DSIF contributes to transcriptional activation by DNA-binding activators by preventing pausing during transcription elongation

The transcription elongation factor 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB) sensitivity-inducing factor (DSIF) regulates RNA polymerase II (RNAPII) processivity by promoting, in concert with negative elongation factor (NELF), promoter-proximal pausing of RNAPII. DSIF is also reportedly involved in transcriptional activation. However, the role of DSIF in transcriptional activation by DNA-binding activators is unclear. Here we show that DSIF acts cooperatively with a DNA-binding activator, Gal4-VP16, to promote transcriptional activation. In the absence of DSIF, Gal4-VP16-activated transcription resulted in frequent pausing of RNAPII during elongation in vitro. The presence of DSIF reduced pausing, thereby supporting Gal4-VP16-mediated activation. We found that DSIF exerts its positive effects within a short time-frame from initiation to elongation, and that NELF does not affect the positive regulatory function of DSIF. Knockdown of the gene encoding the large subunit of DSIF, human Spt5 (hSpt5), in HeLa cells reduced Gal4-VP16-mediated activation of a reporter gene, but had no effect on expression in the absence of activator. Together, these results provide evidence that higher-level transcription has a stronger requirement for DSIF, and that DSIF contributes to efficient transcriptional activation by preventing RNAPII pausing during transcription elongation

PcP_c pentaquarks with chiral tensor and quark dynamics

We investigate the hidden-charm pentaquarks as superpositions of $\Lambda_c \bar{D}^{(*)}$ and $\Sigma_c^{(*)} \bar{D}^{(*)}$ (isospin $I = 1/2$) meson-baryon channels coupled to a $uudc\bar{c}$ compact core by employing an interaction satisfying the heavy quark and chiral symmetries. Our model can consistently explain the masses and decay widths of $P_c^+(4312)$, $P_c^+(4440)$ and $P_c^+(4457)$ with the dominant components of $\Sigma_c \bar D$ and $\Sigma_c \bar D^\ast$ with spin parity assignments $J^P = 1/2^{-}, 3/2^{-}$ and $1/2^{-}$, respectively. We analyze basic properties of the $P_c$'s such as masses and decay widths, and find that the mass ordering is dominantly determined by the quark dynamics while the decay widths by the tensor force of the one-pion exchange.Comment: 6 pages, 2 figure

PDK2 leads to cisplatin resistance through suppression of mitochondrial function in ovarian clear cell carcinoma

Ovarian clear cell carcinoma (CCC) exhibits an association with endometriosis, resistance to oxidative stress, and poor prognosis owing to its resistance to conventional platinum-based chemotherapy. A greater understanding of the molecular characteristics and pathogenesis of ovarian cancer subtypes may facilitate the development of targeted therapeutic strategies, though the mechanism of drug resistance in ovarian CCC has yet to be determined. In this study, we assessed exome sequencing data to identify new therapeutic targets of mitochondrial function in ovarian CCC because of the central role of mitochondria in redox homeostasis. Copy number analyses revealed that chromosome 17q21-24 (chr.17q21-24) amplification was associated with recurrence in ovarian CCC. Cell viability assays identified an association between cisplatin resistance and chr.17q21-24 amplification, and mitochondrion-related genes were enriched in patients with chr.17q21-24 amplification. Patients with high expression of pyruvate dehydrogenase kinase 2 (PDK2) had a worse prognosis than those with low PDK2 expression. Furthermore, inhibition of PDK2 synergistically enhanced cisplatin sensitivity by activating the electron transport chain and by increasing the production of mitochondrial reactive oxygen species. Mouse xenograft models showed that inhibition of PDK2 with cisplatin inhibited tumor growth. This evidence suggests that targeting mitochondrial metabolism and redox homeostasis is an attractive therapeutic strategy for improving drug sensitivity in ovarian CCC

Truss structure tele-manipulation experiment using ETS-7

A robot experiment concept of space truss telemanipulation by National Aerospace Laboratory (NAL) is described in its flight model development. The experiment will be carried out on the Engineering Test Satellite No. 7 (ETS-7) using its robot arm. The satellite is scheduled to be launched in 1997 by National Space Development Agency of Japan (NASDA). The truss flight model is composed of deployable truss system and assemble truss joint. Those truss components will be manipulated by the ETS-7 robot arm using its small grapple fixture type-N (GPF-N), and the experimental task operation will be executed from the ground control station

Neurorehabilitation in neurotrauma

Since time immemorial, neurotrauma has been recorded in various continents. The advancement in neurotraumatology ever since Denny Brown and Trussell’s landmark experimental study of concussion, has come a long way with major contributions from neuropathology, neurophysiology, neurochemistry, biomedical sciences, public policies, intensive care medicine and last but not the least, genetics. A simple introduction of lap and shoulder belt have reduced majority of serious accidents. Continuous recording of intracranial pressures, recognition of acute brain swelling with characteristics of cerebral blood flow in brain damage and development of Glasgow coma and outcome scales by a well-designed multi-centered multi-national outcome study in head injuries brought in major changes in squealae and outcome by preventing and reducing the secondary insults. Computed tomography (CT) and improvement in morbidity and mortality of acute extra axial hematomas by immediate surgery, has influenced and guided several organizations in developing research and formulating guidelines for treatment of acute neurotrauma. The recognition of the spectrum in head injury, aids in prevention of injury and measures to improve outcome by ever developing neuro-rehabilitative measures, apart from advancements in the genetic aspects of understanding the brain’s response to injury along with attention to modern principles of neuro-intensive and critical care, has manipulated neurotrauma towards achieving innovative newer frontiers. Assessment of the extent of injury and the deficits in neurotrauma is as challenging as the management itself. Several criteria including the Japanese Coma Scale and the proposition for the international coma scale have been attempted. Once the baseline characters and the psychology1 of the patient is understood along with the extent and nature of the severity of the injury, a defined patterned timescale with a schedule can be created & tailor made to every patient and all out efforts instituted to rehabilitate not only the individual but also the whole family and the society at large