New thiocyanato and azido adducts of the redox-active Fe(η-C5Me5)(η-dppe) center: Synthesis and study of the Fe(II) and Fe(III) complexes

The new thiocyanato- (5) and azido- (6) complexes were synthesized and studied under their Fe(II) and Fe(III) redox states. For the first time among the various [Fe(η⁵-C₅Me₅)(η²-dppe)]-based cationic radicals studied so far, the magnitude and spatial orientation of the g-tensor diagonal values were experimentally determined for 5[PF₆]. These data are in good agreement with those issued from a DFT modelization. The changes experienced by the electronic structure of the Fe(II) complexes subsequent to oxidation are reminiscent of these previously observed for the known arylalkynyl analogues, albeit some differences can be pointed out. Thus, the differences observed in the ¹H NMR spectra of 5[PF₆] and 6[PF₆] are attributed to a slower electronic spin relaxation and to the differently oriented magnetic anisotropy. The sizeable spin density evidenced by DFT on the terminal atom of the ligands of the Fe(III) complexes renders these new paramagnetic metallo-ligands quite appealing for accessing larger polynuclear molecular assemblies with magnetically interacting centers.     

Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer

Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-β activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8×10⁻¹² in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85–0.94) and 0.80 (0.75–0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9×10⁻⁶ from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6×10⁻⁷), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively.     

Population Genetic Structure and Origins of Native Hawaiians in the Multiethnic Cohort Study

The population genetic structure of Native Hawaiians has yet to be comprehensively studied, and the ancestral origins of Polynesians remain in question. In this study, we utilized high-resolution genome-wide SNP data and mitochondrial genomes of 148 and 160 Native Hawaiians, respectively, to characterize their population structure of the nuclear and mitochondrial genomes, ancestral origins, and population expansion. Native Hawaiians, who self-reported full Native Hawaiian heritage, demonstrated 78% Native Hawaiian, 11.5% European, and 7.8% Asian ancestry with 99% belonging to the B4 mitochondrial haplogroup. The estimated proportions of Native Hawaiian ancestry for those who reported mixed ancestry (i.e. 75% and 50% Native Hawaiian heritage) were found to be consistent with their self-reported heritage. A significant proportion of Melanesian ancestry (mean = 32%) was estimated in 100% self-reported Native Hawaiians in an ADMIXTURE analysis of Asian, Melanesian, and Native Hawaiian populations of K = 2, where K denotes the number of ancestral populations. This notable proportion of Melanesian admixture supports the “Slow-Boat” model of migration of ancestral Polynesian populations from East Asia to the Pacific Islands. In addition, approximately 1,300 years ago a single, strong expansion of the Native Hawaiian population was estimated. By providing important insight into the underlying population structure of Native Hawaiians, this study lays the foundation for future genetic association studies of this U.S. minority population.     

Insights into how nucleotide supplements enhance the peroxidase-mimicking DNAzyme activity of the G-quadruplex/hemin system

Since the initial discovery of the catalytic capability of short DNA fragments, this peculiar enzyme-like property (termed DNAzyme) has continued to garner much interest in the scientific community because of the virtually unlimited applications in developing new molecular devices. Alongside the exponential rise in the number of DNAzyme applications in the last past years, the search for convenient ways to improve its overall efficiency has only started to emerge. Credence has been lent to this strategy by the recent demonstration that the quadruplex-based DNAzyme proficiency can be enhanced by ATP supplements. Herein, we have made a further leap along this path, trying first of all to decipher the actual DNAzyme catalytic cycle (to gain insights into the steps ATP may influence), and subsequently investigating in detail the influence of all the parameters that govern the catalytic efficiency. We have extended this study to other nucleotides and quadruplexes, thus demonstrating the versatility and broad applicability of such an approach. The defined exquisitely efficient DNAzyme protocols were exploited to highlight the enticing advantages of this method via a 96-well plate experiment that enables the detection of nanomolar DNA concentrations in real-time with the naked-eye (see movie as Supplementary Data).     

ecospat: an R package to support spatial analyses and modeling of species niches and distributions

The aim of the ecospat package is to make available novel tools and methods to support spatial analyses and modeling of species niches and distributions in a coherent workflow. The package is written in the R language (R Development Core Team) and contains several features, unique in their implementation, that are complementary to other existing R packages. Pre‐modeling analyses include species niche quantifications and comparisons between distinct ranges or time periods, measures of phylogenetic diversity, and other data exploration functionalities (e.g. extrapolation detection, ExDet). Core modeling brings together the new approach of ensemble of small models (ESM) and various implementations of the spatially‐explicit modeling of species assemblages (SESAM) framework. Post‐modeling analyses include evaluation of species predictions based on presence‐only data (Boyce index) and of community predictions, phylogenetic diversity and environmentally‐constrained species co‐occurrences analyses. The ecospat package also provides some functions to supplement the ‘biomod2’ package (e.g. data preparation, permutation tests and cross‐validation of model predictive power). With this novel package, we intend to stimulate the use of comprehensive approaches in spatial modelling of species and community distributions.     

Two types of store-operated Ca2+ channels with different activation modes and molecular origin in LNCaP human prostate cancer epithelial cells

The one or more coupling mechanisms of store-operated channels (SOCs) to endoplasmic reticulum (ER) Ca2+ store depletion as well as the molecular identity of SOCs per se still remain a mystery. Here, we demonstrate the co-existence of two populations of molecular distinct endogenous SOCs in LNCaP prostate cancer epithelial cells, which are preferentially activated by either active inositol 1,4,5-trisphosphate (IP3)-mediated or passive thapsigargin-facilitated store depletion and have different ER store content sensitivity. The first population, called SOC(CC) (for "conformational coupling"), is characterized by preferential IP3 receptor-dependent mode of activation, as judged from sensitivity to cytoskeleton modifications, and dominant contribution of transient receptor potential (TRP) TRPC1 within it. The second one, called SOC(CIF) (for "calcium influx factor"), depends on Ca(2+)-independent phospholipase A2 for activation with probable CIF involvement and is mostly represented by TRPC4. The previously identified SOC constituent in LNCaP cells, TRPV6, seems to play equal role in both SOC populations. These results provide new insight into the nature of SOCs and their representation in the single cell type as well as permit reconciliation of current SOC activation hypotheses.     

Suppressors of thermosensitive mutations in the DNA polymerase δ gene of Saccharomyces cerevisiae

DNA polymerases (Pol) , and are necessary for replication of nuclear DNA. Po1 interacts permanently or transiently with numerous accessory proteins whose identification may shed light on the function(s) of Po18. In vitro mutagenesis was used to induce thermosensitive (ts) mutations in the DNA polymerase gene (POL3). We have attempted to clone two recessive extragenic suppressors of such is mutants (sdp1 for mutation pol3-14 and sdp5-1 for mutation pol3-11) by transforming thermoresistant haploid strains pol3-14 sdpl and pol3-11 sdp5-1 with wild-type genomic libraries in singlecopy or multicopy vectors. None of the thermosensitive transformants so obtained was identified as being sdp1 or sdp5-1. Instead, three genes were cloned whose products interfere with the activity of suppressors. One of them is the type 1 protein phosphatase gene, D1S2. Another is a novel gene, ASM4, whose gene product is rich in asparagine and glutamine residues.     

Relationship between Sylleptic Branching and Components of Parent Shoot Development in the Peach Tree

Sylleptic branching of main axes was investigated in three peachtree cultivars ('Armking', 'Flavorcrest' and 'Silvergem') duringthe first year of growth. An axis was considered as made upof a series of metamers (internode, node, leaf and associatedbud) and its growth was divided into two components: the increaseof the number of metamers and the lengthening of the metamersthemselves (elongation). The relationship between branchingprobability, type of cultivar, growth components and date ofmetamer production was studied by logistic regression. Branchingprobability varied according to the cultivar, increased whenthe growth components did, and decreased if metamers appearedlate in the season. The logistic model fitted the data closelyand was validated on a data set that had not been used for estimatingthe parameters. Ninety-four percent of branched and 70% of unbranchedmetamers were correctly predicted by the logistic model. Forany given growth rate and date of metamer production, the mainaxes branched most and least often in the 'Flavorcrest' and'Silvergem' cultivars, respectively.Copyright 1994, 1999 AcademicPress Peach tree, Prunus persica (L.) Batsch, branching, syllepsis, shoot growth, quantitative analysis, logistic regression     

Toward the Standardization of Mycological Examination of Sputum Samples in Cystic Fibrosis: Results from a French Multicenter Prospective Study

Fungal respiratory colonization of cystic fibrosis (CF) patients emerges as a new concern; however, the heterogeneity of mycological protocols limits investigations. We first aimed at setting up an efficient standardized protocol for mycological analysis of CF sputa that was assessed during a prospective, multicenter study: “MucoFong” program (PHRC-06/1902). Sputa from 243 CF patients from seven centers in France were collected over a 15-month period and submitted to a standardized protocol based on 6 semi-selective media. After mucolytic pretreatment, sputa were plated in parallel on cycloheximide-enriched (ACT37), erythritol-enriched (ERY37), benomyl dichloran–rose bengal (BENO37) and chromogenic (CAN37) media incubated at 37 °C and on Sabouraud–chloramphenicol (SAB27) and erythritol-enriched (ERY27) media incubated at 20–27 °C. Each plate was checked twice a week during 3 weeks. Fungi were conventionally identified; time for detection of fungal growth was noted for each species. Fungal prevalences and media performances were assessed; an optimal combination of media was determined using the Chi-squared automatic interaction detector method. At least one fungal species was isolated from 81% of sputa. Candida albicans was the most prevalent species (58.8%), followed by Aspergillus fumigatus (35.4%). Cultivation on CAN37, SAB27, ACT37 and ERY27 during 16 days provided an optimal combination, detecting C. albicans, A. fumigatus, Scedosporium apiospermum complex and Exophiala spp. with sensitivities of 96.5, 98.8, 100 and 100%. Combination of these four culture media is recommended to ensure the growth of key fungal pathogens in CF respiratory specimens. The use of such consensual protocol is of major interest for merging results from future epidemiological studies.