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Abstract Translation is regulated mainly in the initiation step, and its dysregulation is implicated in many human diseases. Several proteins have been found to regulate translational initiation, including Pdcd4 (programmed cell death gene 4). Pdcd4 is a tumor suppressor protein that prevents cell growth, invasion, and metastasis. It is downregulated in most tumor cells, while global translation in the cell is upregulated. To understand the mechanisms underlying translational control by Pdcd4, we used single-particle cryo-electron microscopy to determine the structure of human Pdcd4 bound to 40S small ribosomal subunit, including Pdcd4-40S and Pdcd4-40S-eIF4A-eIF3-eIF1 complexes. The structures reveal the binding site of Pdcd4 at the mRNA entry site in the 40S, where the C-terminal domain (CTD) interacts with eIF4A at the mRNA entry site, while the N-terminal domain (NTD) is inserted into the mRNA channel and decoding site. The structures, together with quantitative binding and in vitro translation assays, shed light on the critical role of the NTD for the recruitment of Pdcd4 to the ribosomal complex and suggest a model whereby Pdcd4 blocks the eIF4F-independent role of eIF4A during recruitment and scanning of the 5′ UTR of mRNA.

Introduction: Genetic polymorphism in the BDNF gene has been found to cause neuronal alterations and has been identified as a causal factor for many neuropsychiatric disorders. Therefore, various neurological case–control studies and meta-analyses have been conducted to find the possible link between BDNF and susceptibility to schizophrenia. Method: This meta-analysis gathered data from 25 case–control studies including a total of 8384 patients with schizophrenia and 8821 controls in order to identify the relationship between the rs6265 single nucleotide polymorphism and the disease, evaluating the combined odds ratio and 95% confidence intervals under 5 different genetic models. Validation followed the “Leave one out” method, and we used the Egger test and Begg's funnel plot to identify publication bias. Results: Research into the rs6265 (G/A) polymorphism revealed a non-significant association with schizophrenia in all 5 genetic models; in the subgroup analysis, no association was found between white and Asian populations, with a p value > .05. Conclusions: Overall, the updated meta-analysis revealed that rs6265 exonic polymorphisms do not increase susceptibility to this disease. However, to better understand the pathogenesis of the disease, there is a need for further case–control studies into the BDNF polymorphism including larger sample sizes and different ethnic groups. Resumen: Introducción: Se sabe que los polimorfismos del gen BDNF provocan alteraciones neuronales y parecen ser un factor causal en muchos trastornos neuropsiquiátricos. Es por ello que se han llevado a cabo varios metaanálisis y estudios de casos y controles con el objetivo de evaluar la posible relación entre BDNF y la esquizofrenia. Método: Realizamos un metaanálisis de 25 estudios de casos y controles, que incluyó un total de 8.384 pacientes con esquizofrenia y 8.821 controles. Se analizó la relación entre el polimorfismo de nucleótido simple rs6265 y la esquizofrenia mediante odds ratios combinados y sus intervalos de confianza del 95% con 5 modelos genéticos diferentes. Utilizamos el método de validación cruzada dejando uno fuera («leave one out»), la prueba de Egger y el gráfico en embudo de Begg para identificar posibles sesgos de publicación. Resultados: Los estudios sobre el polimorfismo rs6265 (G/A) muestran una asociación no significativa con la esquizofrenia en los 5 modelos genéticos. En el análisis por subgrupos, no se encontró relación con las poblaciones caucásica y asiática (p > 0,05). Conclusiones: La presencia de polimorfismos rs6265 no aumenta la predisposición a desarrollar esquizofrenia. Sin embargo, se deben realizar más estudios de casos y controles sobre polimorfismos de BDNF, con muestras más numerosas y con individuos de diferentes grupos étnicos, para comprender mejor los mecanismos patogénicos de la enfermedad.

We present extensive optical photometry of the afterglow of GRB 221009A. Our data cover 0.9–59.9 days from the time of Swift and Fermi gamma-ray burst (GRB) detections. Photometry in rizy -band filters was collected primarily with Pan-STARRS and supplemented by multiple 1–4 m imaging facilities. We analyzed the Swift X-ray data of the afterglow and found a single decline rate power law f ( t ) ∝ t ^−1.556±0.002 best describes the light curve. In addition to the high foreground Milky Way dust extinction along this line of sight, the data favor additional extinction to consistently model the optical to X-ray flux with optically thin synchrotron emission. We fit the X-ray-derived power law to the optical light curve and find good agreement with the measured data up to 5−6 days. Thereafter we find a flux excess in the riy bands that peaks in the observer frame at ∼20 days. This excess shares similar light-curve profiles to the Type Ic broad-lined supernovae SN 2016jca and SN 2017iuk once corrected for the GRB redshift of z = 0.151 and arbitrarily scaled. This may be representative of an SN emerging from the declining afterglow. We measure rest-frame absolute peak AB magnitudes of M _g = −19.8 ± 0.6 and M _r = − 19.4 ± 0.3 and M _z = −20.1 ± 0.3. If this is an SN component, then Bayesian modeling of the excess flux would imply explosion parameters of ${M}_{\mathrm{ej}}={7.1}_{-1.7}^{+2.4}$ M _⊙ , ${M}_{\mathrm{Ni}}={1.0}_{-0.4}^{+0.6}$ M _⊙ , and ${v}_{\mathrm{ej}}={{\rm{33,900}}}_{-5700}^{+5900}$ km s ^−1 , for the ejecta mass, nickel mass, and ejecta velocity respectively, inferring an explosion energy of E _kin ≃ 2.6–9.0 × 10 ^52 erg.

Abstract Background Transcranial direct current stimulation (tDCS) is reported to induce irritating skin sensations and occasional skin injuries, which limits the applied tDCS dose. Additionally, tDCS hardware safety profile prevents high current delivery when skin resistance is high. Objective To test if decreasing skin resistance can enable high‐dose tDCS delivery without increasing tDCS‐related skin sensations or device hardware limits. Methods We compared the effect of microdermabrasion and sonication on 2 mA direct current stimulation (DCS) through forearm skin for 2–3 min on 20 subjects. We also surveyed the subjects using a questionnaire throughout the procedure. We used a linear mixed‐effects model for repeated‐measures and multiple logistic regression, with adjustments for age, race, gender and visit. Results Microdermabrasion, with/out sonication, led to significant decrease in skin resistance (1.6 ± 0.1 kΩ or ∼32% decrease, p 0.16), but microdermabrasion (when not combined with sonication) led to increased perceived sensation (p

During stress, protein synthesis is inhibited through phosphorylation of the initiation factor eIF2 on its alpha subunit and its interaction with eIF2B. Here the authors describe a structure of the yeast eIF2B in complex with its substrate - the GDP-bound phosphorylated eIF2, providing insights into how phosphorylation results in a tighter interaction with eIF2B.

We dissect the mechanism of SARS-CoV-2 in human lung host from the initial phase of receptor binding to viral replication machinery. Two independent lung protein interactome were constructed to reveal the signaling process on receptor activation and host protein hijacking machinery in the pathogenesis of virus. Further, we test the functional role of the hubs derived from the interactome. Most hubs proteins were differentially regulated on SARS-CoV-2 infection. Also, the proteins in viral replication hubs were related with cardiovascular disease, diabetes and hypertension confirming the vulnerability and severity of infection in the risk individual. Additionally, the hub proteins were closely linked with other viral infection, including MERS and HCoVs which suggest similar infection pattern in SARS-CoV-2. We identified five hubs that interconnect both networks that show the preparation of optimal environment in the host for viral replication process upon receptor attachment. Interestingly, we propose that seven potential miRNAs, targeting the intermediate phase that connects receptor and viral replication process a better choice as a drug for SARS-CoV-2.

Background: Carcinoma of the cervix is ranked second among the top 5 cancers affecting women globally. Parallel to other cancers, it is also a complex disease involving numerous factors such as human papillomavirus (HPV) infection followed by the activity of oncogenes and environmental factors. The incidence rate of the disease remains high in developing countries due to lack of awareness, followed by mass screening programs, various socioeconomic issues, and low usage of preventive vaccines. Over the past 3 decades, extensive research has taken place in cervical malignancy to elucidate the role of host genes in the pathogenesis of the disease, yet it remains one of the most prevalent diseases. It is imperative that recent genome-wide techniques be used to determine whether carcinogenesis of oncogenes is associated with cervical cancer at the molecular level and to translate that knowledge into developing diagnostic and therapeutic tools. Objective: The aim of this study was to discuss HPV predominance with their genotype distribution worldwide, and in India, as well as to discuss the newly identified oncogenes related to cervical cancer in current scenario. Findings: Using data from various databases and robust technologies, oncogenes associated with cervical malignancies were identified and are explained in concise manner. Conclusion: Due to the advent of recent technologies, new candidate genes are explored and can be used as precise biomarkers for screening and developing drug targets.

The exfoliation of graphene from pristine graphite in a liquid phase was achieved successfully via sonication followed by centrifugation method. Ultraviolet–visible (UV–vis) spectra of the obtained graphene dispersions at different exfoliation time indicated that the concentration of graphene dispersion increased markedly with increasing exfoliation time. The sheet-like morphology of the exfoliated graphene was revealed by Scanning Electron Microscopy (SEM) image. Further, the morphological change in different exfoliation time was investigated by Atomic Force Microscopy (AFM). A complete structural and defect characterization was probed using micro-Raman spectroscopic technique. The shape and position of the 2D band of Raman spectra revealed the formation of bilayer to few layer graphene. Also, Raman mapping confirmed the presence of uniformly distributed bilayer graphene sheets on the substrate.

The growth of ZnO nanostructures under various combinations of argon and oxygen pressures by radio frequency magnetron sputtering has been reported. The anisotropic transformation of nanostructures from the vertical standing nanorods to self branched lateral nanowires has been observed due to the change in the migration length of the adatoms owing to the deposition pressure and temperature. A dominant (002) reflection having narrow full width at half maximum of the vertical standing nanorods depicts the preferential orientation along c-axis of wurtzite ZnO with high crystalline nature. It is further substantiated by a sharp E2high phonon mode of ZnO nanorods at 437.2 cm−1. A broad green emission at 2.28 eV pertaining to oxygen vacancies that quenches with increasing the oxygen pressure due to the compensation of oxygen vacancies while zinc vacancy mediated emission at 3.01 eV is enhanced.

The electron-phonon interactions in InN-GaN core-shell nanowires grown by plasma assisted- molecular beam epitaxy (MBE) on Si (111) substrate have been analysed using micro-Raman spectroscopic technique with the excitation wavelength of 633, 488 and 325 nm. The Raman scattering at 633 nm reveals the characteristic E2 (high) and A1 (LO) phonon mode of InN core at 490 and 590 cm−1 respectively and E2 (high) phonon mode of GaN shell at 573 cm−1. The free carrier concentration of InN core is found to be low in the order ∼ 1016 cm−3 due to the screening of charge carriers by thin GaN shell. Diameter of InN core evaluated using the spatial correlation model is consistent with the transmission electron microscopic measurement of ∼15 nm. The phonon-life time of core-shell nanowire structure is estimated to be ∼0.4 ps. The micro-Raman mapping and its corresponding localised spectra for 325 nm excitation exhibit intense E2 (high) phonon mode of GaN shell at 573 cm−1 as the decrease of laser interaction length and the signal intensity is quenched at the voids due to high spacing of NWs.