bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biologic variability of cardiac troponin I in healthy dogs and dogs with different stages of myxomatous mitral valve disease using standard and high‐sensitivity immunoassays
Authors: Winter Randolph L. , Saunders Ashley B. , Gordon Sonya G. , Miller Matthew W. , Fosgate Geoffrey T. , Suchodolski Jan S. , Steiner Jörg M. 
Published: April 2017

BackgroundBiologic variability (BV) is one aspect of interpreting changes in biomarker concentrations known to be clinically important in people with cardiac disease, but it has not been adequately addressed in dogs so far.ObjectivesThe purpose of the study was to determineBVof cardiac troponin I (cTnI) in healthy dogs and dogs with 3 stages of myxomatous mitral valve disease (MMVD).MethodsHealthy dogs and dogs with 3 stages ofMMVDwere prospectively assigned to groups based on comprehensive clinical evaluation using current guidelines. Concentrations ofcTnIwere measured hourly, daily, and weekly using standard and high‐sensitivity immunoassays. Within‐ (CVI) and between‐subject (CVG) coefficients of variability, percent reference change value (RCV), and index of individuality (IoI) were calculated.ResultsAll 10 healthy dogs and 76/112 (68%) of samples from 28MMVDdogs hadcTnIconcentrations below the limit of detection (LOD) using a standard sensitivity immunoassay. Only 49/160 (31%) of healthy dog samples and noMMVDsamples hadcTnIbelow the high‐sensitivity immunoassayLOD. Data analysis for the high‐sensitivity immunoassay revealedCVIof 48.1%,CVGof 60.1%,RCVof 134.0%, and IoI of 0.804 in healthy dogs. InMMVDdogs,CVIwas 39.6%,CVGwas 80.7%,RCVwas 110%, and IoI was 0.494. Of allMMVDdogs, those with Stage B2 had the lowestRCVof 91%.ConclusionsBiologic variability affectscTnIconcentrations in healthy dogs and dogs withMMVD. Consideration of BV may be clinically relevant when monitoring individual changes incTnIvalues, using high‐sensitivity immunoassays.
Scleromyxoedema in a dog
Authors: Laprais Aurore F. , Bizikova Petra , Lashnits Erin W. , Tucker Alison , Linder Keith E. 
Published: April 2017

BackgroundIn humans, scleromyxoedema is a chronic progressive skin condition traditionally characterized by deposits of mucin, increased number of fibroblasts and fibrosis in the skin, and by systemic disease. Thyroid disease is typically absent. A monoclonal gammopathy is usually present, as are other comorbidities. Descriptions of scleromyxoedema in the veterinary literature are limited to a single feline case. One dog, previously reported as having papular mucinosis, exhibited features that matched the more current diagnostic criteria of scleromyxoedema.ObjectivesTo describe generalized papular mucinosis in a dog with systemic illness and to compare the signs with those of human lichen myxoedematosus conditions, specifically scleromyxoedema.ResultsA nine‐year‐old female, spayed English springer spaniel dog presented with generalized papules and nodules (0.5–5 cm) on the body and proximal fore and hind limbs, sparing the face and distal limbs distal to carpi/tarsi. Larger nodules were erythematous. Nodules occurred in proximal limb muscles. The dog had concurrent osteoarthritis of the elbows and coxofemoral joints, developed generalized weakness, declined in health and was euthanized. Thyroid disease was lacking and a monoclonal gammopathy was not present. Histopathological evaluation revealed the classic triad of mucin, fibroblast proliferation and fibrosis with very mild inflammation, as described for humans.Conclusion and clinical importanceWe document scleromyxoedema in a dog with significant morbidity and features of the human disease. Recognizing the typical histopathology is important for identifying cases and to establish a diagnosis. Systemic evaluation is important to identify evidence of internal disease and associated comorbidities, which are common, variable, and impact classification and prognosis in humans.
Seroepidemiology and molecular characterization of hepatitis E virus infection in swine and occupationally exposed workers in Punjab, India
Authors: Bansal M. , Kaur S. , Deka D. , Singh R. , Gill J. P. S. 
Published: April 2017

SummaryHepatitis E virus (HEV) has two discrete epidemiological patterns: waterborne epidemics in developing countries only, caused by HEV genotype I, and sporadic zoonotic outbreaks in developing and developed countries caused by genotypes III and IV. This study was designed to investigate seroprevalence, molecular detection and the characterization of HEV by nested RT‐PCR in swine as well as the occupational risk to exposed human population in Punjab state of north‐western India. The occupational risk‐exposed group comprised of swine farmers (organized – mixed feed feeders and unorganized – swill feeders), slaughterhouse workers, sewage workers and veterinary internes. During the study period, blood and faecal samples were collected from 320 swine and 360 humans with both high and low occupational exposure risks. The overall seroprevalence of swine HEV was 65.00%, with a significantly higher seropositivity in growing pigs (2–8 months of age). The prevalence of HEV RNA in swine faecal samples by nRT‐PCR was 8.75% with a significantly higher detection in swill‐fed pigs. With humans in the high occupational exposure risk population, significantly higher anti‐HEV IgG seropositivity was observed (60.48%) as compared to control population (10.71%). Strong evidence of association between human anti‐HEV IgG seropositivity and certain occupational exposure risk groups was observed (p < 0.05). This indicates that unorganized swine farmers, slaughterhouse workers and sewage workers have higher odds of HEV infection in this study region. Percentage of nucleotide similarity between swine and human HEV isolates was less than that found in countries with zoonotic HEV outbreaks. Molecular characterization revealed the circulation of G IV and G I genotypes among swine and human population in Punjab state, respectively.
Impact of perinatal exposure to sucrose or high fructose corn syrup (HFCS‐55) on adiposity and hepatic lipid composition in rat offspring
Authors: Toop Carla R. , Muhlhausler Beverly S. , O'Dea Kerin , Gentili Sheridan 
Published: April 2017

Key points
Fructose‐containing sugars, including sucrose and high fructose corn syrup (HFCS), have been implicated in the epidemics of obesity and type 2 diabetes.
Few studies have evaluated the impact of perinatal exposure to these sugars on metabolic and physiological outcomes in the offspring.
Using a rat model, offspring exposed to a maternal sucrose or HFCS diet during the prenatal and/or suckling periods were found to have altered adiposity and liver fat content and composition at weaning.
Plasma levels of free fatty acids remained elevated in young adulthood, but consumption of a control diet following weaning appeared to ameliorate most other effects of perinatal exposure to a maternal high‐sugar diet.
Guidelines for maternal nutrition should advise limiting consumption of fructose‐containing sugars, and it is particularly important that these recommendations include maternal nutrition during lactation.
AbstractPerinatal exposure to excess maternal intake of added sugars, including fructose and sucrose, is associated with an increased risk of obesity and type 2 diabetes in adult life. However, it is unknown to what extent the type of sugar and the timing of exposure affect these outcomes. The aim of this study was to determine the impact of exposure to maternal consumption of a 10% (w/v) beverage containing sucrose or high fructose corn syrup‐55 (HFCS‐55) during the prenatal and/or suckling periods on offspring at 3 and 12 weeks, utilising a cross‐fostering approach in a rodent model. Perinatal sucrose exposure decreased plasma glucose concentrations in offspring at 3 weeks, but did not alter glucose tolerance. Increased adiposity was observed in 3‐week‐old offspring exposed to sucrose or HFCS‐55 during suckling, with increased hepatic fat content in HFCS‐55‐exposed offspring. In terms of specific fatty acids, hepatic monounsaturated (omega‐7 and ‐9) fatty acid content was elevated at weaning, and was most pronounced in sucrose offspring exposed during both the prenatal and suckling periods, and HFCS‐55 offspring exposed during suckling only. By 12 weeks, the effects on adiposity and hepatic lipid composition were largely normalised. However, exposure to either sucrose or HFCS‐55 during the prenatal period only was associated with elevated plasma free fatty acids at weaning, and this effect persisted until 12 weeks. This study suggests that the type of sugar and the timing of exposure (prenatal or suckling periods) are both important for determining the impact on metabolic health outcomes in the offspring.
Pyrazinoic Acid Inhibits a Bifunctional Enzyme in Mycobacterium tuberculosis
Authors: Njire Moses , Wang Na , Wang Bangxing , Tan Yaoju , Cai Xingshan , Liu Yanwen , Mugweru Julius , Guo Jintao , Hameed H. M. Adnan , Tan Shouyong , Liu Jianxiong , Yew Wing Wai , Nuermberger Eric , Lamichhane Gyanu , Liu Jinsong , Zhang Tianyu 
Published: April 2017

ABSTRACT

Pyrazinamide (PZA), an indispensable component of modern tuberculosis treatment, acts as a key sterilizing drug. While the mechanism of activation of this prodrug into pyrazinoic acid (POA) by
Mycobacterium tuberculosis
has been extensively studied, not all molecular determinants that confer resistance to this mysterious drug have been identified. Here, we report how a new PZA resistance determinant, the Asp67Asn substitution in Rv2783, confers
M. tuberculosis
resistance to PZA. Expression of the mutant allele but not the wild-type allele in
M. tuberculosis
recapitulates the PZA resistance observed in clinical isolates. In addition to catalyzing the metabolism of RNA and single-stranded DNA, Rv2783 also metabolized ppGpp, an important signal transducer involved in the stringent response in bacteria. All catalytic activities of the wild-type Rv2783 but not the mutant were significantly inhibited by POA. These results, which indicate that Rv2783 is a target of PZA, provide new insight into the molecular mechanism of the sterilizing activity of this drug and a basis for improving the molecular diagnosis of PZA resistance and developing evolved PZA derivatives to enhance its antituberculosis activity.
Impact of Health Care Exposure on Genotypic Antiseptic Tolerance in Staphylococcus aureus Infections in a Pediatric Population
Authors: McNeil J. Chase , Hultén Kristina G. , Mason Edward O. , Kaplan Sheldon L. 
Published: April 2017

ABSTRACT

Staphylococcus aureus
possessing either the
smr
gene or the
qacA/B
genes is associated with decreased susceptibility to chlorhexidine gluconate (CHG) and other antiseptics. Previous studies of antiseptic-tolerant staphylococci have focused largely on high-risk populations, and the exact role of health care exposure in the acquisition of these organisms is unclear. We sought to describe the risk factors and features of infection caused by antiseptic-tolerant
S. aureus
in a general pediatric population. Isolates were selected from an ongoing
S. aureus
surveillance study. Every third sequential isolate in the year 2014 was selected for inclusion. All isolates underwent PCR for the genes
qacA/B
and
smr
. Medical records were reviewed. Five hundred six isolates were included in the study, with 377 (74.3%) being community acquired. One hundred (19.8%) isolates were
smr
positive and 79 (15.6%)
qacA/B
positive. In univariable analyses, the presence of either gene was associated with underlying medical conditions, nosocomial acquisition, recent hospitalization, central venous lines, and CHG exposure. In multivariable analyses, only differences between patients with chronic medical conditions (odds ratio [OR] = 1.72; 95% confidence interval [CI], 1.22 to 2.64) and nosocomial acquisition (OR = 2.48; 95% CI, 1.16 to 8.17) remained statistically significant. Among patients without risk factors, 27.9% had infection with an antiseptic-tolerant isolate.
smr
- or
qacA/B
-positive
S. aureus
isolates are common in children and are independently associated with nosocomial acquisition and underlying medical conditions. These findings imply a role for the health care environment in acquisition of these organisms. However, genotypic antiseptic tolerance was seen in >25% of healthy children with an
S. aureus
infection, indicating that these organism are prevalent in the community as well.
Correlation between
gyrA
and CmeR Box Polymorphism and Fluoroquinolone Resistance in Campylobacter jejuni Isolates in China
Authors: Zhang Tengfei , Cheng Yiluo , Luo Qingping , Lu Qin , Dong Jun , Zhang Rongrong , Wen Guoyuan , Wang Honglin , Luo Ling , Wang Hongcai , Liu Guoping , Shao Huabin 
Published: April 2017

ABSTRACT

Sequence analysis of 79 ciprofloxacin-resistant
Campylobacter jejuni
isolates collected in China showed resistance-related sequence variations in
gyrA
and CmeR-Box. All the isolates contain an identical Thr-86-Ile substitution in GyrA. Several novel CmeR-Box variations, including point substitutions, deletion, and insertion, were identified. The point insertion or deletion led to dramatically reduced binding of CmeR to the
cmeABC
promoter, which significantly increases the expression of
cmeABC
and contributes to the high fluoroquinolone resistance.
Treatment with Entinostat Heals Experimental Cholera by Affecting Physical and Chemical Barrier Functions of Intestinal Epithelia
Authors: Sarker Protim , Banik Atanu , Stromberg Roger , Gudmundsson Gudmundur H. , Raqib Rubhana , Agerberth Birgitta 
Published: April 2017

ABSTRACT

We have shown previously that oral treatment with sodium butyrate or phenylbutyrate in an experimental model of shigellosis improves clinical outcomes and induces the expression of the antimicrobial peptide CAP-18 in the large intestinal epithelia. In a subsequent study, we found that entinostat, an aroylated phenylenediamine compound, has similar therapeutic potential against shigellosis. In this study, we aimed to evaluate entinostat as a potential candidate for host-directed therapy against cholera in an experimental model.
Vibrio cholerae
-infected rabbits were treated with two different dose regimens of entinostat: either 0.5 mg twice daily for 2 days or 1 mg once daily for 2 days. The effects of treatment on clinical outcomes and
V. cholerae
shedding (CFU count in stool) were observed. Immunohistochemical analysis was carried out to assess CAP-18 expression in ileal and jejunal mucosae. The serum zonulin level was measured by an enzyme-linked immunosorbent assay (ELISA) to evaluate gut permeability. Infection of rabbits with
V. cholerae
downregulated CAP-18 expression in the ileal epithelium; the expression was replenished by oral treatment with entinostat at either dose regimen. The level of zonulin, a marker of gut permeability, in serum was upregulated after infection, and this upregulation was counteracted after treatment with entinostat. Entinostat treatment also led to recovery from cholera and a decline in the
V. cholerae
count in stool. In conclusion, the improved clinical outcome of cholera for rabbits treated with entinostat is associated with the induction of CAP-18 and the reduction of gut epithelial permeability.
Regulation of a Glycerol-Induced Quinoprotein Alcohol Dehydrogenase by σ
54
and a LuxR-Type Regulator in Azospirillum brasilense Sp7
Authors: Singh Vijay Shankar , Dubey Ashutosh Prakash , Gupta Ankush , Singh Sudhir , Singh Bhupendra Narain , Tripathi Anil Kumar 
Published: April 2017

ABSTRACT

Azospirillum brasilense
Sp7 uses glycerol as a carbon source for growth and nitrogen fixation. When grown in medium containing glycerol as a source of carbon, it upregulates the expression of a protein which was identified as quinoprotein alcohol dehydrogenase (ExaA). Inactivation of
exaA
adversely affects the growth of
A. brasilense
on glycerol. A determination of the transcription start site of
exaA
revealed an RpoN-dependent −12/−24 promoter consensus. The expression of an
exaA
::
lacZ
fusion was induced maximally by glycerol and was dependent on σ
54
. Bioinformatic analysis of the sequence flanking the −12/−24 promoter revealed a 17-bp sequence motif with a dyad symmetry of 6 nucleotides upstream of the promoter, the disruption of which caused a drastic reduction in promoter activity. The electrophoretic mobility of a DNA fragment containing the 17-bp sequence motif was retarded by purified EraR, a LuxR-type transcription regulator that is transcribed divergently from
exaA
. EraR also showed a positive interaction with RpoN in two-hybrid and pulldown assays.

IMPORTANCE
Quinoprotein alcohol dehydrogenase (ExaA) plays an important role in the catabolism of alcohols in bacteria. Although
exaA
expression is thought to be regulated by a two-component system consisting of EraS and EraR, the mechanism of regulation was not known. This study shows the details of the regulation of expression of the
exaA
gene in
A. brasilense
. We have shown here that
exaA
of
A. brasilense
is maximally induced by glycerol and harbors a σ
54
-dependent promoter. The response regulator EraR binds to an inverted repeat located upstream of the
exaA
promoter. This study shows that a LuxR-type response regulator (EraR) binds upstream of the
exaA
gene and physically interacts with σ
54
. The unique feature of this regulation is that EraR is a LuxR-type transcription regulator that lacks the GAFTGA motif, a characteristic feature of the enhancer binding proteins that are known to interact with σ
54
in other bacteria.
Regulation, Function, and Detection of Protein Acetylation in Bacteria
Authors: Carabetta Valerie J. , Cristea Ileana M. 
Published: April 2017

ABSTRACT

N
ε
-Lysine acetylation is now recognized as an abundant posttranslational modification (PTM) that influences many essential biological pathways. Advancements in mass spectrometry-based proteomics have led to the discovery that bacteria contain hundreds of acetylated proteins, contrary to the prior notion of acetylation events being rare in bacteria. Although the mechanisms that regulate protein acetylation are still not fully defined, it is understood that this modification is finely tuned via both enzymatic and nonenzymatic mechanisms. The opposing actions of Gcn5-related
N
-acetyltransferases (GNATs) and deacetylases, including sirtuins, provide the enzymatic control of lysine acetylation. A nonenzymatic mechanism of acetylation has also been demonstrated and proven to be prominent in bacteria, as well as in mitochondria. The functional consequences of the vast majority of the identified acetylation sites remain unknown. From studies in mammalian systems, acetylation of critical lysine residues was shown to impact protein function by altering its structure, subcellular localization, and interactions. It is becoming apparent that the same diversity of functions can be found in bacteria. Here, we review current knowledge of the mechanisms and the functional consequences of acetylation in bacteria. Additionally, we discuss the methods available for detecting acetylation sites, including quantitative mass spectrometry-based methods, which promise to promote this field of research. We conclude with possible future directions and broader implications of the study of protein acetylation in bacteria.
Use of GeneXpert Remnants for Drug Resistance Profiling and Molecular Epidemiology of Tuberculosis in Libreville, Gabon
Authors: Alame-Emane Amel Kévin , Pierre-Audigier Catherine , Aboumegone-Biyogo Oriane Cordelia , Nzoghe-Mveang Amandine , Cadet-Daniel Véronique , Sola Christophe , Djoba-Siawaya Joël Fleury , Gicquel Brigitte , Takiff Howard E. 
Published: April 2017

ABSTRACT

Multidrug-resistant (MDR) and extensively drug resistant (XDR) strains of
Mycobacterium tuberculosis
pose major problems for global health. The GeneXpert MTB/RIF (Xpert) assay rapidly detects resistance to rifampin (RIF
r
), but for detection of the additional resistance that defines MDR-TB (MDR tuberculosis) and XDR-TB, and for molecular epidemiology, specimen cultures and a biosafe infrastructure are generally required. We sought to determine whether the remnants of sputa prepared for the Xpert assay could be used directly to find mutations associated with drug resistance and to study molecular epidemiology, thus providing precise characterization of MDR-TB cases in countries lacking biosafety level 3 (BSL3) facilities for
M. tuberculosis
cultures. After sputa were processed and run on the Xpert instrument, the leftovers of the samples prepared for the Xpert assay were used for PCR amplification and sequencing or for a line probe assay to detect mutations associated with resistance to additional drugs, as well as for molecular epidemiology with spoligotyping and selective mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) typing. Of 130 sputum samples from Gabon tested with the Xpert assay, 124 yielded interpretable results; 21 (17%) of these were determined to be RIF
r
. Amplification and sequencing or a line probe assay of the Xpert remnants confirmed 18/21 samples as MDR, corresponding to 12/116 (9.5%) new and 6/8 (75%) previously treated TB patients. Spoligotyping and MIRU typing with hypervariable loci identified an MDR Beijing strain present in five samples. We conclude that the remnants of samples processed for the Xpert assay can be used in PCRs to find mutations associated with the resistance to the additional drugs that defines MDR and XDR-TB and to study molecular epidemiology without the need for culturing or a biosafe infrastructure.
Mouse Saliva Inhibits Transit of Influenza Virus to the Lower Respiratory Tract by Efficiently Blocking Influenza Virus Neuraminidase Activity
Authors: Gilbertson Brad , Ng Wy Ching , Crawford Simon , McKimm-Breschkin Jenny L. , Brown Lorena E. 
Published: April 2017

ABSTRACTWe previously identified a novel inhibitor of influenza virus in mouse saliva that halts the progression of susceptible viruses from the upper to the lower respiratory tract of micein vivoand neutralizes viral infectivity in MDCK cells. Here, we investigated the viral target of the salivary inhibitor by using reverse genetics to create hybrid viruses with some surface proteins derived from an inhibitor-sensitive strain and others from an inhibitor-resistant strain. These viruses demonstrated that the origin of the viral neuraminidase (NA), but not the hemagglutinin or matrix protein, was the determinant of susceptibility to the inhibitor. Comparison of the NA sequences of a panel of H3N2 viruses with differing sensitivities to the salivary inhibitor revealed that surface residues 368 to 370 (N2 numbering) outside the active site played a key role in resistance. Resistant viruses contained an EDS motif at this location, and mutation to either EES or KDS, found in highly susceptible strains, significantly increasedin vitrosusceptibility to the inhibitor and reduced the ability of the virus to progress to the lungs when the viral inoculum was initially confined to the upper respiratory tract. In the presence of saliva, viral strains with a susceptible NA could not be efficiently released from the surfaces of infected MDCK cells and had reduced enzymatic activity based on their ability to cleave substratein vitro. This work indicates that the mouse has evolved an innate inhibitor similar in function, though not in mechanism, to what humans have created synthetically as an antiviral drug for influenza virus.IMPORTANCEDespite widespread use of experimental pulmonary infection of the laboratory mouse to study influenza virus infection and pathogenesis, to our knowledge, mice do not naturally succumb to influenza. Here, we show that mice produce their own natural form of neuraminidase inhibitor in saliva that stops the virus from reaching the lungs, providing a possible mechanism through which the species may not experience severe influenza virus infection in the wild. We show that the murine salivary inhibitor targets the outer surface of the influenza virus neuraminidase, possibly occluding entry to the enzymatic site rather than binding within the active site like commercially available neuraminidase inhibitors. This knowledge sheds light on how the natural inhibitors of particular species combat infection.