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In this study, an E. coli phage JH2 was isolated from swine feces in an industrial farm. Bacteriophage JH2 could carry 85% (n= 32) O8 ETEC (Enterotoxigenic Escherichia coli) strains when 81 alike-strains from Vietnam and China were tested. The genome size could be as large as JH2 had 77187 bps, a linear, double-stranded and CG = 38.89%. It shared a height similarity of 94.9% to Staphylococcus phage SA1 of GU169904 with 147303 bps, which is about double the size. JH2 carried 22 tRNA and no gene for known toxins. Under the electronic microscope the phage presented icosahedral heads, necks, contractile and long tails, and it belonged to the Myoviridae family. The phage demonstrated high stability to the physical and chemical factors, thermal sensitivity at 60°C and acid and alkaline resistance (pH= 5-9). The genome of JH2 contained 131 putative open reading frames (ORFs). One hundred and twenty-six ORFs (out of 131) were predicted and 121 ORFs had putative functions. From database, 22 tRNAs were predicted in the JH2 genome. Staphylococcus phage SA1 contains an almost complete phage genome of JH2 phage. The complete genome sequence of JH2 was analyzed. Comparing the complete genome sequences of JH2 and Staphylococcus phage SA1 showed 94.9% similarity. [ABSTRACT FROM AUTHOR]

Overactive Janus kinases (JAKs) are known to drive leukemia, making them well-suited targets for treatment. We sought to identify new JAK-activating mutations and instead found a JAK1-inactivating pseudokinase mutation, V666G. In contrast to other pseudokinase mutations that canonically lead to an active kinase, the JAK1 V666G mutation led to under-activation seen by reduced phosphorylation. To understand the functional role of JAK1 V666G in modifying kinase activity we investigated its influence on other JAK kinases and within the Interleukin-2 pathway. JAK1 V666G not only inhibited its own activity, but its presence could inhibit other JAK kinases. These findings provide new insights into the potential of JAK1 pseudokinase to modulate its own activity, as well as of other JAK kinases. Thus, the features of the JAK1 V666 region in modifying JAK kinases can be exploited to allosterically inhibit overactive JAKs. [ABSTRACT FROM AUTHOR]

In this paper, both experimental tests and numerical simulations of Polyvinyl Butyral (PVB) laminated glass pane under low-speed impact were carried out. In order to accurately predict the responses of annealed glass under low-speed impact, a constitutive model combined of the Taylor−Chen−Kuszmaul (TCK) model and the Johnson-Holmquist Ceramic (JH2) model is proposed. In order to describe the tensile damage characteristic of annealed glass, a rate-dependent TCK model is employed. The JH2 model is adopted when the glass material is under compression. The velocity and force of impactor, deflection of central point of glass pane, and the cracking pattern are studied to verify the combined TCK-JH2 model. Furthermore, the effects of the thickness of glass layer and PVB interlayer are investigated.

Janus kinases (JAKs) regulate hematopoiesis via the cytokine-mediated JAK-STAT signaling pathway. JAKs contain tandem C-terminal pseudokinase (JH2) and tyrosine kinase (JH1) domains. The JAK2 pseudokinase domain adopts a protein kinase fold and, despite its pseudokinase designation, binds ATP with micromolar affinity. Recent evidence shows that displacing ATP from the JAK2 JH2 domain alters the hyperactivation state of the oncogenic JAK2 V617F protein while sparing the wild type JAK2 protein. In this study, small molecule binders of JAK2 JH2 were identified via an in vitro screen. Top hits were characterized using biophysical and structural approaches. Development of pseudokinase-selective compounds may offer novel pharmacological opportunities for treating cancers driven by JAK2 V617F and other oncogenic JAK mutants.