CHANTI: a Fast and Efficient Charged Particle Veto Detector for the NA62 Experiment at CERN

The design, construction and test of a charged particle detector made of scintillation counters read by Silicon Photomultipliers (SiPM) is described. The detector, which operates in vacuum and is used as a veto counter in the NA62 experiment at CERN, has a single channel time resolution of 1.14 ns, a spatial resolution of ~2.5 mm and an efficiency very close to 1 for penetrating charged particles

The Non-Canonical Wnt/PKC Pathway Regulates Mitochondrial Dynamics through Degradation of the Arm-Like Domain-Containing Protein Alex3

The regulation of mitochondrial dynamics is vital in complex cell types, such as neurons, that transport and localize mitochondria in high energy-demanding cell domains. The Armcx3 gene encodes a mitochondrial-targeted protein (Alex3) that contains several arm-like domains. In a previous study we showed that Alex3 protein regulates mitochondrial aggregation and trafficking. Here we studied the contribution of Wnt proteins to the mitochondrial aggregation and dynamics regulated by Alex3. Overexpression of Alex3 in HEK293 cells caused a marked aggregation of mitochondria, which was attenuated by treatment with several Wnts. We also found that this decrease was caused by Alex3 degradation induced by Wnts. While the Wnt canonical pathway did not alter the pattern of mitochondrial aggregation induced by Alex3, we observed that the Wnt/PKC non-canonical pathway regulated both mitochondrial aggregation and Alex3 protein levels, thereby rendering a mitochondrial phenotype and distribution similar to control patterns. Our data suggest that the Wnt pathway regulates mitochondrial distribution and dynamics through Alex3 protein degradation

Muon Radiography Investigations in Boreholes with a Newly Designed Cylindrical Detector

Muons are constantly produced in cosmic-rays and reach the Earth surface with a flux of about 160 particles per second per square meter. The abundance of muons with respect to other cosmic particles and their capability to cross dense materials with low absorption rate allow them to be exploited for large scale geological or human-made object imaging. Muon radiography is based on similar principles as X-ray radiography, measuring the surviving rate of muons escaping the target and relating it to the mass distribution inside the object. In the course of decades, after the first application in 1955, the methodology has been applied in several different fields. Muography allows us to measure the internal density distribution of the investigated object, or to simply highlight the presence of void regions by observing any excess of muons. Most of these applications require the detector to be installed below the rock being probed. In case that possible installation sites are not easily accessible by people, common instrumentation cannot be installed. A novel borehole cylindrical detector for muon radiography has been recently developed to deal with these conditions. It has been realized with a cylindrical geometry to fit typical borehole dimensions. Its design maximizes the geometrical acceptance, minimizing the dead spaces by the use of arc-shaped scintillators. The details of the construction and preliminary results of the first usage are described in this paper. © 2022 by the authors

The hidden fragility in the heart of the athletes: A review of genetic biomarkers

Sudden cardiac death (SCD) is a devastating event which can also affect people in apparent good health, such as young athletes. It is known that intense and continuous exercise along with a genetic background that predisposes a person to the risk of fatal arrhythmias is a trigger for SCD. Therefore, knowledge of the athlete’s genetic conditions underlying the onset of SCD must be extended, in order to develop new effective prevention and/or therapeutic strategies. Arrhythmic features occur across a broad spectrum of cardiac diseases, sometimes presenting with overlapping phenotypes. The genetic basis of arrhythmogenic disorders has been greatly highlighted in the last 30 years, and has shown marked heterogeneity. The advent of next-generation sequencing has constantly updated our understanding of the genetic basis of arrhythmogenic diseases and is laying the foundation for precision medicine. With the exception of a few clinical cases involving a single athlete showing a highly suspected phenotype for the presence of a heart disease, there are few studies to date that analysed the applicability of genetic testing on cohorts of athletes. This evidence shows that genetic testing can contribute to the diagnosis of up to 13% of athletes; however, the presence of clinical markers is essential. This review aims to provide a reference collection on current knowledge of the genetic basis of sudden cardiac death in athletes and to review updated evidence on the effectiveness of genetic testing in early identification of athletes at risk for SCD

Health related quality of life outcomes in HIV-Infected patients starting different combination regimens in a randomised multinational trial: the INITIO-QoL Substudy

The health-related quality of life (HRQoL) outcomes in HIV-infected, treatment-naive patients starting different HAART regimens in a 3-year, randomized, multinational trial were compared. HRQoL was measured in a subgroup of patients enrolled in the INITIO study (153/911), using a modified version of the MOS-HIV questionnaire. The regimens compared in the INITIO trial were composed by two NRTIs (didanosine + stavudine) plus either an NNRTI (efavirenz) or a PI (nelfinavir), or both (efavirenz + nelfinavir). Primary HRQoL outcomes were Physical and Mental Health Summary scores (PHS and MHS, respectively). During follow-up, an increase of PHS score was observed in all treatment arms. The MHS score remained substantially unchanged with the four-drug combination and showed with both NNRTI- and PI-based three-drug regimens a marked trend toward improvement, which became statistically significant when a multiple imputation method was used to adjust for missing data. Overall, starting all the combination regimens compared in the INITIO study was associated with a maintained or slightly improved HRQOL status, consistently with the positive immunological and virological changes observed in the main study. The observed differences in the MHS indicate a possible HRQoL benefit associated to the use of three-drug, two-class regimens and no additional benefit for the use of four-drug, three-class regimens, confirming that three-drug, two-class regimens that include two NRTIs plus either an NNRTI or a PI should be preferred as initial treatment of HIV infection

Análisis de diversidad genética en poblaciones de Bauhinia forficata subsp. pruinosa (Pezuña de vaca, o buey, Pata de vaca) mediante el uso de marcadores moleculares

Bauhinia. forficata Link. subsp. pruinosa (Vogel) Fortunato & Wunderlin, crece naturalmente desde Paraguay, Sur de Brasil hasta Argentina, y tiene antecedente de uso ornamental y terapéutico (diurético, antidiarreico, hipoglucemiante). Este proyecto tiene como objetivo la caracterización de poblaciones de bauhinia forficata subsp pruinosa utilizando marcadores moleculares. Existen SSRs diseñados en taxones afines: Cercis canadensis L. y C. chinensis, de los que hay antecedentes de transferibilidad entre especies. Por ello se evaluó su transferencia en las poblaciones de Bauhinia. Estos resultados asociados a los que se obtengan de las evaluaciones químicas permitirán conocer su relación con los biotipos que se identifiquen.  Para esto, se extrajo ADN mediante el método de Dellaporta (1983) de 10 individuos del Jardín botánico Arturo E. Ragonese, se cuantificó y se realizó PCR de los SSRs seleccionados. El producto se sembró, junto con un marcador de peso molecular, en geles desnaturalizantes de poliacrilamida en cubas de secuenciación teñidos con nitrato de plata y revelados con hidróxido de sodio. Hasta el momento, se evaluaron 15 SSRs (6 provinieron de C. chinensis   y 9 de C. canandensis). De estos 15 SSRs, 11 mostraron productos de amplificación. De ellos 9 fueron polimórficos indicando diferencias interpoblacionales, que podrían indicar variabilidad química y por lo tanto resta correlacionar la actividad biológica de los distintos biotipos. Además, algunos SSRs mostraron más de un locus, información que respalda lo señalado por Poggio et al. que en la subfamilia Cercidoideae, Bauhinia (2n=28) se generó por hibridación y poliploídia a partir del ancestro Cercis (2n= 14). Además, se realizó el muestreo de 20 puntos de colecta distribuidas en las provincias de Misiones, Córdoba y Buenos Aires de por lo menos tres individuos por punto. Estos individuos serán evaluados mediante técnicas de SSR para determinar mediante distintos parámetros la variabilidad intra e interpoblacional

Peran Kepercayaan Politik Dan Kepuasan Demokrasi Terhadap Partisipasi Politik Mahasiswa

Penelitian ini bertujuan untuk membuktikan hubungan kepercayaan politik dan kepuasan demokrasi dengan partisipasi politik mahasiswa. Sampel dalam penelitian ini sebanyak 307 mahasiswa yang berasal dari Universitas Islam Negeri Sultan Syarif Kasim Riau, Universitas Riau dan Universitas Islam Riau. Dalam mengumpulkan data menggunakan metode survey dengan kuesioner tentang kepercayaan politik, kepuasan demokrasi serta partisipasi politik. Hasil penelitian menunjukkan ada hubungan yang positif antara kepercayaan politik dan kepuasan demokrasi terhadap tingkat partisipasi politik mahasiswa. Artinya, semakin tinggi kepercayaan politik dan kepuasan demokrasi, maka semakin tinggi tingkat partisipasi politik mahasiswa. Sementara kepuasan demokrasi tidak berhubungan langsung dengan partisipasi politik tetapi melalui kepercayaan politik. Artinya kepercayaan politik menjadi variabel mediator antara kepuasan demokrasi dan partisipasi politik

GRP78 Mediates Cell Growth and Invasiveness in Endometrial Cancer.

Abstract Recent studies have indicated that endoplasmic reticulum stress, the unfolded protein response activation and altered GRP78 expression can play an important role in a variety of tumors development and progression. Very recently we reported for the first time that GRP78 is increased in endometrial tumors. However, whether GRP78 could play a role in the growth and/or invasiveness of endometrial cancer cells is still unknown. Here we report that the silencing of GRP78 expression affects both cell growth and invasiveness of Ishikawa and AN3CA cells, analyzed by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell migration assay, respectively. At variance with Ishikawa cells, AN3CA cells showed, besides an endoplasmic reticulum, also a plasma membrane GRP78 localization, evidenced by both immunofluorescence and cell membrane biotinylation experiments. Intriguingly, flow cytometry experiments showed that the treatment with a specific antibody targeting GRP78 C-terminal domain caused apoptosis in AN3CA but not in Ishikawa cells. Induction of apoptosis in AN3CA cells was not mediated by the p53 pathway activation but was rather associated to reduced AKT phosphorylation. Interestingly, immunofluorescence analysis evidenced that endometrioid adenocarcinoma tissues displayed, similarly to AN3CA cells, also a GRP78 plasma membrane localization. These data suggest that GRP78 and its plasma membrane localization, might play a role in endometrial cancer development and progression and might constitute a novel target for the treatment of endometrial cancer