Although we know a great deal about the phenotype and function of haematopoietic stem/progenitor cells, a major challenge has been mapping their dynamic behaviour within living systems. Here we ...describe a strategy to image cells in vivo with high spatial and temporal resolution, and quantify their interactions using a high-throughput computational approach. Using these tools, and a new Msi2 reporter model, we show that haematopoietic stem/progenitor cells display preferential spatial affinity for contacting the vascular niche, and a temporal affinity for making stable associations with these cells. These preferences are markedly diminished as cells mature, suggesting that programs that control differentiation state are key determinants of spatiotemporal behaviour, and thus dictate the signals a cell receives from specific microenvironmental domains. These collectively demonstrate that high-resolution imaging coupled with computational analysis can provide new biological insight, and may in the long term enable creation of a dynamic atlas of cells within their native microenvironment.
Little emphasis has been given to the obstacles that women encounter while looking for gig work, despite the contribution of the gig economy to India’s economic growth is significant. The women’s ...workforce in India ranges from 16% to 28% at the moment. It represents less than half of the global average. Despite the flexibility that the gig economy provides involvement in the gig economy is still low, currently around 28%, according to the Taskmo Gig Index (TGI). The existing literature has yet to investigate the exact causes for the Diversity gap as to why women are not opting for Gig. This study is to fill that void by examining the employment relationship through the eyes of Gig workers as well as employers. The study was investigated using a quantitative survey methodology. According to the study, we found that there is a possibility to reduce the diversity gap in Gig workers, by implementing proper Government laws and Company policies that are usually given to traditional workers.
Chronic myelogenous leukaemia (CML) can progress from a slow growing chronic phase to an aggressive blast crisis phase, but the molecular basis of this transition remains poorly understood. Here we ...have used mouse models of CML to show that disease progression is regulated by the Musashi-Numb signalling axis. Specifically, we find that the chronic phase is marked by high levels of Numb expression whereas the blast crisis phase has low levels of Numb expression, and that ectopic expression of Numb promotes differentiation and impairs advanced-phase disease in vivo. As a possible explanation for the decreased levels of Numb in the blast crisis phase, we show that NUP98-HOXA9, an oncogene associated with blast crisis CML, can trigger expression of the RNA-binding protein Musashi2 (Msi2), which in turn represses Numb. Notably, loss of Msi2 restores Numb expression and significantly impairs the development and propagation of blast crisis CML in vitro and in vivo. Finally we show that Msi2 expression is not only highly upregulated during human CML progression but is also an early indicator of poorer prognosis. These data show that the Musashi-Numb pathway can control the differentiation of CML cells, and raise the possibility that targeting this pathway may provide a new strategy for the therapy of aggressive leukaemias.
Access control (AC) is an important security parameter in industrial networks; a mismanaged AC system leads to security breaches. The existing security solutions significantly consider the AC methods ...in the Industrial Internet of Things (IIoT); however, falsified identity can bypass the secure AC system. Thus, a centralized AC method leads to risks for data security. We are the first to address the risk factors of granted access in an industrial environment and present a risk-adaptive AC framework for IIoT. Our proposed solution framework uses blockchain to provide secure decentralized AC in the industrial environment with privacy-preserved multiparty data sharing. We name our framework "adaptive AC for multiparty data computation in industrial decentralization (AALMOND)." AALMOND uses lightweight cryptographic operations to reduce the complexity of the execution and loosen up the tight bounds on resource-constrained industrial devices. Further, the risk-adaptive AC in AALMOND provides a better security analysis of the multiparty sharing data. Our framework uses role-based, attribute-based, and organization-based ACs to map the assets for risk calculation. We put all the required policies in a smart contract for the ease of multiparty data sharing to obtain a transparent AC execution more suitably. We also pioneer in the calculation of the risk adaptivity of AALMOND considering the National Institute of Standards and Technology recommendations of operation risk, security risk, and heuristic risk. We measure the performance of AALMOND with state-of-the-art frameworks based on throughput, latency, complexity analysis, and risk adaptivity factors. We find that AALMOND is efficient for IIoT as it shows 24% reduced latency and 20% better throughput as compared to the other existing models.
Reduction mammaplasty effectively alleviates symptoms and restores quality of life. However, operating on adolescents remains controversial, partly because of fear of potential postoperative breast ...growth. This cross-sectional study provides surgeons with a method to predict the optimal timing, or biological "sweet spot," for reduction mammaplasty to minimize the risk of breast regrowth in adolescents.
The authors reviewed the medical records of women aged 12 to 21 years who underwent reduction mammaplasty from 2007 to 2019. Collected data included symptomology, perioperative details, and postoperative outcomes.
Four hundred eighty-one subjects were included in analyses and were, on average, 11.9 years old at first menses (menarche) and 17.9 years old at surgery. Six percent of subjects experienced postoperative breast growth. Breast size appears to stabilize considerably later in obese adolescents compared to healthy-weight and overweight patients, and breast growth in obese macromastia patients may not end until 9 years after menarche. Operating on obese women before this time point increased the likelihood of glandular breast regrowth by almost 120 percent (OR, 1.18; 95 percent CI, 1.11 to 1.26). Surgery performed less than 3 years after menarche, the commonly regarded end of puberty, increased the likelihood of glandular regrowth by over 700 percent in healthy-weight and overweight subjects (OR, 7.43; 95 percent CI, 1.37 to 40.41).
Findings suggest that reduction mammaplasty age restrictions imposed by care providers and third-party payors may be arbitrary. Surgical readiness should be determined on an individual basis incorporating the patient's biological and psychological maturity, obesity status, potential for postoperative benefit, and risk tolerance for postoperative breast growth.
Risk, III.
Class switch recombination (CSR) is a DNA recombination reaction that diversifies the effector functions of antibodies. CSR occurs via the formation and non-homologous end joining (NHEJ) repair of ...programmed DNA double-strand breaks (DSBs) at the immunoglobulin heavy chain locus. The DNA repair factors 53BP1 and Rif1 promote NHEJ and CSR by protecting DSBs against resection. However, to what extent repression of DNA end resection contributes to CSR is unknown. Here, we show that B lymphocytes devoid of 53BP1-Rif1-dependent DSB end protection activity undergo robust CSR. Inactivation of specific sets of phospho-sites within 53BP1 N-terminal SQ/TQ motifs abrogates Rif1 recruitment and inhibition of resection but only mildly reduces CSR. Furthermore, mutations within 53BP1 oligomerization domain abolish CSR without substantially affecting DNA end processing. Thus, inhibition of DNA end resection does not correlate with CSR efficiency, indicating that regulation of DSB processing is not a key determinant step in CSR.
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•53BP1 oligomerization is largely dispensable for inhibition of DSB resection•53BP1 higher order oligomerization is a pre-requisite for CSR•B lymphocytes devoid of 53BP1-Rif1 DSB end protection activity undergo robust CSR•53BP1-mediated DSB end mobility is dispensable for CSR
Class switch recombination (CSR) occurs via non-homologous end joining (NHEJ) of programmed DNA double-strand breaks (DSBs) at the immunoglobulin heavy chain locus. Sundaravinayagam et al. show that inhibition of DSB resection does not correlate with CSR efficiency and that regulation of DSB processing plays a limited role during CSR.
Internet-of-Thing (IoT) faces various security attacks. Different solutions exist to mitigate the intrusion problems. However, the existing solutions lack behind in dealing with heterogeneity of ...attack sources and features. The future anticipated demand of devices' connections also urge the need of new solutions addressing the concerns of time consumption and complexity. In this article, we show a novel solution for the intrusion detection in IoT framework. We configure the intrusion detection in the edge computing layer so that the effect of the attack is not propagated to the clouds. Our solution uses cerebellar model articulation controller with kernel map. This combination is very new in the direction of intrusion detection; hence, it emphasizes the novelty of our proposed intrusion detection solution. We name our solution as Cerebellar Model Articulation Controller based Intrusion Detection System (CMACIDS) . Additionally, we use spline fitting to the kernel mapping for the model fit; this adds on another novel contribution to CMACIDS. The results obtained with our detection system are compared with the state-of-the-art solutions in terms of complexity, false alarms, and precision of detection. The analysis of the comparative study proves the efficiency of the solution and makes CMACIDS suitable for IoT paradigm.
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