Identifying areas of high importance for orchid conservation in east Macedonia (NE Greece)

The establishment of a network of reserves is of fundamental importance to the loss of biodiversity. Seven different area selection methods for the establishment of a reserve network were applied in the present study: (a) 5% cut-off value of the grid cells with the highest species richness or conservation value, (b) complementarity analysis using as criteria species richness or conservation value or rarest species richness, and (c) mixed complementarity analysis using as criteria species richness or conservation value. These methods were applied in the orchid taxa of east Macedonia. The conservation values of taxa were estimated on the basis of regional rarity, broad-scale rarity, and species specialization. The spatial overlap between the resulting networks and the Natura 2000 network of the study area was assessed. Furthermore, the efficiency of the latter network to protect the orchid taxa of the study area was examined. Our results suggest that: (a) a multiscale estimation of rarity is necessary for the unbiased estimation of species conservation values; (b) species specialization adds valuable ecological information to the assessment of taxa conservation values; (c) complementarity and mixed complementarity analyses on species richness or conservation value safeguard all the taxa of the region; (d) complementarity analysis on the basis of the richness of the rarest species safeguards all the rarest taxa, but not the total number of the remaining taxa; (e) the 5% cut-off value on species richness or conservation value fails to protect all the taxa of the region, including a large number of the rarest taxa; and (f) the Natura 2000 network, despite its large coverage in the study area, fails to safeguard all the taxa, including some of the rarest.     

A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation

Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8 × 10(-106)), PRMT6 (rs17496332, 1p13.3, p = 1.4 × 10(-11)), GCKR (rs780093, 2p23.3, p = 2.2 × 10(-16)), ZBTB10 (rs440837, 8q21.13, p = 3.4 × 10(-09)), JMJD1C (rs7910927, 10q21.3, p = 6.1 × 10(-35)), SLCO1B1 (rs4149056, 12p12.1, p = 1.9 × 10(-08)), NR2F2 (rs8023580, 15q26.2, p = 8.3 × 10(-12)), ZNF652 (rs2411984, 17q21.32, p = 3.5 × 10(-14)), TDGF3 (rs1573036, Xq22.3, p = 4.1 × 10(-14)), LHCGR (rs10454142, 2p16.3, p = 1.3 × 10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7 × 10(-08)), and UGT2B15 (rs293428, 4q13.2, p = 5.5 × 10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5 × 10(-08), women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ~15.6% and ~8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.     

Systematic single-cell analysis of Pichia pastoris reveals secretory capacity limits productivity

Biopharmaceuticals represent the fastest growing sector of the global pharmaceutical industry. Cost-efficient production of these biologic drugs requires a robust host organism for generating high titers of protein during fermentation. Understanding key cellular processes that limit protein production and secretion is, therefore, essential for rational strain engineering. Here, with single-cell resolution, we systematically analysed the productivity of a series of Pichia pastoris strains that produce different proteins both constitutively and inducibly. We characterized each strain by qPCR, RT-qPCR, microengraving, and imaging cytometry. We then developed a simple mathematical model describing the flux of folded protein through the ER. This combination of single-cell measurements and computational modelling shows that protein trafficking through the secretory machinery is often the rate-limiting step in single-cell production, and strategies to enhance the overall capacity of protein secretion within hosts for the production of heterologous proteins may improve productivity.     

Outcome prediction based on microarray analysis: a critical perspective on methods

Background  

Information extraction from microarrays has not yet been widely used in diagnostic or prognostic decision-support systems, due to the diversity of results produced by the available techniques, their instability on different data sets and the inability to relate statistical significance with biological relevance. Thus, there is an urgent need to address the statistical framework of microarray analysis and identify its drawbacks and limitations, which will enable us to thoroughly compare methodologies under the same experimental set-up and associate results with confidence intervals meaningful to clinicians. In this study we consider gene-selection algorithms with the aim to reveal inefficiencies in performance evaluation and address aspects that can reduce uncertainty in algorithmic validation.     

Localization of an alkyl-acetyl-glycerol-CDP-choline: cholinephosphotransferase activity in submitochondrial fractions of Tetrahymena pyriformis

Tetrahymena pyriformis contains platelet-activating factor (PAF) as a minor lipid, which is biosynthesized de novo. A dithiothreitol-insensitive CDP-choline:cholinephosphotransferase (AAG-CPT), which utilizes alkyl-acetyl-glycerol as a substrate, had been detected in both the mitochondrial and microsomal fractions of the protozoan. In the present report, localization of this enzyme in submitochondrial fractions was studied. Cell fractionation was evaluated with enzyme and morphological markers. In this respect, succinate dehydrogenase, NADPH:cytochrome c reductase, glucose-6-phosphatase, alkaline phosphatase, monoaminoxidase, and cytochrome c oxidase activities were investigated. In the presence of antimycin A, mitochondrial activity of NADPH-cytochrome c reductase, was increased, while the microsomal one was reduced. Cardiolipin was distributed in the inner mitochondrial membrane. Alkaline phosphatase was found exclusively in the cytosol of the protozoan. The main portion of the dithiothreitol-insensitive AAG-CPT was localized in the inner mitochondrial membrane. Our data indicate that mitochondria are able to produce PAF, which might be associated with their function.     

Intralysosomal cystine accumulation in mice lacking cystinosin,the protein defective in cystinosis

Cystinosis is an autosomal recessive disorder characterized by an accumulation of intralysosomal cystine. The causative gene, CTNS, encodes cystinosin, a seven-transmembrane-domain protein, which we recently showed to be a lysosomal cystine transporter. The most severe and frequent form of cystinosis, the infantile form, appears around 6 to 12 months, with a proximal tubulopathy (de Toni-Debré-Fanconi syndrome) and ocular damage. End-stage renal failure is reached by 10 years of age. Accumulation of cystine in all tissues eventually leads to multisystemic disease. Treatment with cysteamine, which reduces the concentration of intracellular cystine, delays disease progression but has undesirable side effects. We report the first Ctns knockout mouse model generated using a promoter trap approach. We replaced the last four Ctns exons by an internal ribosome entry site-betagal-neo cassette and showed that the truncated protein was mislocalized and nonfunctional. Ctns(-/-) mice accumulated cystine in all organs tested, and cystine crystals, pathognomonic of cystinosis, were observed. Ctns(-/-) mice developed ocular changes similar to those observed in affected individuals, bone defects and behavioral anomalies. Interestingly, Ctns(-/-) mice did not develop signs of a proximal tubulopathy, or renal failure. A preliminary therapeutic trial using an oral administration of cysteamine was carried out and demonstrated the efficiency of this treatment for cystine clearance in Ctns(-/-) mice. This animal model will prove an invaluable and unique tool for testing emerging therapeutics for cystinosis.     

Feeding habits and trophic levels of Mediterranean fish

The estimation of fractional trophic levels(TROPHs) is essential for the management offisheries resources as well as for quantifyingthe ecosystem effects of fishing. We gatheredall available information concerning thefeeding habits of 332 fish stocks, belonging to146 species, 59 families and 21 orders,throughout the Mediterranean Sea, and estimatedtheir TROPH values. The latter ranged from 2.0to 4.5 and the following functional trophicgroups were identified: (a) pure herbivores (TROPH = 2.0–2.1, mean = 2.02, SD = 0.03),which were very rare and represented by Siganus luridus, Siganus rivulatus andSarpa salpa, all of which feed on red,brown, green and blue-green algae; (b)omnivores with a preference for vegetablematerial (2.1 < TROPH < 2.9, mean = 2.5,SD = 0.12), but feeding on other prey, such assponges, hydrozoans, anthozoans, polychaetes,ostracods, isopods, amphipods and copepods. This type of omnivore was very rare among thecases reviewed; (c) omnivores with a preferencefor animal material (2.9 < TROPH < 3.7,mean = 3.4, SD = 0.19) feeding on a wide variety ofprey (e.g., algae, foraminifera, brachyurans,balanoids, ascidians, amphipods,appendicularians, annelids, isopods,gastropods, cnidarians, ophiurids, polychaetes,cladocerans, mysids, euphausids, fish larvae,cephalopods). They were the most numerous andwere mainly represented by species of thefamilies Blenniidae, Bothidae, Centracanthidae,Gobiidae, Labridae, Lotidae, Macrouridae,Mullidae, Ophidiidae, Soleidae, Triglidaeand Engraulidae; and (d) carnivores witha preference for large decapods, cephalopodsand fish (3.7 < TROPH < 4.5). They werethe next most abundant group among the casesreviewed. They were mainly represented byspecies of the families Dalatiidae, Lophiidae,Scombridae, Scyliorhinidae, Synodontidae,Torpedinidae, Merlucciidae, Xiphiidae andZeidae. This group was divided into twosubgroups: one exhibiting a preference fordecapods and fish (3.7 < TROPH < 4.0,mean = 3.85, SD = 0.09) and another one exhibitinga preference for fish and cephalopods (4.0 相似文献   

Synthesis and biological evaluation of new tetrahydro-beta-carbolines as inhibitors of the mitotic kinesin Eg5

The mitotic kinesin Eg5 (or KSP) is a crucial player in the development and function of the mitotic spindle. Inhibition of this protein leads to cell cycle arrest and apoptosis without interfering with other microtubule-dependent processes. Therefore, it is a potential target in cancer therapy. Here, we report the synthesis and biological evaluation of a small library of molecules based on the structure of the known Eg5 inhibitor HR22C16. One of these derivatives (compound trans-24) proved to be a potent and specific Eg5 inhibitor.