bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ca2+/calmodulin‐ dependent protein kinase II mediates transforming growth factor‐β‐induced hepatic stellate cells proliferation but not in collagen α1(I) production
Authors: An Ping , Tian Yihao , Chen Mingkai , Luo Hesheng 
Published: February 2012

Aim:  Hepatic stellate cells (HSC) are the major players in hepatic fibrosis. As a most potent mitogen, transforming growth factor‐β (TGF‐β) strongly activates HSC and increases intracellular Ca2+ concentration. Here, we assessed the potential role of Ca2+/calmodulin‐dependent protein kinase II (CaMKII), a main downstream effector of the Ca2+ signal in liver fibrogenesis cascade.Methods:  A human immortal HSC cell line, LX‐2, and primary rat hepatic stellate cells were used in current study. CaMKII blockage and Akt inhibition were performed by KN‐93/CaMKIIα siRNA and LY294002, respectively. HSC proliferation was detected by 5‐bromodeoxyuridine incorporation assay. Real‐time polymerase chain reaction, western blot and enzyme‐linked immunosorbent assay were used to measure mRNA, cellular protein and protein in medium, respectively. Procollagen α1(I) expression was detected by immunocytochemistry. The role of CaMKII on TGF‐β/Smad‐induced collagen α1(I) expression was determined by (CAGA)12‐MLP luciferase activity assay.Results:  TGF‐β dramatically increased CaMKII mRNA, and total and phosphorylated CaMKII expression. KN‐93 and CaMKIIα siRNA suppressed TGF‐β‐mediated HSC proliferation. CaMKII interruption blocked TGF‐β‐elicited Akt activation. LY294002 arrested HSC proliferation and collagen α1(I) production but had no effect on CaMKII. Furthermore, CaMKII led to increased p21 and p27 expression. KN‐93 and CaMKIIα siRNA inhibited TGF‐β‐induced and basal collagen α1(I) production but had no effect on the activity of (CAGA)12‐MLP luciferase in response to TGF‐β stimulation.Conclusion:  CaMKII is a pivotal signal in TGF‐β‐induced fibrogenic cascades by means of stimulating HSC proliferation, and involved in a basal collagen production. Therefore, CaMKII will be a potentially effective target in the development of therapeutic intervention strategies to attenuate hepatic fibrosis.
Hypocalcemia and HypovitaminosisDin Dogs with Induced Endotoxemia
Authors: Holowaychuk M.K. , Birkenheuer A.J. , Li J. , Marr H. , Boll A. , Nordone S.K. 
Published: February 2012

BackgroundHypocalcemia is a documented electrolyte disturbance in people and animals with sepsis, but its mechanism is poorly understood.ObjectiveTo investigate mechanisms of hypocalcemia in dogs with experimentally induced endotoxemia.AnimalsSix healthy mixed breed dogs were included in this nonrandomized, placebo‐controlled, crossover study.MethodsDogs initially were injected with placebo (0.9%NaCl; 1 mL,IV) and then lipopolysaccharide (LPS; 2 μg/kg,IV) after a 5‐day washout period. Blood and urine samples were collected for measurement of serum total calcium (tCa), ionized calcium (iCa), total magnesium (tMg), ionized magnesium (iMg), parathyroid hormone (PTH), 25‐hydroxyvitaminD(vitaminD), venous blood gases, and fractional excretion (FE) of calcium.ResultsAfterLPSadministration, body temperature increased and blood pressure decreased. BothiCa andtCa decreased (P < .01), butiMg was not significantly different between control andLPStreatments.PTHconcentrations increased (P < .01) and vitaminDconcentrations decreased (P < .01). VenouspH, bicarbonate, base excess, and blood glucose also decreased (P < .01). UrinetCa concentration was below the limit of detection for all dogs afterLPSadministration.ConclusionsHypocalcemia occurs during endotoxemia in dogs and is associated with hypovitaminosisD. Hypomagnesemia, hypoparathyroidism, alkalosis, and increased calciuresis are not associated with hypocalcemia in endotoxemic dogs.
Characterization of the Genetic Basis for Autosomal Recessive Hereditary Nephropathy in theEnglishSpringerSpaniel
Authors: Nowend K.L. , Starr‐Moss A.N. , Lees G.E. , Berridge B.R. , Clubb F.J. , Kashtan C.E. , Nabity M.B. , Murphy K.E. 
Published: February 2012

BackgroundAutosomal recessive hereditary nephropathy (ARHN) was diagnosed in 2EnglishSpringerSpaniels (ESS), a breed not previously reported to be affected by hereditary nephropathy (HN).ObjectiveTo identify and characterize the genetic cause ofARHNinESS.AnimalsSixty‐threeESS(2 withARHN, 2 obligate carriers, and 59 others), 2 mixed‐breed dogs with X‐linkedHN, and 2EnglishCockerSpaniels (ECS) withARHNwere included.MethodsARHNwas diagnosed based on transmission electron microscopy and immunostaining of kidney.DNAfrom affected dogs was screened for the mutation known to causeARHNinECS. Quantities ofCOL4A3,COL4A4, andCOL4A5mRNAtranscripts in renal cortex were determined using quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) forARHN‐affected dogs and 7 other dogs. The coding regions ofCOL4A3andCOL4A4were sequenced for the 2ARHN‐affectedESSand an unaffected dog. Exon 30 ofCOL4A4was sequenced for all 63ESS.ResultsqRT‐PCRindicated a significant reduction in transcript levels of bothCOL4A3andCOL4A4mRNAin the kidney ofARHN‐affectedESS. Sequencing identified a single nucleotide substitution inCOL4A4at base 2806 resulting in a premature stop codon. Thirteen of 25 related dogs were identified as carriers.Conclusions and Clinical ImportanceA mutation highly likely to causeARHNinESShas been identified.
Evaluation of the Oral Antimitotic Agent (ABT‐751) in Dogs with Lymphoma
Authors: Silver M. , Rusk A. , Phillips B. , Beck E. , Jankowski M. , Philibert J. , Hahn K. , Hershey E. , McKeegan E. , Bauch J. , Krivoshik A. , Khanna C. 
Published: February 2012

BackgroundABT‐751 is a novel orally available antimitotic agent that targets microtubule polymerization. This mechanism may suggest potential activity in canine lymphoma.ObjectiveDetermine a maximum tolerated dose for ABT‐751, and assess long‐term tolerability and activity in canine lymphoma.AnimalsThirty dogs with newly diagnosed (n = 19) or relapsed (n = 11) non‐Hodgkin's lymphoma.MethodsDogs (n = 11) were enrolled in a rapid dose escalation study to define the maximum tolerated dose. Upon definition of a maximally tolerated dose, a cohort expansion of 19 dogs allowed verification of long‐term tolerability and assessment of activity. Study endpoints in the cohort expansion included chronic tolerability, response rate, response duration, and time to progression. Additional endpoints included serum pharmacokinetics, lymph node drug concentrations, and changes in circulating endothelial cells.ResultsThe maximum tolerated dose of ABT‐751 was 350 mg/m2 PO q24h. Dose‐limiting toxicities included vomiting and diarrhea, which resolved with a schedule adjustment to 350 mg/m2 PO q48h. ABT‐751 was consistently detected in lymphoma tissue samples from dogs treated at or above the maximum tolerated dose. In the cohort expansion, objective responses were seen in 3/15 (20%) dogs with a response duration ranging from 21 to 111 days. Decreases in circulating endothelial cells were seen in 10 dogs at day 7 (2 responding dogs and 8 nonresponding dogs).ConclusionABT‐751 was well tolerated at 350 mg/m2 PO q24h for 7 days and then q48h thereafter. Activity of ABT‐751 suggested a rationale for additional studies of ABT‐751 as part of a combination chemotherapy protocol for lymphoma or other canine cancers.
Regulation of polysynaptic subthalamonigral transmission by D2, D3 and D4 dopamine receptors in rat brain slices
Authors: Shen Ke‐Zhong , Johnson Steven W. 
Published: February 2012

Key points
Symptoms of Parkinson's disease are associated with increased bursting activity in the subthalamic nucleus and substantia nigra zona reticulata (SNR).
In slices of rat brain, a single electrical stimulus to the STN evokes a complex EPSC and bursts of action potentials in SNR neurons.
We show that dopamine acts at D2‐like receptors to cause marked and reversible inhibition of the complex EPSC.
Dopamine also inhibited stimulus‐evoked bursts of action potentials more than reducing spontaneous firing.
Inhibition of synaptically generated burst firing by D2 receptor agonists may be a clinically important mechanism in the treatment of Parkinson's disease.
Excitatory inputs to four types of spinocerebellar tract neurons in the cat and the rat thoraco‐lumbar spinal cord
Authors: Shrestha Sony Shakya , Bannatyne B. Anne , Jankowska Elzbieta , Hammar Ingela , Nilsson Elin , Maxwell David J. 
Published: February 2012

Key points
For co‐ordinated limb movements, the brain needs to be provided with continuous feedback information from the spinal cord.
We investigated the types of information forwarded to the cerebellum by four populations of neurons.
Cells were classified according to their electrophysiological properties in cats and location within the grey matter in rats.
We used immunochemistry to identify excitatory (glutamatergic) terminals and to differentiate between terminals of peripheral sensory fibres and terminals of spinal or supraspinal neurons in contact with labelled cells.
Our results revealed marked differences between these four populations.
These findings improve our understanding of the functional connectivity between the spinal cord and the cerebellum and provide new insights into the role of the cerebellum in controlling limb movements.
Heterosynaptic plasticity induced by intracellular tetanization in layer 2/3 pyramidal neurons in rat auditory cortex
Authors: Lee Christopher M. , Stoelzel Carl , Chistiakova Marina , Volgushev Maxim 
Published: February 2012

Key points summary
Learning systems equipped with Hebbian‐type associative plasticity are prone to runaway dynamics of synaptic weights and lack mechanisms for synaptic competition; these problems can be resolved by heterosynaptic plasticity: changes at synapses which were not active during the induction.
We show that in layer 2/3 pyramidal neurons from auditory cortex a purely postsynaptic challenge, intracellular tetanization, can induce heterosynaptic plasticity; similar to visual cortex, plasticity direction depends on initial properties of synapses: inputs with initially low release probability tend to potentiate, while those with initially high release probability tend to depress.
Induction of heterosynaptic plasticity requires intracellular Ca2+ rise and its maintenance involves presynaptic changes, which depend on the nitric oxide signalling pathway.
We conclude that heterosynaptic plasticity is a common property of supragranular pyramidal neurons mediating cortico‐cortical connections in both auditory and visual cortices; it may serve as a mechanism of synaptic weight normalization and synaptic competition in these cortical regions.
Combined Forced and Free Turbulent Convection in a Vertical Circular
Tube With Volume Heat Sources and Constant Wall Heat Addition
Authors: Ojalvo M. S. , Anand D. K. , Dunbar R. P. 
Published: February 2012

Abstract
A study is made of turbulent heat transfer in a vertical circular tube under conditions of combined forced and free convection with uniform heat flux at the wall and volume heat sources. The basic conservation laws are reduced to three coupled, linear integrodifferential equations which are numerically solved by means of a digital computer. An improved expression for eddy viscosity variation with radial distance and degree of turbulence is used in the solution, as is an expression for the ratio of eddy diffusivity of heat to momentum. The parameters in the integrodifferential equations are: Prandtl number, Pr; Rayleigh number, Ra; friction Reynolds number, Re*; and a volume heat source parameter, F. For fixed values of these parameters, the solution results in: the velocity and temperature profiles; the pressure drop parameter, C; mixed-mean-to-wall temperature difference, φm; Nusselt number, Nu; and Reynolds number, Re. The solutions to this fairly general problem compare very closely to solutions of the following special cases (with no volume heat source): pure forced convection, laminar flow; pure forced convection, turbulent flow; and combined forced and free-convection, laminar flow.
Daptomycin versus Vancomycin in a Methicillin-Resistant Staphylococcus aureus Endophthalmitis Rabbit Model: Bactericidal Effect, Safety, and Ocular Pharmacokinetics
Authors: Lefèvre Sophie , Saleh Maher , Marcellin Luc , Subilia Audrey , Bourcier Tristan , Prévost Gilles , Jehl François 
Published: February 2012

ABSTRACT

Staphylococcus aureus
is a frequent cause of acute endophthalmitis, and infection with this virulent bacterium is often associated with a poor visual outcome. In this study, we investigated the bactericidal efficacy and the safety of intravitreal daptomycin (DAP), a lipopeptide antibiotic with broad-spectrum activity against Gram-positive bacteria, compared with those of intravitreal vancomycin (VAN) in a methicillin-resistant
S. aureus
endophthalmitis rabbit model. The pharmacokinetics and pharmacodynamics of daptomycin in the infected eyes were also studied. Rabbits were randomly divided into three treatment groups (
n
= 8) and one untreated group (
n
= 4), to compare the effect of single intravitreal injections of 0.2 mg and 1 mg of daptomycin (DAP 0.2 and DAP 1 groups, respectively) with that of 1 mg of intravitreal vancomycin (VAN 1 group). Vitreal aspirates were regularly collected and grading of ocular inflammation was regularly performed until euthanasia on day 7. In the DAP 0.2 group, 62.5% of the eyes were sterilized and the mean bacterial count presented a reduction of 1 log unit. In the DAP 1 and VAN 1 groups, the infection was eradicated (100% and 87.5% of eyes sterilized, respectively), with a 4-log-unit reduction of the mean bacterial count. The bactericidal efficacy in the DAP 1 group was not inferior to that in the VAN 1 group and was superior to that of the other regimens in limiting the ocular inflammation and preserving the architecture of the ocular structures (
P
< 0.05). The elimination half-life (
t
1/2β
) of daptomycin was independent of the administered dose (38.8 ± 16.5 h and 40.9 ± 6.7 h, respectively, for the DAP 0.2 and DAP 1 groups) and was significantly longer than the
t
1/2β
of vancomycin (20.5 ± 2.0 h for the VAN 1 group) (
P
< 0.05). This antibiotic could therefore be considered for the treatment of intraocular infections caused by Gram-positive bacteria.
Genomewide Overexpression Screen for Fosfomycin Resistance in Escherichia coli: MurA Confers Clinical Resistance at Low Fitness Cost
Authors: Couce Alejandro , Briales Alejandra , Rodríguez-Rojas Alexandro , Costas Coloma , Pascual Álvaro , Blázquez Jesús 
Published: February 2012

ABSTRACT

To determine whether the overexpression of chromosomal genes can confer fosfomycin resistance, genomewide screening of a complete set of 5,272 plasmid-expressed open reading frames of
Escherichia coli
(ASKA collection) was performed. Major results are that (i) no clinical level of resistance is achieved by overexpressing chromosomal genes, except
murA
; (ii) this level is reached at a low fitness cost; and (iii) this cost is much lower than that imposed by other mutations conferring fosfomycin resistance.
rplC
T460C Identified as a Dominant Mutation in Linezolid-Resistant Mycobacterium tuberculosis Strains
Authors: Beckert Patrick , Hillemann Doris , Kohl Thomas A. , Kalinowski Jörn , Richter Elvira , Niemann Stefan , Feuerriegel Silke 
Published: February 2012

ABSTRACT

The ribosomal L3 protein was identified as a novel target in linezolid (LZD)-resistant
Mycobacterium tuberculosis
strains. Next-generation sequencing confirmed
rplC
T460C as the sole mutation in an LZD-resistant
M. tuberculosis
H37Rv strain selected
in vitro
. Sequencing analysis revealed the
rplC
T460C mutation in eight further LZD-resistant isolates (three
in vitro
-selected mutants and five patient isolates, including isolates from three different patients that developed LZD resistance during treatment) but in none of the susceptible control strains (
n
= 84).
Highly Resistant Salmonella enterica Serovar Typhi with a Novel
gyrA
Mutation Raises Questions about the Long-Term Efficacy of Older Fluoroquinolones for Treating Typhoid Fever
Authors: Koirala Kanika Deshpande , Thanh Duy Pham , Thapa Sudeep Dhoj , Arjyal Amit , Karkey Abhilasha , Dongol Sabina , Shrestha Upendra Man , Farrar Jeremy J. , Basnyat Buddha , Baker Stephen 
Published: February 2012

ABSTRACT

As a consequence of multidrug resistance, clinicians are highly dependent on fluoroquinolones for treating the serious systemic infection typhoid fever. While reduced susceptibility to fluoroquinolones, which lessens clinical efficacy, is becoming ubiquitous, comprehensive resistance is exceptional. Here we report ofloxacin treatment failure in typhoidal patient infected with a novel, highly fluoroquinolone-resistant isolate of
Salmonella enterica
serovar Typhi. The isolation of this organism has serious implications for the long-term efficacy of ciprofloxacin and ofloxacin for typhoid treatment.
Afa/Dr Diffusely Adhering Escherichia coli Strain C1845 Induces Neutrophil Extracellular Traps That Kill Bacteria and Damage Human Enterocyte-Like Cells
Authors: Marin-Esteban Viviana , Turbica Isabelle , Dufour Guillaume , Semiramoth Nicolas , Gleizes Aude , Gorges Roseline , Beau Isabelle , Servin Alain L. , Lievin-Le Moal Vanessa , Sandré Catherine , Chollet-Martin Sylvie 
Published: February 2012

ABSTRACT

We recently documented the neutrophil response to enterovirulent diffusely adherent
Escherichia coli
expressing Afa/Dr fimbriae (Afa/Dr DAEC), using the human myeloid cell line PLB-985 differentiated into fully mature neutrophils. Upon activation, particularly during infections, neutrophils release neutrophil extracellular traps (NETs), composed of a nuclear DNA backbone associated with antimicrobial peptides, histones, and proteases, which entrap and kill pathogens. Here, using fluorescence microscopy and field emission scanning electron microscopy, we observed NET production by PLB-985 cells infected with the Afa/Dr wild-type (WT)
E. coli
strain C1845. We found that these NETs were able to capture, immobilize, and kill WT C1845 bacteria. We also developed a coculture model of human enterocyte-like Caco-2/TC7 cells and PLB-985 cells previously treated with WT C1845 and found, for the first time, that the F-actin cytoskeleton of enterocyte-like cells is damaged in the presence of bacterium-induced NETs and that this deleterious effect is prevented by inhibition of protease release. These findings provide new insights into the neutrophil response to bacterial infection via the production of bactericidal NETs and suggest that NETs may damage the intestinal epithelium, particularly in situations such as inflammatory bowel diseases.
Whole-Genome Sequence of the Human Pathogen Legionella pneumophila Serogroup 12 Strain 570-CO-H
Authors: Amaro Francisco , Gilbert Jack A. , Owens Sarah , Trimble William , Shuman Howard A. 
Published: February 2012

ABSTRACT

We present the genomic sequence of the human pathogen
Legionella pneumophila
serogroup 12 strain 570-CO-H (ATCC 43290), a clinical isolate from the Colorado Department of Health, Denver, CO. This is the first example of a genome sequence of
L. pneumophila
from a serogroup other than serogroup 1. We highlight the similarities and differences relative to six genome sequences that have been reported for serogroup 1 strains.
Complete Genome Sequence of Clinical Isolate Pantoea ananatis LMG 5342
Authors: De Maayer Pieter , Chan Wai Yin , Rezzonico Fabio , Bühlmann Andreas , Venter Stephanus N. , Blom Jochen , Goesmann Alexander , Frey Jürg E. , Smits Theo H. M. , Duffy Brion , Coutinho Teresa A. 
Published: February 2012

ABSTRACT

The enterobacterium
Pantoea ananatis
is an ecologically versatile species. It has been found in the environment, as plant epiphyte and endophyte, as an emerging phytopathogen, and as a presumptive, opportunistic human pathogen. Here, we report the complete genome sequence of
P. ananatis
LMG 5342, isolated from a human wound.
Genome Sequences of Four Divergent Multidrug-Resistant Acinetobacter baumannii Strains Isolated from Patients with Sepsis or Osteomyelitis
Authors: Zurawski Daniel V. , Thompson Mitchell G. , McQueary Christin N. , Matalka Malcolm N. , Sahl Jason W. , Craft David W. , Rasko David A. 
Published: February 2012

ABSTRACT

Acinetobacter baumannii
is a Gram-negative bacterium that causes nosocomial infections worldwide, with recent prevalence and higher frequency in wounded military personnel. Four
A. baumannii
strains from the Walter Reed Army Medical Center (WRAMC) isolated between 2008 and 2009 were sequenced, representing diverse, multidrug-resistant isolates from osteomyelitis or septic patients.
Genome Sequence of Weissella confusa LBAE C39-2, Isolated from a Wheat Sourdough
Authors: Amari Myriam , Laguerre Sandrine , Vuillemin Marlène , Robert Hervé , Loux Valentin , Klopp Christophe , Morel Sandrine , Gabriel Bruno , Remaud-Siméon Magali , Gabriel Valérie , Moulis Claire , Fontagné-Faucher Catherine 
Published: February 2012

ABSTRACT

Weissella confusa
is a rod-shaped heterofermentative lactic acid bacterium from the family of
Leuconostocaceae
. Here we report the draft genome sequence of the strain
W. confusa
LBAE C39-2 isolated from a traditional French wheat sourdough.
Genome Sequences of Three Leuconostoc citreum Strains, LBAE C10, LBAE C11, and LBAE E16, Isolated from Wheat Sourdoughs
Authors: Laguerre Sandrine , Amari Myriam , Vuillemin Marlène , Robert Hervé , Loux Valentin , Klopp Christophe , Morel Sandrine , Gabriel Bruno , Remaud-Siméon Magali , Gabriel Valérie , Moulis Claire , Fontagné-Faucher Catherine 
Published: February 2012

ABSTRACT

Leuconostoc citreum
is a key microorganism in fermented foods of plant origin. Here we report the draft genome sequence for three strains of
Leuconostoc citreum
, LBAE C10, LBAE C11, and LBAE E16, which have been isolated from traditional French wheat sourdoughs.
Genome Sequence of Comamonas testosteroni ATCC 11996, a Representative Strain Involved in Steroid Degradation
Authors: Gong Wenjie , Kisiela Michael , Schilhabel Markus B. , Xiong Guangming , Maser Edmund 
Published: February 2012

ABSTRACT

Comamonas testosteroni
strains belong to the family of
Comamonadaceae
and are known for their ability to utilize steroid compounds as carbon source. Here, we present the draft genome sequence of strain ATCC 11996, with a G+C content of 61.48%.
Climatic determinants of white spruce cone crops in the boreal forest of southwestern Yukon
Authors: Krebs C.J. , LaMontagne J.M. , Kenney A.J. , Boutin S. 
Published: February 2012

White spruce ( Picea glauca (Moench) Voss) cone crops were measured from 1986 to 2011 in the Kluane region of southwestern Yukon to test the hypothesis that the size of cone crops could be predicted from spring and summer temperature and rainfall of years t, t – 1, and t – 2. We counted cones in the top 3 m of an average of 700 white spruce trees each year spread over 3–14 sites along 210 km of the Alaska Highway and the Haines Highway. We tested the conventional explanation for white spruce cone crops that implicates summer temperatures and rainfall in years t and t – 1 and rejected it, since it explained very little of the variation in our 26 years of data. We used exploratory data analysis with robust multiple regressions coupled with Akaike’s information criterion corrected (AICc) analysis to determine the best statistical model to predict the size of cone crops. We could statistically explain 54% of the variation in cone crops from July and August temperatures of years t – 1 and t – 2 and May precipitation of year t – 2. There was no indication of a periodicity in cone crops, and years of large cone crops were synchronous over the Kluane region with few exceptions. This is the first quantitative model developed for the prediction of white spruce cone crops in the Canadian boreal forest and has the surprising result that weather conditions 2 years prior to the cone crop are the most significant predictors.