Unusual peroxidase activity of polynitroxylated pegylated hemoglobin: Elimination of H2O2 coupled with intramolecular oxidation of nitroxides

Polynitroxylated hemoglobin (Hb(AcTPO)₁₂) has been developed as a hemoglobin-based oxygen carrier. While Hb(AcTPO)₁₂ has been shown to exert beneficial effects in a number of models of oxidative injury, its peroxidase activity has not been characterized thus far. In the blood stream, Hb(AcTPO)₁₂ undergoes reduction by ascorbate to its hydroxylamine form Hb(AcTPOH)₁₂. Here we report that Hb(AcTPOH)₁₂ exhibits peroxidase activity where H₂O₂ is utilized for intramolecular oxidation of its TPOH residues to TPO. This represents an unusual redox-catalytic mechanism whereby reduction of H₂O₂ is achieved at the expense of reducing equivalents of ascorbate converted into those of Hb(AcTPOH)₁₂, a new propensity that cannot be directly associated with ascorbate.     

Ultrastructure of long-range transport carriers moving from the trans Golgi network to peripheral endosomes

The delivery of mannose 6-phosphate receptors carrying lysosomal hydrolases from the trans-Golgi network (TGN) to the endosomal system is mediated by selective incorporation of the receptor-hydrolase complexes into vesicular transport carriers (TCs) that are coated with clathrin and the adaptor proteins, GGA and AP-1. Previous electron microscopy (EM) and biochemical studies have shown that these TCs consist of spherical coated vesicles with a diameter of 60-100 nm. The use of fluorescent live cell imaging, however, has revealed that at least some of this transport relies on a subset of apparently larger and highly pleiomorphic carriers that detach from the TGN and translocate toward the peripheral cytoplasm until they meet with distally located endosomes. The ultrastructure of such long-range TCs has remained obscure because of the inability to examine by conventional EM the morphological details of rapidly moving organelles. The recent development of correlative light-EM has now allowed us to obtain ultrastructural 'snapshots' of these TCs immediately after their formation from the TGN in live cells. This approach has revealed that such carriers range from typical 60- to 100-nm clathrin-coated vesicles to larger, convoluted tubular-vesicular structures displaying several coated buds. We propose that this subset of TCs serve as vehicles for long-range distribution of biosynthetic or recycling cargo from the TGN to the peripheral endosomes.     

Lipid and carbohydrate based adjuvant/carriers in immunology.

This review discusses various issues regarding vaccines; what are they and how they work, safety aspects, the role of adjuvants and carriers in vaccination, synthetic peptides as immunogens, and new technologies for vaccine development and delivery including the identification of novel adjuvants for mucosal vaccine delivery. There has been a recent increase of interest in the use of lipids and carbohydrates as adjuvants, and so a particular emphasis is placed on adjuvants derived from lipids or carbohydrates, or from both.     

Effects of G-protein probes on interactions between auxin efflux carriers and phytotropin receptors in zucchini (Cucurbita pepo L.) microsomal membranes

Microsomal vesicles prepared from etiolated hypocotyl tissue of zucchini (Cucurbita pepo L. cv. All Green Bush) exhibited saturable N-1-naphthylphthalamic acid ([³H]NPA) binding, NPA-stimulated association of indol-3yl-acetic acid ([³H]IAA), and saturable binding of guanosine 5-O-[3-thiotriphosphate] (GTP--[³⁵S]). These vesicles were used to test the possibility that NPA receptors might interact with IAA-anion efflux carriers by coupling through a GTP-binding protein (G-protein). Unlabelled GTP--S or guanosine 5-O-[2-thiodiphosphate] (GDP--S) had no effect on saturable NPA binding or on the NPA-stimulated association of IAA with microsomes. NPA did not affect saturable binding of GTP--[³⁵S] to microsomes, either in the presence or absence of saturating concentrations of unlabelled GTP--S or GDP. It is concluded that the occupancy of phytotropin receptors is not transduced to auxin efflux carriers by a GTP-binding protein.     

兰州市婴幼儿艰难梭菌带菌状况

在兰州市随机采集的２１６名健康婴幼儿粪标本经分离并对其培养特性、菌落菌体形态特征、生化反应特性以及毒素原性等进行一系列检查,检出了３７人的粪便含有艰难梭菌（１０４─１０８／ｇ）,检出总阳性率为１７．１％,新生儿、婴儿及幼儿各年龄组的检出阳性率分别为１３．５％（１９／４１）、３３．３％（１３／３９）、１３．９％（５／３６）。３７株分离菌中毒素原性阳性者仅有８株（２１．６％）,均分布于婴儿与幼儿两组。新生儿１４１人中２７人的粪标本为胎粪,只有１人（３．７％）含艰难梭菌（２×１０６／ｇ）,但不产毒素。所有婴幼儿中有２２人因各种原因曾用过抗菌药物,但仅有２人的粪便含艰难梭菌,而且均为非产毒株,表明艰难梭菌检出率与药物服用之间似无显著的相关性。     

Involvement of mitochondrial inner membrane anion carriers in the uncoupling effect of fatty acids

This paper considers stages of the search (initiated by V. P. Skulachev) for a receptor protein for fatty acids that is involved in their uncoupling effect. Based on these studies, mechanism of the ADP/ATP antiporter involvement in the uncoupling induced by fatty acids was proposed (Skulachev, V. P. (1991) FEBS Lett., 294, 158– 162). New data (suppression by carboxyatractylate of the SDS-induced uncoupling, pH-dependence of the ADP/ATP and the glutamate/aspartate antiporter contributions to the uncoupling, etc.) led to modification of this hypothesis. During discussion of the uncoupling effect of fatty acids caused by opening of the Ca²⁺-dependent pore, special attention is given to the effects of carboxyatractylate added in the presence of ADP. The functioning of the uncoupling protein UCP2 in kidney mitochondria is considered, as well as the diversity observed by us in effects of 200 µM GDP on decrease in under the influence of oleic acid added after H₂O₂ (in the presence of succinate, oligomycin, malonate). A speculative explanation of the findings is as follows: 1) products of lipid and/or fatty acid peroxidation (PPO)modify the ADP/ATP antiporter in such a way that its involvement in the fatty acid-induced uncoupling is suppressed by GDP; 2) GDP increases the PPO concentration in the matrix by suppression of efflux of fatty acid hydroperoxide anions through the UCP (Goglia, F., and Skulachev, V. P. (2003) FASEB, 17, 1585–1591)and/or of efflux of PPO anions with involvement of the GDP-sensitive ADP/ATP antiporter; 3) PPO can potentiate the oleate-induced decrease in due to inhibition of succinate oxidation.Translated from Biokhimiya, Vol. 70, No. 2, 2005, pp. 197–202.Original Russian Text Copyright © 2005 by Mokhova, Khailova.This revised version was published online in April 2005 with corrections to the post codes.     

RNA interference-mediated silencing of the syntaxin 5 gene induces Golgi fragmentation but capable of transporting vesicles

It has been suggested that syntaxin 5 (Syx5) participates in vesicular transport. We examined the effects of Syx5 down-regulation on the morphology of the Golgi apparatus and the transport of vesicles in mammalian cells. Knockdown of the Syx5 gene resulted in Golgi fragmentation without changing the level of endoplasmic reticulum (ER)-resident proteins, other Golgi-SNAREs (soluble N-ethylmaleimide-sensitive factor-attachment protein receptors), and coatmer proteins. Strikingly, a major decrease in Syx5 expression barely affected the anterograde transport of vesicular stomatitis virus G (VSVG) protein to the plasma membrane. These results suggest that Syx5 is required for the maintenance of the Golgi structures but may not play a major role in the transport of vesicles carrying VSVG between the ER and the Golgi compartment.     

Bio-efficacy of different oil carriers in ultra low volume sprayer for management of pod borer,Helicoverpa armigera (Hübner) in pigeonpea ecosystem

A study was conducted to evaluate the bioefficacy of different oil carriers (sunflower oil, seamum oil, neem oil, mineral oil), sugar solution and water formulation to be used in ultra low volume sprayer (ULV) along with rynaxypyr 18.5 SC (Coragen) for the management of pod borer at the Agricultural Research Station, Gulbarga, Karnataka, India during the kharif season of 2011–2012. The results revealed that the sesamum oil carrier fits well with rynaxypyr 18.5 SC and recorded the lowest mean pod borer larval population after last spray (1.0 per five plants) the lowest pod damage (23.20%), grain damage (18.30%) and higher grain yield (9.43?q/ha) with a high B:C ratio of 3.64 in the plot sprayed with the sesamum oil carrier. The findings suggested that the sesamum oil carrier in ULV sprayer is suitable and practicable in pigeonpea ecosystem for effective management of pod borer with no risk of phytotoxicity, spray drift and operational difficulties. The foregoing studies indicated that the performance of sesamum oil carriers was superior to other carriers in terms of suppression of larval population, reduction in pod damage and harnessing higher yield.     

Further insight into the neurobehavioral pattern of children carrying the 2p16.3 heterozygous deletion involving NRXN1: Report of five new cases

Increasing evidence links heterozygosity for NRXN1 gene deletions to a clinically wide spectrum of neurodevelopmental, psychiatric, and neurological disorders. However, to date, the neurocognitive and social communication features of children carrying this genomic rearrangement have not been assessed in detail. The cognitive and behavioral profiles of five children carrying a heterozygous NRXN1 deletion were investigated through systematic assessment of the cognitive and developmental levels, adaptive profile and presence of behavioral symptoms and autistic features. Furthermore, four transmitting parents were assessed by means of cognitive, psychopathological and parental stress tests. A below‐average cognitive level was documented in all children, and defective adaptive levels were observed in four of them. Three of the five children were diagnosed as having autism spectrum disorder in comorbidity with intellectual disability/global developmental delay, with a major impairment in social communication skills. The remaining two children presented with isolated intellectual disability and an unclassifiable neurodevelopmental disorder, respectively. This study provide data contributing to a more accurate characterization of the neurobehavioral phenotype of individuals carrying heterozygous NRXN1 deletions. This analysis indicates that these structural rearrangements are associated with a variable expression of neuropsychiatric symptoms, and cast some doubts about the incomplete penetrance of the disorder.