bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pitavastatin inhibits hepatic steatosis and fibrosis in non‐alcoholic steatohepatitis model rats
Authors: Miyaki Tomokatsu , Nojiri Shunsuke , Shinkai Noboru , Kusakabe Atsunori , Matsuura Kentaro , Iio Etsuko , Takahashi Satoru , Yan Ge , Ikeda Kazuo , Joh Takashi 
Published: January 2011

Aim:  Non‐alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and NASH patients with liver cirrhosis are at risk of developing hepatocellular carcinoma. Statins, 3‐hydroxy‐3‐methyglutaryl‐coenzyme A reductase inhibitors, are well known to reduce low‐density lipoprotein cholesterol and reduce the incidence of coronary heart disease and other major vascular events by anti‐inflammatory and antifibrotic effects, and antiproliferative properties in colorectal cancers have also been reported. Recently, statins have been reported to improve hepatic steatosis; however, the effect on fibrosis is controversial.Methods:  The effects of pitavastatin (one of the strongest statins) were examined using a choline‐deficient L‐amino acid‐defined (CDAA) diet liver fibrosis model.Results:  Pitavastatin significantly attenuated increases in serum aspartate aminotransferase, alanine aminotransferase, hepatic steatosis, oxidative stress, pre‐neoplastic lesions (glutathione S‐transferase placental form‐positive lesions), expression of cytokines, such as tumor necrosis factor‐α and transforming growth factor‐β1, and the expression of tissue inhibitor of metalloproteinase‐1, tissue inhibitor of metalloproteinase‐2 and type I procollagen genes followed by attenuating fibrosis of the liver of CDAA‐fed rats.Conclusion:  These results indicate that pitavastatin may inhibit steatosis, hepatic fibrosis and carcinogenesis in rat model of NASH.
Clinical and Histopathologic Characterization of a Central and Peripheral Axonopathy inRouge‐des‐prés(Maine Anjou) Calves
Authors: Timsit E. , Albaric O. , Colle M.A. , Costiou P. , Cesbron N. , Bareille N. , Assié S. 
Published: January 2011

Background:Recently, a progressive pelvic limb ataxia and paraparesis leading invariably to recumbency has been reported inRouge‐des‐préscalves.Objectives:To characterize the clinical and pathological findings of this newly reported disease and to investigate its potential causes.Animals:Nine calves from 7 different farms were prospectively studied from initial diagnosis through postmortem examination.Methods:Physical and neurological examinations, blood tests, cerebrospinal fluid (CSF) analysis, and myelographic examinations were performed. Neuropathology was carried out on both central and peripheral nervous systems. Copper deficiency and organophosphate intoxication also were investigated. Pedigrees were analyzed.Results:Age of onset varied from 2 to 6 weeks. Initial signs included pelvic limb ataxia and paraparesis. The neurological signs systematically progressed, over a 1–3‐month period, to severe pelvic limb and truncal ataxia along with moderate paraparesis, leading to permanent recumbency. Animals remained alert. Cranial nerve function was normal. Muscle atrophy was not observed and spinal reflexes were normal. Blood tests, CSF analysis, and myelographic examination did not identify any abnormality. Neuropathology indicated neuronal fiber degeneration particularly in the dorsolateral and ventromedial funiculi of the spinal cord and in the peripheral nerves. Degenerative lesions also were observed in lateral vestibular and thoracic nuclei. No environmental factors such as copper deficiency or organophosphate intoxication could be incriminated as the cause of this axonopathy. Pedigree analysis suggested an inherited defect.Conclusions and Clinical Importance:The first description of a central and peripheral axonopathy is reported inRouge‐des‐préscalves. An inherited defect is highly suspected.
Effect of Diets Differing in Fat Content on Chronic Diarrhea in Cats
Authors: Laflamme D.P. , Xu H. , Long G.M. 
Published: January 2011

Background: Fat‐restricted diets have been advocated for dogs with diarrhea for many years. Recommendations for cats with diarrhea have varied between low‐fat and high‐fat diets, but there have been no published studies to support either recommendation.Objectives: The objective of this study was to compare the clinical responses of cats with chronic diarrhea to dietary management using either a high fat or a low fat, highly digestible diet.Animals: Sixty pet cats with chronic diarrhea were recruited; 55 cats completed the study.Methods: Randomized, double‐blinded, controlled clinical trial. Upon completion of baseline measures, cats were fed 1 of 2 diets for 6 weeks, during which the owners recorded fecal scores daily using an illustrated fecal score chart ranging from 0 (very watery) to 100 (firm and dry). After 6 weeks, cats were reevaluated by the attending veterinarians.Results: Fecal scores improved significantly, with 78.2% of cats improving by at least 25 points on the 100‐point scale or having a final fecal score of at least 66. Over one third of the cats developed normal stools. There were no differences in clinical responses between the diets. Clinical improvement was noted within the 1st week, and maximized within 3 weeks.Conclusions and Clinical Importance: These results show that dietary management can be helpful in cats with chronic diarrhea, but dietary fat content does not appear to affect the outcome. Cats that do not respond within 3 weeks should be evaluated further.
A Truncated Retrotransposon Disrupts the GRM1 Coding Sequence in Coton de Tulear Dogs with Bandera's Neonatal Ataxia
Authors: Zeng R. , Farias F.H.G. , Johnson G.S. , McKay S.D. , Schnabel R.D. , Decker J.E. , Taylor J.F. , Mann C.S. , Katz M.L. , Johnson G.C. , Coates J.R. , O'Brien D.P. 
Published: January 2011

Background: Bandera's neonatal ataxia (BNAt) is an autosomal recessive cerebellar ataxia that affects members of the Coton de Tulear dog breed.Objective: To identify the mutation that causes BNAt.Animals: The study involved DNA from 112 Cotons de Tulear (including 15 puppies with signs of BNAt) and 87 DNA samples from dogs of 12 other breeds.Methods: The BNAt locus was mapped with a genome‐wide association study (GWAS). The coding exons of positional candidate gene GRM1, which encodes metabotropic glutamate receptor 1, were polymerase chain reaction (PCR)‐amplified and resequenced. A 3‐primer PCR assay was used to genotype individual dogs for a truncated retrotransposon inserted into exon 8 of GRM1.Results: The GWAS indicated that the BNAt locus was in a canine chromosome 1 region that contained candidate gene GRM1. Resequencing this gene from BNAt‐affected puppies indicated that exon 8 was interrupted by the insertion of a 5′‐truncated retrotransposon. All 15 BNAt‐affected puppies were homozygous for the insert, whereas all other Cotons de Tulear were heterozygotes (n = 43) or homozygous (n = 54) for the ancestral allele. None of the 87 dogs from 12 other breeds had the insertion allele.Conclusions and Clinical Importance: BNAt is caused by a retrotransposon inserted into exon 8 of GRM1. A DNA test for the GRM1 retrotransposon insert can be used for genetic counseling and to confirm the diagnosis of BNAt.
Serum Free Cortisol Fraction in Healthy and Septic Neonatal Foals
Authors: Hart K.A. , Barton M.H. , Ferguson D.C. , Berghaus R. , Slovis N.M. , Heusner G.L. , Hurley D.J. 
Published: January 2011

Background: Relative cortisol insufficiency occurs in septic foals and impacts survival. Serum free (biologically available) cortisol concentration might be a better indicator of physiologic cortisol status than serum total cortisol concentration in foals.Hypotheses: In septic foals, (1) low free cortisol concentration correlates with disease severity and survival and (2) predicts disease severity and outcome better than total cortisol concentration.Animals: Fifty‐one septic foals; 11 healthy foals; 6 healthy horses.Methods: In this prospective clinical study, foals meeting criteria for sepsis at admission were enrolled. University‐owned animals served as healthy controls. Basal and cosyntropin‐stimulated total cortisol concentration and percent free cortisol (% free cortisol) were determined by chemiluminescent immunoassay and ultrafiltration/ligand‐binding methods, respectively. Group data were compared by ANOVA, Mann‐Whitney U‐tests, and receiver operator characteristic curves. Significance was set at P < .05.Results: Basal % free cortisol was highest in healthy foals at birth (58±8% mean±SD), and was higher (P≤.004) in healthy foals of all ages (33±6 to 58±8%) than in adult horses (7±3%). Cosyntropin‐stimulated total and free cortisol concentrations were lower (P≤.03) in foals with shock (total = 6.2±8.1 μg/dL; free = 3.5±4.8 μg/dL versus total = 10.8±6.0 μg/dL; free = 6.9±3.3 μg/dL in foals without shock) and in nonsurvivors (total = 3.8±6.9 μg/dL; free = 1.9±3.9 μg/dL versus total = 9.1±7.7 μg/dL; free = 5.5±4.4 μg/dL in survivors). Free cortisol was no better than total cortisol at predicting disease severity or outcome in septic foals.Conclusions and Clinical Importance: Serum free cortisol is impacted by age and illness in the horse. There is no advantage to measuring free over total cortisol in septic foals.
Comparison of Signalment, Clinicopathologic Findings, Histologic Diagnosis, and Prognosis in Dogs with Glomerular Disease with or without Nephrotic Syndrome
Authors: Klosterman E.S. , Moore G.E. , de Brito Galvao J.F. , DiBartola S.P. , Groman R.P. , Whittemore J.C. , Vaden S.L. , Harris T.L. , Byron J.K. , Dowling S.R. , Grant D.C. , Grauer G.F. , Pressler B.M. 
Published: January 2011

Background: Nephrotic syndrome (NS) develops most commonly in people with glomerular diseases associated with marked albuminuria. Hypernatremia, hypertension, and progressive renal failure are more prevalent in nephrotic than nonnephrotic human patients.Hypothesis/Objectives: Dogs with NS have higher serum cholesterol, triglyceride, and sodium concentrations, higher urine protein:creatinine ratios (UPC) and systolic blood pressure, and lower serum albumin concentrations than dogs with nonnephrotic glomerular disease (NNGD). NS is associated with membranous glomerulopathy and amyloidosis. Affected dogs are more likely to be azotemic and have shorter survival times.Animals: Two hundred and thirty‐four pet dogs (78 NS dogs, 156 NNGD dogs).Methods: Multicenter retrospective case‐control study comparing time‐matched NS and NNGD dogs. NS was defined as the concurrent presence of hypoalbuminemia, hypercholesterolemia, proteinuria, and extravascular fluid accumulation. Signalment, clinicopathologic variables, histopathologic diagnoses, and survival time were compared between groups.Results: Age, serum albumin, chloride, calcium, phosphate, creatinine, and cholesterol concentrations, and UPC differed significantly between NS and NNGD dogs. Both groups were equally likely to be azotemic at time of diagnosis, and NS was not associated with histologic diagnosis. Median survival was significantly shorter for NS (12.5 days) versus NNGD dogs (104.5 days). When subgrouped based on serum creatinine (< or ≥1.5 mg/dL), survival of NS versus NNGD dogs was only significantly different in nonazotemic dogs (51 versus 605 days, respectively).Conclusions and Clinical Importance: Presence of NS is associated with poorer prognosis in dogs with nonazotemic glomerular disease. Preventing development of NS is warranted; however, specific interventions were not evaluated in this study.
Physiological and molecular characterization of genetic competence in Streptococcus sanguinis
Authors: Rodriguez A.M. , Callahan J.E. , Fawcett P. , Ge X. , Xu P. , Kitten T. 
Published: January 2011

Summary Streptococcus sanguinis is a major component of the oral flora and an important cause of infective endocarditis. Although S. sanguinis is naturally competent, genome sequencing has suggested significant differences in the S. sanguinis competence system relative to those of other streptococci. An S. sanguinis mutant possessing an in‐frame deletion in the comC gene, which encodes competence‐stimulating peptide (CSP), was created. Addition of synthetic CSP induced competence in this strain. Gene expression in this strain was monitored by microarray analysis at multiple time‐points from 2.5 to 30 min after CSP addition, and verified by quantitative reverse transcription–polymerase chain reaction. Over 200 genes were identified whose expression was altered at least two‐fold in at least one time point, with the majority upregulated. The ‘late’ response was typical of that seen in previous studies. However, comparison of the ‘early’ response in S. sanguinis with that of other oral streptococci revealed unexpected differences with regard to the number of genes induced, the nature of those genes, and their putative upstream regulatory sequences. Streptococcus sanguinis possesses a comparatively limited early response, which may define a minimal streptococcal competence regulatory circuit.
Streptococcus mutans strains recovered from caries‐active or caries‐free individuals differ in sensitivity to host antimicrobial peptides
Authors: Phattarataratip E. , Olson B. , Broffitt B. , Qian F. , Brogden K.A. , Drake D.R. , Levy S.M. , Banas J.A. 
Published: January 2011

SummaryAntimicrobial peptides (AMPs) are among the repertoire of host innate immune defenses. In the oral cavity, several AMPs are present in saliva and have antimicrobial activities against oral bacteria, including Streptococcus mutans, a primary etiological agent of dental caries. In this study, we hypothesized that unique S. mutans strains, as determined by DNA fingerprinting from sixty 13‐year‐old subjects with or without experience of caries, would have different susceptibilities to α‐defensins‐1–3 (HNP‐1–3), β‐defensins‐2–3 (HBD‐2–3) and LL‐37. The salivary levels of these peptides in subjects were also measured by enzyme‐linked immunosorbent assays. We found that S. mutans strains from children with active caries showed greater resistance to salivary HNP‐1–2, HBD‐2–3 and LL‐37 at varying concentrations than those from caries‐free subjects. In addition, combinations of these peptides increased their antimicrobial activity against S. mutans either additively or synergistically. The salivary levels of these peptides were highly variable among subjects with no correlation to host caries experience. However, the levels of a number of these peptides in saliva appeared to be positively correlated within an individual. Our findings suggest that the relative ability of S. mutans to resist host salivary AMPs may be considered a potential virulence factor for this species such that S. mutans strains that are more resistant to these peptides may have an ecological advantage to preferentially colonize within dental plaque and increase the risk of dental caries.
Impact of deception detection errors on public's trust in the police
Authors: Hurst‐Wagner Melanie , Oswald Margit E. 
Published: January 2011

Purpose. The present study explored the public's attitude towards errors in police officers’ detection of deception. Based on findings on trust in the police after responses to terrorist threats, we predicted a positive influence of a correct credibility assessment and of a risk‐averse response bias of police officers on public's trust.Methods. A general population sample (N= 151) read a hypothetical scenario concerning a credibility judgment and indicated their trust in the officers making the judgment. Decision outcome was manipulated by varying the four outcomes of a signal‐detection task, namely, Hit, Miss, False Alarm, and Correct Rejection.Results. In line with findings on trust in the police following responses to terrorist threats, people trusted police officers more if they judged the credibility of a suspect correctly. Moreover, officers who disbelieved the suspect's statement were trusted more than officers who believed, independently of outcome correctness. Furthermore, this effect was moderated by individual differences in error weighting.Conclusions. In sum, these findings indicate that lie‐biased credibility judgments made by police officers are supported by the public and increase their trust in the police. In addition, the present findings suggest that an asymmetrical weighting of judgment errors is a relevant factor in explaining the development of and attitude towards lie bias.
Microneedle Vaccination with Stabilized Recombinant Influenza Virus Hemagglutinin Induces Improved Protective Immunity
Authors: Weldon William C. , Martin Maria P. , Zarnitsyn Vladimir , Wang Baozhong , Koutsonanos Dimitrios , Skountzou Ioanna , Prausnitz Mark R. , Compans Richard W. 
Published: February 2011

ABSTRACTThe emergence of the swine-origin 2009 influenza pandemic illustrates the need for improved vaccine production and delivery strategies. Skin-based immunization represents an attractive alternative to traditional hypodermic needle vaccination routes. Microneedles (MNs) can deliver vaccine to the epidermis and dermis, which are rich in antigen-presenting cells (APC) such as Langerhans cells and dermal dendritic cells. Previous studies using coated or dissolvable microneedles emphasized the use of inactivated influenza virus or virus-like particles as skin-based vaccines. However, most currently available influenza vaccines consist of solubilized viral protein antigens. Here we test the hypothesis that a recombinant subunit influenza vaccine can be delivered to the skin by coated microneedles and can induce protective immunity. We found that mice vaccinated via MN delivery with a stabilized recombinant trimeric soluble hemagglutinin (sHA) derived from A/Aichi/2/68 (H3) virus had significantly higher immune responses than did mice vaccinated with unmodified sHA. These mice were fully protected against a lethal challenge with influenza virus. Analysis of postchallenge lung titers showed that MN-immunized mice had completely cleared the virus from their lungs, in contrast to mice given the same vaccine by a standard subcutaneous route. In addition, we observed a higher ratio of antigen-specific Th1 cells in trimeric sHA-vaccinated mice and a greater mucosal antibody response. Our data therefore demonstrate the improved efficacy of a skin-based recombinant subunit influenza vaccine and emphasize the advantage of this route of vaccination for a protein subunit vaccine.
Serum IgG Response to Cryptosporidium Immunodominant Antigen gp15 and Polymorphic Antigen gp40 in Children with Cryptosporidiosis in South India
Authors: Ajjampur Sitara Swarna Rao , Sarkar Rajiv , Allison Geneve , Banda Kalyan , Kane Anne , Muliyil Jayaprakash , Naumova Elena , Ward Honorine , Kang Gagandeep 
Published: February 2011

ABSTRACTThe surface-associated glycopeptides gp40, one of the most polymorphicCryptosporidiumantigens, and gp15, one of the most immunodominantCryptosporidiumantigens, are putative vaccine candidates because they mediate infectionin vitroand induce immune responsesin vivo. We evaluated antibody responses to these antigens before and after the first episode of symptomatic cryptosporidiosis in 51 children from a birth cohort study in an area in South India whereCryptosporidiumis endemic and a major cause of parasitic diarrhea. IgG levels to gp15 and to homotypic and heterotypic gp40 antigens were measured in pre- and postdiarrheal sera by enzyme-linked immunosorbent assay (ELISA). There was a significant IgG response to gp15 (P< 0.001) following the first episode of cryptosporidial diarrhea. Using a general additive model, we determined the estimated time of the peak IgG response to gp15 to be 9.3 weeks (confidence interval, 5.2 to 13.4) following the diarrheal episode. In a subset of 30 children infected withCryptosporidium hominissubtype Ia, there was a significant difference in IgG responses to homotypicC. hominisIa and to heterotypicCryptosporidium parvumII gp40 antigens (P= 0.035). However, there was also a significant correlation (P= 0.001) in the responses to both antigens in individual children, suggesting that while responses are in part subtype specific, there is significant cross-reactivity to both antigens. This is the first report of the characterization of immune responses to cryptosporidiosis in Indian children and the first study to investigate human immune responses to the polymorphic gp40 antigen. However, further studies are needed to determine whether immune responses to these antigens are protective against subsequent infections.
Improved Method for Rapid and Efficient Determination of Genome Replication and Protein Expression of Clinical Hepatitis B Virus Isolates
Authors: Qin Yanli , Zhang Jiming , Garcia Tamako , Ito Kiyoaki , Gutelius Danielle , Li Jisu , Wands Jack , Tong Shuping 
Published: February 2011

ABSTRACT

Different hepatitis B virus (HBV) genotypes and variants are associated with different clinical outcomes and/or response to antiviral therapy, yet the comparison of the
in vitro
replication capacity of a large number of clinical isolates remains technically challenging and time-consuming. Although the full-length HBV genome can be amplified from high-titer blood samples by PCR using

High Fidelity
plus

DNA polymerase and primers targeting the conserved precore region, the HBV clones thus generated are replication deficient due to the inability to generate the terminally redundant pregenomic RNA essential for genome replication. The transfection experiment is further complicated by PCR errors and the presence of viral quasispecies. A previous study found that the precise removal of non-HBV sequence by SapI digestion led to HBV replication in transfected cells, possibly due to low-level genome circularization by a cellular enzyme. We released HBV genome from the cloning vector using BspQI, an inexpensive isoschizomer of SapI, and increased the efficiency of genome replication by an extra step of
in vitro
DNA ligation. The uncut plasmid DNA can be used for transfection if the sole purpose is to study envelope protein expression. We found significant PCR errors associated with the

High Fidelity
plus

DNA polymerase, which could be greatly diminished using
Phusion
DNA polymerase or masked by the use of a clone pool. The reduced PCR error and modified enzymatic steps prior to transfection should facilitate a more widespread functional characterization of clinical HBV isolates, while the clone pool approach is useful for samples with significant sequence heterogeneity.
The NLRP3 Inflammasome Detects Encephalomyocarditis Virus and Vesicular Stomatitis Virus Infection
Authors: Rajan Jayant V. , Rodriguez David , Miao Edward A. , Aderem Alan 
Published: February 2011

ABSTRACT
Inflammasomes are cytosolic protein complexes that regulate caspase-1 activation and the secretion of interleukin-1β (IL-1β) and IL-18. Several different inflammasome complexes have been identified, but the NLRP3 inflammasome is particularly notable because of its central role in diseases of inflammation. Recent work has demonstrated an essential role for the NLRP3 inflammasome in host defense against influenza virus. We show here that two other RNA viruses, encephalomyocarditis virus (EMCV) and vesicular stomatitis virus (VSV), activate the NLRP3 inflammasome in dendritic cells and macrophages through a mechanism requiring viral replication. Inflammasome activation in response to both viruses does not require MDA5 or RIG-I signaling. Despite the ability of the NLRP3 inflammasome to detect EMCV and VSV, wild-type and caspase-1-deficient mice were equally susceptible to infection with both viruses. These findings indicate that the NLRP3 inflammasome may be a common pathway for RNA virus detection, but its precise role in the host response may be variable.