Feedback inhibition of pantothenate kinase regulates pantothenol uptake by the malaria parasite

To survive, the human malaria parasite Plasmodium falciparum must acquire pantothenate (vitamin B5) from the external medium. Pantothenol (provitamin B5) inhibits parasite growth by competing with pantothenate for pantothenate kinase, the first enzyme in the coenzyme A biosynthesis pathway. In this study we investigated pantothenol uptake by P. falciparum and in doing so gained insights into the regulation of the parasite's coenzyme A biosynthesis pathway. Pantothenol was shown to enter P. falciparum-infected erythrocytes via two routes, the furosemide-inhibited "new permeation pathways" induced by the parasite in the infected erythrocyte membrane (the sole access route for pantothenate) and a second, furosemide-insensitive pathway. Having entered the erythrocyte, pantothenol is taken up by the intracellular parasite via a mechanism showing functional characteristics distinct from those of the parasite's pantothenate uptake mechanism. On reaching the parasite cytosol, pantothenol is phosphorylated and thereby trapped by pantothenate kinase, shown here to be under feedback inhibition control by coenzyme A. Furosemide reduced this inherent feedback inhibition by competing with coenzyme A for binding to pantothenate kinase, thereby increasing pantothenol uptake.     

c-Myc and Sp1 contribute to proviral latency by recruiting histone deacetylase 1 to the human immunodeficiency virus type 1 promoter

Histone deacetylase (HDAC) inhibitors such as valproic acid (VPA) induce the expression of quiescent proviral human immunodeficiency virus type 1 (HIV-1) and may deplete proviral infection in vivo. To uncover novel molecular mechanisms that maintain HIV latency, we sought cellular mRNAs whose expression was diminished in resting CD4(+) T cells of HIV-1-infected patients exposed to VPA. c-Myc was prominent among genes markedly downregulated upon exposure to VPA. c-Myc expression repressed HIV-1 expression in chronically infected cell lines. Chromatin immunoprecipitation (ChIP) assays revealed that c-Myc and HDAC1 are coordinately resident at the HIV-1 long terminal repeat (LTR) promoter and absent from the promoter after VPA treatment in concert with histone acetylation, RNA polymerase II recruitment, and LTR expression. Sequential ChIP assays demonstrated that c-Myc, Sp1, and HDAC1 coexist in the same DNA-protein complex at the HIV promoter. Short hairpin RNA inhibition of c-Myc reduces both c-Myc and HDAC1 occupancy, blocks c-Myc repression of Tat activation, and increases LTR expression. These results expand the understanding of mechanisms that recruit HDAC and maintain the latency of HIV-1, suggesting novel therapeutic approaches against latent proviral HIV infection.     

Cajal bodies and the nucleolus are required for a plant virus systemic infection

The nucleolus and Cajal bodies (CBs) are prominent interacting subnuclear domains involved in a number of crucial aspects of cell function. Certain viruses interact with these compartments but the functions of such interactions are largely uncharacterized. Here, we show that the ability of the groundnut rosette virus open reading frame (ORF) 3 protein to move viral RNA long distances through the phloem strictly depends on its interaction with CBs and the nucleolus. The ORF3 protein targets and reorganizes CBs into multiple CB-like structures and then enters the nucleolus by causing fusion of these structures with the nucleolus. The nucleolar localization of the ORF3 protein is essential for subsequent formation of viral ribonucleoprotein (RNP) particles capable of virus long-distance movement and systemic infection. We provide a model whereby the ORF3 protein utilizes trafficking pathways involving CBs to enter the nucleolus and, along with fibrillarin, exit the nucleus to form viral 'transport-competent' RNP particles in the cytoplasm.     

Metamorphosis of cinctoblastula larvae (Homoscleromorpha, porifera)

The metamorphosis of the cinctoblastula of Homoscleromorpha is studied in five species belonging to three genera. The different steps of metamorphosis are similar in all species. The metamorphosis occurs by the invagination and involution of either the anterior epithelium or the posterior epithelium of the larva. During metamorphosis, morphogenetic polymorphism was observed, which has an individual character and does not depend on either external or species specific factors. In the rhagon, the development of the aquiferous system occurs only by epithelial morphogenesis and subsequent differentiation of cells. Mesohylar cells derive from flagellated cells after ingression. The formation of pinacoderm and choanoderm occurs by the differentiation of the larval flagellated epithelium. This is possibly due to the conservation of cell junctions in the external surface of the larval flagellated cells and of the basement membrane in their internal surface. The main difference in homoscleromorph metamorphosis compared with Demospongiae is the persistence of the flagellated epithelium throughout this process and even in the adult since exo- and endopinacoderm remain flagellated. The antero-posterior axis of the larva corresponds to the baso-apical axis of the adult in Homoscleromorpha.     

A potent and orally active HIV-1 integrase inhibitor

A 1,6-naphthyridine inhibitor of HIV-1 integrase has been discovered with excellent inhibitory activity in cells, good pharmacokinetics, and an excellent ability to inhibit virus with mutant enzyme.     

Savanna chimpanzees, Pan troglodytes verus, hunt with tools

Although tool use is known to occur in species ranging from naked mole rats [1] to owls [2], chimpanzees are the most accomplished tool users [3-5]. The modification and use of tools during hunting, however, is still considered to be a uniquely human trait among primates. Here, we report the first account of habitual tool use during vertebrate hunting by nonhumans. At the Fongoli site in Senegal, we observed ten different chimpanzees use tools to hunt prosimian prey in 22 bouts. This includes immature chimpanzees and females, members of age-sex classes not normally characterized by extensive hunting behavior. Chimpanzees made 26 different tools, and we were able to recover and analyze 12 of these. Tool construction entailed up to five steps, including trimming the tool tip to a point. Tools were used in the manner of a spear, rather than a probe or rousing tool. This new information on chimpanzee tool use has important implications for the evolution of tool use and construction for hunting in the earliest hominids, especially given our observations that females and immature chimpanzees exhibited this behavior more frequently than adult males.     

Long-term data reveal effects of climate,road access,and latitude on mountain goat horn size

Potential negative artificial selection on horn size is a concern for many harvested ungulates. The mountain goat (Oreamnos americanus) has distinct black horns, but targeting animals based on horn size in the field can be challenging. We analyzed over 23,000 horn records that included base circumference and total length, from which we also derived horn volume, from mountain goats harvested in Alaska, British Columbia, and the Northwest Territories from 1980 to 2016. We tested 3 potential drivers of horn size variation: geographical location, environmental conditions, and artificial selection. We found no support for a latitudinal effect with surprisingly little variation across the sampling distribution. The Pacific Decadal Oscillation had the largest effect outside age in the model, suggesting a role of climate in shaping variation. Mountain goats harvested closer to roads had larger horns, indicating that ease of access might allow hunters to be more selective, though the effect size was small. Our findings reinforce the value of accurate and complete record keeping on horn size, age, and sex of harvested animals, and highlight the importance of explicitly considering climate and accessibility when devising management strategies for the mountain goat.     

Feeding Ecology and Regurgitation–Reingestion Behavior of the Critically Endangered Indri indri in the Maromizaha Protected Area,Eastern Madagascar

International Journal of Primatology - Deforestation around the world is a major threat to primates. Understanding primate species’ habitat and dietary requirements is critical in creating...