interface properties and the NF-YA sequence appetite for the bases flanking the CCAAT motif. These data explain the logic of plant NF-Y gene expansion: the trimerization adaptability and the flexible DNA-binding rules serve the scopes of accommodating the large number of NF-YAs, CCTs and possibly other NF-Y HFD binding partners and a diverse audience of genomic motifs.
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Proteínas de Arabidopsis/metabolismo , Factor de Unión a CCAAT/metabolismo , ADN de Plantas/metabolismo , Secuencia de Aminoácidos , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Sitios de Unión , Factor de Unión a CCAAT/química , Factor de Unión a CCAAT/genética , ADN de Plantas/química , Dimerización , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estructura Terciaria de ProteínaRESUMEN
BACKGROUND: Sheep (Ovis aries) have been largely used as animal models in a multitude of specialties in biomedical research. The similarity to human brain anatomy in terms of brain size, skull features, and gyrification index, gives to ovine as a large animal model a better translational value than small animal models in neuroscience. Despite this evidence and the availability of advanced imaging techniques, morphometric brain studies are lacking. We herein present the morphometric ovine brain indexes and anatomical measures developed by two observers in a double-blinded study and validated via an intra- and inter-observer analysis. RESULTS: For this retrospective study, T1-weighted Magnetic Resonance Imaging (MRI) scans were performed at 1.5 T on 15 sheep, under general anaesthesia. The animals were female Ovis aries, in the age of 18-24 months. Two observers assessed the scans, twice time each. The statistical analysis of intra-observer and inter-observer agreement was obtained via the Bland-Altman plot and Spearman rank correlation test. The results are as follows (mean ± Standard deviation): Indexes: Bifrontal 0,338 ± 0,032 cm; Bicaudate 0,080 ± 0,012 cm; Evans' 0,218 ± 0,035 cm; Ventricular 0,241 ± 0,039 cm; Huckman 1693 ± 0,174 cm; Cella Media 0,096 ± 0,037 cm; Third ventricle ratio 0,040 ± 0,007 cm. Anatomical measures: Fourth ventricle length 0,295 ± 0,073 cm; Fourth ventricle width 0,344 ± 0,074 cm; Left lateral ventricle 4175 ± 0,275 cm; Right lateral ventricle 4182 ± 0,269 cm; Frontal horn length 1795 ± 0,303 cm; Interventricular foramen left 1794 ± 0,301 cm; Interventricular foramen right 1,78 ± 0,317 cm. CONCLUSIONS: The present study provides baseline values of linear indexes of the ventricles in the ovine models. The acquisition of these data contributes to filling the knowledge void on important anatomical and morphological features of the sheep brain.
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Ventrículos Cardíacos , Imagen por Resonancia Magnética , Animales , Pesos y Medidas Corporales/veterinaria , Femenino , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/veterinaria , Estudios Retrospectivos , OvinosRESUMEN
AIMS: Brugada syndrome (BrS) is associated with an increased risk of sudden cardiac death due to ventricular tachycardia/fibrillation (VT/VF) in young, otherwise healthy individuals. Despite SCN5A being the most commonly known mutated gene to date, the genotype-phenotype relationship is poorly understood and remains uncertain. This study aimed to elucidate the genotype-phenotype correlation in BrS. METHODS AND RESULTS: Brugada syndrome probands deemed at high risk of future arrhythmic events underwent genetic testing and phenotype characterization by the means of epicardial arrhythmogenic substrate (AS) mapping, and were divided into two groups according to the presence or absence of SCN5A mutation. Two-hundred probands (160 males, 80%; mean age 42.6 ± 12.2 years) were included in this study. Patients harbouring SCN5A mutations exhibited a spontaneous type 1 pattern and experienced aborted cardiac arrest or spontaneous VT/VF more frequently than the other subjects. SCN5A-positive patients exhibited a larger epicardial AS area, more prolonged electrograms and more frequently observed non-invasive late potentials. The presence of an SCN5A mutation explained >26% of the variation in the epicardial AS area and was the strongest predictor of a large epicardial area. CONCLUSION: In BrS, the genetic background is the main determinant for the extent of the electrophysiological abnormalities. SCN5A mutation carriers exhibit more pronounced epicardial electrical abnormalities and a more aggressive clinical presentation. These results contribute to the understanding of the genetic determinants of the BrS phenotypic expression and provide possible explanations for the varying degrees of disease expression.
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Síndrome de Brugada , Taquicardia Ventricular , Adulto , Síndrome de Brugada/genética , Electrocardiografía , Mapeo Epicárdico , Humanos , Masculino , Persona de Mediana Edad , Canal de Sodio Activado por Voltaje NAV1.5/genética , Fenotipo , Taquicardia Ventricular/genética , Fibrilación VentricularRESUMEN
NF-Y is a trimeric Transcription Factor -TF- which binds with high selectivity to the conserved CCAAT element. Individual ChIP-seq analysis as well as ENCODE have progressively identified locations shared by other TFs. Here, we have analyzed data introduced by ENCODE over the last five years in K562, HeLa-S3 and GM12878, including several chromatin features, as well RNA-seq profiling of HeLa cells after NF-Y inactivation. We double the number of sequence-specific TFs and co-factors reported. We catalogue them in 4 classes based on co-association criteria, infer target genes categorizations, identify positional bias of binding sites and gene expression changes. Larger and novel co-associations emerge, specifically concerning subunits of repressive complexes as well as RNA-binding proteins. On the one hand, these data better define NF-Y association with single members of major classes of TFs, on the other, they suggest that it might have a wider role in the control of mRNA production.
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Factor de Unión a CCAAT/metabolismo , Cromatina/metabolismo , Inmunoprecipitación de Cromatina , Conjuntos de Datos como Asunto , Células HeLa , Humanos , Análisis de Secuencia de ARNRESUMEN
Dilated cardiomyopathy (DCM) is the leading indication for heart transplantation. TTN gene truncating mutations account for about 25% of familial DCM cases and for 18% of sporadic DCM cases. The clinical relevance of specific variants in TTN has been difficult to determine because of the sheer size of the protein for which TTN encodes, as well as existing extensive genetic variation. Clinicians should communicate novel clinically-relevant variants and genotype-phenotype associations, so that animal studies evaluating the molecular mechanisms are always conducted with a focus on clinical significance. In the present study, we report for the first time the novel truncating heterozygous variant NM_001256850.1:c.72777_72783del (p.Phe24259Leufs*51) in the TTN gene and its association with DCM in a family with sudden death. This variant occurs in the A-band region of the sarcomere, in a known mutational hotspot of the gene. Truncating titin variants that occur in this region are the most common cause of DCM and have been rarely reported in asymptomatic individuals, differently from other pathogenic TTN gene variants. Further studies are warranted to better understand this particular clinically-relevant variant.
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Cardiomiopatía Dilatada/complicaciones , Cardiomiopatía Dilatada/genética , Conectina/genética , Muerte Súbita Cardíaca/etiología , Mutación del Sistema de Lectura , Biomarcadores , Cardiomiopatía Dilatada/diagnóstico , Análisis Mutacional de ADN , Diagnóstico por Imagen , Electrocardiografía , Femenino , Estudios de Asociación Genética/métodos , Predisposición Genética a la Enfermedad , Pruebas de Función Cardíaca , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Nuclear factor Y (NF-Y) is a transcription factor trimer binding to the functionally important CCAAT box, present in promoters of growth-promoting and cell cycle-regulated genes. The regulatory nuclear factor YA (NF-YA) subunit confers sequence-specificity to the histone-like nuclear factor YB/YC dimer. NF-YA harbors 2 serines-Ser320 and Ser326-shown to be phosphorylated by cyclin-dependent kinase 2. High-throughput proteomics data indicate that they are phosphorylated in vivo. Specifically, Ser320 makes structural contacts with the DNA phosphate backbone; Ser320-P is the major NF-YA phosphorylation isoform following overexpression in HeLa cells, increasing upon mitotic arrest. EMSA with recombinant Ala and Glu mutants confirm a role of Ser320, but not Ser326, in stabilization of DNA binding. Transactivation assays of the CCAAT-dependent MDR1 and RHOB promoters show loss in transcription function for Ser320Glu and Ser320Ala NF-YA mutants. Phylogenetic analysis of NF-YA proteins indicates that Ser320 is indeed evolutionarily conserved. We conclude that phosphorylation of this residue belongs to the core mechanisms of DNA-binding control, possibly driven by the necessity to unfasten binding of or to evict NF-Y from CCAAT sites under specific conditions of growth regulation.-Bernardini, A., Lorenzo, M., Nardini, M., Mantovani, R., Gnesutta, N. The phosphorylatable Ser320 of NF-YA is involved in DNA binding of the NF-Y trimer.
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Factor de Unión a CCAAT/metabolismo , Serina/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Western Blotting , Factor de Unión a CCAAT/genética , Electroforesis en Gel de Poliacrilamida , Células HeLa , Humanos , Fosforilación , Unión Proteica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteína de Unión al GTP rhoB/metabolismoRESUMEN
OBJECTIVE: The aim of the study was to assess the prognostic impact of successful chronic total occlusion (CTO) percutaneous coronary intervention (PCI) and completeness of revascularization in the elderly. BACKGROUND: Successful CTO-PCI is associated with clinical benefit. Notwithstanding elderly patients are currently underrepresented in CTO-PCI randomized controlled trials and registries. METHODS: From the Florence CTO-PCI registry 1,405 patients underwent CTO-PCI between 2004 and 2015; out of these, 460 consecutive patients were ≥75 years. End point of the study was long-term cardiac survival. The prognostic impact of successful CTO-PCI and complete revascularization on survival was assessed by Kaplan-Meier estimation and by Cox multivariable regression analysis. RESULTS: Patients were stratified according to success (72%) or failure of CTO-PCI. Completeness of revascularization was achieved in 57% of patients. Five-year cardiac survival was significantly higher in the successful CTO-PCI group (84 ± 3% vs. 72 ± 6%; p = .006) and it was further improved if complete coronary revascularization was achieved (90 ± 3% vs. 68 ± 5%; p < .001). At multivariable analysis, increasing age (hazard ratio [HR] 1.08; p = .001), diabetes (HR 1.55; p = .033), chronic kidney disease (HR 1.96, p = .002), left ventricular ejection fraction <0.40 (HR 2.10; p < .001), and completeness of revascularization (HR 0.58; p < .005) resulted independently associated with long-term cardiac survival. CONCLUSIONS: In the elderly successful CTO-PCI is associated with a long-term survival benefit. The results of this study suggest that, even in the elderly, a CTO-PCI attempt should be considered to achieve complete coronary revascularization.
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Oclusión Coronaria/terapia , Intervención Coronaria Percutánea , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/mortalidad , Oclusión Coronaria/fisiopatología , Femenino , Humanos , Italia , Masculino , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
We investigated early effects of Whole-Body Electromyostimulation added to hypocaloric diet on metabolic syndrome features in sedentary middle-aged individuals. We randomly assigned 25 patients to Whole-Body Electromyostimulation plus caloric restriction or caloric restriction alone for 26 weeks. Anthropometrics, blood pressure, fasting glucose and insulin, HOMA-IR, glycated hemoglobin, lipids, uric acid, creatinphosphokynase, C-reactive protein were assessed. Body composition was evaluated with direct-segmental, multi-frequency Bioelectrical Impedance Analysis. Both groups lost approximately 10% of weight, with similar effects on waist circumference and fat mass. Change in free-fat mass was significantly different between groups (caloric restriction -1.5±0.2 vs. Whole-Body Electromyostimulation plus caloric restriction +1.1±0.4 kg, p=0.03). Whole-Body Electromyostimulation plus caloric restriction group experienced greater percent reductions in insulin (-45.5±4.4 vs. -28.2±3.6%, p=0.002), HOMA-IR (-51.3±3.2 vs. -25.1±1.8%, p=0.001), triglycerides (-22.5±2.9 vs. -4.1±1.6%, p=0.004) and triglycerides/HDL (p=0.028). Subjects trained with Whole-Body Electromyostimulation had also significant improvement in systolic pressure (138±4 vs. 126±7 mmHg, p=0.038). No discontinuations for adverse events occurred. In middle-aged sedentary subjects with the metabolic syndrome, Whole-Body Electromyostimulation with caloric restriction for 26 weeks can improve insulin-resistance and lipid profile compared to diet alone. Further studies are needed to ascertain long-term efficacy and feasibility of this approach in individuals with the metabolic syndrome.
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Restricción Calórica , Terapia por Estimulación Eléctrica/métodos , Síndrome Metabólico/terapia , Antropometría , Biomarcadores/sangre , Glucemia/metabolismo , Colesterol/sangre , HDL-Colesterol/sangre , Creatina Quinasa/sangre , Dieta Reductora , Terapia por Estimulación Eléctrica/efectos adversos , Femenino , Humanos , Insulina/sangre , Resistencia a la Insulina , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/dietoterapia , Persona de Mediana Edad , Músculo Esquelético/enzimología , Músculo Esquelético/lesiones , Prueba de Estudio Conceptual , Triglicéridos/sangre , Pérdida de PesoRESUMEN
Paraneoplastic cerebellar degeneration (PCD) is usually thought to have a subacute progression over several weeks. We report herein incidence and clinical features of hyperacute onset PCD, a vertebrobasilar stroke mimic. We performed a retrospective analysis of all suspected PCD cases referred to the Udine University Hospital between 2009 and 2017. Our center provides the only neuroimmunology laboratory for three provinces of the Friuli-Venezia Giulia region, Italy (983,190 people as of January 1, 2017). Inclusion criteria were (1) abrupt onset of neurological symptoms; (2) initial consideration of a vascular etiology; (3) final diagnosis of "definite PCD." We also carried out a systematic review of the literature in order to identify previous stroke-like PCD cases. Between 2009 and 2017, 24 patients received a final diagnosis of PCD. The age-standardized incidence rate of PCD was 0.22/100,000 person-years. Two cases (8.3%) had a stroke-like onset, with an incidence of 0.02/100,000 person-years. Additionally, 10 previously reported stroke-like PCD cases were identified. Among all cases (n = 12), 67% were female; median age was 51 years (range, 22-69). An associated cancer was discovered in all cases. Brain imaging was normal in most (75%) of the patients. Cerebrospinal fluid (CSF) analysis showed inflammatory alterations in 73% of the cases. Cancer treatment was more effective than immunotherapy in improving the neurological syndrome. Typical patients with hyperacute PCD are middle-aged women with normal brain imaging, inflammatory markers in CSF, and cancer. Surgery of the underlying cancer is probably the best treatment. PCD must be considered in the differential diagnosis of acute-onset ataxia and/or vertigo.
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Degeneración Cerebelosa Paraneoplásica/diagnóstico por imagen , Degeneración Cerebelosa Paraneoplásica/epidemiología , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Diagnóstico Diferencial , Humanos , Italia/epidemiologíaRESUMEN
The main purpose of this study was to compare the effects on strength and muscle power of a training program based on two different modalities of whole-body electrostimulation (WB-EMS) with respect to a resistance-training program aimed at improving dynamic strength. Twenty-two subjects participated in this study: Thirteen male (age 25.2±2.8 years; height 1.78±0.1 m; body mass 72.8±6.4 kg; body fat 11.6±2.3%) and nine female (age 28.2±3.5 years; height 1.63±0.05 m; body mass 56.8±7.6 kg; body fat 19.1±4.7%). Participants were randomly assigned to three groups that underwent three different 6-week training programs: two modalities of WB-EMS, based on different electrical parameters (experimental), and circuit training with overloads (control). Force-velocity curves were calculated for each participant before and after treatment. All groups improved their level of strength and muscle power (paired sample t-Test, p<0.01; d>1) with a similar magnitude. No significant differences were observed between groups (two-way 2×3 Anova, p>0.05) at the end of the experimentation. This study suggests that WB-EMS might be considered as a valid and faster alternative - or an important complementary procedure - to a traditional overload-based resistance-training program for the development of the DS.
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Ejercicio en Circuitos/métodos , Estimulación Eléctrica/métodos , Fuerza Muscular/fisiología , Músculo Esquelético/fisiología , Entrenamiento de Fuerza/instrumentación , Adulto , Prueba de Esfuerzo/métodos , Femenino , Humanos , Extremidad Inferior/fisiología , Masculino , Extremidad Superior/fisiología , Levantamiento de Peso , Adulto JovenRESUMEN
Castagna, C, Krustrup, P, D'Ottavio, S, Pollastro, C, Bernardini, A, and Araújo Póvoas, SC. Ecological validity and reliability of an age-adapted endurance field test in young male soccer players. J Strength Cond Res 33(12): 3400-3405, 2019-The purpose of this study was to examine the reliability and the association with relevant match activities (ecological validity) of an age-adapted field test for intermittent high-intensity endurance known as Yo-Yo intermittent recovery level 1 children's test (YYIR1C) in young male soccer players. Twenty-eight young male outfield soccer players (age 11.1 ± 0.9 years, height 142 ± 4.4 cm, body mass 37.0 ± 5.9 kg) with at least 2 years of experience in soccer competitions were tested twice using YYIR1C and an age-adapted competitive small-sided game (i.e., 9v9), 7 days apart in a random order. The YYIR1C performance showed an excellent relative (intraclass correlation coefficient = 0.94) and a good absolute reliability (typical error of measurement as percentage of the coefficient of variation = 5.1%). Very large and significant associations were found between YYIR1C performance and match high-intensity activity (r = 0.53). Large correlations were found between YYIR1C and match sprinting (r = 0.42) and high-intensity metabolic power (r = 0.46) distances. Match total distance was largely associated with YYIR1C (r = 0.30). The results of this study showed that YYIR1C may be considered a valid and reliable field test for assessing intermittent high-intensity endurance in young male soccer players. Because of the relevance of aerobic fitness in youth soccer, future studies testing the sensitiveness of YYIR1C are necessary.
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Rendimiento Atlético , Prueba de Esfuerzo/métodos , Resistencia Física/fisiología , Fútbol/fisiología , Niño , Humanos , Masculino , Aptitud Física , Distribución Aleatoria , Reproducibilidad de los Resultados , CarreraRESUMEN
Castagna, C, Lorenzo, F, Krustrup, P, Fernandes-da-Silva, J, Póvoas, SCA, Bernardini, A, and D'Ottavio, S. Reliability characteristics and applicability of a repeated sprint ability test in young male soccer players. J Strength Cond Res 32(6): 1538-1544, 2018-The aim of this study was to examine the usefulness and reliability characteristics of a repeated sprint ability test considering 5 line sprints of 30 m interspersed with 30 seconds of active recovery in nonelite, outfield, young, male soccer players. Twenty-six (age, 14.9 ± 1.2 years; height, 1.72 ± 0.12 cm; body mass, 62.2 ± 5.1 kg) players were tested 48 hours and 7 days apart for 5 × 30-m performance over 5 trials (T1-T5). Short-term (T1-T2) and long-term (T1-T3-T4-T5) reliabilities were assessed with intraclass correlation coefficient (ICC) and with typical error for measurement (TEM). Short- and long-term reliability ICCs and TEMs for total sprint time and best sprint performance were nearly perfect and satisfactory, respectively. Usefulness (as smallest worthwhile change and TEM ratio) resulted acceptable (i.e., = 1) and good (i.e., >1) for total sprint time and best sprint performance, respectively. The present study revealed that the 5 × 30-m sprint test is a reliable field test in short and long terms when the sum of sprint times and the best sprint performance are considered as outcome variables. Sprint performance decrements variables showed large variability across trials.
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Rendimiento Atlético , Prueba de Esfuerzo , Carrera , Fútbol , Adolescente , Prueba de Esfuerzo/métodos , Humanos , Masculino , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
Most factors that regulate gene transcription in eukaryotic cells are multimeric, often large, protein complexes. The understanding of the biogenesis pathways of such large and heterogeneous protein assemblies, as well as the dimerization partner choice among transcription factors, is crucial to interpret and control gene expression programs and consequent cell fate decisions. Co-translational assembly (Co-TA) is thought to play key roles in the biogenesis of protein complexes by directing complex formation during protein synthesis. In this review we discuss the principles of Co-TA with a special focus for the assembly of transcription regulatory complexes. We outline the expected molecular advantages of establishing co-translational interactions, pointing at the available, or missing, evidence for each of them. We hypothesize different molecular mechanisms based on Co-TA to explain the allocation "dilemma" of paralog proteins and subunits shared by different transcription complexes. By taking as a paradigm the different assembly pathways employed by three related transcription regulatory complexes (TFIID, SAGA and ATAC), we discuss alternative Co-TA strategies for nuclear multiprotein complexes and the widespread - yet specific - use of Co-TA for the formation of nuclear complexes involved in gene transcription. Ultimately, we outlined a series of open questions which demand well-defined lines of research to investigate the principles of gene regulation that rely on the coordinated assembly of protein complexes.
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Regulación Enzimológica de la Expresión Génica , Complejos Multiproteicos , Biosíntesis de Proteínas , Complejos Multiproteicos/genética , Complejos Multiproteicos/metabolismo , Biosíntesis de Proteínas/genética , Factor de Transcripción TFIID/metabolismo , Factores de Transcripción/metabolismo , Transcripción Genética , HumanosRESUMEN
BACKGROUND: Drugs used for sedation/analgesia may affect the basic cardiac electrophysiologic properties or even supraventricular tachycardia (SVT) inducibility. Dexmedetomidine (DEX) is a selective alpha-2 adrenergic agonist with sedative and analgesic properties. A comprehensive evaluation on use of DEX for reentrant SVT ablation in adults is lacking. The present study aims to systematically assess the impact of DEX on cardiac electrophysiology and SVT inducibility. METHODS: Hemodynamic, electrocardiographic, and electrophysiological parameters and SVT inducibility were assessed before and after DEX infusion in patients scheduled for ablation of reentrant SVT. RESULTS: The population of this prospective observational study included 55 patients (mean age of 58.7 ± 14 years, 29 males [52.7%]). A decrease in systolic and diastolic blood pressure and in heart rate was observed after DEX infusion (p = 0.001 for all). DEX increased corrected sinus node refractory time, atrial effective refractory period, AH interval, AV Wenckebach cycle length, and AV node effective refractory period without affecting the His-Purkinje conduction or ventricular myocardium refractoriness. No AV blocks or sinus arrests occurred during DEX infusion. Globally, there was no difference in SVT inducibility in basal condition or after DEX infusion (46/55 [83.6%] vs. 43/55 [78.1%] patients; p = 0.55), without a difference in isoprenaline use (p = 1.0). In 4 (7.3%) cases, the SVT was inducible only after DEX infusion. In 34.5% of cases, DEX infusion unmasked the presence of an obstructive sleeping respiratory pattern, represented mainly by snoring. CONCLUSIONS: DEX depresses sinus node function and prolongs atrioventricular refractoriness without significantly affecting the rate of SVT inducibility in patients scheduled for reentrant SVT ablation.