Bloom Syndrome and Maternal Uniparental Disomy for Chromosome 15

Bloom syndrome (BS) is an autosomal recessive disorder characterized by increases in the frequency of sister-chromatid exchange and in the incidence of malignancy. Chromosome-transfer studies have shown the BS locus to map to chromosome 15q. This report describes a subject with features of both BS and Prader-Willi syndrome (PWS). Molecular analysis showed maternal uniparental disomy for chromosome 15. Meiotic recombination between the two disomic chromosomes 15 has resulted in heterodisomy for proximal 15q and isodisomy for distal 15q. In this individual BS is probably due to homozygosity for a gene that is telomeric to D15S95 (15q25), rather than to genetic imprinting, the mechanism responsible for the development of PWS. This report represents the first application of disomy analysis to the regional localization of a disease gene. This strategy promises to be useful in the genetic mapping of other uncommon autosomal recessive conditions.     

Apical Shoot Meristem Culture in Red Pepper (Capsicum annuum L.)

A protocol has been developed to obtain whole plants from apical shoot meristems of red pepper (Capsicum annuum L. cv. Bhivapuri), susceptible to viral infections. The meristems (～ 0.8 mm long), from aseptically grown seedlings (one-month-old), cultured on filter paper bridge in liquid Murashige and Skoog medium supplemented with 2 mg/l benzylaminopurine produced multiple shoots (5–7 per explant). The differentiated shoots developed further upon transfer to agar-solidified medium. Complete plantlets were obtained after rooting of shoots on MS medium fortified with 1 mg/l naphthaleneacetic acid.     

Combined action of isoniazid and para-aminosalicylic acid in vivo on human chromosomes in lymphocyte cultures

Summary Two antitubercular drugs, viz., isoniazid (INH) and para-aminosalicylic acid (PAS), in combination, were evaluated for their in vivo clastogenic effects on human lymphocyte chromosomes. Lymphocyte cultures from tuberculosis patients taking a therapeutic dose of INH and PAS for a period of not less then 3 months and from two sets of controls were used: (1) newly diagnosed tuberculosis patients who were not yet under therapy and (2) healthy individuals from the general population. Chromosome aberration frequency was very significantly increased in the patients exposed to combined INH and PAS therapy as compared with controls. The most frequently observed aberrations were chromatid breaks and gaps. Isoniazid, the major antituberculosis drug, has been reported not to be clastogenic by itself. However, we observed that the INH-PAS combination commonly used in therapy was clastogenic. From this observation it may be concluded that INH and PAS act synergistically in producing chromosomal aberrations.     

Structural coupling of the EF hand and C‐terminal GTPase domains in the mitochondrial protein Miro

Miro is a highly conserved calcium‐binding GTPase at the regulatory nexus of mitochondrial transport and autophagy. Here we present crystal structures comprising the tandem EF hand and carboxy terminal GTPase (cGTPase) domains of Drosophila Miro. The structures reveal two previously unidentified ‘hidden’ EF hands, each paired with a canonical EF hand. Each EF hand pair is bound to a helix that structurally mimics an EF hand ligand. A key nucleotide‐sensing element and a Pink1 phosphorylation site both lie within an extensive EF hand–cGTPase interface. Our results indicate structural mechanisms for calcium, nucleotide and phosphorylation‐dependent regulation of mitochondrial function by Miro.     

Novel Neuroprotective Function of Apical-Basal Polarity Gene Crumbs in Amyloid Beta 42 (Aβ42) Mediated Neurodegeneration

Alzheimer''s disease (AD, OMIM: 104300), a progressive neurodegenerative disorder with no cure to date, is caused by the generation of amyloid-beta-42 (Aβ42) aggregates that trigger neuronal cell death by unknown mechanism(s). We have developed a transgenic Drosophila eye model where misexpression of human Aβ42 results in AD-like neuropathology in the neural retina. We have identified an apical-basal polarity gene crumbs (crb) as a genetic modifier of Aβ42-mediated-neuropathology. Misexpression of Aβ42 caused upregulation of Crb expression, whereas downregulation of Crb either by RNAi or null allele approach rescued the Aβ42-mediated-neurodegeneration. Co-expression of full length Crb with Aβ42 increased severity of Aβ42-mediated-neurodegeneration, due to three fold induction of cell death in comparison to the wild type. Higher Crb levels affect axonal targeting from the retina to the brain. The structure function analysis identified intracellular domain of Crb to be required for Aβ42-mediated-neurodegeneration. We demonstrate a novel neuroprotective role of Crb in Aβ42-mediated-neurodegeneration.     

Genetic and physiological relatedness of antagonistic Trichoderma isolates against soil borne plant pathogenic fungi

In this study, the in vitro potential of 42 Trichoderma spp. were evaluated against four isolates of soil borne phytopathogenic fungi viz., Rhizoctonia solani, Macrophomina sp., Sclerotium rolfsii and Pythium aphanidermatum in dual culture techniques and through production of volatile and non-volatile inhibitors. In vitro screening results showed that the proportion of isolates with antagonistic activities was highest for the S. rolfsii followed by R. solani, Macrophomina sp. and P. aphanidermatum, respectively. The isolates TNT1, TNP2 and TWP1 showed consistent results in volatile and non-volatile activity in vitro against any of the two pathogens tested. Based on genomic finger prints, potential isolates showed no particular correlation between the origin of the isolates and the Random Amplified Polymorphic DNA (RAPD) groups could not be established. However, the polymorphism shown by the isolates did not correlate to their level of antagonism. Whereas, in physiology studies using BIOLOG (microbial identification system), three groups were formed, one group consists with 14 different Trichoderma species and two groups with two isolates each comprised of only T. koningii and T. viride.     

Could pericytic mimicry represent another type of melanoma cell plasticity with embryonic properties?

We hypothesize that the interaction between angiotropic melanoma cells and the abluminal vascular surface can induce or sustain embryonic and/or stem cell migratory properties in these tumor cells. As a result, such angiotropic melanoma cells may migrate along the abluminal vascular surface, demonstrating pericytic mimicry. Through these cellular interactions, melanoma cells may migrate toward secondary sites.