bluuebunny/crossref_metadata_2025 huggingface dataset:
Virion Instability of Human Immunodeficiency Virus Type 1 Reverse Transcriptase (RT) Mutated in the Protease Cleavage Site between RT p51 and the RT RNase H Domain
Authors: Abram Michael E. , Parniak Michael A.
Published: September 2005

Each of the human immunodeficiency virus type 1 (HIV-1)
pol
-encoded enzymes, protease (PR), reverse transcriptase (RT), and integrase (IN), is active only as a dimer (or higher-order oligomer in the case of IN), but only RT comprises subunits of different masses. RT is a heterodimer of 66-kDa and 51-kDa subunits. The latter is formed by HIV PR-catalyzed cleavage of p66 during virion maturation, resulting in the removal of the RNase H (RNH) domain of a p66 subunit. In order to study the apparent need for RT heterodimers in the context of the virion, we introduced a variety of mutations in the RT p51-RNH protease cleavage site of an infectious HIV-1 molecular clone. Surprisingly, rather than leading to virions with increased RT p66 content, most of the mutations resulted in significantly attenuated virus that contained greatly decreased levels of RT that in many cases was primarily p51 RT. IN levels were also reduced in several mutants. However, most mutants showed normal levels of the Pr160
gag-pol
precursor polyprotein, suggesting that reduced virion RT arose from proteolytic instability rather than decreased incorporation. Mutant virion p24 Gag levels were equivalent to wild type, indicating that Gag incorporation and processing were not affected. Repeated passage of MT-2 cells exposed to mutant viruses led to the appearance of virus with improved replication capacity; these virions contained normally processed RT at near-wild-type levels. These results imply that additional proteolytic processing of RT to the p66/p51 heterodimer is essential to provide proteolytic stability of RT during HIV-1 maturation.
The Extracellular Domain of Herpes Simplex Virus gE Is Indispensable for Efficient Cell-to-Cell Spread: Evidence for gE/gI Receptors
Authors: Polcicova Katarina , Goldsmith Kim , Rainish Barb L. , Wisner Todd W. , Johnson David C.
Published: September 2005

Herpes simplex virus (HSV) spreads rapidly and efficiently within epithelial and neuronal tissues. The HSV glycoprotein heterodimer gE/gI plays a critical role in promoting cell-to-cell spread but does not obviously function during entry of extracellular virus into cells. Thus, gE/gI is an important molecular handle on the poorly understood process of cell-to-cell spread. There was previous evidence that the large extracellular (ET) domains of gE/gI might be important in cell-to-cell spread. First, gE/gI extensively accumulates at cell junctions, consistent with being tethered there. Second, expression of gE/gI intransinterfered with HSV spread between epithelial cells. To directly test whether the gE ET domain was necessary for gE/gI to promote virus spread, a panel of gE mutants with small insertions in the ET domain was constructed. Cell-to-cell spread was reduced when insertions were made within either of two regions, residues 256 to 291 or 348 to 380. There was a strong correlation between loss of cell-to-cell spread function and binding of immunoglobulin. gE ET domain mutants 277, 291, and 348 bound gI, produced mature forms of gE that reached the cell surface, and were incorporated into virions yet produced plaques similar to gE null mutants. Moreover, all three mutants were highly restricted in spread within the corneal epithelium, in the case of mutant 277 to only 4 to 6% of the number of cells compared with wild-type HSV. Therefore, the ET domain of gE is indispensable for efficient cell-to-cell spread. These observations are consistent with our working hypothesis that gE/gI can bind extracellular ligands, so-called gE/gI receptors that are concentrated at epithelial cell junctions. This fits with similarities in structure and function of gE/gI and gD, which is a receptor binding protein.
Effects of Substitutions of Arginine Residues on the Basic Surface of Herpes Simplex Virus UL42 Support a Role for DNA Binding in Processive DNA Synthesis
Authors: Randell John C. W. , Komazin Gloria , Jiang Changying , Hwang Charles B. C. , Coen Donald M.
Published: September 2005

The way that UL42, the processivity subunit of the herpes simplex virus DNA polymerase, interacts with DNA and promotes processivity remains unclear. A positively charged face of UL42 has been proposed to participate in electrostatic interactions with DNA that would tether the polymerase to a template without preventing its translocation via DNA sliding. An alternative model proposes that DNA binding by UL42 is not important for processivity. To investigate these issues, we substituted alanine for each of four conserved arginine residues on the positively charged surface. Each single substitution decreased the DNA binding affinity of UL42, with 14- to 30-fold increases in apparent dissociation constants. The mutant proteins exhibited no meaningful change in affinity for binding to the C terminus of the catalytic subunit of the polymerase, indicating that the substitutions exert a specific effect on DNA binding. The substitutions decreased UL42-mediated long-chain DNA synthesis by the polymerase in the same rank order in which they affected DNA binding, consistent with a role for DNA binding in polymerase processivity. Combining these substitutions decreased DNA binding further and impaired the complementation of a
UL42
null virus in transfected cells. Additionally, using a revised mathematical model to analyze rates of dissociation of UL42 from DNAs of various lengths, we found that dissociation from internal sites, which would be the most important for tethering the polymerase, was relatively slow, even at ionic strengths that permit processive DNA synthesis by the holoenzyme. These data provide evidence that the basic surface of UL42 interacts with DNA and support a model in which DNA binding by UL42 is important for processive DNA synthesis.
Membrane Structures of the Hemifusion-Inducing Fusion Peptide Mutant G1S and theFusion-Blocking Mutant G1V of Influenza Virus HemagglutininSuggest a Mechanism for Pore Opening in MembraneFusion
Authors: Li Yinling , Han Xing , Lai Alex L. , Bushweller John H. , Cafiso David S. , Tamm Lukas K.
Published: September 2005

Influenza
virus hemagglutinin (HA)-mediated membrane fusion is initiated by a
conformational change that releases a V-shaped hydrophobic fusion
domain, the fusion peptide, into the lipid bilayer of the target
membrane. The most N-terminal residue of this domain, a glycine, is
highly conserved and is particularly critical for HA function; G1S and
G1V mutant HAs cause hemifusion and abolish fusion, respectively. We
have determined the atomic resolution structures of the G1S and G1V
mutant fusion domains in membrane environments. G1S forms a V with a
disrupted “glycine edge” on its N-terminal arm and G1V
adopts a slightly tilted linear helical structure in membranes.
Abolishment of the kink in G1V results in reduced hydrophobic
penetration of the lipid bilayer and an increased propensity to formβ
-structures at the membrane surface. These results underline
the functional importance of the kink in the fusion peptide and suggest
a structural role for the N-terminal glycine ridge in viral membrane
fusion.
Complete Deletion of
Wheat Streak Mosaic Virus
HC-Pro: a Null Mutant Is Viable for Systemic Infection
Authors: Stenger Drake C. , French Roy , Gildow Frederick E.
Published: September 2005

A
Wheat streak mosaic virus
(WSMV) genome lacking HC-Pro was constructed and confirmed by reverse transcription-PCR to systemically infect wheat, oat, and corn. Coupled in vitro transcription/translation reactions indicated that WSMV P1 proteinase cleaved the polyprotein at the P1/P3 junction of the HC-Pro null mutant. The WSMV HC-Pro null mutant was competent for virion formation, but the virus titer was reduced 4.5-fold relative to that of the wild type. Collectively, these results indicate that WSMV HC-Pro is dispensable for replication and movement, two essential processes that are disrupted by point and small-insertion mutations introduced into potyvirus HC-Pro.
Increased Expression of the NK Cell Receptor KLRG1 by Virus-Specific CD8 T Cells during Persistent Antigen Stimulation
Authors: Thimme Robert , Appay Victor , Koschella Marie , Panther Elisabeth , Roth Evelyn , Hislop Andrew D. , Rickinson Alan B. , Rowland-Jones Sarah L. , Blum Hubert E. , Pircher Hanspeter
Published: September 2005

The killer cell lectin-like receptor G1 (KLRG1) is a natural killer cell receptor expressed by T cells that exhibit impaired proliferative capacity. Here, we determined the KLRG1 expression by virus-specific T cells. We found that repetitive and persistent antigen stimulation leads to an increase in KLRG1 expression of virus-specific CD8+T cells in mice and that virus-specific CD8+T cells are mostly KLRG1+in chronic human viral infections (human immunodeficiency virus, cytomegalovirus, and Epstein-Barr virus) but not in resolved infection (influenza virus). Thus, by using KLRG1 as a T-cell marker, our results suggest that the differentiation status and function of virus-specific CD8+T cells are directly influenced by persistent antigen stimulation.
GIANT MAGNETOIMPEDANCE EFFECT IN AS-DEPOSITED (Fe88Zr7B5)0.97Cu0.03 AMORPHOUS FILMS
Authors: CHEN WEI-PING , XIAO SHU-QIN , LIU YI-HUA
Published: August 2005

The giant magnetoimpedance (GMI) effect has been observed in as-deposited ( Fe 88 Zr 7 B 5)0.97 Cu 0.03 amorphous film prepared by radio frequency sputtering. The maximum magnetoimpedance ratio of 17% was obtained at a frequency of 13 MHz. The field and frequency dependences of magnetoimpedance, magnetoresistance, magnetoreactance and transverse permeability have been investigated in detail. Our results show that a close correlation between longitudinal GMI and transverse permeability exists. Our results indicate that the amorphous ( Fe 88 Zr 7 B 5)0.97 Cu 0.03 films have good soft magnetic properties and remarkable GMI effect even though in the as-deposited state.
SPIN POLARIZED LIQUID 3He
Authors: BORDBAR G. H. , ZEBARJAD S. M. , VAHDANI M. R. , BIGDELI M.
Published: August 2005

We have employed the constrained variational method to study the influence of spin polarization on the ground state properties of liquid 3 He . The spin polarized phase, we have found, has stronger correlation with respect to the unpolarized phase. It is shown that the internal energy of liquid 3 He increases by increasing polarization with no crossing point between polarized and unpolarized energy curves over the liquid density range. The obtained internal energy curves show a bound state, even in the case of fully spin polarized matter. We have also investigated the validity of using a parabolic formula for calculating the energy of spin polarized liquid 3 He . Finally, we have compared our results with other calculations.
QUANTUM PHASE TRANSITION OF DIPOLAR BOSONS IN OPTICAL LATTICES
Authors: LI QIU-YAN , XIE ZHENG-WEI , LI ZAI-DONG
Published: August 2005

In terms of the Green's function method we study the energy spectrum of dipolar boson atoms with the dipole-dipole interaction in an optical lattice. The Superfluid-Mott-Insulator phase transition condition of the dipolar bosons is determined from the energy-band structure of the excitation spectrum as a function of interatomic repulsion, dipolar bosons interaction and the tunnel coupling constants. The superfluid phase is explained explicitly from the energy spectrum derived in terms of the Bogoliubov approach as well.
CHARACTERIZATION OF Al-ALLOYS (50xx) BY USING POSITRON ANNIHILATION, X-RAY DIFFRACTION AND VIBRATING REED TECHNIQUES
Authors: KUMAR UDAY , BADAWI EMAD , MUKHOPADHYAY P. K.
Published: August 2005

A series of Al – Mg x alloys, with x = 0.82, 2.09, 2.28, 2.49 and 4.47 wt.%, respectively were characterized by using positron annihilation lifetime studies (PAL), X-ray diffraction (XRD), and sound velocity and internal friction using a vibrating reed technique (VRT). PAL lifetime values increase linearly as the composition is varied, but texturing or preferential orientation is maximum at an intermediate value of composition (x = 2.49%). The internal friction shows a minimum at the same composition, and the sound velocity changes show the maximum value here too. This means that at this composition the sample is the most ordered and defect free.
THE MONTE CARLO METHOD APPLIED TO CARRIER TRANSPORT IN Si/SiGe QUANTUM WELLS
Authors: VETTCHINKINA V. A. , BLOM A. , ODNOBLYUDOV M. A.
Published: August 2005

We present a complete Monte Carlo simulation of the transport properties of a Si/SiGe quantum well. The scattering mechanisms, viz. intervalley phonons, acoustic phonons, interface roughness and impurity scattering (including resonant scattering), are considered in detail, and we derive analytic expressions for the scattering rates, in each case properly taking the quantized electron wave functions into account. The numerically obtained distribution function is used to discuss the influence of each scattering mechanism for different electric fields applied parallel to the interfaces and also different temperatures.
HORSESHOES IN A NEW SWITCHING CIRCUIT VIA WIEN-BRIDGE OSCILLATOR
Authors: YANG XIAO-SONG , LI QINGDU
Published: August 2005

In this paper we revisit a switching circuit designed by the authors and present a theoretical analysis on the existence of chaos in this circuit. For the ordinary differential equations describing this circuit, we give a computer-aided proof in terms of cross-section and Poincare map, by applying a modern theory of topological horseshoes theory to the obtained Poincare map, that this map is semiconjugate to the two-shift map. This implies that the corresponding differential equations exhibit chaos.
SYMBOLIC ANALYSIS OF BIFURCATION IN SWITCHING POWER CONVERTERS: A PRACTICAL ALTERNATIVE VIEWPOINT OF BORDER COLLISION
Authors: TSE CHI K. , DAI DONG , MA XIKUI
Published: August 2005

In this letter, a symbolic method is proposed for analyzing the bifurcation in switching power converters. This method focuses on the cyclic operation of the system which characterizes its bifurcation behavior. The concept of block switching sequence is introduced, which, in conjunction with the waveform periodicity of the system, can be used to distinguish the various types of bifurcation behavior, e.g. "smooth" period doubling and "nonsmooth" border collision. This concept explicitly exposes the mechanism of border collision from a circuit operational viewpoint and leads to a direct detection criterion for this global bifurcation. The proposed method is applied, as an illustrative example, to develop two-dimensional bifurcation diagrams for a voltage-mode controlled buck converter.
STABILITY AND BIFURCATION OF BIDIRECTIONAL ASSOCIATIVE MEMORY NEURAL NETWORKS WITH DELAYED SELF-FEEDBACK
Authors: WANG LIN , ZOU XINGFU
Published: August 2005

Some delay independent and delay dependent conditions are derived for the global stability of the bidirectional associative memory neural networks with delayed self-feedback. Regarding the self-connection delay as the parameter to be varied, the linear stability and Hopf bifurcation analysis are carried out. An algorithm to determine the direction and stability of the Hopf bifurcations is also worked out. Some examples and numerical simulations are presented.
REALIZATION AND BIFURCATION OF BOOLEAN FUNCTIONS VIA CELLULAR NEURAL NETWORKS
Authors: CHEN FANGYUE , CHEN GUANRONG
Published: August 2005

In this work, we study the realization and bifurcation of Boolean functions of four variables via a Cellular Neural Network (CNN). We characterize the basic relations between the genes and the offsets of an uncoupled CNN as well as the basis of the binary input vectors set. Based on the analysis, we have rigorously proved that there are exactly 1882 linearly separable Boolean functions of four variables, and found an effective method for realizing all linearly separable Boolean functions via an uncoupled CNN. Consequently, any kind of linearly separable Boolean function can be implemented by an uncoupled CNN, and all CNN genes that are associated with these Boolean functions, called the CNN gene bank of four variables, can be easily determined. Through this work, we will show that the standard CNN invented by Chua and Yang in 1988 indeed is very essential not only in terms of engineering applications but also in the sense of fundamental mathematics.
ANTISYMMETRIC ELEMENTS IN GROUP RINGS
Authors: JESPERS ERIC , MARÍN MANUEL RUIZ
Published: August 2005

Let R be a commutative ring, G a group and RG its group ring. Let φ: RG → RG denote the R-linear extension of an involution φ defined on G. An element x in RG is said to be antisymmetric if φ(x) = -x. A characterization is given of when the antisymmetric elements [Formula: see text] of RG commute except when Char(R) = 3.
TEST OF EPIMORPHISM FOR FINITELY GENERATED MORPHISMS BETWEEN AFFINE ALGEBRAS OVER COMPUTATIONAL RINGS
Authors: MESNAGER SIHEM
Published: August 2005

In this paper, based on a characterization of epimorphisms of R-algebras given by Roby [15], we bring an algorithm testing whether a given finitely generated morphism f : A → B, where A and B are finitely presented affine algebras over the same Nœtherian commutative ring R, is an epimorphism of R-algebras or not. We require two computational conditions on R, which we call a computational ring.
INDISPENSABLE BINOMIALS OF FINITE GRAPHS
Authors: OHSUGI HIDEFUMI , HIBI TAKAYUKI
Published: August 2005

A binomial f belonging to a toric ideal I is indispensable if, for any system [Formula: see text] of binomial generators of I, either f or -f belongs to [Formula: see text]. In the present paper, we study indispensable binomials of the toric ideals IG arising from a finite graph G. First, we show that the toric ideal IG arising from a finite graph G whose complementary graph is weakly chordal is generated by the indispensable binomials if and only if no complete graph of order ≥4 is a subgraph of G. Second, we completely classify indispensable binomials of the toric ideal IG arising from a finite graph G satisfying the odd cycle condition. Finally, the existence of indispensable binomials of IG will be discussed.
PURE BRAIDS AS AUTOMORPHISMS OF FREE GROUPS
Authors: ABDULRAHIM MOHAMMAD N.
Published: August 2005

We study the composition of F. R. Cohen's map Pn → Pnk with the Gassner representation, where Pn is the pure braid group. This gives us a linear representation of Pn whose composition factors are one copy of the Gassner representation of Pn and k - 1 copies of a diagonal representation, hence a direct sum of one-dimensional representations.
An Exploratory Study on Knowledge Management Characteristics and Challenges in Mass Customisation
Authors: Cho Sung-Eui , Lee Won Jun , Kim Jonguk
Published: August 2005

The characteristics of knowledge management (KM) in mass customisation were newly extracted and the effect of those characteristics on KM performance was examined through case studies in this research. The firms implementing mass customisation are good cases adopting recent changes in business environment including increased variability of customer needs, technologies, and increase of the need for KM. From the results of this research, several differentiated characteristics compared to the cases not implementing mass customisation were extracted. These include: (1) extended scope of KM (customer, product and process knowledge); (2) increase in the volume of knowledge and knowledge processes; and (3) increase in the need for knowledge flexibility and knowledge variability. In addition, it was found that the capability to manage these characteristics positively affected KM performance in mass customisation. Therefore, firms intending to implement KM for mass customisation need to consider the differentiated characteristics of KM. Research was conducted through interviews with company directors or managers in charge of KM in selected companies implementing mass customisation.
Information Technology Strategy for Knowledge Management in Indian Industry
Authors: Pillania Rajesh K.
Published: August 2005

Information technology (IT) has a crucial role in knowledge management (KM), as the facilitator or enabler. To find the IT strategy for KM and related aspects such as the tools being utilised, and the problems faced by Indian firms, research was conducted in leading firms in three sectors of the Indian economy; namely software, pharmaceutical and petroleum marketing, covering both the private and public sectors. The results indicated that Indian firms have implemented many IT tools. The internet is the most widely used tool, whereas KM software is the least used. The way IT is growing or implemented and maintained in the firms under study is not encouraging. Barring a few software sector firms, IT tools are neither well maintained nor fully exploited by the firms. In addition, Indian firms lack an IT strategy for KM.
Information Integration Practices and Performance Outcomes
Authors: Liao Ying , Hong Paul , Fang Xiao
Published: August 2005

Because of the importance of information integration in obtaining competitive advantage in today's information-intensive environment, many organisations continue to search for better information integration practices that will support effective business processes across the value chain. However, effective information integration practices are not well understood; measures of information integration outcomes are not adequately presented either. This paper classifies effective information integration practices into technological and organisational aspects and identifies technological and organisational outcome measures that correspond to technological and organisational practices.
BIOGEOGRAPHIC AREAS AND TRANSITION ZONES OF LATIN AMERICA AND THE CARIBBEAN ISLANDS BASED ON PANBIOGEOGRAPHIC AND CLADISTIC ANALYSES OF THE ENTOMOFAUNA
Authors: Morrone Juan J.
Published: August 2005

▪ Abstract  Track and cladistic biogeographic analyses based on insect taxa are used as a framework to interpret patterns of the Latin American and Caribbean entomofauna by identifying biogeographic areas on the basis of endemicity and arranging them hierarchically in a system of regions, subregions, dominions, and provinces. The Nearctic region, inhabited by Holarctic insect taxa, comprises five provinces: California, Baja California, Sonora, Mexican Plateau, and Tamaulipas. The Mexican transition zone comprises five provinces: Sierra Madre Occidental, Sierra Madre Oriental, Transmexican Volcanic Belt, Balsas Basin, and Sierra Madre del Sur. The Neotropical region, which harbors many insect taxa with close relatives in the tropical areas of the Old World, comprises four subregions: Caribbean, Amazonian, Chacoan, and Parana. The South American transition zone comprises five provinces: North Andean Paramo, Coastal Peruvian Desert, Puna, Atacama, Prepuna, and Monte. The Andean region, which harbors insect taxa with close relatives in the Austral continents, comprises three subregions: Central Chilean, Subantarctic, and Patagonian.
TACHINIDAE: Evolution, Behavior, and Ecology
Authors: Stireman John O. , O'Hara James E. , Wood D. Monty
Published: August 2005

▪ Abstract  Tachinidae are one of the most diverse and ecologically important families in the order Diptera. As parasitoids, they are important natural enemies in most terrestrial ecological communities, particularly as natural enemies of larval Lepidoptera. Despite their diversity and ecological impact, relatively little is known about the evolution and ecology of tachinids, and what is known tends to be widely dispersed in specialized reports, journals, or texts. In this review we synthesize information on the evolutionary history, behavior, and ecology of tachinids and discuss promising directions for future research involving tachinids. We provide an overview of the phylogenetic history and geographic diversity of tachinids, examine the evolution of oviposition strategies and host associations, review known mechanisms of host location, and discuss recent studies dealing with the ecological interactions between tachinids and their hosts. In doing so, we highlight ways in which investigation of these parasitoids provides insight into such topics as biogeographic patterns of diversity, the evolution of ecological specialization, the tritrophic context of enemy-herbivore interactions, and the role of host location behavior in shaping host range.
Molecular Signatures of Natural Selection
Authors: Nielsen Rasmus
Published: August 2005

There is an increasing interest in detecting genes, or genomic regions, that have been targeted by natural selection. The interest stems from a basic desire to learn more about evolutionary processes in humans and other organisms, and from the realization that inferences regarding selection may provide important functional information. This review provides a nonmathematical description of the issues involved in detecting selection from DNA sequences and SNP data and is intended for readers who are not familiar with population genetic theory. Particular attention is placed on issues relating to the analysis of large-scale genomic data sets.
Prostatitis/Chronic Pelvic Pain Syndrome
Authors: Habermacher Geoffrey M. , Chason Judd T. , Schaeffer Anthony J.
Published: August 2005

We review the diagnosis, categorization, and treatment of prostatitis/chronic pelvic pain syndrome based on the National Institutes of Health (NIH) classification. Prostatitis is an extremely common syndrome that afflicts 2%–10% of men. Formerly a purely clinical diagnosis, prostatitis is now classified within a complex series of syndromes (NIH category I–IV prostatitis) that vary widely in clinical presentation and response to treatment. Acute bacterial prostatitis (category I) and chronic bacterial prostatitis (category II) are characterized by uropathogenic infections of the prostate gland that respond well to antimicrobial treatment. In contrast, chronic prostatitis/chronic pelvic pain syndrome (category III), which accounts for 90%–95% of prostatitis cases, is of unknown etiology and is marked by a mixture of pain, urinary, and ejaculatory symptoms with no uniformly effective therapy. Asymptomatic inflammatory prostatitis (category IV) is an incidental finding of unknown clinical significance. This review describes the current status of prostatitis syndromes and explores the future prospects of new diagnostic tools and therapies.
THE PROTEASOME AND PROTEASOME INHIBITORS IN CANCER THERAPY
Authors: Voorhees Peter M. , Orlowski Robert Z.
Published: August 2005

▪ Abstract  The proteasome, a multicatalytic proteinase complex, is responsible for the majority of intracellular protein degradation. Pharmacologic inhibitors of the proteasome possess in vitro and in vivo antitumor activity, and bortezomib, the first such agent to undergo clinical testing, has significant efficacy against multiple myeloma and non-Hodgkin lymphoma (NHL). Preclinical studies demonstrate that proteasome inhibition potentiates the activity of other cancer therapeutics, in part by downregulating chemoresistance pathways. Early clinical studies of bortezomib-based combinations, showing encouraging activity, support this observation. Molecular characterization of resistance to proteasome inhibitors has revealed novel therapeutic targets for sensitizing malignancies to these agents, such as the heat shock pathway. Below, we review the pharmacologic, preclinical, and clinical data that have paved the way for the use of proteasome inhibitors for cancer therapy; outline strategies aimed at enhancing the efficacy of proteasome inhibitors; and review other potential targets in the ubiquitin proteasome pathway for the treatment of cancer.
Family Violence
Authors: Tolan Patrick , Gorman-Smith Deborah , Henry David
Published: August 2005

Family violence occurs in many forms; the most prominent are domestic violence, child abuse, and elder abuse. Family violence affects many persons at some point in their life and constitutes the majority of violent acts in our society. Although there has been considerable study of the patterns, risk factors, and interventions for each form of family violence, great controversy still exists within each area. There is growing recognition of an overlap in the patterns, causes, and effective interventions across types of family violence. There is also an increasing awareness of the value of greater integration of theory and research across areas into a family violence approach through an ecological perspective. This review focuses on current knowledge related to these problems and suggests integrative steps to advance knowledge.
Role of calreticulin in the sensitivity of myocardiac H9c2 cells to oxidative stress caused by hydrogen peroxide
Authors: Ihara Yoshito , Urata Yoshishige , Goto Shinji , Kondo Takahito
Published: September 2005

Calreticulin (CRT), a Ca2+-binding molecular chaperone in the endoplasmic reticulum, plays a vital role in cardiac physiology and pathology. Oxidative stress is a main cause of myocardiac apoptosis in the ischemic heart, but the function of CRT under oxidative stress is not fully understood. In the present study, the effect of overexpression of CRT on susceptibility to apoptosis under oxidative stress was examined using myocardiac H9c2 cells transfected with the CRT gene. Under oxidative stress due to H2O2, the CRT-overexpressing cells were highly susceptible to apoptosis compared with controls. In the overexpressing cells, the levels of cytoplasmic free Ca2+ ([Ca2+]i) were significantly increased by H2O2, whereas in controls, only a slight increase was observed. The H2O2-induced apoptosis was enhanced by the increase in [Ca2+]i caused by thapsigargin in control cells but was suppressed by BAPTA-AM, a cell-permeable Ca2+ chelator in the CRT-overexpressing cells, indicating the importance of the level of [Ca2+]i in the sensitivity to H2O2-induced apoptosis. Suppression of CRT by the introduction of the antisense cDNA of CRT enhanced cytoprotection against oxidative stress compared with controls. Furthermore, we found that the levels of activity of calpain and caspase-12 were elevated through the regulation of [Ca2+]i in the CRT-overexpressing cells treated with H2O2 compared with controls. Thus we conclude that the level of CRT regulates the sensitivity to apoptosis under oxidative stress due to H2O2 through a change in Ca2+ homeostasis and the regulation of the Ca2+-calpain-caspase-12 pathway in myocardiac cells.
Acceleration of K+ channel inactivation by MEK inhibitor U0126
Authors: Yuan Li-Lian , Chen Xixi , Kunjilwar Kumud , Pfaffinger Paul , Johnston Daniel
Published: September 2005

Voltage-dependent (Kv)4.2-encoded A-type K+ channels play an important role in controlling neuronal excitability and are subject to modulation by various protein kinases, including ERK. In studies of ERK modulation, the organic compound U0126 is often used to suppress the activity of MEK, which is a kinase immediately upstream from ERK. We have observed that the inactivation time constant of heterologously expressed Kv4.2 channels was accelerated by U0126 at 1–20 μM. This effect, however, was not Kv4 family specific, because U0126 also converted noninactivating K+ currents mediated by Kv1.1 subunits into transient ones. To determine whether U0126 exerted these effects through kinase inhibition, we tested U0125, a derivative of U0126 that is less potent in MEK inhibition. At the same concentrations, U0125 had effects similar to those of U0126 on channel inactivation. Finally, we expressed a mutant form of Kv4.2 in which three identified ERK phosphorylation sites (T602, T607, and S616) were replaced with alanines. The inactivation of K+ currents mediated by this mutant was still accelerated by U0126. Our data favor the conclusion that the increase in the rate of channel inactivation by U0126 is likely to be independent of protein kinase inhibition and instead represents a direct action on channel gating.
Patch-clamp study reveals that the importance of connexin43-mediated gap junctional communication for ovarian folliculogenesis is strain specific in the mouse
Authors: Tong Dan , Gittens Joanne E. I. , Kidder Gerald M. , Bai Donglin
Published: September 2005

Genetic ablation of connexin37 (Cx37) or connexin43 (Cx43), the two gap junction proteins expressed by mouse ovarian granulosa cells, has been shown to result in impaired follicle development. We used patch-clamp techniques to evaluate quantitatively the contribution of these connexins to gap junctional intercellular communication (GJIC) among granulosa cells. The coupling conductance derived from a voltage step-induced capacitive current transient was used as a measure of GJIC in cultured granulosa cells. Using this method, we determined that the conductance of wild-type (84.1 ± 28.6 nS; n = 6) and Cx37-deficient granulosa cells (83.7 ± 6.4 nS; n = 11) does not differ significantly ( P = 0.35), suggesting a limited contribution, if any, of Cx37 to granulosa cell coupling. In contrast, the conductance between granulosa cells of Cx43-deficient mice (2.6 ± 0.8 nS; n = 5) was not significantly different from that of single, isolated wild-type granulosa cells (2.5 ± 0.7 nS, n = 5; P = 0.83), indicating that Cx43-deficient granulosa cells were not electrically coupled. A direct measurement of transjunctional conductance between isolated granulosa cell pairs using a dual patch-clamp technique confirmed this conclusion. Interestingly, a partial rescue of folliculogenesis was observed when the Cx43-null mutation in C57BL/6 mice was crossed into the CD1 strain, and capacitive current measurement demonstrated that this rescue was not due to reestablishment of GJIC. These results demonstrate that folliculogenesis is impaired in the absence of GJIC between granulosa cells, but they also indicate that the severity is dependent on genetic background, a phenomenon that cannot be attributed to the expression of additional connexins.
Depot-specific regulation of glucose uptake and insulin sensitivity in HIV-lipodystrophy
Authors: Hadigan C. , Kamin D. , Liebau J. , Mazza S. , Barrow S. , Torriani M. , Rubin R. , Weise S. , Fischman A. , Grinspoon S.
Published: August 2005

Altered fat distribution is associated with insulin resistance in HIV, but little is known about regional glucose metabolism in fat and muscle depots in this patient population. The aim of the present study was to quantify regional fat, muscle, and whole body glucose disposal in HIV-infected men with lipoatrophy. Whole body glucose disposal was determined by hyperinsulinemic clamp technique (80 mU·m−2·min−1) in 6 HIV-infected men and 5 age/weight-matched healthy volunteers. Regional glucose uptake in muscle and subcutaneous (SAT) and visceral adipose tissue (VAT) was quantified in fasting and insulin-stimulated states using 2-deoxy-[18F]fluoro-d-glucose positron emission tomography. HIV-infected subjects with lipoatrophy had significantly increased glucose uptake into SAT (3.8 ± 0.4 vs. 2.3 ± 0.5 μmol·kg tissue−1·min−1, P < 0.05) in the fasted state. Glucose uptake into VAT did not differ between groups. VAT area was inversely related with whole body glucose disposal, insulin sensitivity, and muscle glucose uptake during insulin stimulation. VAT area was highly predictive of whole body glucose disposal ( r2= 0.94, P < 0.0001). This may be mediated by adiponectin, which was significantly associated with VAT area ( r = −0.75, P = 0.008), and whole body glucose disposal ( r = 0.80, P = 0.003). This is the first study to directly demonstrate increased glucose uptake in subcutaneous fat of lipoatrophic patients, which may partially compensate for loss of SAT. Furthermore, we demonstrate a clear relationship between VAT and glucose metabolism in multiple fat and muscle depots, suggesting the critical importance of this depot in the regulation of glucose and highlighting the significant potential role of adiponectin in this process.
Mesangial cell NADPH oxidase upregulation in high glucose is protein kinase C dependent and required for collagen IV expression
Authors: Xia L. , Wang H. , Goldberg H. J. , Munk S. , Fantus I. G. , Whiteside C. I.
Published: August 2005

Excess collagen IV expression by mesangial cells contributes to diabetic glomerulosclerosis. We hypothesized that in high glucose reactive oxygen species (ROS) generation by NADPH oxidase is PKC dependent and required for collagen IV expression by mesangial cells. In rat mesangial cells cultured in 5 mM (NG) or 25 mM d-glucose (HG), RT-PCR and Western immunoblotting detected p22phoxand p47phoxmRNA and protein, respectively. Quantitative real-time RT-PCR analyzed collagen IV mRNA. With the use of confocal microscopy, ROS were detected with dichlorofluorescein and intracellular collagen IV by immunofluorescence. In HG, ROS were generated within 1 h, sustained up to 48 h, and prevented by a NADPH oxidase inhibitor, diphenylenechloride iodonium (DPI), or a conventional PKC isozyme inhibitor, Gö6976. In NG, phorbol myristate acetate stimulated ROS generation that was inhibited with DPI. In HG, expression of p22phoxand p47phoxwas increased within 3 to 6 h and inhibited by Gö6976. In HG, Gö6976 or transfection with antisense against p22phoxreversed the 1.8-fold increase in collagen IV mRNA. In HG, the antioxidants Tempol or Tiron, or transfection with antisense against p22phoxor p47phox, prevented ROS generation and the 2.3-fold increase in collagen IV protein. Increased mitochondrial redox potential in HG was unaffected by transfection with antisense against p22phox. We conclude that in HG, mesangial cell ROS generation by upregulated NADPH oxidase is dependent on conventional PKC isozymes and also required for collagen IV expression.
Characterization of ammonia transport by the kidney Rh glycoproteins RhBG and RhCG
Authors: Mak Don-On Daniel , Dang Binh , Weiner I. David , Foskett J. Kevin , Westhoff Connie M.
Published: August 2005

The erythrocyte Rh-associated glycoprotein (RhAG) was recently found to mediate transport of ammonia/ammonium when expressed in Xenopus laevis oocytes and yeast Saccharomyces cerevisiae. Nonerythroid homologs, RhBG and RhCG, are expressed in the mammalian kidney connecting segment and the collecting duct, major sites of urinary ammonia secretion. This study characterizes the transport properties of murine RhBG and RhCG by ammonium analog [14C]methylamine (MA) uptake and two-electrode voltage clamping of X. laevis oocytes. Both RhBG and RhCG mediated transport of ammonia, but differed in affinity for substrate ( Km= 2.5 and 10 mM, respectively). The rates of RhBG- and RhCG-mediated transport were sensitive to the concentration of the protonated MA species and were stimulated by extracellular alkalosis and inhibited by acidosis, suggesting a role for H+in the transport process. Whereas expression of RhBG or RhCG caused a small increase in plasma membrane conductance, [14C]MA uptake was not affected by depolarization of oocytes with 100 mM extracellular K+or by clamping the membrane potential between 0 and −100 mV, indicating that RhBG- and RhCG-mediated transport was independent of the membrane potential. These results strongly suggest that RhBG and RhCG transport ammonia by an electroneutral process that involves NH4+/H+exchange resulting in net NH3translocation. The polarized localization of RhBG and RhCG in kidney tubules and the different substrate affinities may enable these proteins to participate in transepithelial ammonia secretion and to therefore play an important role in whole animal acid-base regulation.
Adaptive Stimulus Optimization for Auditory Cortical Neurons
Authors: O'Connor Kevin N. , Petkov Christopher I. , Sutter Mitchell L.
Published: August 2005

Despite the extensive physiological work performed on auditory cortex, our understanding of the basic functional properties of auditory cortical neurons is incomplete. For example, it remains unclear what stimulus features are most important for these cells. Determining these features is challenging given the considerable size of the relevant stimulus parameter space as well as the unpredictable nature of many neurons' responses to complex stimuli due to nonlinear integration across frequency. Here we used an adaptive stimulus optimization technique to obtain the preferred spectral input for neurons in macaque primary auditory cortex (AI). This method uses a neuron's response to progressively modify the frequency composition of a stimulus to determine the preferred spectrum. This technique has the advantage of being able to incorporate nonlinear stimulus interactions into a “best estimate” of a neuron's preferred spectrum. The resulting spectra displayed a consistent, relatively simple circumscribed form that was similar across scale and frequency in which excitation and inhibition appeared about equally prominent. In most cases, this structure could be described using two simple models, the Gabor and difference of Gaussians functions. The findings indicate that AI neurons are well suited for extracting important scale-invariant features in sound spectra and suggest that they are designed to efficiently represent natural sounds.
Simple Metric For Scaling Motor Threshold Based on Scalp-Cortex Distance: Application to Studies Using Transcranial Magnetic Stimulation
Authors: Stokes Mark G. , Chambers Christopher D. , Gould Ian C. , Henderson Tracy R. , Janko Natasha E. , Allen Nicholas B. , Mattingley Jason B.
Published: August 2005

Transcranial magnetic stimulation (TMS) is a unique method in neuroscience used to stimulate focal regions of the human brain. As TMS gains popularity in experimental and clinical domains, techniques for controlling the extent of brain stimulation are becoming increasingly important. At present, TMS intensity is typically calibrated to the excitability of the human motor cortex, a measure referred to as motor threshold (MT). Although TMS is commonly applied to nonmotor regions, most applications do not consider the effect of changes in distance between the stimulating device and underlying neural tissue. Here we show that for every millimeter from the stimulating coil, an additional 3% of TMS output is required to induce an equivalent level of brain stimulation at the motor cortex. This abrupt spatial gradient will have crucial consequences when TMS is applied to nonmotor regions because of substantial variance in scalp-cortex distances over different regions of the head. Stimulation protocols that do not account for cortical distance therefore risk substantial under- or overstimulation. We describe a simple method for adjusting MT to account for variations in cortical distance, thus providing a more accurate calibration than unadjusted MT for the safe and effective application of TMS in clinical and experimental neuroscience.
Intraoperative Direct Mechanical Stimulation of the Anterior Cruciate Ligament Elicits Short- and Medium-Latency Hamstring Reflexes
Authors: Friemert B. , Faist M. , Spengler C. , Gerngross H. , Claes L. , Melnyk M.
Published: September 2005

The anterior cruciate ligament (ACL) has not only a mechanical but also a sensorimotor function. Patients with injuries of the ACL frequently complain of knee instability despite good mechanical stabilization after surgical reconstruction. Compared with healthy subjects, their latencies of hamstring reflexes after anterior tibia translation are considerably increased. There is evidence for the existence of a reflex arc between the ACL and the hamstrings. The aim of this study was to determine if there is a direct reflex response after an isolated mechanical stimulation of the ACL in humans. In 10 patients who underwent arthroscopy, hamstring electromyographic (EMG) responses were assessed intraoperatively after applying an isolated load on the ACL. Latencies, amplitudes, and integrals of the EMG responses were analyzed. In four patients, the measurements were repeated after injection of local anesthetics into the ACL. In all subjects, responses with mean latencies of 42 ± 4.4 (SD) ms corresponding to a medium latency response (MLR) were found. In seven subjects, they were preceded by responses with a short-latency (SLR) of 24 ± 2.7 ms. The maximum amplitude was 8.6 ± 7 mV, the integral 0.064 ± 0.05 mV*s. The injection of local anesthetics reduced the amplitude by 34 ± 12% and the integral by 50 ± 20%. Direct mechanical stimulation of the ACL evokes considerably smaller SLRs and MLRs than anterior tibia translation during standing. It is argued that latency changes observed in patients with ACL ruptures may be rather due to changes in the sensorimotor integration of the afferent input from the knee joint than to the absence of the direct ACL reflex.
GAT-3 Transporters Regulate Inhibition in the Neocortex
Authors: Kinney Gregory A.
Published: September 2005

The role of GAT-3 transporters in regulating GABAA receptor-mediated inhibition was examined in the rat neocortex using an in vitro slice preparation. Pharmacologically isolated GABAA receptor-mediated responses were recorded from layer V neocortical pyramidal cells, and the effects of SNAP-5114, a GAT-3 GABA transporter-selective antagonist, were evaluated. Application of SNAP-5114 resulted in a reversible increase in the amplitude of an evoked GABAA response in most cells examined, although no effect on the decay time was observed. Examination of the spontaneous output of inhibitory interneurons revealed a reversible increase in the frequency and amplitude of spontaneous inhibitory synaptic currents as a consequence of GAT-3 inhibition. This effect of GAT-3 inhibition on spontaneous inhibitory events was action potential-dependent because no such increases were observed when SNAP-5114 was applied in the presence of TTX. These results demonstrate that GAT-3 transporters regulate inhibitory interneuron output in the neocortex. The increase in inhibitory interneuron excitability resulting from application of SNAP-5114 suggests that inhibition of GAT-3 transporter function results in a reduction in ambient GABA levels, possibly by a reduction in carrier-mediated GABA release via the GAT-3 transporter.
Tilt Aftereffect and Adaptation-Induced Changes in Orientation Tuning in Visual Cortex
Authors: Jin Dezhe Z. , Dragoi Valentin , Sur Mriganka , Seung H. Sebastian
Published: August 2005

The tilt aftereffect (TAE) is a visual illusion in which prolonged adaptation to an oriented stimulus causes shifts in subsequent perceived orientations. Historically, neural models of the TAE have explained it as the outcome of response suppression of neurons tuned to the adapting orientation. Recent physiological studies of neurons in primary visual cortex (V1) have confirmed that such response suppression exists. However, it was also found that the preferred orientations of neurons shift away from the adapting orientation. Here we show that adding this second factor to a population coding model of V1 improves the correspondence between neurophysiological data and TAE measurements. According to our model, the shifts in preferred orientation have the opposite effect as response suppression, reducing the magnitude of the TAE.