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Daily co-trimoxazole is recommended for African adults living with HIV irrespective of antiretroviral treatment, immune status, or disease stage. Benefits of continued prophylaxis and whether co-trimoxazole can be stopped following immune reconstitution are unknown.<br /><br /> We conducted a randomized, controlled trial at two sites in Malawi that enrolled HIV-infected adults with undetectable viral load and CD4 count of &gt;250/mm 3 and randomized them to continue daily co-trimoxazole, discontinue daily co-trimoxazole and begin weekly chloroquine, or discontinue daily co-trimoxazole. The primary endpoint was the preventive effect of co-trimoxazole prophylaxis against death or World Health Organization (WHO) HIV/AIDS Stage 3-4 events, using Cox proportional hazards modelling, intention to treat population.<br /><br /> 1499 adults were enrolled. The preventive effect of co-trimoxazole on the primary endpoint was 22% (95%CI -14-47%, p=0.20) versus no prophylaxis and 25% (95%CI -10-48%, p=0.14) versus chloroquine. When WHO HIV/Axis discontinuation, though statistical significance was not achieved. Cotrimoxazole prevented a composite of death plus WHO HIV/AIDS Stage 2-4 events. Given poor healthcare access and lack of routine viral load monitoring, co-trimoxazole prophylaxis should continue in adults on ART after immune reconstitution in sub-Saharan Africa.Argonaute proteins are programmable nucleases that are found in both eukaryotes and prokaryotes and provide defense against invading genetic elements. Although some prokaryotic argonautes (pAgos) were shown to recognize RNA targets in vitro, the majority of studied pAgos have strict specificity toward DNA, which limits their practical use in RNA-centric applications. Here, we describe a unique pAgo nuclease, KmAgo, from the mesophilic bacterium Kurthia massiliensis that can be programmed with either DNA or RNA guides and can precisely cleave both DNA and RNA targets. KmAgo binds 16-20 nt long 5'-phosphorylated guide molecules with no strict specificity for their sequence and is active in a wide range of temperatures. In bacterial cells, KmAgo is loaded with small DNAs with no obvious sequence preferences suggesting that it can uniformly target genomic sequences. Mismatches between the guide and target sequences greatly affect the efficiency and precision of target cleavage, depending on the mismatch position and the nature of the reacting nucleic acids. Target RNA cleavage by KmAgo depends on the formation of secondary structure indicating that KmAgo can be used for structural probing of RNA. These properties of KmAgo open the way for its use for highly specific nucleic acid detection and cleavage.The cichlids of Lake Victoria are a textbook example of adaptive radiation, as &gt; 500 endemic species arose in just 14,600 years. The degree of genetic differentiation among species is very low due to the short period of time after the radiation, which allows us to ascertain highly differentiated genes that are strong candidates for driving speciation and adaptation. Previous studies have revealed the critical contribution of vision to speciation by showing the existence of highly differentiated alleles in the visual opsin gene among species with different habitat depths. In contrast, the processes of species-specific adaptation to different ecological backgrounds remain to be investigated. Here we used genome-wide comparative analyses of three species of Lake Victoria cichlids that inhabit different environments-Haplochromis chilotes, Haplochromis sauvagei and Lithochromis rufus-to elucidate the processes of adaptation by estimating population history and by searching for candidate genes that contribute to adaptation. The patterns of changes in population size were quite distinct among the species according to their habitats. We identified many novel adaptive candidate genes, some of which had surprisingly long divergent haplotypes between species, thus showing the footprint of selective sweep events. Molecular phylogenetic analyses revealed that a large fraction of the allelic diversity among Lake Victoria cichlids was derived from standing genetic variation that originated before the adaptive radiation. Our analyses uncovered the processes of species-specific adaptation of Lake Victoria cichlids and the complexity of the genomic substrate that facilitated this adaptation.Communication is a social process and usually occurs in a network of signalers and receivers. While social network analysis has received enormous recent attention from animal behaviorists, there have been relatively few attempts to apply these techniques to communication networks. [https://www.selleckchem.com/products/tideglusib.html find more] Communication networks have the potential to offer novel insights into social network studies, and yet are especially challenging subjects, largely because of their unique spatiotemporal characteristics. Namely, signals propagate through the environment, often dissociating from the body of the signaler, to influence receiver behavior. The speed of signal propagation and the signal's active space will affect the congruence of communication networks and other types of social network; in extreme cases the signal may persist and only first be detected long after the signaler has left the area. Other signals move more rapidly and over greater distances than the signaler could possibly move to reach receivers. We discuss the spatial and temporal consequences of signaling in networks and highlight the distinction between the physical location of the signaler and the spread of influence of its signals, the effects of signal modality and receiver sensitivity on communication network properties, the potential for feedbacks between network layers, and approaches to analyzing spatial and temporal change in communication networks in conjunction with other network layers.Cis-regulatory elements play important roles in tissue-specific gene expression and in the evolution of various phenotypes, and mutations in promoters and enhancers may be responsible for adaptations of species to environments. TRIM72 is a highly conserved protein that is involved in energy metabolism. Its expression in the heart varies considerably in primates, with high levels of expression in Old World monkeys and near absence in hominids. Here, we combine phylogenetic hypothesis testing and experimentation to demonstrate that mutations in promoter are responsible for the differences among primate species in the heart-specific expression of TRIM72. Maximum likelihood estimates of lineage-specific substitution rates under local-clock models show that relative to the evolutionary rate of introns, the rate of promoter was accelerated by 78% in the common ancestor of Old World monkeys, suggesting a role for positive selection in the evolution of the TRIM72 promoter, possibly driven by selective pressure due to changes in cardiac physiology after species divergence.