Developmental Splicing Deregulation in Leukodystrophies Related to EIF2B Mutations

Leukodystrophies (LD) are rare inherited disorders that primarily affect the white matter (WM) of the central nervous system. The large heterogeneity of LD results from the diversity of the genetically determined defects that interfere with glial cells functions. Astrocytes have been identified as the primary target of LD with cystic myelin breakdown including those related to mutations in the ubiquitous translation initiation factor eIF2B. EIF2B is involved in global protein synthesis and its regulation under normal and stress conditions. Little is known about how eIF2B mutations have a major effect on WM. We performed a transcriptomic analysis using fibroblasts of 10 eIF2B-mutated patients with a severe phenotype and 10 age matched patients with other types of LD in comparison to control fibroblasts. ANOVA was used to identify genes that were statistically significantly differentially expressed at basal state and after ER-stress. The pattern of differentially expressed genes between basal state and ER-stress did not differ significantly among each of the three conditions. However, 70 genes were specifically differentially expressed in eIF2B-mutated fibroblasts whatever the stress conditions tested compared to controls, 96% being under-expressed. Most of these genes were involved in mRNA regulation and mitochondrial metabolism. The 13 most representative genes, including genes belonging to the Heterogeneous Nuclear Ribonucleoprotein (HNRNP) family, described as regulators of splicing events and stability of mRNA, were dysregulated during the development of eIF2B-mutated brains. HNRNPH1, F and C mRNA were over-expressed in foetus but under-expressed in children and adult brains. The abnormal regulation of HNRNP expression in the brain of eIF2B-mutated patients was concomitant with splicing dysregulation of the main genes involved in glial maturation such as PLP1 for oligodendrocytes and GFAP in astrocytes. These findings demonstrate a developmental deregulation of splicing events in glial cells that is related to abnormal production of HNRNP, in eIF2B-mutated brains

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

The First JWST Spectrum of a GRB Afterglow: No Bright Supernova in Observations of the Brightest GRB of all Time, GRB 221009A

We present James Webb Space Telescope (JWST) and Hubble Space Telescope (HST) observations of the afterglow of GRB 221009A, the brightest gamma-ray burst (GRB) ever observed. This includes the first mid-IR spectra of any GRB, obtained with JWST/Near Infrared Spectrograph (0.6-5.5 micron) and Mid-Infrared Instrument (5-12 micron), 12 days after the burst. Assuming that the intrinsic spectral slope is a single power law, with F ν ∝ ν −β , we obtain β ≈ 0.35, modified by substantial dust extinction with A V = 4.9. This suggests extinction above the notional Galactic value, possibly due to patchy extinction within the Milky Way or dust in the GRB host galaxy. It further implies that the X-ray and optical/IR regimes are not on the same segment of the synchrotron spectrum of the afterglow. If the cooling break lies between the X-ray and optical/IR, then the temporal decay rates would only match a post-jet-break model, with electron index p < 2, and with the jet expanding into a uniform ISM medium. The shape of the JWST spectrum is near-identical in the optical/near-IR to X-SHOOTER spectroscopy obtained at 0.5 days and to later time observations with HST. The lack of spectral evolution suggests that any accompanying supernova (SN) is either substantially fainter or bluer than SN 1998bw, the proto-type GRB-SN. Our HST observations also reveal a disk-like host galaxy, viewed close to edge-on, that further complicates the isolation of any SN component. The host galaxy appears rather typical among long-GRB hosts and suggests that the extreme properties of GRB 221009A are not directly tied to its galaxy-scale environment

Riesgo cardiovascular en estudiantes de medicina del municipio Puerto Padre de Las Tunas

Introduction: cardiovascular diseases are the first cause of death in Cuba; as a result, the identification of cardiovascular risks from early ages allows the implementation of health promotion and prevention strategies to reduce their impact in the futureObjective: to identify the cardiovascular risk in medical students in Puerto Padre Municipality, Las Tunas province.Methods: an observational, descriptive and cross-sectional study was conducted. The target group included 545 medical students, 237 of whom were selected by means of a simple random sample. The body mass index and waist-hip ratio were studied. Descriptive statistics was applied.Results: the predominant age group was 18-21 years old (50,2 %). The 51,47 % of the students presented a high waist-hip ratio, 54,02 % a high abdominal circumference, 52,74 % a high body mass index, and in all groups 35,44 % presented blood pressure figures lower than 120/80 mmHg; 39 % had a cardiovascular risk.Conclusions: low percentages of cardiovascular risk were identified in medical students from Puerto Padre Municipality, Las Tunas province, determined by high values of waist-hip index, body mass index and abdominal circumference.Introducción: las enfermedades cardiovasculares constituyen la primera causa de mortalidad en Cuba; por lo cual la identificación de riesgos cardiovasculares desde edades tempranas permite implementar estrategias de promoción y prevención de salud para disminuir su impacto en el futuroObjetivo: identificar el riesgo cardiovascular en estudiantes de medicina del municipio Puerto Padre de Las Tunas.Método: se realizó un estudio observacional, descriptivo y transversal. El universo estuvo constituido por 545 estudiantes de medicina, seleccionándose 237 mediante un muestreo aleatorio simple. Se estudió el índice de masa corporal, la circunferencia abdominal y la índice cintura cadera. Se empleó estadística descriptiva.Resultados: se encontró predominio del grupo etario de 18 a 21 años (50,2 %). El 51,47 % de los estudiantes presentó un índice cintura-cadera alto, el 54,02 % una circunferencia abdominal alta, el 52,74 % un índice de masa corporal alta, así como en todos los grupos el 35,44 % presentó cifras de tensión arterial inferiores a 120/80 mmHg. El 39 % presentó riesgo cardiovascular.Conclusiones: se identificaron bajos porcientos de riesgo cardiovascular en los estudiantes de medicina del municipio Puerto Padre de Las Tunas, determinado por altos valores los índice cintura-cadera, índice de masa corporal y circunferencia abdominal

Photometric redshift estimation for gamma-ray bursts from the early Universe

Future detection of high-redshift gamma-ray bursts (GRBs) will be an important tool for studying the early Universe. Fast and accurate redshift estimation for detected GRBs is key for encouraging rapid follow-up observations by ground- and space-based telescopes. Low-redshift dusty interlopers pose the biggest challenge for GRB redshift estimation using broad photometric bands, as their high extinction can mimic a high-redshift GRB. To assess false alarms of high-redshift GRB photometric measurements, we simulate and fit a variety of GRBs using phozzy, a simulation code developed to estimate GRB photometric redshifts, and test the ability to distinguish between high- and low-redshift GRBs when using simultaneously observed photometric bands. We run the code with the wavelength bands and instrument parameters for the Photo-z Infrared Telescope (PIRT), an instrument designed for the Gamow mission concept. We explore various distributions of host galaxy extinction as a function of redshift, and their effect on the completeness and purity of a high-redshift GRB search with the PIRT. We find that for assumptions based on current observations, the completeness and purity range from ∼82 to 88 per cent and from ∼84 to, respectively. For the priors optimized to reduce false positives, only of low-redshift GRBs will be mistaken as a high-redshift one, corresponding to ∼1 false alarm per 500 detected GRBs