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Search Results: 1 - 10 of 47 matches for " Luba Dankulich-Nagrudny "
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Cholecystokinin: An Excitatory Modulator of Mitral/Tufted Cells in the Mouse Olfactory Bulb
Jie Ma, Luba Dankulich-Nagrudny, Graeme Lowe
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0064170
Abstract: Cholecystokinin (CCK) is widely distributed in the brain as a sulfated octapeptide (CCK-8S). In the olfactory bulb, CCK-8S is concentrated in two laminae: an infraglomerular band in the external plexiform layer, and an inframitral band in the internal plexiform layer (IPL), corresponding to somata and terminals of superficial tufted cells with intrabulbar projections linking duplicate glomerular maps of olfactory receptors. The physiological role of CCK in this circuit is unknown. We made patch clamp recordings of CCK effects on mitral cell spike activity in mouse olfactory bulb slices, and applied immunohistochemistry to localize CCKB receptors. In cell-attached recordings, mitral cells responded to 300 nM –1 μM CCK-8S by spike excitation, suppression, or mixed excitation-suppression. Antagonists of GABAA and ionotropic glutamate receptors blocked suppression, but excitation persisted. Whole-cell recordings revealed that excitation was mediated by a slow inward current, and suppression by spike inactivation or inhibitory synaptic input. Similar responses were elicited by the CCKB receptor-selective agonist CCK-4 (1 μM). Excitation was less frequent but still occurred when CCKB receptors were blocked by LY225910, or disrupted in CCKB knockout mice, and was also observed in CCKA knockouts. CCKB receptor immunoreactivity was detected on mitral and superficial tufted cells, colocalized with Tbx21, and was absent from granule cells and the IPL. Our data indicate that CCK excites mitral cells postsynaptically, via both CCKA and CCKB receptors. We hypothesize that extrasynaptic CCK released from tufted cell terminals in the IPL may diffuse to and directly excite mitral cell bodies, creating a positive feedback loop that can amplify output from pairs of glomeruli receiving sensory inputs encoded by the same olfactory receptor. Dynamic plasticity of intrabulbar projections suggests that this could be an experience-dependent amplification mechanism for tuning and optimizing olfactory bulb signal processing in different odor environments.
Sour Ageusia in Two Individuals Implicates Ion Channels of the ASIC and PKD Families in Human Sour Taste Perception at the Anterior Tongue
Taufiqul Huque, Beverly J. Cowart, Luba Dankulich-Nagrudny, Edmund A. Pribitkin, Douglas L. Bayley, Andrew I. Spielman, Roy S. Feldman, Scott A. Mackler, Joseph G. Brand
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0007347
Abstract: Background The perception of sour taste in humans is incompletely understood at the receptor cell level. We report here on two patients with an acquired sour ageusia. Each patient was unresponsive to sour stimuli, but both showed normal responses to bitter, sweet, and salty stimuli. Methods and Findings Lingual fungiform papillae, containing taste cells, were obtained by biopsy from the two patients, and from three sour-normal individuals, and analyzed by RT-PCR. The following transcripts were undetectable in the patients, even after 50 cycles of amplification, but readily detectable in the sour-normal subjects: acid sensing ion channels (ASICs) 1a, 1β, 2a, 2b, and 3; and polycystic kidney disease (PKD) channels PKD1L3 and PKD2L1. Patients and sour-normals expressed the taste-related phospholipase C-β2, the δ-subunit of epithelial sodium channel (ENaC) and the bitter receptor T2R14, as well as β-actin. Genomic analysis of one patient, using buccal tissue, did not show absence of the genes for ASIC1a and PKD2L1. Immunohistochemistry of fungiform papillae from sour-normal subjects revealed labeling of taste bud cells by antibodies to ASICs 1a and 1β, PKD2L1, phospholipase C-β2, and δ-ENaC. An antibody to PKD1L3 labeled tissue outside taste bud cells. Conclusions These data suggest a role for ASICs and PKDs in human sour perception. This is the first report of sour ageusia in humans, and the very existence of such individuals (“natural knockouts”) suggests a cell lineage for sour that is independent of the other taste modalities.
Congenital Cataracts – Facial Dysmorphism – Neuropathy
Luba Kalaydjieva
Orphanet Journal of Rare Diseases , 2006, DOI: 10.1186/1750-1172-1-32
Abstract: Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndromeCCFDN is a complex developmental disorder of autosomal recessive inheritance which, so far, has been found to occur exclusively in patients of Roma (Gypsy) ethnicity [1,2].? Bilateral congenital cataracts, microcornea, microphthalmos, micropupils? Developmental delay? Small stature and low weight? Hypo/demyelinating neuropathy? Mild facial dysmorphism? Mild hypogonadism? Mild cognitive deficit? Cerebral and spinal cord atrophy on neuroimaging? Post-infectious rhabdomyolysis? OsteoporosisThe CCFDN mutation is particularly common among the Rudari, an endogamous, recently founded Roma population, in whom the carrier rate is around 6–7% [3,4]. In other Gypsy groups, it is ~1%. The disorder has so far been diagnosed in over 100 Roma patients, whose countries of residence reflect past and recent migrations of the affected population, as well as access to healthcare and awareness of this syndrome among health care providers. Most known affected subjects belong to the traditional Roma population of Balkan and Central European countries (Bulgaria, Romania, Serbia, Greece, Hungary, the Czech Republic), or are recent migrants to Austria and Germany; with cases also diagnosed in Italy, France, The Netherlands, USA and Canada. CCFDN should be considered as the most likely diagnosis in infants of Roma ethnicity presenting with congenital cataracts.The CCFDN phenotype is complex and affects multiple organs and tissues, mostly during intra-uterine development. Detailed descriptions of the clinical manifestations are available [2,5-7].Prenatal eye development is invariably affected and the congenital cataracts are the first CCFDN manifestation, recognisable in early infancy. The cataracts are bilateral and are characterised by anterior or posterior cortical dense opacities with clouding of the adjacent part of the lens nucleus or total cataracts involving the whole lens. These are accompanied by microcornea, micropht
Expert rule versus majority rule under partial information, II
Daniel Berend,Luba Sapir
Advances in Decision Sciences , 2002, DOI: 10.1155/s1173912602000068
Abstract: The main purpose of this paper is clarifying the connection between some characteristics of a deciding body and the probability of its making correct decisions. In our model a group of decision makers is required to select one of two alternatives. We assume the probabilities of the decision makers being correct are independent random variables distributed according to the same given distribution rule. This distribution belongs to a general family, containing the uniform distribution as a particular case. We investigate the behavior of the probability of the expert rule being optimal, as well as that of the majority rule, both as functions of the distribution parameter and the group size. The main result is that for any value of the distribution parameter the expert rule is far more likely to be optimal than the majority rule, especially as the deciding body becomes larger.
Allosteric Communication across the Native and Mutated KIT Receptor Tyrosine Kinase
Elodie Laine,Christian Auclair,Luba Tchertanov
PLOS Computational Biology , 2012, DOI: 10.1371/journal.pcbi.1002661
Abstract: A fundamental goal in cellular signaling is to understand allosteric communication, the process by which signals originated at one site in a protein propagate dependably to affect remote functional sites. Here, we describe the allosteric regulation of the receptor tyrosine kinase KIT. Our analysis evidenced that communication routes established between the activation loop (A-loop) and the distant juxtamembrane region (JMR) in the native protein were disrupted by the oncogenic mutation D816V positioned in the A-loop. In silico mutagenesis provided a plausible way of restoring the protein communication detected in the native KIT by introducing a counter-balancing second mutation D792E. The communication patterns observed in the native and mutated KIT correlate perfectly with the structural and dynamical features of these proteins. Particularly, a long-distance effect of the D816V mutation manifested as an important structural re-organization of the JMR in the oncogenic mutant was completely vanished in the double mutant D816V/D792E. This detailed characterization of the allosteric communication in the different forms of KIT, native and mutants, was performed by using a modular network representation composed of communication pathways and independent dynamic segments. Such representation permits to enrich a purely mechanistic interaction-based model of protein communication by the introduction of concerted local atomic fluctuations. This method, validated on KIT receptor, may guide a rational modulation of the physiopathological activities of other receptor tyrosine kinases.
Genetic studies of the Roma (Gypsies): a review
Luba Kalaydjieva, David Gresham, Francesc Calafell
BMC Medical Genetics , 2001, DOI: 10.1186/1471-2350-2-5
Abstract: Recent medical genetic research has identified a number of novel, or previously known but rare conditions, caused by private founder mutations. A summary of the findings, provided in this review, should assist diagnosis and counselling in affected families, and promote future collaborative research. The available incomplete epidemiological data suggest a non-random distribution of disease-causing mutations among Romani groups.Although far from systematic, the published information indicates that medical genetics has an important role to play in improving the health of this underprivileged and forgotten people of Europe. Reported carrier rates for some Mendelian disorders are in the range of 5 -15%, sufficient to justify newborn screening and early treatment, or community-based education and carrier testing programs for disorders where no therapy is currently available. To be most productive, future studies of the epidemiology of single gene disorders should take social organisation and cultural anthropology into consideration, thus allowing the targeting of public health programs and contributing to the understanding of population structure and demographic history of the Roma.The Roma (Gypsies) became one of the peoples of Europe around one thousand years ago, when they first arrived in the Balkans [1,2]. The current size of the European Romani population, around 8 million [2], is equivalent to that of an average European country (Figure 1). While human rights and socio-economic issues related to the Roma are increasingly becoming the focus of political debate and media coverage throughout Europe, their poor health status [[3-6]] is rarely discussed and still awaits the attention of the medical profession.This review of genetic studies of the Roma was prompted by two recent developments: (i) Studies conducted over the last decade have resulted in the identification of a number of novel single gene disorders and disease-causing mutations. The accumulating data are al
Raltegravir: molecular basis of its mechanism of action
Mouscadet Jean-Fran?ois,Tchertanov Luba
European Journal of Medical Research , 2009, DOI: 10.1186/2047-783x-14-s3-5
Abstract: Integration of the HIV-1 viral DNA generated by reverse transcription of the RNA genome into the host cell chromosomes is a key step of viral replication, catalyzed by the viral integrase. In October 2007, the first integrase inhibitor, raltegravir, was approved for clinical use under the name of Isentress . The results of the various clinical trials that have evaluated raltegravir have been very encouraging with regard to the immunological and virological efficacy and tolerance. However, as observed for other anti-retrovirals, specific resistance mutations have been identified in patients failing to respond to treatment with raltegravir. Although knowledge of the integrase structural biology remains fragmentary, the structures and modeling data available might provide relevant clues on the origin of the emergence of these resistance mutations. In this review, we describe the mechanism of action of this drug and the main data relating to its use in vivo, together with recent structural data important to our understanding of the origin of viral resistance.
Discrete charging of metallic grains: Statistics of addition spectra
Yshai Avishai,Daniel Berend,Luba Bromberg
Physics , 2005, DOI: 10.1088/0305-4470/39/18/002
Abstract: We analyze the statistics of electrostatic energies (and their differences) for a quantum dot system composed of a finite number $K$ of electron islands (metallic grains) with random capacitance-inductance matrix $C$, for which the total charge is discrete, $Q=Ne$ (where $e$ is the charge of an electron and $N$ is an integer). The analysis is based on a generalized charging model, where the electrons are distributed among the grains such that the electrostatic energy E(N) is minimal. Its second difference (inverse compressibility) $\chi_{N}=E(N+1)-2 E(N)+E(N-1)$ represents the spacing between adjacent Coulomb blockade peaks appearing when the conductance of the quantum dot is plotted against gate voltage. The statistics of this quantity has been the focus of experimental and theoretical investigations during the last two decades. We provide an algorithm for calculating the distribution function corresponding to $\chi_{N}$ and show that this function is piecewise polynomial.
Ontogenèse des marqueurs génétiques sanguins chez le cheval
Marie Kaminski, Y Bouquet, A Weghe, Luba Podliachouk
Genetics Selection Evolution , 1974, DOI: 10.1186/1297-9686-6-2-195
Synthesis and Biological Activity of Silyl- and GermylsubstitutedTrifluroacetylfurans
Luba Ignatovich,Dzintra Zarina,Irina Shestakova,Skaidrite Germane
Metal-Based Drugs , 2001, DOI: 10.1155/mbd.2001.211
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