bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered Expression of Transforming Growth Factor‐Beta Isoforms in Bovine Cystic Ovarian Disease
Authors: Matiller V , Stangaferro ML , Díaz PU , Ortega HH , Rey F , Huber E , Salvetti NR 
Published: August 2014

ContentsCystic ovarian disease (COD) is one of the main causes of infertility in dairy cattle. It has been shown that intra‐ovarian factors may contribute to follicular persistence. Transforming growth factor‐beta (TGFB) isoforms are important paracrine and autocrine signalling molecules that regulate ovarian follicle growth and physiology. Considering the importance of these factors in the ovarian physiology, in this study, we examined the expression of TGFB isoforms (TGFB1, TGFB2 and TGFB3) in the ovary of healthy cows and animals with spontaneous and adrenocorticotrophic hormone (ACTH)‐induced COD. In the oestrous‐synchronized control group, the expression of TGFB1 in granulosa and theca cells was higher in spontaneous cysts than in atretic or tertiary follicles. When we compared TGFB2 expression in granulosa cells from atretic or tertiary follicles from the oestrous‐synchronized control group with that in ACTH‐induced or spontaneous follicular cysts, we found a higher expression in the latter. The expression of the TGFB isoforms studied was also altered during folliculogenesis in both the spontaneous and ACTH‐induced COD groups. As it has been previously shown that TGFB influences steroidogenesis, ovarian follicular proliferation and apoptosis, an alteration in its expression may contribute to the pathogenesis of this disease.
Identity, Causality, and Pronoun Ambiguity
Authors: Sagi Eyal , Rips Lance J. 
Published: August 2014

AbstractThis article looks at the way people determine the antecedent of a pronoun in sentence pairs, such as: Albert invited Ron to dinner. He spent hours cleaning the house. The experiment reported here is motivated by the idea that such judgments depend on reasoning about identity (e.g., the identity of the he who cleaned the house). Because the identity of an individual over time depends on the causal‐historical path connecting the stages of the individual, the correct antecedent will also depend on causal connections. The experiment varied how likely it is that the event of the first sentence (e.g., the invitation) would cause the event of the second (the house cleaning) for each of the two individuals (the likelihood that if Albert invited Ron to dinner, this would cause Albert to clean the house, versus cause Ron to clean the house). Decisions about the antecedent followed causal likelihood. A mathematical model of causal identity accounted for most of the key aspects of the data from the individual sentence pairs.
Assessment and Monitoring of Ballistic and Maximal Upper-Body Strength Qualities in Athletes
Authors: Young Kieran P. , Haff G. Gregory , Newton Robert U. , Gabbett Tim J. , Sheppard Jeremy M. 
Published: August 2014

Purpose:To evaluate whether the dynamic strength index (DSI: ballistic peak force/isometric peak force) could be effectively used to guide specific training interventions and detect training-induced changes in maximal and ballistic strength.Methods:Twenty-four elite male athletes were assessed in the isometric bench press and a 45% 1-repetition-maximum (1RM) ballistic bench throw using a force plate and linear position transducer. The DSI was calculated using the peak force values obtained during the ballistic bench throw and isometric bench press. Athletes were then allocated into 2 groups as matched pairs based on their DSI and strength in the 1RM bench press. Over the 5 wk of training, athletes performed either high-load (80–100% 1RM) bench press or moderate-load (40–55% 1RM) ballistic bench throws.Results:The DSI was sensitive to disparate training methods, with the bench-press group increasing isometric bench-press peak force (P = .035, 91% likely), and the ballistic-bench-throw group increasing bench-throw peak force to a greater extent (P ≤ .001, 83% likely). A significant increase (P ≤ .001, 93% likely) in the DSI was observed for both groups.Conclusions:The DSI can be used to guide specific training interventions and can detect training-induced changes in isometric bench-press and ballistic bench-throw peak force over periods as short as 5 wk.
Effects of a Very Congested Match Schedule on Body-Load Impacts, Accelerations, and Running Measures in Youth Soccer Players
Authors: Arruda Ademir F.S. , Carling Christopher , Zanetti Vinicius , Aoki Marcelo S. , Coutts Aaron J. , Moreira Alexandre 
Published: August 2014

Purpose:To analyze the effects of a very congested match schedule on the total distance (TD) covered, high-intensity-running (HIR) distance, and frequency of accelerations and body-load impacts (BLIs) performed in a team of under-15 soccer players (N = 10; 15.1 ± 0.2 y, 171.8 ± 4.7 cm, 61 ± 6.0 kg) during an international youth competition.Methods:Using global positioning systems, player performances were repeatedly monitored in 5 matches performed over 3 successive days.Results:Significant differences were observed between matches (P < .05) for the frequency of accelerations per minute, BLIs, and BLIs per minute. No differences were observed for the TD covered, TD run per minute, number of high-intensity runs, distance covered in HIR, per-minute peak running speed attained, or frequency of accelerations. The frequency of accelerations per minute decreased across the competition while BLIs were higher during the final than in all other matches.Conclusions:These results suggest that BLIs and acceleration might be used as an alternative means to represent the external load during congested match schedules rather than measures related to running speed or distance covered.
Ascorbate Peroxidase, a Key Molecule Regulating Amphotericin B Resistance in Clinical Isolates of Leishmania donovani
Authors: Kumar Ashish , Das Sushmita , Purkait Bidyut , Sardar Abul Hasan , Ghosh Ayan Kumar , Dikhit Manas Ranjan , Abhishek Kumar , Das Pradeep 
Published: August 2014

ABSTRACT

Amphotericin B (AmB), a polyene macrolide, is now a first-line treatment of visceral leishmaniasis cases refractory to antimonials in India. AmB relapse cases and the emergence of secondary resistance have now been reported. To understand the mechanism of AmB, differentially expressed genes in AmB resistance strains were identified by a DNA microarray and real-time reverse transcriptase PCR (RT-PCR) approach. Of the many genes functionally overexpressed in the presence of AmB, the ascorbate peroxidase gene from a resistant
Leishmania donovani
strain (LdAPx gene) was selected because the gene is present only in
Leishmania
, not in humans. Apoptosis-like cell death after exposure to AmB was investigated in a wild-type (WT) strain in which the LdAPx gene was overexpressed and in AmB-sensitive and -resistant strains. A higher percentage of apoptosis-like cell death after AmB treatment was noticed in the sensitive strain than in both the resistant isolate and the strain sensitive to LdAPx overexpression. This event is preceded by AmB-induced formation of reactive oxygen species and elevation of the cytosolic calcium level. Enhanced cytosolic calcium was found to be responsible for depolarization of the mitochondrial membrane potential and the release of cytochrome
c
(Cyt
c
) into the cytosol. The redox behavior of Cyt
c
showed that it has a role in the regulation of apoptosis-like cell death by activating metacaspase- and caspase-like proteins and causing concomitant nuclear alterations, as determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) and DNA fragmentation in the resistant strain. The present study suggests that constitutive overexpression of LdAPx in the
L. donovani
AmB-resistant strain prevents cells from the deleterious effect of oxidative stress, i.e., mitochondrial dysfunction and cellular death induced by AmB.
Evolution of Oseltamivir Resistance Mutations in Influenza A(H1N1) and A(H3N2) Viruses during Selection in Experimentally Infected Mice
Authors: Pizzorno Andrés , Abed Yacine , Plante Pier-Luc , Carbonneau Julie , Baz Mariana , Hamelin Marie-Ève , Corbeil Jacques , Boivin Guy 
Published: August 2014

ABSTRACTThe evolution of oseltamivir resistance mutations during selection through serial passages in animals is still poorly described. Herein, we assessed the evolution of neuraminidase (NA) and hemagglutinin (HA) genes of influenza A/WSN/33 (H1N1) and A/Victoria/3/75 (H3N2) viruses recovered from the lungs of experimentally infected BALB/c mice receiving suboptimal doses (0.05 and 1 mg/kg of body weight/day) of oseltamivir over two generations. The traditional phenotypic and genotypic methods as well as deep-sequencing analysis were used to characterize the potential selection of mutations and population dynamics of oseltamivir-resistant variants. No oseltamivir-resistant NA or HA changes were detected in the recovered A/WSN/33 viruses. However, we observed a positive selection of the I222T NA substitution in the recovered A/Victoria/3/75 viruses, with a frequency increasing over time and with an oseltamivir concentration from 4% in the initial pretherapy inoculum up to 28% after two lung passages. Although the presence of mixed I222T viral populations in mouse lungs only led to a minimal increase in oseltamivir 50% enzyme-inhibitory concentrations (IC50s) (by a mean of 5.7-fold) compared to that of the baseline virus, the expressed recombinant A/Victoria/3/75 I222T NA protein displayed a 16-fold increase in the oseltamivir IC50level compared to that of the recombinant wild type (WT). In conclusion, the combination of serialin vivopassages under neuraminidase inhibitor (NAI) pressure and temporal deep-sequencing analysis enabled, for the first time, the identification and selection of the oseltamivir-resistant I222T NA mutation in an influenza H3N2 virus. Additionalin vivoselection experiments with other antivirals and drug combinations might provide important information on the evolution of antiviral resistance in influenza viruses.
Pharmacokinetics ofpara-Aminosalicylic Acid in HIV-Uninfected and HIV-Coinfected Tuberculosis Patients Receiving Antiretroviral Therapy, Managed for Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis
Authors: de Kock Lizanne , Sy Sherwin K. B. , Rosenkranz Bernd , Diacon Andreas H. , Prescott Kim , Hernandez Kenneth R. , Yu Mingming , Derendorf Hartmut , Donald Peter R. 
Published: August 2014

ABSTRACTThe emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR)Mycobacterium tuberculosisprompted the reintroduction ofpara-aminosalicylic acid (PAS) to protect companion anti-tuberculosis drugs from additional acquired resistance. In sub-Saharan Africa, MDR/XDR tuberculosis with HIV coinfection is common, and concurrent treatment of HIV infection and MDR/XDR tuberculosis is required. Out of necessity, patients receive multiple drugs, and PAS therapy is frequent; however, neither potential drug interactions nor the effects of HIV infection are known. Potential drug-drug interaction with PAS and the effect of HIV infection was examined in 73 pulmonary tuberculosis patients; 22 (30.1%) were HIV coinfected. Forty-one pulmonary MDR or XDR tuberculosis patients received 4 g PAS twice daily, and in a second crossover study, another 32 patients were randomized, receiving 4 g PAS twice daily or 8 g PAS once daily. A PAS population pharmacokinetic model in two dosing regimens was developed; potential covariates affecting its pharmacokinetics were examined, and Monte Carlo simulations were conducted evaluating the pharmacokinetic-pharmacodynamic index. The probability of target attainment (PTA) to maintain PAS levels above MIC during the dosing interval was estimated by simulation of once-, twice-, and thrice-daily dosing regimens not exceeding 12 g daily. Concurrent efavirenz (EFV) medication resulted in a 52% increase in PAS clearance and a corresponding >30% reduction in mean PAS area under the concentration curve in 19 of 22 HIV-M. tuberculosis-coinfected patients. Current practice recommends maintenance of PAS concentrations at ≥1 μg/ml (the MIC ofM. tuberculosis), but the model predicts that at only a minimum dose of 4 g twice daily can this PTA be achieved in at least 90% of the population, whether or not EFV is concomitantly administered. Once-daily dosing of 12 g PAS will not provide PAS concentrations exceeding the MIC over the entire dosing interval if coadministered with EFV, while 4 g twice daily ensures concentrations exceeding MIC over the entire dosing interval, even in HIV-infected patients who received EFV.
Chloroquine Has a Cytotoxic Effect on Acanthamoeba Encystation through Modulation of Autophagy
Authors: Jha Bijay Kumar , Jung Hui-Jung , Seo Incheol , Kim Hyun Ah , Suh Seong-Il , Suh Min-Ho , Baek Won-Ki 
Published: August 2014

ABSTRACT

Encystation of
Acanthamoeba castellanii
is associated with resistance to chemotherapeutic agents. Blocking the encystation process could potentiate the efficacy of chemotherapeutic agents and biocides. During encystation, autophagy is highly stimulated and required for proper encystation of
Acanthamoeba
. In this study, the cytotoxic effect of chloroquine, a well-known autophagy-inhibitory drug, was tested in
A. castellanii
. Chloroquine was able to selectively reduce cell survival during the encystation of
A. castellanii
. However,
A. castellanii
trophozoites and mature cysts were resistant to chloroquine. Chloroquine treatment led to an increase in the number and size of lysosomes in encysting cells. Moreover, chloroquine inhibited the degradation of long-lived proteins in the encysting cells. Decreased autophagic flux, indicated by an increased number of lysosomes and decreased degradation of long-lived proteins, may be the mechanism by which cell death is induced by chloroquine in encysting
Acanthamoeba
. These results suggest a potential novel therapeutic application of chloroquine as an anti-
Acanthamoeba
drug. Our findings also suggest that targeting autophagy could be a therapeutic strategy against
Acanthamoeba
infection.
Comparison of the Antibiotic Activities of Daptomycin, Vancomycin, and the Investigational Fluoroquinolone Delafloxacin against Biofilms from Staphylococcus aureus Clinical Isolates
Authors: Siala Wafi , Mingeot-Leclercq Marie-Paule , Tulkens Paul M. , Hallin Marie , Denis Olivier , Van Bambeke Françoise 
Published: August 2014

ABSTRACT

Biofilm-related infections remain a scourge. In an
in vitro
model of biofilms using
Staphylococcus aureus
reference strains, delafloxacin and daptomycin were found to be the most active among the antibiotics from 8 different pharmacological classes (J. Bauer, W. Siala, P. M. Tulkens, and F. Van Bambeke, Antimicrob. Agents Chemother. 57:2726–2737, 2013, doi:10.1128/AAC.00181-13). In this study, we compared delafloxacin to daptomycin and vancomycin using biofilms produced by 7 clinical strains (
S. aureus
epidemic clones CC5 and CC8) in order to rationalize the differences observed between the antibiotics and strains. The effects of the antibiotics on bacterial viability (resazurin reduction assay) and biomass (crystal violet staining) were measured and correlated with the proportion of polysaccharides in the matrix, the local microenvironmental pH (micro-pH), and the antibiotic penetration in the biofilm. At clinically meaningful concentrations, delafloxacin, daptomycin, and vancomycin caused a ≥25% reduction in viability against the biofilms formed by 5, 4, and 3 strains, respectively. The antibiotic penetration within the biofilms ranged from 0.6 to 52% for delafloxacin, 0.2 to 10% for daptomycin, and 0.2 to 1% for vancomycin; for delafloxacin, this was inversely related to the polysaccharide proportion in the matrix. Six biofilms were acidic, explaining the high potency of delafloxacin (lower MICs at acidic pH). Norspermidine and norspermine (disassembling the biofilm matrix) drastically increased delafloxacin potency and efficacy (50% reduction in viability for 6 biofilms at clinically meaningful concentrations) in direct correlation with its increased penetration within the biofilm, while they only modestly improved daptomycin efficacy (50% reduction in viability for 2 biofilms) and penetration, and they showed marginal effects with vancomycin. Delafloxacin potency and efficacy against biofilms are benefited by its penetration into the matrix and the local acidic micro-pH.
Identification of Acinetobacter baumannii Serum-Associated Antibiotic Efflux Pump Inhibitors
Authors: Blanchard Catlyn , Barnett Pamela , Perlmutter Jessamyn , Dunman Paul M. 
Published: August 2014

ABSTRACT

Adaptive antibiotic resistance is a newly described phenomenon by which
Acinetobacter baumannii
induces efflux pump activity in response to host-associated environmental cues that may, in part, account for antibiotic treatment failures against clinically defined susceptible strains. To that end, during adaptation to growth in human serum, the organism induces approximately 22 putative efflux-associated genes and displays efflux-mediated minocycline tolerance at antibiotic concentrations corresponding to patient serum levels. Here, we show that in addition to minocycline, growth in human serum elicits
A. baumannii
efflux-mediated tolerance to the antibiotics ciprofloxacin, meropenem, tetracycline, and tigecycline. Moreover, using a whole-cell high-throughput screen and secondary assays, we identified novel serum-associated antibiotic efflux inhibitors that potentiated the activities of antibiotics toward serum-grown
A. baumannii
. Two compounds,

A

cinetobacter

b

aumannii
e
fflux
p
ump
i
nhibitor 1 (ABEPI1) [(
E
)-4-((4-chlorobenzylidene)amino)benezenesulfonamide] and ABEPI2 [
N
-tert-butyl-2-(1-tert-butyltetrazol-5-yl)sulfanylacetamide], were shown to lead to minocycline accumulation within
A. baumannii
during serum growth and inhibit the efflux potential of the organism. While both compounds also inhibited the antibiotic efflux properties of the bacterial pathogen
Pseudomonas aeruginosa
, they did not display significant cytotoxicity toward human cells or mammalian Ca
2+
channel inhibitory effects, suggesting that ABEPI1 and ABEPI2 represent promising structural scaffolds for the development of new classes of bacterial antibiotic efflux pump inhibitors that can be used to potentiate the activities of current and future antibiotics for the therapeutic intervention of Gram-negative bacterial infections.
Epithelial Innate Immune Response to Acinetobacter baumannii Challenge
Authors: Feng Zhimin , Jia Xun , Adams Mark D. , Ghosh Santosh K. , Bonomo Robert A. , Weinberg Aaron 
Published: August 2014

ABSTRACT

Currently,
Acinetobacter baumannii
is recognized as one of the major pathogens seriously threatening our health care delivery system. Aspects of the innate immune response to
A. baumannii
infection are not yet well understood. Human β-defensins (hBDs) are epithelial cell-derived cationic antimicrobial peptides (AMPs) that also function to bridge the innate and adaptive immune system. We tested the induction of hBD-2 and -3 by
A. baumannii
on primary oral and skin epithelial cells and found that
A. baumannii
induces hBD-3 transcripts to a greater extent than it induces hBD-2 transcripts on both types of cells. In addition, we found that
A. baumannii
is susceptible to hBD-2 and -3 killing at submicromolar concentrations. Moreover, hBD-3 induction by
A. baumannii
was found to be dependent on epidermal growth factor receptor (EGFR) signaling. Inhibition of mitogen-activated protein kinase resulted in reduced expression of both hBD-2 and -3. Lastly, a disintegrin and metalloprotease 17 (ADAM17; also known as TACE) was found to be critical for hBD-3 induction, while ADAM10 and dual oxidase 1 (Duox1) were not required for hBD-3 induction. Induction of AMPs is an important component of innate sensing of pathogens and may play an important role in triggering systemic immune responses to
A. baumannii
infection. Further studies on the interactions between epithelial cells and
A. baumannii
will help us understand early stages of infection and may shed light on why some individuals are more vulnerable to
A. baumannii
infection.
Polymorphonuclear Leukocytes Restrict Growth of Pseudomonas aeruginosa in the Lungs of Cystic Fibrosis Patients
Authors: Kragh Kasper N. , Alhede Morten , Jensen Peter Ø. , Moser Claus , Scheike Thomas , Jacobsen Carsten S. , Seier Poulsen Steen , Eickhardt-Sørensen Steffen Robert , Trøstrup Hannah , Christoffersen Lars , Hougen Hans-Petter , Rickelt Lars F. , Kühl Michael , Høiby Niels , Bjarnsholt Thomas 
Published: August 2014

ABSTRACT

Cystic fibrosis (CF) patients have increased susceptibility to chronic lung infections by
Pseudomonas aeruginosa
, but the ecophysiology within the CF lung during infections is poorly understood. The aim of this study was to elucidate the
in vivo
growth physiology of
P. aeruginosa
within lungs of chronically infected CF patients. A novel, quantitative peptide nucleic acid (PNA) fluorescence
in situ
hybridization (PNA-FISH)-based method was used to estimate the
in vivo
growth rates of
P. aeruginosa
directly in lung tissue samples from CF patients and the growth rates of
P. aeruginosa
in infected lungs in a mouse model. The growth rate of
P. aeruginosa
within CF lungs did not correlate with the dimensions of bacterial aggregates but showed an inverse correlation to the concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A growth-limiting effect on
P. aeruginosa
by PMNs was also observed
in vitro
, where this limitation was alleviated in the presence of the alternative electron acceptor nitrate. The finding that
P. aeruginosa
growth patterns correlate with the number of surrounding PMNs points to a bacteriostatic effect by PMNs via their strong O
2
consumption, which slows the growth of
P. aeruginosa
in infected CF lungs. In support of this, the growth of
P. aeruginosa
was significantly higher in the respiratory airways than in the conducting airways of mice. These results indicate a complex host-pathogen interaction in chronic
P. aeruginosa
infection of the CF lung whereby PMNs slow the growth of the bacteria and render them less susceptible to antibiotic treatment while enabling them to persist by anaerobic respiration.
Human Monocyte Subsets at Homeostasis and Their Perturbation in Numbers and Function in Filarial Infection
Authors: Tolouei Semnani Roshanak , Moore Vanessa , Bennuru Sasisekhar , McDonald-Fleming Renee , Ganesan Sundar , Cotton Rachel , Anuradha Rajamanickam , Babu Subash , Nutman Thomas B. 
Published: August 2014

ABSTRACTTo characterize the function and plasticity of the major human circulating monocyte populations and to explore their role in systemic helminth infection, highly purified (by flow-based sorting) human monocyte subsets (CD14hi/CD16neg[classical], CD14+ or hi/CD16med[intermediate], and CD14neg/CD16hi[nonclassical]) were examined at homeostasis and after activation. Among these three subsets the classical and intermediate subsets were found to be the major sources of inflammatory and regulatory cytokines, as well as cytokines/chemokines associated with alternative activation, whereas the nonclassical and classical populations demonstrated an ability to transmigrate through endothelial monolayers. Moreover, it was primarily the classical subset that was the most efficient in promoting autologous T cell proliferation. The distribution of these subsets changed in the context of a systemic helminth (Wuchereria bancrofti) infection such that patent infection altered the frequency and distribution of these monocyte subsets with the nonclassical monocytes being expanded (almost 2-fold) in filarial infection. To understand further the filarial/monocyte interface,in vitromodeling demonstrated that the classical subset internalized filarial antigens more efficiently than the other two subsets but that the parasite-driven regulatory cytokine interleukin-10 was exclusively coming from the intermediate subset. Our data suggest that monocyte subsets have a differential function at homeostasis and in response to helminth parasites.