Combined venomics, venom gland transcriptomics, bioactivities, and antivenomics of two Bothrops jararaca populations from geographic isolated regions within the Brazilian Atlantic rainforest.

Bothrops jararaca is a slender and semi-arboreal medically relevant pit viper species endemic to tropical and subtropical forests in southern Brazil, Paraguay, and northern Argentina (Misiones). Within its geographic range, it is often abundant and is an important cause of snakebite. Although no subspecies are currently recognized, geographic analyses have revealed the existence of two well-supported B.

Astrocyte-induced synaptogenesis is mediated by transforming growth factor β signaling through modulation of D-serine levels in cerebral cortex neurons.

Assembly of synapses requires proper coordination between pre- and postsynaptic elements. Identification of cellular and molecular events in synapse formation and maintenance is a key step to understand human perception, learning, memory, and cognition. A key role for astrocytes in synapse formation and function has been proposed.

Toll-like receptor 3 regulates neural stem cell proliferation by modulating the Sonic Hedgehog pathway.

Toll-like receptor 3 (TLR3) signaling has been implicated in neural stem/precursor cell (NPC) proliferation. However, the molecular mechanisms involved, and their relationship to classical TLR-mediated innate immune pathways, remain unknown. Here, we report investigation of the mechanics of TLR3 signaling in neurospheres comprised of epidermal growth factor (EGF)-responsive NPC isolated from murine embryonic cerebral cortex of C57BL/6 (WT) or TLR3 deficient (TLR3(-/-)) mice.

Protein kinase C activity regulates D-serine availability in the brain.

D-serine is a co-agonist of NMDA receptor (NMDAR) and plays important roles in synaptic plasticity mechanisms. Serine racemase (SR) is a brain-enriched enzyme that converts L-serine to D-serine. SR interacts with the protein interacting with C-kinase 1 (PICK1), which is known to direct protein kinase C (PKC) to its targets in cells.

Induction of Toll-like receptor 3-mediated immunity during gestation inhibits cortical neurogenesis and causes behavioral disturbances.

Maternal infection during pregnancy with a wide range of RNA and DNA viruses is associated with increased risk for schizophrenia and autism in their offspring. A common feature in these exposures is that virus replication induces innate immunity through interaction with Toll-like receptors (TLRs). We employed a mouse model wherein pregnant mice were exposed to polyinosinic-polycytidylic acid [poly(I ⋅ C)], a synthetic, double-stranded RNA molecular mimic of replicating virus.

Astrocytes recognize intracellular polyinosinic-polycytidylic acid via MDA-5.

RNA virus replication results in expression of double-stranded RNA (ds-RNA) molecules that trigger innate immune responses through interactions with both intracellular and extracellular receptors. We investigated the contributions of the extracellular and intracellular pathways to innate immunity in murine astrocyte primary cultures using polyinosinic-polycytidylic acid (poly I:C), a synthetic ds-RNA molecule designed to mimic RNA virus infection. Whereas extracellular poly I:C (naked poly I:C) mainly induced the expression of regulated on activation normal T-cell expressed and secreted (RANTES), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-alpha), intracellular delivery of poly I:C (complexed poly I:C) chiefly induced expression of IFN-beta and IL-6.

New chemical method of viral inactivation for vaccine development based on membrane fusion inhibition.

Membrane fusion is an essential step in the entry of enveloped viruses into their host cells. This process is triggered by conformational changes in viral surface glycoproteins. We have demonstrated previously that modification of vesicular stomatitis virus (VSV) with diethylpyrocarbonate (DEPC) abolished the conformational changes on VSV glycoprotein and the fusion reaction induced by the virus.

A CSF and postmortem brain study of D-serine metabolic parameters in schizophrenia.

Clinical trials demonstrated that D-serine administration improves schizophrenia symptoms, raising the possibility that altered levels of endogenous D-serine may contribute to the N-methyl D-aspartate receptor hypofunction thought to play a role in the disease. We hypothesized that cerebro-spinal fluid (CSF) D-serine levels are decreased in the patients due to reduced synthesis and/or increased degradation in brain. We now monitored amino acid levels in CSF from 12 schizophrenia patients vs.

Inactivation of vesicular stomatitis virus through inhibition of membrane fusion by chemical modification of the viral glycoprotein.

Membrane fusion is an essential step in the entry of enveloped viruses into their host cells triggered by conformational changes in viral glycoproteins. We have demonstrated previously that modification of vesicular stomatitis virus (VSV) with diethylpyrocarbonate (DEPC) abolished conformational changes on VSV glycoprotein and the fusion reaction catalyzed by the virus. In the present study, we evaluated whether treatment with DEPC was able to inactivate the virus.

Serine racemase modulates intracellular D-serine levels through an alpha,beta-elimination activity.

Mammalian brain contains high levels of d-serine, an endogenous co-agonist of N-methyl D-aspartate type of glutamate receptors. D-Serine is synthesized by serine racemase, a brain enriched enzyme converting L- to D-serine. Degradation of D-serine is achieved by D-amino acid oxidase, but this enzyme is not present in forebrain areas that are highly enriched in D-serine.

Cofactors of serine racemase that physiologically stimulate the synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine.

High levels of d-serine occur in the brain, challenging the notion that d-amino acids would not be present or play a role in mammals. d-serine levels in the brain are even higher than many l-amino acids, such as asparagine, valine, isoleucine, and tryptophan, among others. d-serine is synthesized by a serine racemase (SR) enzyme, which directly converts l- to d-serine.

Neurobiology through the looking-glass: D-serine as a new glial-derived transmitter.

D-Amino acids have been known to be present in bacteria for more than 50 years, but only recently they were identified in mammals. The occurrence of D-amino acids in mammals challenge classic concepts in biology in which only L-amino acids would be present or thought to play important roles. Recent discoveries uncovered a role of endogenous D-serine as a putative glial-derived transmitter that regulates glutamatergic neurotransmission in mammalian brain.

Glial transport of the neuromodulator D-serine.

D-Serine is an endogenous agonist of NMDA receptors that occurs in astrocytes in gray matter areas of the brain. D-Serine is synthesized from L-serine by the activity of a glial enriched serine racemase, but little is known on the properties of D-serine transport and factors regulating its synaptic concentration. In the present report we characterize the transport of D-serine in astrocytes.