CBM Experiment local and global implications

The research area of the compressed baryonic matter - CBM experiment (FAIR/GSI in Darmstadt) is sub-nuclear physics, thus hadron-baryon and quark-gluon, and the essence of phase transitions in the area of hot nuclear matter, and dense strongly interacting matter. Our interest in this paper are mainly considerations on the impact of such large infrastructural experiments and possibilities they give to local, smaller but very active, university based research groups and communities. Research and technical input from such groups is depicted on the background of the CBM detector infrastructure and electronic instrumentation just under design and test fabrication for this experiment. An essential input to this research originates from Poland via the agreed  in-kind contribution. The areas of expertise of these groups are: superconductivity, structural large scale cabling, precision machined parts, RF and microwave technology, analog and advanced digital electronics, distributed measurement and control systems, etc

A new paradigm for transcription factor TFIIB functionality

Experimental and bioinformatic studies of transcription initiation by RNA polymerase II (RNAP2) have revealed a mechanism of RNAP2 transcription initiation less uniform across gene promoters than initially thought. However, the general transcription factor TFIIB is presumed to be universally required for RNAP2 transcription initiation. Based on bioinformatic analysis of data and effects of TFIIB knockdown in primary and transformed cell lines on cellular functionality and global gene expression, we report that TFIIB is dispensable for transcription of many human promoters, but is essential for herpes simplex virus-1 (HSV-1) gene transcription and replication. We report a novel cell cycle TFIIB regulation and localization of the acetylated TFIIB variant on the transcriptionally silent mitotic chromatids. Taken together, these results establish a new paradigm for TFIIB functionality in human gene expression, which when downregulated has potent anti-viral effects

PTP1B Regulates Leptin Signal Transduction In Vivo

AbstractMice lacking the protein-tyrosine phosphatase PTP1B are hypersensitive to insulin and resistant to obesity. However, the molecular basis for resistance to obesity has been unclear. Here we show that PTP1B regulates leptin signaling. In transfection studies, PTP1B dephosphorylates the leptin receptor-associated kinase, Jak2. PTP1B is expressed in hypothalamic regions harboring leptin-responsive neurons. Compared to wild-type littermates, PTP1B−/− mice have decreased leptin/body fat ratios, leptin hypersensitivity, and enhanced leptin-induced hypothalamic Stat3 tyrosyl phosphorylation. Gold thioglucose treatment, which ablates leptin-responsive hypothalamic neurons, partially overcomes resistance to obesity in PTP1B−/− mice. Our data indicate that PTP1B regulates leptin signaling in vivo, likely by targeting Jak2. PTP1B may be a novel target to treat leptin resistance in obesity

Dynamics of immunological reactivity indices in patients with laryngal papillomatosis at different periods after complex treatment with antivirus qudrivalent vaccine "Gardasil"

The aim of the study is to determine di­sorders of immune homeostasis in patients with laryngeal papillomatosis at different periods after complex treatment with the inclusion of the “Gardasil” quadrivalent vaccine in the adjuvant therapy. Studies of the immunity state were conducted in 26 patients with laryngeal papillomatosis (LP) before, 2-12 and 13-29 months after complex treatment, consisting of surgical removal of papillomas and anti-relapse therapy, including inhalation of Laferobion, taking a vitamin-mineral complex and a course of vaccination with antiviral “Gardasil” quadrivalent vaccine according to which the second and third injections were administered in 2 and 6 months after the first. Significant disorders of cellular and humoral immunity indices in patients with LP were revealed in the form of multidirectional changes in the functional activity of natural killer cells, a decrease in the total number of T lymphocytes, mainly due to CD4 + subpopulation, increase in circulating immune complexes level in blood serum and concentration of secretory IgA in the secretion of the oropharynx. Disbalance in the patient’s cytokine system resulted in increased γ-IFN and TNF-α serum levels, an increase in spontaneous production of interferon and inhibition of stimulated production of λ - and γ-interferon by blood cells in vitro. Complex treatment with the use of the “Gardasil” quadrivalent antiviral vaccine in the postoperative period contributed to the normalization of most immunological reactivity indices that were altered in patients. The results indicate the prospects of using the antiviral vaccine as part of adjuvant antirelapse therapy after surgical treatment of LP patients and indicate the advisability of long-term clinical and immunological monitoring at different periods after vaccination

Rho-kinase Regulates Energy Balance by Targeting Hypothalamic Leptin Receptor Signaling

Leptin regulates energy balance. However, knowledge of the critical intracellular transducers of leptin signaling remains incomplete. Here we report that Rho-kinase 1 (ROCK1) regulates leptin action on body weight homeostasis by activating JAK2, an initial trigger of leptin receptor signaling. Leptin promotes the physical interaction of JAK2 and ROCK1, thereby increasing phosphorylation of JAK2 and downstream activation of Stat3 and FOXO1. Mice lacking ROCK1 in either POMC or AgRP neurons, mediators of leptin action, display obesity and impaired leptin sensitivity. In addition, deletion of ROCK1 in the arcuate nucleus markedly enhances food intake, resulting in severe obesity. Of note, ROCK1 is a specific mediator of leptin, but not insulin, regulation of POMC neuronal activity. Our data identify ROCK1 as a key regulator of leptin action on energy homeostasis