Ancient Migratory Events in the Middle East: New Clues from the Y-Chromosome Variation of Modern Iranians

Knowledge of high resolution Y-chromosome haplogroup diversification within Iran provides important geographic context regarding the spread and compartmentalization of male lineages in the Middle East and southwestern Asia. At present, the Iranian population is characterized by an extraordinary mix of different ethnic groups speaking a variety of Indo-Iranian, Semitic and Turkic languages. Despite these features, only few studies have investigated the multiethnic components of the Iranian gene pool. In this survey 938 Iranian male DNAs belonging to 15 ethnic groups from 14 Iranian provinces were analyzed for 84 Y-chromosome biallelic markers and 10 STRs. The results show an autochthonous but non-homogeneous ancient background mainly composed by J2a sub-clades with different external contributions. The phylogeography of the main haplogroups allowed identifying post-glacial and Neolithic expansions toward western Eurasia but also recent movements towards the Iranian region from western Eurasia (R1b-L23), Central Asia (Q-M25), Asia Minor (J2a-M92) and southern Mesopotamia (J1-Page08). In spite of the presence of important geographic barriers (Zagros and Alborz mountain ranges, and the Dasht-e Kavir and Dash-e Lut deserts) which may have limited gene flow, AMOVA analysis revealed that language, in addition to geography, has played an important role in shaping the nowadays Iranian gene pool. Overall, this study provides a portrait of the Y-chromosomal variation in Iran, useful for depicting a more comprehensive history of the peoples of this area as well as for reconstructing ancient migration routes. In addition, our results evidence the important role of the Iranian plateau as source and recipient of gene flow between culturally and genetically distinct population

Ultrathin graphene-based membrane with precise molecular sieving and ultrafast solvent permeation

Graphene oxide (GO) membranes continue to attract intense interest due to their unique molecular sieving properties combined with fast permeation. However, their use is limited to aqueous solutions because GO membranes appear impermeable to organic solvents, a phenomenon not yet fully understood. Here, we report efficient and fast filtration of organic solutions through GO laminates containing smooth two-dimensional (2D) capillaries made from large (10-20 μm) flakes. Without modification of sieving characteristics, these membranes can be made exceptionally thin, down to â 1/410 nm, which translates into fast water and organic solvent permeation. We attribute organic solvent permeation and sieving properties to randomly distributed pinholes interconnected by short graphene channels with a width of 1 nm. With increasing membrane thickness, organic solvent permeation rates decay exponentially but water continues to permeate quickly, in agreement with previous reports. The potential of ultrathin GO laminates for organic solvent nanofiltration is demonstrated by showing >99.9% rejection of small molecular weight organic dyes dissolved in methanol. Our work significantly expands possibilities for the use of GO membranes in purification and filtration technologies

RNA Silencing of Mcl-1 Enhances ABT-737-Mediated Apoptosis in Melanoma: Role for a Caspase-8-Dependent Pathway

BACKGROUND: Malignant melanoma is resistant to almost all conventional forms of chemotherapy. Recent evidence suggests that anti-apoptotic proteins of the Bcl-2 family are overexpressed in melanoma and may contribute to melanoma's striking resistance to apoptosis. ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-xl and Bcl-w, has demonstrated efficacy in several forms of leukemia, lymphoma as well as solid tumors. However, overexpression of Mcl-1, a frequent observance in melanoma, is known to confer ABT-737 resistance. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that knockdown of Mcl-1 greatly reduces cell viability in combination with ABT-737 in six different melanoma cell lines. We demonstrate that the cytotoxic effect of this combination treatment is due to apoptotic cell death involving not only caspase-9 activation but also activation of caspase-8, caspase-10 and Bid, which are normally associated with the extrinsic pathway of apoptosis. Caspase-8 (and caspase-10) activation is abrogated by inhibition of caspase-9 but not by inhibitors of the death receptor pathways. Furthermore, while caspase-8/-10 activity is required for the full induction of cell death with treatment, the death receptor pathways are not. Finally, we demonstrate that basal levels of caspase-8 and Bid correlate with treatment sensitivity. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the combination of ABT-737 and Mcl-1 knockdown represents a promising, new treatment strategy for malignant melanoma. We also report a death receptor-independent role for extrinsic pathway proteins in treatment response and suggest that caspase-8 and Bid may represent potential markers of treatment sensitivity

De Novo assembly and transcriptome analysis of the mediterranean fruit fly ceratitis capitata early embryos

The agricultural pest Ceratitis capitata, also known as the Mediterranean fruit fly or Medfly, belongs to the Tephritidae family, which includes a large number of other damaging pest species. The Medfly has been the first non-drosophilid fly species which has been genetically transformed paving the way for designing geneticbased pest control strategies. Furthermore, it is an experimentally tractable model, in which transient and transgene-mediated RNAi have been successfully used. We applied Illumina sequencing to total RNA preparations of 8-10 hours old embryos of C. capitata, This developmental window corresponds to the blastoderm cellularization stage. In summary, we assembled 42,614 transcripts which cluster in 26,319 unique transcripts of which 11,045 correspond to protein coding genes; we identified several hundreds of long ncRNAs; we found an enrichment of transcripts encoding RNA binding proteins among the highly expressed transcripts, such as CcTRA-2, known to be necessary to establish and, most likely, to maintain female sex of C. capitata. Our study is the first de novo assembly performed for Ceratitis capitata based on Illumina NGS technology during embryogenesis and it adds novel data to the previously published C. capitata EST databases. We expect that it will be useful for a variety of applications such as gene cloning and phylogenetic analyses, as well as to advance genetic research and biotechnological applications in the Medfly and other related Tephritidae

Effects of urban green infrastructure (UGI) on local outdoor microclimate during the growing season

This study analyzed how the variations of plant area index (PAI) and weather conditions alter the influence of urban green infrastructure (UGI) on microclimate. To observe how diverse UGIs affect the ambient microclimate through the seasons, microclimatic data were measured during the growing season at five sites in a local urban area in The Netherlands. Site A was located in an open space; sites B, C, and D were covered by different types and configurations of green infrastructure (grove, a single deciduous tree, and street trees, respectively); and site E was adjacent to buildings to study the effects of their façades on microclimate. Hemispherical photography and globe thermometers were used to quantify PAI and thermal comfort at both shaded and unshaded locations. The results showed that groves with high tree density (site B) have the strongest effect on microclimate conditions. Monthly variations in the differences of mean radiant temperature (∆Tmrt) between shaded and unshaded areas followed the same pattern as the PAI. Linear regression showed a significant positive correlation between PAI and ∆Tmrt. The difference of daily average air temperature (∆Ta) between shaded and unshaded areas was also positively correlated to PAI, but with a slope coefficient below the measurement accuracy (±0.5 °C). This study showed that weather conditions can significantly impact the effectiveness of UGI in regulating microclimate. The results of this study can support the development of appropriate UGI measures to enhance thermal comfort in urban areas