bluuebunny/crossref_metadata_2025_split huggingface dataset:
Some Implications of a Copy Theory of Labeling
Authors: Sheehan Michelle L. 
Published: July 2013

AbstractA copy theory of labeling makes interesting empirical predictions when combined with a revised version of Kayne's (1994) Linear Correspondence Axiom and a category‐based version of c‐command. First, it forces the pronunciation of the highest copy in a chain, all else being equal, without the need for copy deletion. Second, it predicts certain differences between underlying and derived head‐initial specifiers and between head‐final and head‐initial specifiers. This serves to extend Uriagereka's (1999)PF‐based explanation of Huang's Condition on Extraction Domain (CED) to cover previously problematic or unexplained phenomena: (i) the apparent lack of subject‐island effects with head‐final specifiers; (ii) the nonislandhood of many derived specifiers (externally merged as complements); (iii) patterns of complement extraposition; and (iv) the Final‐over‐Final Constraint (see Holmberg 2000; Biberauer, Holmberg & Roberts 2008, to appear). All of the above phenomena arise under the copy theory of labeling as side effects of a revised version of Kayne's (1994) Linear Correspondence Axiom incorporating a head parameter, whereby asymmetric c‐command, defined between categories and unmediated by dominance, maps to precedence as a last resort.
Confidence intervals of reference limits in small reference sample groups
Authors: Braun J.P. , Concordet D. , Geffré A. , Bourges Abella N. , Trumel C. 
Published: July 2013

BackgroundReference intervals are the most common tool used to interpret results of laboratory tests. However, in veterinary clinical pathology, the number of available reference individuals is often small.ObjectivesThe purpose of this study was to investigate the effects of small reference sample groups on the imprecision of the reference limits.MethodsGaussian and log‐Gaussian distributions of 10 ≤ n ≤ 750 values were analyzed. Reference limits and 90% confidence interval of limits (90% CI) were calculated. Imprecision of limits was estimated by the ratio of the width of the 90% CI: width of the reference interval (WCI/WRI).ResultsFor Gaussian distributions, the WCI/WRI ratio cannot be expected to be lower than 0.2 when n < 55. In log‐Gaussian distributions, the ratio greatly increases for the upper limit with skewness toward high values, whereas it moderately decreases for the lower limit.ConclusionIndependent of the size of the reference sample group, it is very important to report the CIs of the reference limits, which can be very large for small reference sample groups. When the sample size is very small (n < 20), calculations maybe misleading and it is better to instead report all values.
Breed‐specific biochemical reference intervals for the adult Dogue de Bordeaux
Authors: Lavoué R. , Geffré A. , Braun J.P. , Peeters D. , Trumel C. 
Published: July 2013

BackgroundBreed‐specific reference intervals are of increasing interest in veterinary medicine. The health monitoring of the Dogue de Bordeaux, a breed predisposed to familial juvenile glomerulonephropathy and hypothyroidism, would benefit from specific reference intervals.ObjectiveThe purpose of this study was to establish breed‐specific biochemical reference intervals for the Dogue de Bordeaux in accordance with the International Federation of Clinical Chemistry and Clinical and Laboratory Standards Institute guidelines.MethodsOne hundred and twenty Dogues de Bordeaux from France and Belgium were recruited. Complete urinalysis and chemistry panels, venous blood gas variables, total thyroxin and thyroid stimulating hormone, and fibrinogen and antithrombin were measured for each dog. Reference intervals were determined using the non‐parametric method. Confounding variables such as sex, age and color of facial mask were analyzed.ResultsDue to pre‐defined criteria for exclusion, 62 healthy dogs were finally selected for the reference intervals determination. Using the instrument manufacturer's generic canineRIfor most analytes did not have a significant impact on potential clinical decisions, except for total proteins,ALT,AST, total cholesterol, lipase and total thyroxin, for which possible clinically relevant differences were noted.ConclusionSpecific reference intervals for biochemical analytes in the Dogue de Bordeaux were determined under controlled pre‐analytical and analytical conditions, and according to international recommendations. The use of these breed‐specific reference intervals is recommended when using the specified analytic instruments, especially for the 6 analytes for which the reference intervals differed considerably from those provided by manufacturers.
Spike timing‐dependent plasticity at GABAergic synapses in the ventral tegmental area
Authors: Kodangattil Jayaraj N. , Dacher Matthieu , Authement Michael E. , Nugent Fereshteh S. 
Published: July 2013

Key points
GABAergic synapses onto ventral tegmental area (VTA) dopamine neurons express a bidirectional spike timing‐dependent plasticity (STDP; both long‐term potentiation and long‐term depression).
GABAergic synapses in the VTA obey the classical Hebbian learning rules of STDP.
GABAergic STDP in VTA dopamine neurons is expressed postsynaptically.
GABAergic STDP is heterosynaptic and NMDA receptor dependent.
Pairing of pre‐ and postsynaptic spiking is necessary for induction of GABAergic STDP.
Abstract  Persistent changes in excitatory and inhibitory synaptic strengths to the ventral tegmental area (VTA) dopamine (DA) neurons in response to addictive drugs may underlie the transition from casual to compulsive drug use. While an enormous amount of work has been done in the area of glutamatergic plasticity of the VTA, little is known regarding the learning rules governing GABAergic plasticity in the VTA. Spike timing‐dependent plasticity, STDP, has attracted considerable attention primarily due to its potential roles in processing and storage of information in the brain and there is emerging evidence for the existence of STDP at inhibitory synapses. We therefore used whole‐cell recordings in rat midbrain slices to investigate whether near‐coincident pre‐ and postsynaptic firing induces a lasting change in synaptic efficacy of VTA GABAergic synapses. We found that a Hebbian form of STDP including long‐term potentiation (LTP) and long‐term depression (LTD) can be induced at GABAergic synapses onto VTA DA neurons and relies on the precise temporal order of pre‐ and postsynaptic spiking. Importantly, GABAergic STDP is heterosynaptic (NMDA receptor dependent): triggered by correlated activities of the presynaptic glutamatergic input and postsynaptic DA cells. GABAergic STDP is postsynaptic and has an associative component since pre‐ or postsynaptic spiking per se did not induce STDP. STDP of GABAergic synapses in the VTA provides physiologically relevant forms of inhibitory plasticity that may underlie natural reinforcement of reward‐related behaviours. Moreover, this form of inhibitory plasticity may mediate some of the reinforcing, aversive and addictive properties of drugs of abuse.
Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides
Authors: Scallan Joshua P. , Davis Michael J. , Huxley Virginia H. 
Published: July 2013

Key points
Atrial and brain natriuretic peptides (ANP and BNP, respectively) are hormones released into the bloodstream when heart muscle is stretched (e.g. zero‐gravity, hypertension, congestive heart failure) and serve to reduce the blood volume.
One way that these peptides relieve blood volume is to increase the permeability of the smallest blood vessels, facilitating fluid and protein distribution into the tissue spaces.
Whether these peptides target lymphatic vessel function to participate in fluid distribution is currently unknown.
ANP and BNP (100 nm) both elicited significant increases in lymphatic vessel permeability, but altered contractile function differentially in vivo.
A likely consequence is that more fluid leaks from the lymphatics into the tissues, which represents a novel compensation for volume overload. This work demonstrates for the first time that lymphatic vessel permeability can be regulated in vivo.
Abstract  Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin–angiotensin–aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 nm) would likewise elevate lymphatic permeability (Ps) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic Ps to rat serum albumin increased by 2.0 ± 0.4‐fold (P= 0.01, n= 7) and 2.7 ± 0.8‐fold (P= 0.07, n= 7) with ANP and BNP, respectively. In addition to measuring Ps responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo. Notably, ANP abolished spontaneous contraction amplitude (P= 0.005) and frequency (P= 0.006), while BNP augmented both parameters by ∼2‐fold (P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion.
Chromosome 5 Monosomy of Candida albicans Controls Susceptibility to Various Toxic Agents, Including Major Antifungals
Authors: Yang Feng , Kravets Anatoliy , Bethlendy Gabor , Welle Stephen , Rustchenko Elena 
Published: July 2013

ABSTRACTCandida albicansis a prevailing fungal pathogen with a diploid genome that can adapt to environmental stresses by losing or gaining an entire chromosome or a large portion of a chromosome. We have previously found that the loss of one copy of chromosome 5 (Ch5) allows for adaptation to the toxic sugarl-sorbose.l-Sorbose is similar to caspofungin and other antifungals from the echinocandins class, in that it represses synthesis of cell wall glucan in fungi. Here, we extended the study of the phenotypes controlled by Ch5 copy number. We examined 57 strains, either disomic or monosomic for Ch5 and representing five different genetic backgrounds, and found that the monosomy of Ch5 causes elevated levels of chitin and repressed levels of 1,3-β-glucan components of the cell wall, as well as diminished cellular ergosterol. Increased deposition of chitin in the cell wall could be explained, at least partially, by a 2-fold downregulation ofCHT2on the monosomic Ch5 that encodes chitinase and a 1.5-fold upregulation ofCHS7on Ch1 that encodes the protein required for wild-type chitin synthase III activity. Other important outcomes of Ch5 monosomy consist of susceptibility changes to agents representing four major classes of antifungals. Susceptibility to caspofungin increased or decreased and susceptibility to 5-fluorocytosine decreased, whereas susceptibility to fluconazole and amphotericin B increased. Our results suggest that Ch5 monosomy represents an unrecognizedC. albicansregulatory strategy that impinges on multiple stress response pathways.
β-Lactam Antibiotics Targeting PBP1 Selectively Enhance Daptomycin Activity against Methicillin-Resistant Staphylococcus aureus
Authors: Berti Andrew D. , Sakoulas George , Nizet Victor , Tewhey Ryan , Rose Warren E. 
Published: July 2013

ABSTRACT

The activity of daptomycin (DAP) against methicillin-resistant
Staphylococcus aureus
(MRSA) is enhanced in the presence of subinhibitory concentrations of antistaphylococcal β-lactam antibiotics by an undefined mechanism. Given the variability in the penicillin-binding protein (PBP)-binding profiles of different β-lactam antibiotics, the purpose of this study was to examine the relative enhancement of DAP activity against MRSA by different β-lactam antibiotics to determine if a specific PBP-binding profile is associated with the ability to enhance the anti-MRSA activity of DAP. We determined that both broad- and narrow-spectrum β-lactam antibiotics known to exhibit PBP1 binding demonstrated potent enhancement of DAP anti-MRSA activity, whereas β-lactam antibiotics with minimal PBP1 binding (cefoxitin, ceftriaxone, cefaclor, and cefotaxime) were less effective. We suspect that PBP1 disruption by β-lactam antibiotics affects pathways of cell division in
S. aureus
that may be a compensatory response to DAP membrane insertion, resulting in DAP hypersusceptibility.
DNA Duplexes with Hydrophobic Modifications Inhibit Fusion between HIV-1 and Cell Membranes
Authors: Xu Liang , Cai Lifeng , Chen Xueliang , Jiang Xifeng , Chong Huihui , Zheng Baohua , Wang Kun , He Junlin , Chen Wei , Zhang Tao , Cheng Maosheng , He Yuxian , Liu Keliang 
Published: July 2013

ABSTRACT
Discovery of new drugs for the treatment of AIDS typically possessing unique structures associated with novel mechanisms of action has been of great importance due to the quick drug-resistant mutations of HIV-1 strains. The work presented in this report describes a novel class of DNA duplex-based HIV-1 fusion inhibitors. Hydrophobic groups were introduced into a DNA duplex skeleton either at one end, at both ends, or in the middle. These modified DNA duplexes inhibited fusion between HIV-1 and human cell membranes at micro- or submicromolar concentrations. Respective inhibitors adopted an aptamer pattern instead of a base-pairing interaction pattern. Structure-activity relationship studies of the respective DNA duplexes showed that the rigid and negatively charged DNA skeletons, in addition to the presence of hydrophobic groups, were crucial to the anti-HIV-1 activity of these compounds. A fluorescent resonance energy transfer (FRET)-based inhibitory assay showed that these duplex inhibitors interacted with the primary pocket in the gp41 N-terminal heptad repeat (NHR) instead of interacting with the lipid bilayers.
Clotrimazole Dampens Vaginal Inflammation and Neutrophil Infiltration in Response to Candida albicans Infection
Authors: Wilson Duncan , Hebecker Betty , Moyes David L. , Miramón Pedro , Jablonowski Nadja , Wisgott Stephanie , Allert Stefanie , Naglik Julian R. , Hube Bernhard 
Published: July 2013

ABSTRACT

The pathology of vulvovaginal candidiasis (VVC) caused by
Candida albicans
is associated with a nonprotective inflammatory response and is frequently treated with clotrimazole. We investigated the mechanisms by which clotrimazole resolves VVC. Low levels of clotrimazole, which do not block fungal growth, inhibit expression of a “danger response” transcription factor, c-Fos, block production of proinflammatory cytokines, and inhibit neutrophil infiltration to the site of infection.
Reconstitution of an Active Arginine Deiminase Pathway in Mycoplasma pneumoniae M129
Authors: Rechnitzer Hagai , Rottem Shlomo , Herrmann Richard 
Published: July 2013

ABSTRACTSome species of the genusMycoplasmacode for the arginine deiminase pathway (ADI), which enables these bacteria to produce ATP from arginine by the successive reaction of three enzymes: arginine deiminase (ArcA), ornithine carbamoyltransferase (ArcB), and carbamate kinase (ArcC). It so far appears that independently isolated strains ofMycoplasma pneumoniaeencode an almost identical truncated version of the ADI pathway in which the proteins ArcA and ArcB have lost their original enzymatic activities due to the deletion of significant regions of these proteins. To study the consequences of a functional ADI pathway,M. pneumoniaeM129 was successfully transformed with the cloned functionalarcA,arcB, andarcCgenes fromMycoplasma fermentans. Enzymatic tests showed that while theM. pneumoniaeArcAB and ArcABC transformants possess functional arginine deiminase, ornithine carbamoyltransferase, and carbamate kinase, they were unable to grow on arginine as the sole energy source. Nevertheless, infection of a lung epithelial cell line, A549, with theM. pneumoniaetransformants showed that almost 100% of the infected host cells were nonviable, while most of the lung cells infected with nontransformedM. pneumoniaewere viable under the same experimental conditions.
Combined Stimulation of Toll-Like Receptor 5 and NOD1 Strongly Potentiates Activity of NF-κB, Resulting in Enhanced Innate Immune Reactions and Resistance to Salmonella enterica Serovar Typhimurium Infection
Authors: Tukhvatulin Amir I. , Gitlin Ilya I. , Shcheblyakov Dmitry V. , Artemicheva Natalia M. , Burdelya Lyudmila G. , Shmarov Maxim M. , Naroditsky Boris S. , Gudkov Andrei V. , Gintsburg Alexander L. , Logunov Denis Y. 
Published: July 2013

ABSTRACT

Pathogen recognition receptors (PRRs) are essential components of host innate immune systems that detect specific conserved pathogen-associated molecular patterns (PAMPs) presented by microorganisms. Members of two families of PRRs, transmembrane Toll-like receptors (TLRs 1, 2, 4, 5, and 6) and cytosolic NOD receptors (NOD1 and NOD2), are stimulated upon recognition of various bacterial PAMPs. Such stimulation leads to induction of a number of immune defense reactions, mainly triggered via activation of the transcription factor NF-κB. While coordination of responses initiated via different PRRs sensing multiple PAMPS present during an infection makes clear biological sense for the host, such interactions have not been fully characterized. Here, we demonstrate that combined stimulation of NOD1 and TLR5 (as well as other NOD and TLR family members) strongly potentiates activity of NF-κB and induces enhanced levels of innate immune reactions (e.g., cytokine production) both
in vitro
and
in vivo
. Moreover, we show that an increased level of NF-κB activity plays a critical role in formation of downstream responses. In live mice, synergy between these receptors resulting in potentiation of NF-κB activity was organ specific, being most prominent in the gastrointestinal tract. Coordinated activity of NOD1 and TLR5 significantly increased protection of mice against enteroinvasive
Salmonella
infection. Obtained results suggest that cooperation of NOD and TLR receptors is important for effective responses to microbial infection
in vivo
.
Identification of Salmonella enterica Serovar Typhimurium Genes Regulated during Biofilm Formation on Cholesterol Gallstone Surfaces
Authors: Gonzalez-Escobedo Geoffrey , Gunn John S. 
Published: July 2013

ABSTRACTSalmonellaspp. are able to form biofilms on abiotic and biotic surfaces.In vivostudies in our laboratory have shown thatSalmonellacan form biofilms on the surfaces of cholesterol gallstones in the gallbladders of mice and human carriers. Biofilm formation on gallstones has been demonstrated to be a mechanism of persistence. The purpose of this work was to identify and evaluateSalmonellasp. cholesterol-dependent biofilm factors. Differential gene expression analysis between biofilms on glass or cholesterol-coated surfaces and subsequent quantitative real-time PCR (qRT-PCR) revealed that type 1 fimbria structural genes and a gene encoding a putative outer membrane protein (ycfR) were specifically upregulated inSalmonella entericaserovar Typhimurium biofilms grown on cholesterol-coated surfaces. Spatiotemporal expression ofycfRand FimA verified their regulation during biofilm development on cholesterol-coated surfaces. Surprisingly, confocal and scanning electron microscopy demonstrated that a mutant of type 1 fimbria structural genes (ΔfimAICDHF) and aycfRmutant showed increased biofilm formation on cholesterol-coated surfaces.In vivoexperiments usingNramp1+/+mice harboring gallstones showed that only the ΔycfRmutant formed extensive biofilms on mouse gallstones at 7 and 21 days postinfection; ΔfimAICDHFwas not observed on gallstone surfaces after the 7-day-postinfection time point. These data suggest that inSalmonellaspp., wild-type type 1 fimbriae are important for attachment to and/or persistence on gallstones at later points of chronic infection, whereas YcfR may represent a specific potential natural inhibitor of initial biofilm formation on gallstones.
In VivoPhysiological and Transcriptional Profiling Reveals Host Responses to Clostridium difficile Toxin A and Toxin B
Authors: D'Auria Kevin M. , Kolling Glynis L. , Donato Gina M. , Warren Cirle A. , Gray Mary C. , Hewlett Erik L. , Papin Jason A. 
Published: July 2013

ABSTRACTToxin A (TcdA) and toxin B (TcdB) ofClostridium difficilecause gross pathological changes (e.g., inflammation, secretion, and diarrhea) in the infected host, yet the molecular and cellular pathways leading to observed host responses are poorly understood. To address this gap, we evaluated the effects of single doses of TcdA and/or TcdB injected into the ceca of mice, and several endpoints were analyzed, including tissue pathology, neutrophil infiltration, epithelial-layer gene expression, chemokine levels, and blood cell counts, 2, 6, and 16 h after injection. In addition to confirming TcdA's gross pathological effects, we found that both TcdA and TcdB resulted in neutrophil infiltration. Bioinformatics analyses identified altered expression of genes associated with the metabolism of lipids, fatty acids, and detoxification; small GTPase activity; and immune function and inflammation. Further analysis revealed transient expression of several chemokines (e.g.,Cxcl1andCxcl2). Antibody neutralization of CXCL1 and CXCL2 did not affect TcdA-induced local pathology or neutrophil infiltration, but it did decrease the peripheral blood neutrophil count. Additionally, low serum levels of CXCL1 and CXCL2 corresponded with greater survival. Although TcdA induced more pronounced transcriptional changes than TcdB and the upregulated chemokine expression was unique to TcdA, the overall transcriptional responses to TcdA and TcdB were strongly correlated, supporting differences primarily in timing and potency rather than differences in the type of intracellular host response. In addition, the transcriptional data revealed novel toxin effects (e.g., altered expression of GTPase-associated and metabolic genes) underlying observed physiological responses toC. difficiletoxins.