Análisis de la cuestión de confianza facultativa y disolución del Congreso de la República en la sentencia del Expediente N° 0006-2019-CC-TC

El presente Trabajo de Suficiencia Profesional pretende evidenciar que la sentencia, emitida en bloque de mayoría por los magistrados miembros del Tribunal Constitucional, en el Expediente 0006-2019-CC/TC, ratificó el ejercicio arbitrario e inconstitucional del pedido de la cuestión de confianza por parte del Poder Ejecutivo en menoscabo estricto de las competencias del Congreso de la República: (i) La función de designar a los magistrados del Tribunal Constitucional, y (ii) la función de deliberar sus actos legislativos como la negación de la cuestión de confianza. Primero, se sintetizó la controversia desde los alegados empleados por el Congreso y el Poder Ejecutivo, hasta el análisis de los puntos controvertidos y pronunciamiento final por parte del Tribunal Constitucional. Segundo, se definió la esencia conceptual de los principios de separación, balance y cooperación de poderes, la cuestión de confianza y sus tipos, y sobre la disolución del Congreso. Tercero, se criticó, mediante la legislación y la jurisprudencia, los errores que adolece la sentencia. Por último, concluimos que los actos del Poder Ejecutivo fueron inconstitucionales al menoscabar deliberadamente las funciones del Poder Legislativo.This Professional Sufficiency Work intends to demonstrate that the sentence, issued in majority block by the judges of the Constitutional Court, in Case 0006-2019-CC/TC, ratified the arbitrary and unconstitutional exercise of the question of confidence by the Executive Branch in strict detriment of the competences of the Congress of the Republic: (i) the exclusive and excluding function of electing the judges of the Constitutional Court, and (ii) the function of deliberating its legislative acts such as the denial of the question of confidence. First, the controversy was synthesized from the allegations used by the Congress and the Executive Branch, to the analysis of the controversial points and the final pronouncement by the Constitutional Court. Second, the conceptual essence of the principles of separation, balance and cooperation of powers, the question of trust and its types, and the dissolution of Congress were defined. Third, we criticized, through legislation and jurisprudence, the errors in the sentence. Finally, we conclude that the acts of the Executive Branch were unconstitutional by deliberately undermining the powers of the Legislative Branch.Trabajo de Suficiencia Profesiona

Human adaptations to multiday saturation on NASA NEEMO

Human adaptation to extreme environments has been explored for over a century to understand human psychology, integrated physiology, comparative pathologies, and exploratory potential. It has been demonstrated that these environments can provide multiple external stimuli and stressors, which are sufficient to disrupt internal homeostasis and induce adaptation processes. Multiday hyperbaric and/or saturated (HBS) environments represent the most understudied of environmental extremes due to inherent experimental, analytical, technical, temporal, and safety limitations. National Aeronautic Space Agency (NASA) Extreme Environment Mission Operation (NEEMO) is a space-flight analog mission conducted within Florida International University's Aquarius Undersea Research Laboratory (AURL), the only existing operational and habitable undersea saturated environment. To investigate human objective and subjective adaptations to multiday HBS, we evaluated aquanauts living at saturation for 9-10 days via NASA NEEMO 22 and 23, across psychologic, cardiac, respiratory, autonomic, thermic, hemodynamic, sleep, and body composition parameters. We found that aquanauts exposed to saturation over 9-10 days experienced intrapersonal physical and mental burden, sustained good mood and work satisfaction, decreased heart and respiratory rates, increased parasympathetic and reduced sympathetic modulation, lower cerebral blood flow velocity, intact cerebral autoregulation and maintenance of baroreflex functionality, as well as losses in systemic bodyweight and adipose tissue. Together, these findings illustrate novel insights into human adaptation across multiple body systems in response to multiday hyperbaric saturation

Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration

Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency < 0.00026) whilst the others were rare in both patients and control individuals. When pooling all variants with a minor allele frequency < 0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology demonstrated that mutations in SQSTM1 associate with widespread neuronal and glial phospho-TDP-43 pathology. With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology

The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr

Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants

The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to both reduced vaccine efficacy and escape from neutralizing antibody therapeutics. It is, therefore, paramount to develop therapeutic strategies that inhibit all known and future SARS-CoV-2 variants. Here, we report that all SARS-CoV-2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, Delta, and Omicron, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01). Importantly, soluble ACE2 neutralized infection of VeroE6 cells and human lung epithelial cells by all current VOC strains with markedly enhanced potency when compared to reference SARS-CoV-2 isolates. Effective inhibition of infections with SARS-CoV-2 variants was validated and confirmed in two independent laboratories. These data show that SARS-CoV-2 variants that have emerged around the world, including current VOC and several variants of interest, can be inhibited by soluble ACE2, providing proof of principle of a pan-SARS-CoV-2 therapeutic

No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients

We evaluated the genetic contribution of the T cell-erestricted intracellular antigen-1 gene (TIA1) in a European cohort of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) patients. Exonic resequencing of TIA1 in 1120 patients (693 FTD, 341 ALS, 86 FTD-ALS) and 1039 controls identified in total 5 rare heterozygous missense variants, affecting the TIA1 low-complexity domain (LCD). Only 1 missense variant, p.Met290Thr, identified in a familial FTD patient with disease onset at 64 years, was absent from controls yet received a combined annotation-dependent depletion score of 11.42. By contrast, 3 of the 4 variants also detected in unaffected controls, p.Val294Glu, p.Gln318Arg, and p.Ala381Thr, had combined annotation-dependent depletion scores greater than 20. Our findings in a large European patient-control series indicate that variants in TIA1 are not a common cause of ALS and FTD. The observation of recurring TIA1 missense variants in unaffected individuals lead us to conclude that the exact genetic contribution of TIA1 to ALS and FTD pathogenesis remains to be further elucidated

Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimer's disease

Altres ajuts: The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The research was funded in part by the European Commission Seventh Framework Programme for research, technological development, and demonstration under grant agreement 305299 (AgedBrainSYSBIO), the Belgian Science Policy Office Interuniversity Attraction Poles program, the Alzheimer Research Foundation (SAO-FRA), the Flemish government-initiated Flanders Impulse Program on Networks for Dementia Research (VIND), the Flemish government-initiated Methusalem Excellence Program, the Research Foundation Flanders (FWO), the VIB Technology Fund, the University of Antwerp Research Fund, Belgium; European Regional Development Fund, the Italian Ministry of Health (Ricerca Corrente and RF-2010-2319722), and the Fondazione Cassa di Risparmio di Pistoia e Pescia grant (2014.0365).Premature termination codon (PTC) mutations in the ATP-Binding Cassette, Sub-Family A, Member 7 gene (ABCA7) have recently been identified as intermediate-to-high penetrant risk factor for late-onset Alzheimer's disease (LOAD). High variability, however, is observed in downstream ABCA7 mRNA and protein expression, disease penetrance, and onset age, indicative of unknown modifying factors. Here, we investigated the prevalence and disease penetrance of ABCA7 PTC mutations in a large early onset AD (EOAD)-control cohort, and examined the effect on transcript level with comprehensive third-generation long-read sequencing. We characterized the ABCA7 coding sequence with next-generation sequencing in 928 EOAD patients and 980 matched control individuals. With MetaSKAT rare variant association analysis, we observed a fivefold enrichment (p = 0.0004) of PTC mutations in EOAD patients (3%) versus controls (0.6%). Ten novel PTC mutations were only observed in patients, and PTC mutation carriers in general had an increased familial AD load. In addition, we observed nominal risk reducing trends for three common coding variants. Seven PTC mutations were further analyzed using targeted long-read cDNA sequencing on an Oxford Nanopore MinION platform. PTC-containing transcripts for each investigated PTC mutation were observed at varying proportion (5-41% of the total read count), implying incomplete nonsense-mediated mRNA decay (NMD). Furthermore, we distinguished and phased several previously unknown alternative splicing events (up to 30% of transcripts). In conjunction with PTC mutations, several of these novel ABCA7 isoforms have the potential to rescue deleterious PTC effects. In conclusion, ABCA7 PTC mutations play a substantial role in EOAD, warranting genetic screening of ABCA7 in genetically unexplained patients. Long-read cDNA sequencing revealed both varying degrees of NMD and transcript-modifying events, which may influence ABCA7 dosage, disease severity, and may create opportunities for therapeutic interventions in AD