In Vivo Consequences of Disrupting SH3-Mediated Interactions of the Inducible T-Cell Kinase

ITK-SH3-mediated interactions, both with exogenous ligands and via intermolecular self-association with ITK-SH2, have been shown to be important for regulation of ITK activity. The biological significance of these competing SH3 interactions is not completely understood. A mutant of ITK where substitution of the SH3 domain with that of the related kinase BTK (ITK-BTK(SH3)) was used to disrupt intermolecular self-association of ITK while maintaining canonical binding to exogenous ligands such as SLP-76. ITK-BTK(SH3) displays reduced association with SLP-76 leading to inefficient transphosphorylation, reduced phosphorylation of PLCγ1, and diminished Th2 cytokine production. In contrast, ITK-BTK(SH3) displays no defect in its localization to the T-cell-APC contact site. Another mutation, Y511F, in the activation loop of ITK, impairs ITK activation. T cells expressing ITK-Y511F display defective phosphorylation of ITK and its downstream target PLCγ1, as well as significant inhibition of Th2 cytokines. In contrast, the inducible localization of ITK-Y511F to the T cell-APC contact site and its association with SLP-76 are not affected. The presented data lend further support to the hypothesis that precise interactions between ITK and its signaling partners are required to support ITK signaling downstream of the TCR

A Look at Technology Use Across the Country: State Implementation of AT Practices for Infants and Toddlers

EI professionals from across the country recently participated in the Tots-n-Tech’s (TnT) Assistive Technology (AT) Program Self-Assessment. Part C Coordinators designated agency and program directors, regional coordinators, or other relevant people in their states to respond to the on-line self assessment of AT practices. The self-assessment is designed to provide a picture of how well recommended AT practices are implemented within state communities. Information from all respondents is combined to provide state-wide and regional views of how programs are doing in making AT available for infants and toddlers with disabilities or delayed development

Why Terrorist Networks Maintain Viability within Today’s Modern Society.

Common concepts of terrorism refer to acts which are intended to create a system of fear. The ideological argument for terrorism relates to a politically and emotionally charged scenario in which terrorism is necessary. The development of a terrorist organization requires an environment that is ripe with social degradation and has idealistic minded people who are able to believe in a cause. The organization utilizes a social system to maintain its own stability and to retain the people who are involved within its self-contained community. Suffering oppression from its own government or an-other nation is a crucial component in fostering the development of terrorist organizations. The system of development is entrenched within the culture of a people who feel separated from the traditions and cultures of societal expectation. The perceived oppression is vital for creating blame for the current status of the surviving people. Furthermore, oppression allows for the development of hate to occur, which in turn creates a psychological opportunity to develop a terrorist narrative. This paper seeks to discuss how terrorist organizations like Hezbollah and Al Qaeda are developed around an oppressed society which has found its voice through aggression and violence. Their cause is said to be for the benefit of a societies which is enveloped into the ideological word of God. Terrorist organizations have targeted different types of nations for their continued existence; yet, these organizations still use the primary focuses of psychological influence of world view and prejudice theories to maintain their existence.In understanding terrorism, the characteristics of involvement must also be evaluated from a lens of world view understanding in combination of prejudice and psychological theories

In Vivo Consequences of Disrupting SH3-Mediated Interactions of the Inducible T-Cell Kinase

ITK-SH3-mediated interactions, both with exogenous ligands and via intermolecular self-association with ITK-SH2, have been shown to be important for regulation of ITK activity. The biological significance of these competing SH3 interactions is not completely understood. A mutant of ITK where substitution of the SH3 domain with that of the related kinase BTK (ITK-BTK(SH3)) was used to disrupt intermolecular self-association of ITK while maintaining canonical binding to exogenous ligands such as SLP-76. ITK-BTK(SH3)displays reduced association with SLP-76 leading to inefficient transphosphorylation, reduced phosphorylation of PLCγ1, and diminished Th2 cytokine production. In contrast, ITK-BTK(SH3) displays no defect in its localization to the T-cell-APC contact site. Another mutation, Y511F, in the activation loop of ITK, impairs ITK activation. T cells expressing ITK-Y511F display defective phosphorylation of ITK and its downstream target PLCγ1, as well as significant inhibition of Th2 cytokines. In contrast, the inducible localization of ITK-Y511F to the T cell-APC contact site and its association with SLP-76 are not affected. The presented data lend further support to the hypothesis that precise interactions between ITK and its signaling partners are required to support ITK signaling downstream of the TCR.This article is from Journal of Signal Transduction 2012 (2012): Article ID 694386, doi:10.1155/2012/694386. Posted with permission.</p

A Human CD34(+) Subset Resides in Lymph Nodes and Differentiates into CD56brightNatural Killer Cells

SummaryIn humans, T cells differentiate in thymus and B cells develop in bone marrow (BM), but the natural killer (NK) precursor cell(s) and site(s) of NK development are unclear. The CD56bright NK subset predominates in lymph nodes (LN) and produces abundant cytokines compared to the cytolytic CD56dim NK cell that predominates in blood. Here, we identify a novel CD34dimCD45RA(+) hematopoietic precursor cell (HPC) that is integrin α4β7bright. CD34dimCD45RA(+)β7bright HPCs constitute <1% of BM CD34(+) HPCs and ∼6% of blood CD34(+) HPCs, but >95% of LN CD34(+) HPCs. They reside in the parafollicular T cell regions of LN with CD56bright NK cells, and when stimulated by IL-15, IL-2, or activated LN T cells, they become CD56bright NK cells. The data identify a new NK precursor and support a model of human NK development in which BM-derived CD34dimCD45RA(+)β7bright HPCs reside in LN where endogenous cytokines drive their differentiation to CD56bright NK cells in vivo