SummaryThe firing of eukaryotic origins of DNA replication requires CDK and DDK kinase activities. DDK, in particular, is involved in setting the temporal program of origin activation, a conserved feature of eukaryotes. Rif1, originally identified as a telomeric protein, was recently implicated in specifying replication timing in yeast and mammals. We show that this function of Rif1 depends on its interaction with PP1 phosphatases. Mutations of two PP1 docking motifs in Rif1 lead to early replication of telomeres in budding yeast and misregulation of origin firing in fission yeast. Several lines of evidence indicate that Rif1/PP1 counteract DDK activity on the replicative MCM helicase. Our data suggest that the PP1/Rif1 interaction is downregulated by the phosphorylation of Rif1, most likely by CDK/DDK. These findings elucidate the mechanism of action of Rif1 in the control of DNA replication and demonstrate a role of PP1 phosphatases in the regulation of origin firing.

Summary Streptococcus agalactiae (Group B Streptococcus, GBS) is a frequent commensal organism of the vaginal tract of healthy women. However, GBS can transition to a pathogen in susceptible hosts, but host and microbial factors that contribute to this conversion are not well understood. GBS CovR/S (CsrR/S) is a two component regulatory system that regulates key virulence elements including adherence and toxin production. We performed global transcription profiling of human vaginal epithelial cells exposed to WT, CovR deficient, and toxin deficient strains, and observed that insufficient regulation by CovR and subsequent increased toxin production results in a drastic increase in host inflammatory responses, particularly in cytokine signaling pathways promoted by IL-8 and CXCL2. Additionally, we observed that CovR regulation impacts epithelial cell attachment and intracellular invasion. In our mouse model of GBS vaginal colonization, we further demonstrated that CovR regulation promotes vaginal persistence, as infection with a CovR deficient strain resulted in a heightened host immune response as measured by cytokine production and neutrophil activation. Using CXCr2 KO mice, we determined that this immune alteration occurs, at least in part, via signaling through the CXCL2 receptor. Taken together, we conclude that CovR is an important regulator of GBS vaginal colonization and loss of this regulatory function may contribute to the inflammatory havoc seen during the course of infection.

No abstract

No abstract

No abstract

Fabrication of heterojunction between 2D molybdenum disulfide (MoS2) and gallium nitride (GaN) and its photodetection properties have been reported in the present work. Surface potential mapping at the MoS2/GaN heterojunction is done using Kelvin Probe Force Microscopy to measure the conduction band offset. Current-voltage measurements show a diode like behavior of the heterojunction. The origin of diode like behavior is attributed to unique type II band alignment of the heterojunction. The photocurrent, photoresponsivity and detectivity of the heterojunction are found to be dependent on power density of the light. Photoresponse investigations reveal that the heterojunction is highly sensitive to 405 nm laser with very high responsivity up to 105 A/W. The heterojunction also shows very high detectivity of the order of 1014 Jones. Moreover, the device shows photoresponse in UV region also. These observations suggest that MoS2/GaN heterojunction can have great potential for photodetection applications.

No abstract

High-temperature operation of metal-semiconductor-metal (MSM) UV photodetectors fabricated on pulsed laser deposited β-Ga2O3 thin films has been investigated. These photodetectors were operated up to 250 °C temperature under 255 nm illumination. The photo current to dark current (PDCR) ratio of about 7100 was observed at room temperature (RT) while it had a value 2.3 at 250 °C at 10 V applied bias. A decline in photocurrent was observed from RT to 150 °C and then it increased with temperature up to 250 °C. The suppression of the blue band was also observed from 150 °C temperature which indicated that self-trapped holes in Ga2O3 became unstable. Temperature-dependent rise and decay times of carriers were analyzed to understand the photocurrent mechanism and persistence photocurrent at high temperatures. Coupled electron-phonon interaction with holes was found to influence the photoresponse in the devices. The obtained results are encouraging and significant for high-temperature applications of β-Ga2O3 MSM deep UV photodetectors.