Vittatispora, a new melanosporaceous genus from Indian soil

Vittatispora coorgii gen. sp. nov., isolated from soil in India, is described and illustrated. The fungus has morphological characteristics of the genera Melanospora, Sphaerodes and Syspastospora. The most striking feature is the presence of a thick hyaline ridge along the vertical axis of the lemon-shaped ascospores wall. Perithecia also have a long neck composed of adhering hyphae, similar to that of Syspatospora. Phylogenetic studies on the 28S rDNA indicate it is closely related to Melanospora and Sphaerodes and belongs in the Ceratostomataceae. The new genus is based on the distinctive morphology and phylogenetic analyses. The fungus grew in culture only conjointly with a sterile fungus which a BLAST analysis suggested was close to Tetracladium marchalianum.     

Interaction of aliphatic cap group in inhibition of histone deacetylases by cyclic tetrapeptides

Inhibitors of histone deacetylases (HDACs) are a promising class of anticancer agents that effect gene regulation. To know the interaction of aliphatic cap groups with HDACs, cyclic tetrapeptide and bicyclic peptide disulfide hybrids were synthesized without aromatic ring in their macrocyclic framework. Benzene ring of l-Phe in chlamydocin was replaced with several aliphatic amino acids and also a fused bicyclic tetrapeptide was synthesized by ring closing metathesis using Grubb's first generation catalyst. The inhibitory activities of the cyclic peptides against histone deacetylase enzymes were evaluated, which demonstrated most of them are interesting candidates as anticancer agents.     

Curcuma Oil: Reduces Early Accumulation of Oxidative Product and is Anti-apoptogenic in Transient Focal Ischemia in Rat Brain

Turmeric is a source of numerous aromatic compounds isolated from powdered rhizomes of Curcuma longa Linn. The constituents are present as volatile oil, the Curcuma oil (C.oil), semi-solid oleoresins and non-volatile compounds such as curcumin. A rapidly expanding body of data provides evidence of the anti-cancer action of Curcumin, and most importantly in the present context, its neuroprotective activity. Almost nothing is known about such activity of C.oil. We report that C.oil (500 mg Kg⁻¹ i.p.) 15 min before 2 h middle cerebral artery occlusion (MCAo) followed by 24 h reflow in rats significantly diminished infarct volume, improved neurological deficit and counteracted oxidative stress. The percent ischemic lesion volume on diffusion-weighted imaging was significantly attenuated. Mitochondrial membrane potential, reactive oxygen species, peroxynitrite levels, caspase-3 activities leading to delayed neuronal death were significantly inhibited after treatment with C.oil. These results suggest that the neuroprotective activity of C.oil against cerebral ischemia is associated with its antioxidant activities and further; there is attenuation of delayed neuronal death via a caspase-dependent pathway. C.oil appears to be a promising agent not only for the treatment of cerebral stroke, but also for the treatment of other disorders associated with oxidative stress. An erratum to this article can be found at     

Phenyl-tert-butylnitrone induces tumor regression and decreases angiogenesis in a C6 rat glioma model

The prognosis of patients who are diagnosed with glioblastoma multiforme is very poor, due to the difficulty of an early and accurate diagnosis and the lack of currently efficient therapeutic compounds. The efficacy of phenyl-tert-butylnitrone (PBN) as a potential anti-glioma therapeutic drug was assessed by magnetic resonance (MR) imaging (T(1)/T(2)-weighted imaging) and MR angiography (time-of-flight imaging, in conjunction with a Mathematica-based program) methods by monitoring morphologic properties, growth patterns, and angiogenic behaviors of a moderately aggressive rat C6 glioma model. MR results from untreated rats showed the diffusive invasiveness of C6 gliomas, with some associated angiogenesis. PBN administration as a pretreatment was found to clearly induce a decrease in growth rate and tumor regression as well as preventing angiogenesis. This compound even had a 40% efficiency in reducing well-established tumors. MR findings rivaled those from histology and angiogenesis marker immunostaining evaluations. In this study we demonstrated the efficiency of PBN as a potential anti-glioma drug and found it to inhibit tumor cell proliferation and prevent vascular alterations in early stages of glioma progression. The MR methods that we used also proved to be particularly suitable in following the angiogenic behavior and treatment response of a potential anti-glioma agent in a rat C6 glioma model.     

Liposome fluidity alters interactions between the ganglioside GM1 and cholera toxin B subunit

Cholera toxin is a complex protein with a biologically active protein (A subunit) and a cell targeting portion (B subunit). The B subunit is responsible for specific cell binding and entry of the A subunit. One way to limit potential toxicity of the toxin after exposure is to introduce cellular decoys to bind the toxin before it can enter cells. In this study the ganglioside GM1, a natural ligand for cholera toxin, was incorporated into liposomes and the interaction between fluorescent B subunit and the liposome determined. Liposome membrane fluidity was determined to play a major role in the binding between liposomes and the cholera toxin B subunit. Liposomes with lower fluidity demonstrated greater binding with the B subunit. The findings from this study could have important implications on formulation strategies for liposome decoys of toxins.     

CreA-mediated repression in Aspergillus nidulans does not require transcriptional auto-regulation, regulated intracellular localisation or degradation of CreA.

The major regulatory protein in carbon repression in Aspergillus nidulans is CreA. Strains constitutively over-expressing creA show normal responses to carbon repression, indicating that auto-regulation of creA is not essential for CreA-mediated regulation. In these strains, high levels of CreA are present whether cells are grown in repressing or derepressing conditions, indicating large-scale degradation of CreA does not play a key role. CreA is located in the nucleus and cytoplasm in cells when grown in either repressing or derepressing conditions, and absence of CreB, CreD or AcrB does not affect either the localisation or amount of CreA. Therefore, CreA must require some modification or interaction to act as a repressor. Deletion analysis indicates that a region of CreA thought to be important for repression in Trichoderma reesei and Sclerotina sclerotiorum CreA homologues is not critical for function in Aspergillus nidulans.     

Formation of Toxic Oligomeric α-Synuclein Species in Living Cells

Background

Misfolding, oligomerization, and fibrillization of α-synuclein are thought to be central events in the onset and progression of Parkinson''s disease (PD) and related disorders. Although fibrillar α-synuclein is a major component of Lewy bodies (LBs), recent data implicate prefibrillar, oligomeric intermediates as the toxic species. However, to date, oligomeric species have not been identified in living cells.

Methodology/Principal Findings

Here we used bimolecular fluorescence complementation (BiFC) to directly visualize α-synuclein oligomerization in living cells, allowing us to study the initial events leading to α-synuclein oligomerization, the precursor to aggregate formation. This novel assay provides us with a tool with which to investigate how manipulations affecting α-synuclein aggregation affect the process over time. Stabilization of α-synuclein oligomers via BiFC results in increased cytotoxicity, which can be rescued by Hsp70 in a process that reduces the formation of α-synuclein oligomers. Introduction of PD-associated mutations in α-synuclein did not affect oligomer formation but the biochemical properties of the mutant α-synuclein oligomers differ from those of wild type α-synuclein.

Conclusions/Significance

This novel application of the BiFC assay to the study of the molecular basis of neurodegenerative disorders enabled the direct visualization of α-synuclein oligomeric species in living cells and its modulation by Hsp70, constituting a novel important tool in the search for therapeutics for synucleinopathies.     

In Vitro Culture of Kodo Millet: Influence of 2,4-D and Picloram in Combination with Kinetin on Callus Initiation and Regeneration

Immature inflorescences of kodo millet (Paspalum scrobiculatum L. cv. GPUK-3) were cultured on MS medium. Induction of embryogenic callus and subsequent somatic embryogenesis was possible on both 2,4-D and Picloram alone or with kinetin from spikelets as well as rachis. Immature inflorescence cultured on medium supplemented with lower levels of Picloram in combination with kinetin developed organogenic callus with shoot buds. Direct somatic embryo formation on rachis was observed at higher levels of Picloram in combination with kinetin. Plant regeneration was observed when calluses were transferred to α-napthaleneacetic acid (NAA) plus 6-benzylaminopurine (BA) supplemented MS medium. Histological observations provided a clear evidence for both somatic embryogenesis and shoot organogenesis. Profuse rooting was induced on phenylacetic acid (PAA) supplemented medium. Regenerated plants were successfully transferred to pots under field conditions where most of the plants survived and set normal seeds.     

Analysis of the lambdoid prophage element e14 in the E. coli K-12 genome

Background  

Many sequenced bacterial genomes harbor phage-like elements or cryptic prophages. These elements have been implicated in pathogenesis, serotype conversion and phage immunity. The e14 element is a defective lambdoid prophage element present at 25 min in the E. coli K-12 genome. This prophage encodes important functional genes such as lit (T4 exclusion), mcrA (modified cytosine restriction activity) and pin (recombinase).