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CRISPR/Cas technology has revolutionized the fields of the genome- and epigenome-editing by supplying unparalleled control over genomic sequences and expression. Lentiviral vector (LV) systems are one of the main delivery vehicles for the CRISPR/Cas systems due to (i) its ability to carry bulky and complex transgenes and (ii) sustain robust and long-term expression in a broad range of dividing and non-dividing cells in vitro and in vivo. It is thus reasonable that substantial effort has been allocated towards the development of the improved and optimized LV systems for effective and accurate gene-to-cell transfer of CRISPR/Cas tools. The main effort on that end has been put towards the improvement and optimization of the vector's expression, development of integrase-deficient lentiviral vector (IDLV), aiming to minimize the risk of oncogenicity, toxicity, and pathogenicity, and enhancing manufacturing protocols for clinical applications required large-scale production. In this review, we will devote attention to (i) the basic biology of lentiviruses, and (ii) recent advances in the development of safer and more efficient CRISPR/Cas vector systems towards their use in preclinical and clinical applications. In addition, we will discuss in detail the recent progress in the repurposing of CRISPR/Cas systems related to base-editing and prime-editing applications.Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a significant public health problem. HIV and METH use are each associated with immune system dysfunction; however, the combined effects on the immune system are poorly understood. This cross-sectional project measured soluble immune biomarkers in plasma and cerebrospinal fluid (CSF) collected from a control group, people with a history of a METH use disorder (METH+), PWH with no history of METH use disorder (HIV+), and PWH with a history of METH use disorder (HIV+/METH+). HIV, METH, and immune dysfunction can also be associated with affective and cognitive deficits, so we characterized mood and cognition in our participants. Two factor analyses were performed for the plasma and CSF biomarkers. Plasma IL-8, Ccl2, VEGF, and 8-isoprostane loaded onto one factor that was highest in the HIV+/METH+ group (p less then 0.047) reflecting worse inflammation, vascular injury, and oxidative stress. This plasma factor was also negatively correlated with delayed recall (R = -0.49, p = 0.010), which was worst in the HIV+/METH+ group (p = 0.030 compared to the control group). Overall, these data implicate that combined HIV-1 infection and METH use may exacerbate inflammation, leading to worse cognition.The discovery of genetically distinct hantaviruses (family Hantaviridae) in multiple species of shrews, moles and bats has revealed a complex evolutionary history involving cross-species transmission. Seewis virus (SWSV) is widely distributed throughout the geographic ranges of its soricid hosts, including the Eurasian common shrew (Sorex araneus), tundra shrew (Sorex tundrensis) and Siberian large-toothed shrew (Sorex daphaenodon), suggesting host sharing. In addition, genetic variants of SWSV, previously named Artybash virus (ARTV) and Amga virus, have been detected in the Laxmann's shrew (Sorex caecutiens). Here, we describe the geographic distribution and phylogeny of SWSV and Altai virus (ALTV) in Asian Russia. The complete genomic sequence analysis showed that ALTV, also harbored by the Eurasian common shrew, is a new hantavirus species, distantly related to SWSV. Moreover, Lena River virus (LENV) appears to be a distinct hantavirus species, harbored by Laxmann's shrews and flat-skulled shrews (Sorex roboratus) in Eastern Siberia and far-eastern Russia. Another ALTV-related virus, which is more closely related to Camp Ripley virus from the United States, has been identified in the Eurasian least shrew (Sorex minutissimus) from far-eastern Russia. Two highly divergent viruses, ALTV and SWSV co-circulate among common shrews in Western Siberia, while LENV and the ARTV variant of SWSV co-circulate among Laxmann's shrews in Eastern Siberia and far-eastern Russia. ALTV and ALTV-related viruses appear to belong to the Mobatvirus genus, while SWSV is a member of the Orthohantavirus genus. These findings suggest that ALTV and ALTV-related hantaviruses might have emerged from ancient cross-species transmission with subsequent diversification within Sorex shrews in Eurasia.Infection has recently started receiving greater attention as an unusual causative/inducing factor of obesity. Indeed, the biological plausibility of infectobesity includes direct roles of some viruses to reprogram host metabolism toward a more lipogenic and adipogenic status. Furthermore, the probability that humans may exchange microbiota components (virome/virobiota) points out that the altered response of IFN and other cytokines, which surfaces as a central mechanism for adipogenesis and obesity-associated immune suppression, is due to the fact that gut microbiota uphold intrinsic IFN signaling. Last but not least, the adaptation of both host immune and metabolic system under persistent viral infections play a central role in these phenomena. We hereby discuss the possible link between adenovirus and obesity-related nonalcoholic fatty liver disease (NAFLD). The mechanisms of adenovirus-36 (Ad-36) involvement in hepatic steatosis/NAFLD consist in reducing leptin gene expression and insulin sensitivity, augmenting glucose uptake, activating the lipogenic and pro-inflammatory pathways in adipose tissue, and increasing the level of macrophage chemoattractant protein-1, all of these ultimately leading to chronic inflammation and altered lipid metabolism. Moreover, by reducing leptin expression and secretion Ad-36 may have in turn an obesogenic effect through increased food intake or decreased energy expenditure via altered fat metabolism. Finally, Ad-36 is involved in upregulation of cAMP, phosphatidylinositol 3-kinase, and p38 signaling pathways, downregulation of Wnt10b expression, increased expression of CCAAT/enhancer binding protein-beta, and peroxisome proliferator-activated receptor gamma 2 with consequential lipid accumulation.Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in children less then 5 years of age worldwide and repeated infections throughout life leading to serious disease in the elderly and persons with compromised immune, cardiac, and pulmonary systems. The disease burden has made it a high priority for vaccine and antiviral drug development but without success except for immune prophylaxis for certain young infants. Two RSV proteins are associated with protection, F and G, and F is most often pursued for vaccine and antiviral drug development. Several features of the G protein suggest it could also be an important to vaccine or antiviral drug target design. We review features of G that effect biology of infection, the host immune response, and disease associated with infection. Though it is not clear how to fit these together into an integrated picture, it is clear that G mediates cell surface binding and facilitates cellular infection, modulates host responses that affect both immunity and disease, and its CX3C aa motif contributes to many of these effects. These features of G and the ability to block the effects with antibody, suggest G has substantial potential in vaccine and antiviral drug design.This paper discusses the valuable role recommender systems may play in cybersecurity. First, a comprehensive presentation of recommender system types is presented, as well as their advantages and disadvantages, possible applications and security concerns. read more Then, the paper collects and presents the state of the art concerning the use of recommender systems in cybersecurity; both the existing solutions and future ideas are presented. The contribution of this paper is two-fold to date, to the best of our knowledge, there has been no work collecting the applications of recommenders for cybersecurity. Moreover, this paper attempts to complete a comprehensive survey of recommender types, after noticing that other works usually mention two-three types at once and neglect the others.Nowadays, after suffering a fracture in an upper or lower limb, a plaster cast is placed on the affected limb. It is a very old and efficient technique for recovery from an injury that has not had significant changes since its origin. This project aims to develop a new low-cost smart 3D printed splint concept by using new sensing techniques. Two rapidly evolving Advanced Manufacturing (AM) technologies will be used 3D scanning and 3D printing, thus combining engineering, medicine and materials evolution. The splint will include new small and lightweight sensors to detect any problem during the treatment process. Previous studies have already incorporated this kind of sensor for medical purposes. However, in this study it is implemented with a new concept the possibility of applying treatments during the immobilization process and obtaining information from the sensors to modify the treatment. Due to this, rehabilitation treatments like infrared, ultrasounds or electroshock may be applied during the treatment, and the sensors (as it is showed in the study) will be able to detect changes during the rehabilitation process. Data of the pressure, temperature, humidity and colour of the skin will be collected in real time and sent to a mobile device so that they can be consulted remotely by a specialist. Moreover, it would be possible to include these data into the Internet of Things movement. This way, all the collected data might be compared and studied in order to find the best treatment for each kind of injury. It will be necessary to use a biocompatible material, submersible and suitable for contact with skin. These materials make it necessary to control the conditions in which the splint is produced, to assure that the properties are maintained. This development, makes it possible to design a new methodology that will help to provide faster and easier treatment.An innovative smart concrete anchorage (SCA) has been developed for monitoring the stress of prestressing (PS) tendons by utilizing smart ultra-high-performance concrete (UHPC). The smart UHPC contained 2 vol% steel fibers and fine steel slag aggregates instead of silica sands. The effects of different electrode materials, arrangements, and connectors on the self-stress sensing capacity of the SCA are discussed. A prototype SCA demonstrated its feasibility and sufficient self-stress sensing capacity to be used in monitoring the prestressing loss of the PS tendon. As the tensile stress of the PS tendon increased from 0 to 1488 MPa, the fractional change in resistivity (FCR) of the prototype SCA, with horizontally paired copper wire electrodes and a plug-in type connector, decreased linearly from 0% to -1.53%, whereas the FCR increased linearly from -1.53% to -0.04% as the tensile stress of the PS tendon decreased from 1488 to 331 MPa.Flying safely in complex urban environments is a challenge for unmanned aerial vehicles because path planning in urban environments with many narrow passages and few dynamic flight obstacles is difficult. The path planning problem is decomposed into global path planning and local path adjustment in this paper. First, a branch-selected rapidly-exploring random tree (BS-RRT) algorithm is proposed to solve the global path planning problem in environments with narrow passages. A cyclic pruning algorithm is proposed to shorten the length of the planned path. Second, the GM(1,1) model is improved with optimized background value named RMGM(1,1) to predict the flight path of dynamic obstacles. Herein, the local path adjustment is made by analyzing the prediction results. BS-RRT demonstrated a faster convergence speed and higher stability in narrow passage environments when compared with RRT, RRT-Connect, P-RRT, 1-0 Bg-RRT, and RRT*. In addition, the path planned by BS-RRT through the use of the cyclic pruning algorithm was the shortest.
Read More: https://www.selleckchem.com/products/2-2-2-tribromoethanol.html
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