Structural features and in vivo antitussive activity of the water extracted polymer from Glycyrrhiza glabra

Antitussive drugs are amongst the most widely used medications worldwide; however no new class of drugs has been introduced into the market for many years. Herein, we have analyzed the water-extracted polymeric fraction (WE) of Glycyrrhiza glabra. This arabinogalactan protein enriched fraction, ≥ 85% of which gets precipitated with Yariv reagent, consisted mainly of 3- and 3,6-linked galactopyranosyl, and 5- and 3,5-linked arabinofuranosyl residues. Peroral administration of this polymer in a dose of 50mg/kg body weight decreases the number of citric acid induced cough efforts in guinea pigs more effectively than codeine. It does not induce significant change in the values of specific airway resistance or provoked any observable adverse effects.     

Insights from Caenorhabditis elegans on the role of metals in neurodegenerative diseases

Neurodegeneration is characterized by the cell death or loss of structure and/or function of neurons. Many neurodegenerative diseases including Parkinson's disease (PD) and Alzheimer's disease (AD) are the result of neurodegenerative processes. Metals are essential for many life processes, but they are also culpable for several neurodegenerative mechanisms. In this review, we discuss the role of metals in neurodegenerative diseases with emphasis on the utility of Caenorhabditis elegans (C. elegans) genetic models in deciphering mechanisms associated with the etiology of PD and AD.     

An Asymmetric Opening of HIV-1 Envelope Mediates Antibody-Dependent Cellular Cytotoxicity

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Steric Crowding of the Turn Region Alters the Tertiary Fold of Amyloid-β18–35 and Makes It Soluble

Aβ self-assembles into parallel cross-β fibrillar aggregates, which is associated with Alzheimer''s disease pathology. A central hairpin turn around residues 23–29 is a defining characteristic of Aβ in its aggregated state. Major biophysical properties of Aβ, including this turn, remain unaltered in the central fragment Aβ_18–35. Here, we synthesize a single deletion mutant, ΔG25, with the aim of sterically hindering the hairpin turn in Aβ_18–35. We find that the solubility of the peptide goes up by more than 20-fold. Although some oligomeric structures do form, solution state NMR spectroscopy shows that they have mostly random coil conformations. Fibrils ultimately form at a much higher concentration but have widths approximately twice that of Aβ_18–35, suggesting an opening of the hairpin bend. Surprisingly, two-dimensional solid state NMR shows that the contact between Phe¹⁹ and Leu³⁴ residues, observed in full-length Aβ and Aβ_18–35, is still intact in these fibrils. This is possible if the monomers in the fibril are arranged in an antiparallel β-sheet conformation. Indeed, IR measurements, supported by tyrosine cross-linking experiments, provide a characteristic signature of the antiparallel β-sheet. We conclude that the self-assembly of Aβ is critically dependent on the hairpin turn and on the contact between the Phe¹⁹ and Leu³⁴ regions, making them potentially sensitive targets for Alzheimer''s therapeutics. Our results show the importance of specific conformations in an aggregation process thought to be primarily driven by nonspecific hydrophobic interactions.     

Ectopic overexpression of a mungbean vacuolar Na+/H+ antiporter gene (VrNHX1) leads to increased salinity stress tolerance in transgenic Vigna unguiculata L. Walp

Salinity is a major threat to sustainable agriculture worldwide. Plant NHX exchangers play an important role in conferring salt tolerance under salinity stress. In this study, a vacuolar Na⁺/H⁺ antiporter gene VrNHX1 (Genbank Accession No. JN656211.1) from mungbean (Vigna radiata) was introduced into cowpea (Vigna unguiculata) by the Agrobacterium tumefaciens-mediated transformation method. Polymerase chain reaction and Southern blot hybridization confirmed the stable integration of VrNHX1 into the cowpea genome. Comparative expression analysis by semi-quantitative RT-PCR revealed higher expression of VrNHX1 in transgenic cowpea plants than wild-type. Under salt stress conditions, T2 transgenic 35S:VrNHX1 cowpea lines exhibited higher tolerance to 200 mM NaCl treatment than wild-type. Furthermore, T2 transgenic 35S:VrNHX1 lines maintained a higher K⁺/Na⁺ ratio in the aerial parts under salt stress and accumulated higher [Na⁺] in roots than wild-type. Physiological analysis revealed lower levels of lipid peroxidation, hydrogen peroxide and oxygen radical production but higher levels of relative water content and proline, ascorbate and chlorophyll contents in T2 transgenic 35S:VrNHX1 lines.     

Structural studies of arginine induced enhancement in the activity of T7 RNA polymerase

The PrP(C) protein, which is especially present in the cellular membrane of nervous system cells, has been extensively studied for its controversial antioxidant activity. In this study, we elucidated the free radical scavenger activity of purified murine PrP(C) in solution and its participation as a cell protector in astrocytes that were subjected to treatment with an oxidant. In vitro and using an EPR spin-trapping technique, we observed that PrP(C) decreased the oxidation of the DMPO trap in a Fenton reaction system (Cu(2+)/ascorbate/H(2)O(2)), which was demonstrated by approximately 70% less DMPO/OH(). In cultured PrP(C)-knockout astrocytes from mice, the absence of PrP(C) caused an increase in intracellular ROS (reactive oxygen species) generation during the first 3h of H(2)O(2) treatment. This rapid increase in ROS disrupted the cell cycle in the PrP(C)-knockout astrocytes, which increased the population of cells in the sub-G1 phase when compared with cultured wild-type astrocytes. We conclude that PrP(C) in solution acts as a radical scavenger, and in astrocytes, it is essential for protection from oxidative stress caused by an external chemical agent, which is a likely condition in human neurodegenerative CNS disorders and pathological conditions such as ischemia.     

A case with unilateral hypoglossal nerve injury in branchial cyst surgery

ABSTRACT: An 11 years old boy came, with complain of mild dysarthria. Examination revealed marked hemiatrophy of left side of the tongue. Five months back he underwent ipsilateral branchial cyst operation. To our knowledge, no case was reported. After branchial cyst operation if there is any residual remnant chance of recurrence is very high.     

Agrobacterium-mediated Transformation of Brassica juncea with a Cyanobacterial (Synechocystis PCC6803) Delta-6 Desaturase Gene Leads to Production of Gamma-linolenic Acid

Genetic manipulation of the oil-yielding crop plants for better oil quality through biotechnological methods is an important aspect of crop improvement. Due to the inherent absence of the Δ⁶-desaturase (d6D) function, Brassica juncea, an oil-yielding crop plant, is unable to synthesize γ-linolenic acid (GLA), a nutritionally important fatty acid although the crop plant synthesizes the precursor fatty acids required for GLA production. Cyanobacterial d6D introduces carbon–carbon double bond onto linoleic acid (C18:2) and α-linolenic acid (C18:3) by desaturation processes for production of GLA and octadecatetraenoic acid (OTA) respectively. In the present investigation, d6D coding sequence from Synechocystis sp. PCC6803 was cloned by polymerase chain reaction and introduced into B. juncea through Agrobacterium-mediated transformation technique. Both cytosolic as well as seed-specific expression of d6D were attempted. The transformed plants show production of GLA and OTA in contrast to their absence in the untransformed control plants adducing evidence for introgression and functional expression of the cyanobacterial d6D gene in B. juncea.     

Phage display of functional, full-length human and viral membrane proteins

Phage display of protein and peptide libraries offers a powerful technology for the selection and isolation of ligands and receptors. To date, the technique has been considered limited to soluble, non-membrane proteins. We report two examples of phage display of full-length, folded and functional membrane proteins. Consistent display required the recently reported KO7(+) helper phage. The two proteins, full-length caveolin-1 and HIV gp41, display well on the surface of the phage, and maintain their binding activities as shown by in vitro assays.