Branched chain amino acid transaminases in brain in methionine sulphoximine (MSI) toxicity

The effect of intraperitoneal administration of L-methionine-DL-sulphoximine (MSI) was studied on branched-chain amino acid transaminases (BCAA-T) in different regions of rat brain and in liver. Administration of an acute dose of MSI (300 mg/kg body weight) resulted in a significant decrease in leucine aminotransferase activity in cerebral cortex, cerebellum, and brain-stem, while the activity of isoleucine aminotransferase was enhanced in hippocampus, corpus striatum, brain stem, and midbrain. Activities of both these enzymes changed marginally or remained unaltered in other regions of the brain. Valine aminotransferase showed a significant decrease in all the regions of the brain except in cerebellum. Following the administration of a sub-acute dose of MSI (150 mg/kg body wt.), the activities of the three BCAA aminotransferases were found to be enhanced in all regions of the brain. The results are discussed in relation to the utilization of BCAA for the production of glutamate and glutamine in hyperammonemia.     

Near Neutral pH Redox Flow Battery with Low Permeability and Long‐Lifetime Phosphonated Viologen Active Species

A highly stable phosphonate‐functionalized viologen is introduced as the redox‐active material in a negative potential electrolyte for aqueous redox flow batteries (ARFBs) operating at nearly neutral pH. The solubility is 1.23 m and the reduction potential is the lowest of any substituted viologen utilized in a flow battery, reaching ?0.462 V versus SHE at pH = 9. The negative charges in both the oxidized and the reduced states of 1,1′‐bis(3‐phosphonopropyl)‐[4,4′‐bipyridine]‐1,1′‐diium dibromide ( BPP?Vi ) effect low permeability in cation exchange membranes and suppress a bimolecular mechanism of viologen decomposition. A flow battery pairing BPP?Vi with a ferrocyanide‐based positive potential electrolyte across an inexpensive, non‐fluorinated cation exchange membrane at pH = 9 exhibits an open‐circuit voltage of 0.9 V and a capacity fade rate of 0.016% per day or 0.00069% per cycle. Overcharging leads to viologen decomposition, causing irreversible capacity fade. This work introduces extremely stable, extremely low‐permeating and low reduction potential redox active materials into near neutral ARFBs.     

Proteomic Profiling of the TRAF3 Interactome Network Reveals a New Role for the ER-to-Golgi Transport Compartments in Innate Immunity

Tumor Necrosis Factor receptor-associated factor-3 (TRAF3) is a central mediator important for inducing type I interferon (IFN) production in response to intracellular double-stranded RNA (dsRNA). Here, we report the identification of Sec16A and p115, two proteins of the ER-to-Golgi vesicular transport system, as novel components of the TRAF3 interactome network. Notably, in non-infected cells, TRAF3 was found associated with markers of the ER-Exit-Sites (ERES), ER-to-Golgi intermediate compartment (ERGIC) and the cis-Golgi apparatus. Upon dsRNA and dsDNA sensing however, the Golgi apparatus fragmented into cytoplasmic punctated structures containing TRAF3 allowing its colocalization and interaction with Mitochondrial AntiViral Signaling (MAVS), the essential mitochondria-bound RIG-I-like Helicase (RLH) adaptor. In contrast, retention of TRAF3 at the ER-to-Golgi vesicular transport system blunted the ability of TRAF3 to interact with MAVS upon viral infection and consequently decreased type I IFN response. Moreover, depletion of Sec16A and p115 led to a drastic disorganization of the Golgi paralleled by the relocalization of TRAF3, which under these conditions was unable to associate with MAVS. Consequently, upon dsRNA and dsDNA sensing, ablation of Sec16A and p115 was found to inhibit IRF3 activation and anti-viral gene expression. Reciprocally, mild overexpression of Sec16A or p115 in Hec1B cells increased the activation of IFNβ, ISG56 and NF-κB -dependent promoters following viral infection and ectopic expression of MAVS and Tank-binding kinase-1 (TBK1). In line with these results, TRAF3 was found enriched in immunocomplexes composed of p115, Sec16A and TBK1 upon infection. Hence, we propose a model where dsDNA and dsRNA sensing induces the formation of membrane-bound compartments originating from the Golgi, which mediate the dynamic association of TRAF3 with MAVS leading to an optimal induction of innate immune responses.     

Expression of protective antigen in transgenic plants: a step towards edible vaccine against anthrax

Protective antigen (PA) is the most potent molecule for vaccination against anthrax. In the present study, we have successfully integrated protective antigen gene in nuclear genome of tobacco plants by Agrobacterium mediated leaf-disc transformation method. Expression of protective antigen gene was detected by immunoblot analysis using antisera raised against purified PA. A distinct band of approximately 83kDa lighted up in the protein extracted from transformed plants while there was no such band in untransformed plants. The plant expressed PA showed biological activity just like native PA, which was demonstrated by cytolytic assay on macrophage like cell lines with lethal factor. This study establishes for the first time expression of PA gene in a plant system and thus marks the first milestone towards developing edible vaccine against anthrax.     

Time Course Study of Blood Pressure in Term and Preterm Infants Immediately after Birth

Objective

To describe temporal changes in systolic, diastolic, and mean blood pressure (SBP, DBP, and MBP, respectively) in term and preterm infants immediately after birth.

Methods

Prospective observational two-center study. In term infants SBP, DBP, and MBP were assessed non-invasively every minute for the first 15 minutes, and in preterm infants every minute for the first 15 minutes, as well as at 20, 25, 30, 45, and 60 minutes after birth. Regression analyses were performed by gender and respiratory support in all neonates; and by mode of delivery, cord clamping time, and development of ultrasound-detected brain injury in preterm neonates.

Results

Term infants (n = 54) had a mean (SD) birth weight of 3298 (442) g and gestational age of 38 (1) weeks, and preterm infants (n = 94) weighed 1340 (672) g and were 30 (3) weeks gestation. Term infants’ SBP, DBP and MBP within the first 15 minutes after birth were independent of gender or respiratory support. Linear mixed regression analysis showed that preterm infants, who were female, born vaginally, had delayed cord clamping and did not require positive pressure ventilation nor develop periventricular injury or ventriculomegaly, had significantly higher SBP, DBP, and MBP at some measurement points within the first hour after birth.

Conclusions

We present novel reference ranges of BP immediately after birth in a cohort of term and preterm neonates. They may aid in optimization of cardiovascular support during early transition at all gestations.     

DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps

The innate immune response plays a crucial role in satisfactory host resolution of bacterial infection. In response to chemotactic signals, neutrophils are early responding cells that migrate in large numbers to sites of infection. The recent discovery of secreted neutrophil extracellular traps (NETs) composed of DNA and histones opened a novel dimension in our understanding of the microbial killing capacity of these specialized leukocytes. M1 serotype strains of the pathogen Group A Streptococcus (GAS) are associated with invasive infections including necrotizing fasciitis (NF) and express a potent DNase (Sda1). Here we apply a molecular genetic approach of allelic replacement mutagenesis, single gene complementation, and heterologous expression to demonstrate that DNase Sda1 is both necessary and sufficient to promote GAS neutrophil resistance and virulence in a murine model of NF. Live fluorescent microscopic cell imaging and histopathological analysis are used to establish for the first time a direct linkage between NET degradation and bacterial pathogenicity. Inhibition of GAS DNase activity with G-actin enhanced neutrophil clearance of the pathogen in vitro and reduced virulence in vivo. The results demonstrate a significant role for NETs in neutrophil-mediated innate immunity, and at the same time identify a novel therapeutic target against invasive GAS infection.     

Photo-movement of coral larvae influences vertical positioning in the ocean

Coral Reefs - Behaviour can have profound consequences for the dispersal potential of an organism. In the marine environment, larvae rely heavily on oceanic currents to migrate from one area to...