Cerebral cavernous malformations (CCMs) are hamartomatous vascular malformations characterized by abnormally enlarged capillary cavities without intervening brain parenchyma. They cause seizures and cerebral hemorrhages, which can result in focal neurological deficits. Three CCM loci have been mapped, and loss-of-function mutations were identified in the KRIT1 (CCM1) and MGC4607 (CCM2) genes. We report herein the identification of PDCD10 (programmed cell death 10) as the CCM3 gene. The CCM3 locus has been previously mapped to 3q26-27 within a 22-cM interval that is bracketed by D3S1763 and D3S1262. We hypothesized that genomic deletions might occur at the CCM3 locus, as reported previously to occur at the CCM2 locus. Through high-density microsatellite genotyping of 20 families, we identified, in one family, null alleles that resulted from a deletion within a 4-Mb interval flanked by markers D3S3668 and D3S1614. This de novo deletion encompassed D3S1763, which strongly suggests that the CCM3 gene lies within a 970-kb region bracketed by D3S1763 and D3S1614. Six additional distinct deleterious mutations within PDCD10, one of the five known genes mapped within this interval, were identified in seven families. Three of these mutations were nonsense mutations, and two led to an aberrant splicing of exon 9, with a frameshift and a longer open reading frame within exon 10. The last of the six mutations led to an aberrant splicing of exon 5, without frameshift. Three of these mutations occurred de novo. All of them cosegregated with the disease in the families and were not observed in 200 control chromosomes. PDCD10, also called "TFAR15," had been initially identified through a screening for genes differentially expressed during the induction of apoptosis in the TF-1 premyeloid cell line. It is highly conserved in both vertebrates and invertebrates. Its implication in cerebral cavernous malformations strongly suggests that it is a new player in vascular morphogenesis and/or remodeling.

In the present study, two accessions of Centella asiatica (CA03 and CA23) were subjected to gamma radiation to examine the response of these accessions in terms of survival rate, flavonoid contents, leaf gas exchange and leaf mass. Radiation Sensitivity Tests revealed that based on the survival rate, the LD50 (gamma doses that killed 50% of the plantlets) of the plantlets were achieved at 60 Gy for CA03 and 40 Gy for CA23. The nodal segments were irradiated with gamma rays at does of 30 and 40 Gy for Centella asiatica accession ‘CA03’ and 20 and 30 Gy for accession ‘CA23. The nodal segment response to the radiation was evaluated by recording the flavonoid content, leaf gas exchange and leaf biomass. The experiment was designed as RCBD with five replications. Results demonstrated that the irradiated plantlets exhibited greater total flavonoid contents (in eight weeks) significantly than the control where the control also exhibited the highest total flavonoid contents in the sixth week of growth; 2.64 ± 0.02 mg/g DW in CA03 and 8.94 ± 0.04 mg/g DW in CA23. The total flavonoid content was found to be highest after eight weeks of growth, and this, accordingly, stands as the best time for leaf harvest. Biochemical differentiation based on total flavonoid content revealed that irradiated plantlets in CA23 at 20 and 30 Gy after eight weeks contained the highest total flavonoid concentrations (16.827 ± 0.02; 16.837 ± 0.008 mg/g DW, respectively) whereas in CA03 exposed to 30 and 40 Gy was found to have the lowest total flavonid content (5.83 ± 0.11; 5.75 ± 0.03 mg/g DW). Based on the results gathered in this study, significant differences were found between irradiated accessions and control ones in relation to the leaf gas. The highest PN and gs were detected in CA23 as control followed by CA23 irradiated to 20Gy (CA23G20) and CA23G30 and the lowest PN and gs were observed in CA03 irradiated to 40Gy (CA03G40). Moreover, there were no significant differences in terms of PN and gs among the irradiated plants in each accession. The WUE of both irradiated accessions of Centella asiatica were reduced as compared with the control plants (p < 0.01) while Ci and E were enhanced. There were no significant differences in the gas exchange parameters among radiated plants in each accession. Moreover, malondialdehyde (MDA) of accessions after gamma treatments were significantly higher than the control, however, flavonoids which were higher concentration in irradiated plants can scavenge surplus free radicals. Therefore, the findings of this study have proven an efficient method of in vitro mutagenesis through gamma radiation based on the pharmaceutical demand to create economically superior mutants of C. asiatica. In other words, the results of this study suggest that gamma irradiation on C. asiatica can produce mutants of agricultural and economical importance.

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M-CHAT as a screening tool for ASD has flagged a considerable percent of the enrolled toddlers that necessitates referral for further evaluation (stage II) to settle the diagnosis of ASD in the true positive cases. Perfecting the delicate balance between sensitivity and specificity for ASD screening tools is crucial in order not to miss early detection of ASD cases and at the same time, to avoid over-diagnosis with subsequent abuse of the limited healthcare resources in developing countries.

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Eurycoma longifolia Jack is well known among the communities in Southeast Asia because of its aphrodisiac properties and its effectiveness as the cytotoxic, anti-malarial, anti-ulcer, anti-tumor promoting and anti-parasitic agent. Micropropagation through direct plant regeneration from in vivo shoot tip explants was carried out. The highest regeneration percentage (90%) and multiple shoots formation were obtained with the basal Murashige and Skoog (MS) medium supplemented with 5.0 mg l Ϫ1 kinetin. Roots were induced after 14 days of culture in the basal MS medium supplemented with 0.5 mg l Ϫ1 of indole-3-butyric acid. Plantlets regenerated from shoot tip explants survived well with no morphological differences from parent plants after two months of transplantation to soil.

Effects of N6-benzylaminopurine (BAP) concentration, initial cell density and carbon sources and concentrations for producing cell suspension and somatic embryos of Limau madu (Citrus suhuiensis Hort. ex Tanaka) were investigated using cell suspension culture. Cells were first inoculated into Murashige and Skoog (MS) medium (1962) supplemented with 4.4 to 13.3 µM BAP. Growth rate of cells was at its maximum (6.69 mg day-1) in media supplemented with a lower concentration of BAP (6.7 µM). Embryogenic cell at 2 mg ml-1 was found to be the most effective inoculum size for the highest growth rate (3.35 mg day-1) of cell proliferation within a period of 15 to 30 days after inoculation (DAI). This inoculum size resulted in 31.75% faster embryo growth than those with inoculum densities of 4 to 6 mg ml-1. Sucrose (88, 117 and 146 mM), glycerol (16, 22 and 27 mM) and combinations of sorbitol and galactose (146:0, 110:36, 73:73, 36:110 and 0:146 mM) were tested for their effects on embryogenic cell proliferation and somatic embryo induction. Results indicates that sucrose at 146 mM induced cell proliferation (7.65 mg day-1) and produced a higher quantity of cells than glycerol at 27 mM (2.33 mg day-1) and a combination of sorbitol and galactose at 73:73 mM (4.64 mg day-1), but failed to induce somatic embryos. Glycerol in different concentrations was ineffective in cell proliferation and somatic embryo induction. At optimal BAP concentration (6.7 µM), a small amount of embryogenic cells (100 mg in 50 ml) can be multiplied profusely in sucrose-containing medium. A large number of somatic embryos (951) were induced in a medium containing 110 mM sorbitol and 36 mM galactose as the most effective carbon source for inducing somatic embryos without BAP.