Tel Aviv University is a public university located in Ramat Aviv, Tel Aviv, Israel. With over 30,000 students, TAU is Israel's largest university.Located in Israel's cultural, financial and technological core, Tel Aviv University is a major center of teaching and research, comprising 9 faculties, 27 schools, 98 departments and nearly 130 research institutes and centers. Wikipedia.
Kupiec M.,Tel Aviv University
FEMS Microbiology Reviews | Year: 2014
Telomeres are nucleoprotein structures that cap the ends of the linear eukaryotic chromosomes and thereby protect their stability and integrity. Telomeres play central roles in maintaining the genome's integrity, distinguishing between the natural chromosomal ends and unwanted double-stranded breaks. In addition, telomeres are replicated by a special reverse transcriptase called telomerase, in a complex mechanism that is coordinated with the genome's replication. Telomeres also play an important role in tethering the chromosomes to the nuclear envelope, thus helping in positioning the chromosomes within the nucleus. The special chromatin configuration of telomeres affects the expression of nearby genes; nonetheless, telomeres are transcribed, creating noncoding RNA molecules that hybridize to the chromosomal ends and seem to play regulatory roles. The yeast Saccharomyces cerevisiae, with its sophisticated genetics and molecular biology, has provided many fundamental concepts in telomere biology, which were later found to be conserved in all organisms. Here, we present an overview of all the aspects of telomere biology investigated in yeast, which continues to provide new insights into this complex and important subject, which has significant medical implications, especially in the fields of aging and cancer. Telomeres, the eukaryotic chromosomal ends, preserve genome stability and help duplicate the genome. They play important roles in aging and cancer. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.
Frenkel D.,Tel Aviv University
Nature communications | Year: 2013
In Alzheimer's disease, soluble amyloid-β causes synaptic dysfunction and neuronal loss. Receptors involved in clearance of soluble amyloid-β are not known. Here we use short hairpin RNA screening and identify the scavenger receptor Scara1 as a receptor for soluble amyloid-β expressed on myeloid cells. To determine the role of Scara1 in clearance of soluble amyloid-β in vivo, we cross Scara1 null mice with PS1-APP mice, a mouse model of Alzheimer's disease, and generate PS1-APP-Scara1-deficient mice. Scara1 deficiency markedly accelerates Aβ accumulation, leading to increased mortality. In contrast, pharmacological upregulation of Scara1 expression on mononuclear phagocytes increases Aβ clearance. This approach is a potential treatment strategy for Alzheimer's disease.
Oz S.,Tel Aviv University
Molecular Psychiatry | Year: 2014
The NAP motif of activity-dependent neuroprotective protein (ADNP) enhanced memory scores in patients suffering from mild cognitive impairment and protected activities of daily living in schizophrenia patients, while fortifying microtubule (MT)-dependent axonal transport, in mice and flies. The question is how does NAP fortify MTs? Our sequence analysis identified the MT end-binding protein (EB1)-interacting motif SxIP (SIP, Ser-Ile-Pro) in ADNP/NAP and showed specific SxIP binding sites in all members of the EB protein family (EB1-3). Others found that EB1 enhancement of neurite outgrowth is attenuated by EB2, while EB3 interacts with postsynaptic density protein 95 (PSD-95) to modulate dendritic plasticity. Here, NAP increased PSD-95 expression in dendritic spines, which was inhibited by EB3 silencing. EB1 or EB3, but not EB2 silencing inhibited NAP-mediated cell protection, which reflected NAP binding specificity. NAPVSKIPQ (SxIP=SKIP), but not NAPVAAAAQ mimicked NAP activity. ADNP, essential for neuronal differentiation and brain formation in mouse, a member of the SWI/SNF chromatin remodeling complex and a major protein mutated in autism and deregulated in schizophrenia in men, showed similar EB interactions, which were enhanced by NAP treatment. The newly identified shared MT target of NAP/ADNP is directly implicated in synaptic plasticity, explaining the breadth and efficiency of neuroprotective/neurotrophic capacities.Molecular Psychiatry advance online publication, 2 September 2014; doi:10.1038/mp.2014.97.
Fridman E.,Tel Aviv University
Automatica | Year: 2010
This paper considers sampled-data control of linear systems under uncertain sampling with the known upper bound on the sampling intervals. Recently a discontinuous Lyapunov function method was introduced by using impulsive system representation of the sampled-data systems (Naghshtabrizi, Hespanha, & Teel, 2008). The latter method improved the existing results, based on the input delay approach via time-independent Lyapunov functionals. The present paper introduces novel time-dependent Lyapunov functionals in the framework of the input delay approach, which essentially improve the existing results. These Lyapunov functionals do not grow after the sampling times. For the first time, for systems with time-varying delays, the introduced Lyapunov functionals can guarantee the stability under the sampling which may be greater than the analytical upper bound on the constant delay that preserves the stability. We show also that the term of the Lyapunov function, which was introduced in the above mentioned reference for the analysis of systems with constant sampling, is applicable to systems with variable sampling. © 2009 Elsevier Ltd. All rights reserved.
Khananshvili D.,Tel Aviv University
Molecular Aspects of Medicine | Year: 2013
The SLC8 gene family encoding Na+/Ca2+ exchangers (NCX) belongs to the CaCA (Ca2+/Cation Antiporter) superfamily. Three mammalian genes (SLC8A1, SLC8A2, and SLC8A3) and their splice variants are expressed in a tissue-specific manner to mediate Ca2+-fluxes across the cell-membrane and thus, significantly contribute to regulation of Ca 2+-dependent events in many cell types. A long-wanted mitochondrial Na+/Ca2+ exchanger has been recently identified as NCLX protein, representing a gene product of SLC8B1. Distinct NCX isoform/splice variants contribute to excitation-contraction coupling, long-term potentiation of the brain and learning, blood pressure regulation, immune response, neurotransmitter and insulin secretion, mitochondrial bioenergetics, etc. Altered expression and regulation of NCX proteins contribute to distorted Ca2+-homeostasis in heart failure, arrhythmia, cerebral ischemia, hypertension, diabetes, renal Ca2+ reabsorption, muscle dystrophy, etc. Recently, high-resolution X-ray structures of Ca2+-binding regulatory domains of eukaryotic NCX and of full-size prokaryotic NCX have become available and the dynamic properties have been analyzed by advanced biophysical approaches. Molecular silencing/overexpression of NCX in cellular systems and organ-specific KO mouse models provided useful information on the contribution of distinct NCX variants to cellular and systemic functions under various pathophysiological conditions. Selective inhibition or activation of predefined NCX variants in specific diseases might have clinical relevance, although this breakthrough has not yet been realized. A better understanding of the underlying molecular mechanisms as well as the development of in vitro procedures for high-throughput screening of "drug-like" compounds may lead to selective pharmacological targeting of NCX variants. © 2012 Elsevier Ltd. All rights reserved.