Dual role for Insulin/TOR signaling in the control of hematopoietic progenitor maintenance in Drosophila

The interconnected Insulin/IGF signaling (IlS) and Target of Rapamycin (TOR) signaling pathways constitute the main branches of the nutrient-sensing system that couples growth to nutritional conditions in Drosophila. Here, we addressed the influence of these pathways and of diet restriction on the balance between the maintenance of multipotent hematopoietic progenitors and their differentiation in the Drosophila lymph gland. In this larval hematopoietic organ, a pool of stem-like progenitor blood cells (prohemocytes) is kept undifferentiated in response to signaling from a specialized group of cells forming the posterior signaling center (PSC), which serves as a stem cell niche. We show that, reminiscent of the situation in human, loss of the negative regulator of IIS Pten results in lymph gland hyperplasia, aberrant blood cell differentiation and hematopoietic progenitor exhaustion. Using site-directed loss- and gain-of-function analysis, we demonstrate that components of the IIS/TOR pathways control lymph gland homeostasis at two levels. First, they cell-autonomously regulate the size and activity of the hematopoietic niche. Second, they are required within the prohemocytes to control their growth and maintenance. Moreover, we show that diet restriction or genetic alteration mimicking amino acid deprivation triggers progenitor cell differentiation. Hence, our study highlights the role of the IIS/TOR pathways in orchestrating hematopoietic progenitor fate and links blood cell fate to nutritional status.     

Optical Confinements in Correlated Spectral Characteristics of Vertically Aligned Silicon Nanometric Wires Followed by a Facile Fabrication Thereof

Nanometric wires, in particular, vertically aligned silicon nanowires, possess a huge prospect in current thin film solar cell technologies. A bottom-up process to acquire vertically aligned silicon nanowire (Si-NW) on c-Si wafer was demonstrated and characterized. A well coverage of Si-NWs on c-Si, ca. 6.5 × 10⁸/cm², was obtained. SEM micrograph confirmed a variation in Si-NW size in length as well as in diameter. On the other hand, inherent optical characteristics of nanometric wires define the performance of such nanowire-based thin film solar cell. Therefore, key factors, such as absorption profile, energy flow, electromagnetic (EM) field, and generation rate distribution in typical model, “Si-NW on c-Si slab,” have been observed at different wavelengths of solar spectrum. A single Si-NW of cylindrical shape was modelled on c-Si and optimized to elucidate the aforementioned characteristics. Light absorption at 700 nm was found to be the best in this scenario, and therefore, EM field and Poynting vector distribution were simulated at the same wavelength. It was revealed that at 700 nm, strongest sites of EM field and energy flow became more available and confined. Exciton generation rate was found to be distributed and confined all the way down to the bottom of the wire. A correlated phenomenon such as optical confinements in spectral characteristics in nanoscale is elucidated. Such a focused prediction in spectral optical characteristics and facile fabrication route is indispensable in optoelectronics as well as nanowire-based advanced electronic design.     

SHLD2/FAM35A co‐operates with REV7 to coordinate DNA double‐strand break repair pathway choice

DNA double‐strand breaks (DSBs) can be repaired by two major pathways: non‐homologous end‐joining (NHEJ) and homologous recombination (HR). DNA repair pathway choice is governed by the opposing activities of 53BP1, in complex with its effectors RIF1 and REV7, and BRCA1. However, it remains unknown how the 53BP1/RIF1/REV7 complex stimulates NHEJ and restricts HR to the S/G2 phases of the cell cycle. Using a mass spectrometry (MS)‐based approach, we identify 11 high‐confidence REV7 interactors and elucidate the role of SHLD2 (previously annotated as FAM35A and RINN2) as an effector of REV7 in the NHEJ pathway. FAM35A depletion impairs NHEJ‐mediated DNA repair and compromises antibody diversification by class switch recombination (CSR) in B cells. FAM35A accumulates at DSBs in a 53BP1‐, RIF1‐, and REV7‐dependent manner and antagonizes HR by limiting DNA end resection. In fact, FAM35A is part of a larger complex composed of REV7 and SHLD1 (previously annotated as C20orf196 and RINN3), which promotes NHEJ and limits HR. Together, these results establish SHLD2 as a novel effector of REV7 in controlling the decision‐making process during DSB repair.