Molecular Co-occupancy Identifies Transcription Factor Binding Cooperativity In Vivo

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Thirteen years of change in trees and lianas in a Gabonese rainforest

Inventories of trees and lianas were performed at a 13-year interval (1979–1992) in an evergreen forest in north-east Gabon. The number of trees decreased while their basal area and species richness increased. In contrast, both the richness and density of lianas decreased. Lianas with active climbing mechanisms were the main types to disappear.     

Systematic Phenotyping of a Large-Scale Candida glabrata Deletion Collection Reveals Novel Antifungal Tolerance Genes

The opportunistic fungal pathogen Candida glabrata is a frequent cause of candidiasis, causing infections ranging from superficial to life-threatening disseminated disease. The inherent tolerance of C. glabrata to azole drugs makes this pathogen a serious clinical threat. To identify novel genes implicated in antifungal drug tolerance, we have constructed a large-scale C. glabrata deletion library consisting of 619 unique, individually bar-coded mutant strains, each lacking one specific gene, all together representing almost 12% of the genome. Functional analysis of this library in a series of phenotypic and fitness assays identified numerous genes required for growth of C. glabrata under normal or specific stress conditions, as well as a number of novel genes involved in tolerance to clinically important antifungal drugs such as azoles and echinocandins. We identified 38 deletion strains displaying strongly increased susceptibility to caspofungin, 28 of which encoding proteins that have not previously been linked to echinocandin tolerance. Our results demonstrate the potential of the C. glabrata mutant collection as a valuable resource in functional genomics studies of this important fungal pathogen of humans, and to facilitate the identification of putative novel antifungal drug target and virulence genes.     

ICSI diagnostic: a way to prevent total fertilization failure after 4 unsuccessful IUI

Background

The aim of this retrospective study is to investigate the relevance of dividing oocytes and using some for traditional in vitro fertilization (IVF) and others for intracytoplasmic sperm injection (ICSI) as of the first IVF cycle in patients with unexplained infertility who have undergone 4 intrauterine insemination (IUI) cycles which produced no pregnancies.

Methods

This retrospective study includes patients with unexplained infertility who have failed to become pregnant, after 4 IUI, despite normal semen parameters after sperm capacitation. These women were treated in our assisted fertilization program from 2008 until 2015. We analysed the first cycles of women in whom more than 4 oocyte cumulus complexes (OCC) were retrieved and single embryo transfer was performed.

Results

Dividing oocytes between two fertilization techniques reduce the rate of total fertilization failure during the first IVF cycle. No statistical difference were observed for 2 pronuclei (PN) rate between the two techniques. On the other hand, we observed a significantly lower rate of 3 PN, 1 PN, 0 PN with ICSI in comparison with conventional fertilization.

Conclusions

Splitting the oocytes between classical IVF and ICSI increases the chance of embryo transfer on a first IVF cycle after 4 unsuccessful IUI cycles. This half-and-half policy reduces the risk, for the infertile couple, of facing total failure of fertilization and also can provide useful information for the next attempts.

     

The Trw Type IV Secretion System of Bartonella Mediates Host-Specific Adhesion to Erythrocytes

Bacterial pathogens typically infect only a limited range of hosts; however, the genetic mechanisms governing host-specificity are poorly understood. The α-proteobacterial genus Bartonella comprises 21 species that cause host-specific intraerythrocytic bacteremia as hallmark of infection in their respective mammalian reservoirs, including the human-specific pathogens Bartonella quintana and Bartonella bacilliformis that cause trench fever and Oroya fever, respectively. Here, we have identified bacterial factors that mediate host-specific erythrocyte colonization in the mammalian reservoirs. Using mouse-specific Bartonella birtlesii, human-specific Bartonella quintana, cat-specific Bartonella henselae and rat-specific Bartonella tribocorum, we established in vitro adhesion and invasion assays with isolated erythrocytes that fully reproduce the host-specificity of erythrocyte infection as observed in vivo. By signature-tagged mutagenesis of B. birtlesii and mutant selection in a mouse infection model we identified mutants impaired in establishing intraerythrocytic bacteremia. Among 45 abacteremic mutants, five failed to adhere to and invade mouse erythrocytes in vitro. The corresponding genes encode components of the type IV secretion system (T4SS) Trw, demonstrating that this virulence factor laterally acquired by the Bartonella lineage is directly involved in adherence to erythrocytes. Strikingly, ectopic expression of Trw of rat-specific B. tribocorum in cat-specific B. henselae or human-specific B. quintana expanded their host range for erythrocyte infection to rat, demonstrating that Trw mediates host-specific erythrocyte infection. A molecular evolutionary analysis of the trw locus further indicated that the variable, surface-located TrwL and TrwJ might represent the T4SS components that determine host-specificity of erythrocyte parasitism. In conclusion, we show that the laterally acquired Trw T4SS diversified in the Bartonella lineage to facilitate host-restricted adhesion to erythrocytes in a wide range of mammals.