Apoptosis of uninfected cells induced by HIV envelope glycoproteins

Apoptosis, or programmed cell death, is a key event in biologic homeostasis but is also involved in the pathogenesis of many human diseases including human immunodeficiency virus (HIV) infection. Although multiple mechanisms contribute to the gradual T cell decline that occurs in HIV-infected patients, programmed cell death of uninfected bystander T lymphocytes, including CD4+ and CD8+ T cells, is an important event leading to immunodeficiency. The HIV envelope glycoproteins (Env) play a crucial role in transducing this apoptotic signal after binding to its receptors, the CD4 molecule and a coreceptor, essentially CCR5 and CXCR4. Depending on Env presentation, the receptor involved and the complexity of target cell contact, apoptosis induction is related to death receptor and/or mitochondria-dependent pathways. This review summarizes current knowledge of Env-mediated cell death leading to T cell depletion and clinical complications and covers the sometimes conflicting studies that address the possible mechanisms of T cell death

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Mengurut bayi: kebugaran dan ketenangan bagi bayi anda/ Ahr

73 hal.: ill.; 21 cm

Mengurut bayi: kebugaran dan ketenangan bagi bayi anda/ Ahr

73 hal.: ill.; 21 cm

Mengurut bayi: kebugaran dan ketenangan bagi bayi anda/ Ahr

73 hal.: ill.; 21 cm

Electron Acceleration With a Ultrafast Gun Driven by Single-Cycle Terahertz Pulses

We present results on an improved THz-driven electron gun using transversely-incident single-cycle THz pulses using a horn-coupler. Intrinsic synchronization between the electrons and the driving field was achieved by using a single laser system to create electrons by UV photoemission and to create THz radiation by difference frequency generation in a tilted-pulse front geometry. Details of the optical setups for the UV and THz pulses will be described as well as preliminary results showing evidence of electron acceleration

A Review of the Implementation of the Embryonic Stem Cell Test (EST)

The EST has been developed as an in vitro screening test for evaluating the potential embryotoxic effects of substances, to allow their classification into three major classes: non-embryotoxic; weakly embryotoxic; and strongly embryotoxic). It is biologically based on the assumption that chemicals with an embryotoxic potential will block the spontaneous development of embryonic stem cells into beating cardiac muscle cells within the first 10 days of embryonic development . In 2002, the assay was endorsed by the ECVAM Scientific Advisory Committee (ESAC) as scientifically validated and ready to be considered for regulatory acceptance and application. the workshop has reviewed the post validated status of the EST so far.JRC.DDG.I.3-In-vitro method

Characterization of the methylation-sensitive promoter of the imprinted ZAC gene supports its role in transient neonatal diabetes mellitus

ZAC is a recently isolated zinc finger protein that induces apoptosis and cell cycle arrest. The corresponding gene is imprinted maternally through an unknown mechanism and maps to 6q24-q25, within the minimal interval harboring the gene responsible for transient neonatal diabetes mellitus (TNDM) and a tumor suppressor gene involved in breast cancer. Because of its functional properties, imprinting status, and expression pattern in mammary cell lines and tumors, ZAC is the best candidate so far for both disease conditions. In the present work, we delineated ZAC genomic organization and mapped its transcriptional start site. It is noteworthy that the ZAC promoter localized to the CpG island harboring the methylation imprint associated with TNDM and methylation of this promoter silenced its activity. These data indicate that the methylation mark may have a direct effect on the silencing of the ZAC imprinted allele. Our findings further strengthen the hypothesis that ZAC is the gene responsible for TNDM and suggest a novel mechanism for ZAC inactivation in breast tumors

JAK tyrosine kinases promote hierarchical activation of Rho and Rap modules of integrin activation

Item does not contain fulltextLymphocyte recruitment is regulated by signaling modules based on the activity of Rho and Rap small guanosine triphosphatases that control integrin activation by chemokines. We show that Janus kinase (JAK) protein tyrosine kinases control chemokine-induced LFA-1- and VLA-4-mediated adhesion as well as human T lymphocyte homing to secondary lymphoid organs. JAK2 and JAK3 isoforms, but not JAK1, mediate CXCL12-induced LFA-1 triggering to a high affinity state. Signal transduction analysis showed that chemokine-induced activation of the Rho module of LFA-1 affinity triggering is dependent on JAK activity, with VAV1 mediating Rho activation by JAKs in a Galphai-independent manner. Furthermore, activation of Rap1A by chemokines is also dependent on JAK2 and JAK3 activity. Importantly, activation of Rap1A by JAKs is mediated by RhoA and PLD1, thus establishing Rap1A as a downstream effector of the Rho module. Thus, JAK tyrosine kinases control integrin activation and dependent lymphocyte trafficking by bridging chemokine receptors to the concurrent and hierarchical activation of the Rho and Rap modules of integrin activation