Plasticity in Major Ampullate Silk Production in Relation to Spider Phylogeny and Ecology

Spider major ampullate silk is a high-performance biomaterial that has received much attention. However, most studies ignore plasticity in silk properties. A better understanding of silk plasticity could clarify the relative importance of chemical composition versus processing of silk dope for silk properties. It could also provide insight into how control of silk properties relates to spider ecology and silk uses

Altered miRNA expression network in locus coeruleus of depressed suicide subjects

Norepinephrine (NE) is produced primarily by neurons in the locus coeruleus (LC). Retrograde and ultrastructural examinations reveal that the core of the LC and its surrounding region receives afferent projections from several brain areas which provide multiple neurochemical inputs to the LC with changes in LC neuronal firing, making it a highly coordinated event. Although NE and mediated signaling systems have been studied in relation to suicide and psychiatric disorders that increase the risk of suicide including depression, less is known about the corresponding changes in molecular network within LC. In this study, we examined miRNA networks in the LC of depressed suicide completers and healthy controls. Expression array revealed differential regulation of 13 miRNAs. Interaction between altered miRNAs and target genes showed dense interconnected molecular network. Functional clustering of predicated target genes yielded stress induced disorders that collectively showed the complex nature of suicidal behavior. In addition, 25 miRNAs were pairwise correlated specifically in the depressed suicide group, but not in the control group. Altogether, our study revealed for the first time the involvement of LC based dysregulated miRNA network in disrupting cellular pathways associated with suicidal behavior

Molecular Evolution of Lepidopteran Silk Proteins: Insights from the Ghost Moth, Hepialus californicus

Silk production has independently evolved in numerous arthropod lineages, such as Lepidoptera, the moths and butterflies. Lepidopteran larvae (caterpillars) synthesize silk proteins in modified salivary glands and spin silk fibers into protective tunnels, escape lines, and pupation cocoons. Molecular sequence data for these proteins are necessary to determine critical features of their function and evolution. To this end, we constructed an expression library from the silk glands of the ghost moth, Hepialus californicus, and characterized light chainfibroin and heavy chain fibroin gene transcripts. The predicted H. californicus silk fibroins share many elements with other lepidopteran and trichopteran fibroins, such as conserved placements of cysteine, aromatic, and polar amino acid residues. Further comparative analyses were performed to determine site-specific signatures of selection and to assess whether fibroin genes are informative as phylogenetic markers. We found that purifying selection has constrained mutation within the fibroins and that light chain fibroin is a promising molecular marker. Thus, by characterizing the H. californicus fibroins, we identified key functional amino acids and gained insight into the evolutionary processes that have shaped these adaptive molecules

Leishmania infantum Asparagine Synthetase A Is Dispensable for Parasites Survival and Infectivity

A growing interest in asparagine (Asn) metabolism has currently been observed in cancer and infection fields. Asparagine synthetase (AS) is responsible for the conversion of aspartate into Asn in an ATP-dependent manner, using ammonia or glutamine as a nitrogen source. There are two structurally distinct AS: the strictly ammonia dependent, type A, and the type B, which preferably uses glutamine. Absent in humans and present in trypanosomatids, AS-A was worthy of exploring as a potential drug target candidate. Appealingly, it was reported that AS-A was essential in Leishmania donovani, making it a promising drug target. In the work herein we demonstrate that Leishmania infantum AS-A, similarly to Trypanosoma spp. and L. donovani, is able to use both ammonia and glutamine as nitrogen donors. Moreover, we have successfully generated LiASA null mutants by targeted gene replacement in L. infantum, and these parasites do not display any significant growth or infectivity defect. Indeed, a severe impairment of in vitro growth was only observed when null mutants were cultured in asparagine limiting conditions. Altogether our results demonstrate that despite being important under asparagine limitation, LiAS-A is not essential for parasite survival, growth or infectivity in normal in vitro and in vivo conditions. Therefore we exclude AS-A as a suitable drug target against L. infantum parasites