Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion

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Integrin Ligation Results in Nephrin Tyrosine Phosphorylation In Vitro

Nephrin is expressed at the basolateral aspect of podocytes and is an important signaling protein at the glomerular slit diaphragm. In vitro studies have demonstrated that Nephrin phosphorylation-dependent signaling is able to assemble a protein complex that is able to polymerize actin. However, proximal signaling events that result in nephrin tyrosine phosphorylation are not well understood. Nephrin deletion in mice and human nephrin mutations result in developmental failure of the podocyte intercellular junction resutling in proteinuria. This has been presumed to be due to a failure to respond to an external polarized cue in the absence of nephrin or a failure to transduce an outside-in signal in patients with nephrin mutations. The nephrin extracellular domain binds to itself or neph1 across the foot process intercellular junction. Nephrin is tyrosine phosphorylation-silent in healthy glomeruli when presumably the nephrin extracellular domain is in an engaged state. These observations raise the possibility of an alternate proximal signaling mechanism that might be responsible for nephrin tyrosine phosphorylation. Here we present data showing that integrin engagement at the basal aspect of cultured podocytes results in nephrin tyrosine phosphorylation. This is abrogated by incubating podocytes with an antibody that prevents integrin β1 ligation and activation in response to binding to extracellular matrix. Furthermore, nephrin tyrosine phosphorylation was observed in podocytes expressing a membrane-targeted nephrin construct that lacks the extracellular domain. We propose, integrin-activation based signaling might be responsible for nephrin phosphorylation rather than engagment of the nephrin extracellular domain by a ligand.     

Plants used by the bhat community for regulating fertility

A survey was conducted among medicinal plant sellers, healers, priests and local people in the rural population of Bhat, India. In this rural community medicinal plants are used for regulating fertility. Due to the fact that the majority of the Bhat community is illiterate, oral interviews were held in the villages. The information was then recorded. Plant samples were collected and preserved for future reference. Information on 28 plants and 11 recipes for doses from 2 or more vegetable species are presented, and popular names, empirical properties, and manner of using recipes are described. More than 90% of the information gathered was consistent among the informants, but some of the informants differed in their reports on the way to use the same plants. There is no certainty as to which of the plants are effective. Since the Bhat community has frequently observed the positive effects of their preparations, they have much faith in their recipes. The acceptability of these preparations is quite high among 95% of the Bhat population.     

On the dynamics of the hanuman langur populations of jodhpur (Rajasthan,India)

The city of Jodhpur (26°18′N, 73°8′E) supports a population of about 900 hanuman langurs (Presbytis entellus) divided into 24 bisexual troops and 12 all-male bands in an area of 60 km². This population has been censused from 1968 to 1978. Over this period the population of bisexual troops has remained stable around 700, while the population of all-male bands has increased from 160 to 230 individuals. The bisexual troops show a tendency towards a reduction in population growth rate with increasing troop size, with troops over 50–60 tending to split. Very small troops may grow by large scale immigration. Although a number of male changes and mortality through infanticide have been recorded, there is no evidence of a regular periodicity in the occurrence of initial, growth and mature phases in the life history of a bisexual troop. Unlike the bisexual troops, the all-male bands show no tendency towards a reduction in growth rate with the increase in band size, but show a continuous growth of band size over the study period. Langurs of Jodhpur rely heavily on cultivated fields for their sustenance. This cultivation has been on increase over the study period, and since the males invade cultivation more readily, they may have been able to take fuller advantage of these increasing resources and affect a population increase that has not been possible for the bisexual troops.     

Improved microscopic observation of mammalian cells on microcarriers by fluorescent staining

Many microcarriers used for the cultivation of animal cells do not allow for convenient microscopic observation of cell morphology and viability due to their optical properties. Using fluorescent viable stain combining fluorescein diacetate and ethidium bromide, we observed the distribution, morphology and viability of cells on various microcarriers.     

Neuronal c-Jun is required for successful axonal regeneration, but the effects of phosphorylation of its N-terminus are moderate

Although neural c-Jun is essential for successful peripheral nerve regeneration, the cellular basis of this effect and the impact of c-Jun activation are incompletely understood. In the current study, we explored the effects of neuron-selective c-Jun deletion, substitution of serine 63 and 73 phosphoacceptor sites with non-phosphorylatable alanine, and deletion of Jun N-terminal kinases 1, 2 and 3 in mouse facial nerve regeneration. Removal of the floxed c-jun gene in facial motoneurons using cre recombinase under control of a neuron-specific synapsin promoter (junΔS) abolished basal and injury-induced neuronal c-Jun immunoreactivity, as well as most of the molecular responses following facial axotomy. Absence of neuronal Jun reduced the speed of axonal regeneration following crush, and prevented most cut axons from reconnecting to their target, significantly reducing functional recovery. Despite blocking cell death, this was associated with a large number of shrunken neurons. Finally, junΔS mutants also had diminished astrocyte and microglial activation and T-cell influx, suggesting that these non-neuronal responses depend on the release of Jun-dependent signals from neighboring injured motoneurons. The effects of substituting serine 63 and 73 phosphoacceptor sites (junAA), or of global deletion of individual kinases responsible for N-terminal c-Jun phosphorylation were mild. junAA mutants showed decrease in neuronal cell size, a moderate reduction in post-axotomy CD44 levels and slightly increased astrogliosis. Deletion of Jun N-terminal kinase (JNK)1 or JNK3 showed delayed functional recovery; deletion of JNK3 also interfered with T-cell influx, and reduced CD44 levels. Deletion of JNK2 had no effect. Thus, neuronal c-Jun is needed in regeneration, but JNK phosphorylation of the N-terminus mostly appears to not be required for its function.     

The nucleolar protein Esf2 interacts directly with the DExD/H box RNA helicase, Dbp8, to stimulate ATP hydrolysis

While 18 putative RNA helicases are involved in ribosome biogenesis in Saccharomyces cerevisiae, their enzymatic properties have remained largely biochemically uncharacterized. To better understand their function, we examined the enzymatic properties of Dpb8, a DExD/H box protein previously shown to be required for the synthesis of the 18S rRNA. As expected for an RNA helicase, we demonstrate that recombinant Dbp8 has ATPase activity in vitro, and that this activity is dependent on an intact ATPase domain. Strikingly, we identify Esf2, a nucleolar putative RNA binding protein, as a binding partner for Dbp8, and show that it enhances Dbp8 ATPase activity by decreasing the K_M for ATP. Thus, we have uncovered Esf2 as the first example of a protein co-factor that has a stimulatory effect on a nucleolar RNA helicase. We show that Esf2 can bind to pre-rRNAs and speculate that it may function to bring Dbp8 to the pre-rRNA, thereby both regulating its enzymatic activity and guiding Dbp8 to its site of action.