bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population genomic footprints of fine‐scale differentiation between habitats in Mediterranean blue tits
Authors: Szulkin M. , Gagnaire P.‐A. , Bierne N. , Charmantier A. 
Published: November 2015

AbstractLinking population genetic variation to the spatial heterogeneity of the environment is of fundamental interest to evolutionary biology and ecology, in particular when phenotypic differences between populations are observed at biologically small spatial scales. Here, we applied restriction‐site associated DNA sequencing (RAD‐Seq) to test whether phenotypically differentiated populations of wild blue tits (Cyanistes caeruleus) breeding in a highly heterogeneous environment exhibit genetic structure related to habitat type. Using 12 106 SNPs in 197 individuals from deciduous and evergreen oak woodlands, we applied complementary population genomic analyses, which revealed that genetic variation is influenced by both geographical distance and habitat type. A fine‐scale genetic differentiation supported by genome‐ and transcriptome‐wide analyses was found within Corsica, between two adjacent habitats where blue tits exhibit marked differences in breeding time while nesting < 6 km apart. Using redundancy analysis (RDA), we show that genomic variation remains associated with habitat type when controlling for spatial and temporal effects. Finally, our results suggest that the observed patterns of genomic differentiation were not driven by a small proportion of highly differentiated loci, but rather emerged through a process such as habitat choice, which reduces gene flow between habitats across the entire genome. The pattern of genomic isolation‐by‐environment closely matches differentiation observed at the phenotypic level, thereby offering significant potential for future inference of phenotype‐genotype associations in a heterogeneous environment.
Red fluorescence in coral larvae is associated with a diapause‐like state
Authors: Strader Marie E. , Aglyamova Galina V. , Matz Mikhail V. 
Published: November 2015

AbstractEffective dispersal across environmental gradients is the key to species resilience to environmental perturbation, including climate change. Coral reefs are among the most sensitive ecosystems to global warming, but factors predicting coral dispersal potential remain unknown. In a reef‐building coral Acropora millepora, larval fluorescence emerged as a possible indicator of dispersal potential since it correlates with responsiveness to a settlement cue. Here, we show that gene expression in red fluorescent larvae of A. millepora is correlated with diapause‐like characteristics highly likely to be associated with extended dispersal. We compared gene expression among three larval fluorescent morphs under three coloured light treatments. While colour morphs did not differ in their gene expression responses to light colour, red larvae demonstrated gene expression signatures of cell cycle arrest and decreased transcription accompanied by elevated ribosome production and heightened defenses against oxidative stress. A meta‐analysis revealed that this profile was highly similar to the signatures of elevated thermal tolerance in the same coral species, and moreover, functionally resembled diapause states in an insect and a nematode. Our results support a connection between red fluorescence and long‐range dispersal, which offers a new perspective on the molecular underpinnings of coral larval dispersal and the biological function of GFP‐like fluorescent proteins.
A systematic review to determine the most effective interventions to increase water intake
Authors: Chua Teresa X.W. , Prasad Neha S. , Rangan Gopala K. , Allman‐Farinelli Margaret , Rangan Anna M. 
Published: November 2015

AbstractBackgroundMaintaining adequate fluid intake has been hypothesized to be beneficial for the progression of chronic kidney disease (CKD). The aim of this study was to undertake a systematic review to determine the most effective interventions to increase water intake.MethodsSix electronic databases were searched from 1910 until March 2015 in the English language. Additional sources through hand‐searches, expert recommendations and reviews were checked. Intervention studies increasing water intake in adults through non‐pharmacological methods were eligible for inclusion. The quality of included studies was assessed.ResultsA total of 950 studies were found of which 16 met the inclusion criteria. Eight studies were randomized controlled trials, and seven studies spanned 6 months or longer. The study populations varied and included patients with recurrent nephrolithiasis (n = 6), autosomal dominant polycystic kidney disease (n = 3), CKD (n = 1), urinary tract infection (n = 1) and other miscellaneous conditions (n = 5). The quality of the studies was mostly neutral (63%) with no studies of high quality. Interventions ranged from instruction alone to self‐monitoring tools, providing water bottles and counselling and education. Most interventions successfully increased water intake with 13 studies reporting an increase of at least 500 mL. The most effective strategies were instruction and self‐monitoring using urine dipstick or 24 h urine volume.ConclusionAll interventions carried out in the studies succeeded in increasing water intake, with none leading to decreases in intake, and these could be implemented in potential clinical trials in CKD. However, more high quality long‐term intervention studies are required to further validate findings.
Hypodontia, a prospective predictive marker for tumor?
Authors: Yin W , Bian Z 
Published: November 2015

Tooth agenesis and tumor are two totally different diseases occurring at different ages. In the past 10 years, more and more evidences suggested there was a relationship between them. High prevalence of breast, colon, lung, and ovary tumor was observed in tooth agenesis patients. But it is still controversial. Therefore, to have a greater understanding of the possible association, a critical review on molecular association for genes involving tooth agenesis and tumorigenesis is necessary. In this current review, we summarized the reported cases of tooth agenesis with different kinds of tumors and the molecular relationship between these two diseases through causative genes. The results indicated tooth agenesis might be a prospective predictive marker for tumor. Through this review, we want to draw more attention on this topic and hope it will be an effective way to predict the risk of tumor.
Biogeographic patterns of nutrient resorption from Quercus variabilis Blume leaves across China
Authors: Sun X. , Kang H. , Chen H. Y. H. , Björn B. , Samuel B. F. , Liu C. 
Published: November 2015

AbstractThe variation in nutrient resorption has been studied at different taxonomic levels and geographic ranges. However, the variable traits of nutrient resorption at the individual species level across its distribution are poorly understood. We examined the variability and environmental controls of leaf nutrient resorption of Quercus variabilis, a widely distributed species of important ecological and economic value in China. The mean resorption efficiency was highest for phosphorus (P), followed by potassium (K), nitrogen (N), sulphur (S), magnesium (Mg) and carbon (C). Resorption efficiencies and proficiencies were strongly affected by climate and respective nutrients concentrations in soils and green leaves, but had little association with leaf mass per area. Climate factors, especially growing season length, were dominant drivers of nutrient resorption efficiencies, except for C, which was strongly related to green leaf C status. In contrast, green leaf nutritional status was the primary controlling factor of leaf nutrient proficiencies, except for C. Resorption efficiencies of N, P, K and S increased significantly with latitude, and were negatively related to growing season length and mean annual temperature. In turn, N, P, K and S in senesced leaves decreased with latitude, likely due to their efficient resorption response to variation in climate, but increased for Mg and did not change for C. Our results indicate that the nutrient resorption efficiency and proficiency of Q. variabilis differed strongly among nutrients, as well as growing environments. Our findings provide important insights into understanding the nutrient conservation strategy at the individual species level and its possible influence on nutrient cycling.
Genotypic characterisation of human papillomavirus infections among persons living with HIV infection; a case–control study in Kumasi, Ghana
Authors: Yar Denis Dekugmen , Salifu Samson Pandam , Darko Samuel Nkansah , Annan Augustina Angelina , Gyimah Akosua Adumea , Buabeng Kwame Ohene , Owusu‐Dabo Ellis 
Published: November 2015

AbstractObjectivesThe objective of this study is to describe the burden of human papillomavirus (HPV) infection among women living with HIV and non‐infected women in Ghana.MethodsA case–control study was conducted involving 107 women living with HIV aged between 18 and 59 years (cases) and 100 non‐HIV‐infected apparently healthy women (controls) who were recruited from the Kumasi South Hospital, from July to December, 2014. Cervicovaginal swabs were taken from study participants to characterise 28 high‐ and low‐risk HPV genotypes using a multiplex real‐time PCR.ResultsThe overall mean age for the participants was 40.10 ± 9.76 years. The prevalence of high‐risk (hr)‐HPV genotypes was significantly higher among the cases than the controls (77.4% vs. 41.6%, P < 0.0001). Overall, HPV 58 and 54 were the most predominant high‐risk (18.8%) and low‐risk (15.0%) genotypes detected. The two most common hr‐HPV genotype isolates were 58 (18.8%) and 35 (15.9%) with 58 being the most prevalent among age group 35–44 years compared with hr‐HPV 16, 18, 35 and 45, found predominantly among 18–34 age group.ConclusionsSignificant variations exist in HPV genotypes among HIV‐infected and uninfected women.
Cord blood banking and quality issues
Authors: Murphy Amanda , McKenna David , McCullough Jeffrey 
Published: November 2015

BACKGROUNDFood and Drug Administration guidelines are designed to assure the quality and safety of the cord blood product used for transplantation. It is valuable to determine whether the actions called for in these guidelines are effective.STUDY DESIGN AND METHODSWe applied our cell therapy quality system to all cord blood units shipped into our cellular therapy laboratory for transplant at the University of Minnesota between 2011 and 2013. The quality issues were categorized as likely, potentially, or unlikely to have a clinical impact.RESULTSA total of 249 units of umbilical cord blood (UCB) were received from 16 cord blood banks. A total of 159 units (64%) had a total of 245 issues. Of these, 117 (48%) pertained to medical history, 120 (49%) to quality control, and eight (3%) to labeling and documentation. Units with quality issues were no more likely to fail to engraft, and no specific kind of quality issue was associated with failure to engraft. Compared to a similar study 10 years ago, there was a decrease in the number of issues per unit.DISCUSSIONThe cost of collecting, testing, processing, and storing UCB is very high. However, there may be activities that do not contribute to the quality or safety of the cord blood. The guidelines could be reviewed to determine their value based on years of experience.
Sympathetic‐mediated activation versus suppression of the immune system: consequences for hypertension
Authors: Case Adam J. , Zimmerman Matthew C. 
Published: November 2015

AbstractIt is generally well‐accepted that the immune system is a significant contributor in the pathogenesis of hypertension. Specifically, activated and pro‐inflammatory T‐lymphocytes located primarily in the vasculature and kidneys appear to have a causal role in exacerbating elevated blood pressure. It has been proposed that increased sympathetic nerve activity and noradrenaline outflow associated with hypertension may be primary contributors to the initial activation of the immune system early in the disease progression. However, it has been repeatedly demonstrated in many different human and experimental diseases that sympathoexcitation is immunosuppressive in nature. Moreover, human hypertensive patients have demonstrated increased susceptibility to secondary immune insults like infections. Thus, it is plausible, and perhaps even likely, that in diseases like hypertension, specific immune cells are activated by increased noradrenaline, while others are in fact suppressed. We propose a model in which this differential regulation is based upon activation status of the immune cell as well as the resident organ. With this, the concept of global immunosuppression is obfuscated as a viable target for hypertension treatment, and we put forth the concept of focused organ‐specific immunotherapy as an alternative option.
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Mutant Alleles of
lptD
Increase the Permeability of Pseudomonas aeruginosa and Define Determinants of Intrinsic Resistance to Antibiotics
Authors: Balibar Carl J. , Grabowicz Marcin 
Published: November 2015

ABSTRACT

Gram-negative bacteria provide a particular challenge to antibacterial drug discovery due to their cell envelope structure. Compound entry is impeded by the lipopolysaccharide (LPS) of the outer membrane (OM), and those molecules that overcome this barrier are often expelled by multidrug efflux pumps. Understanding how efflux and permeability affect the ability of a compound to reach its target is paramount to translating
in vitro
biochemical potency to cellular bioactivity. Herein, a suite of
Pseudomonas aeruginosa
strains were constructed in either a wild-type or efflux-null background in which mutations were engineered in LptD, the final protein involved in LPS transport to the OM. These mutants were demonstrated to be defective in LPS transport, resulting in compromised barrier function. Using isogenic strain sets harboring these newly created alleles, we were able to define the contributions of permeability and efflux to the intrinsic resistance of
P. aeruginosa
to a variety of antibiotics. These strains will be useful in the design and optimization of future antibiotics against Gram-negative pathogens.
Mechanism of Action of ME1111, a Novel Antifungal Agent for Topical Treatment of Onychomycosis
Authors: Takahata Sho , Kubota Natsuki , Takei-Masuda Naomi , Yamada Tsuyoshi , Maeda Mari , Alshahni Mohamed Mahdi , Abe Shigeru , Tabata Yuji , Maebashi Kazunori 
Published: November 2015

ABSTRACT

Despite the existing treatment options for onychomycosis, there remains a strong demand for potent topical medications. ME1111 is a novel antifungal agent that is active against dermatophytes, has an excellent ability to penetrate human nails, and is being developed as a topical agent for onychomycosis. In the present study, we investigated its mechanism of action.
Trichophyton mentagrophytes
mutants with reduced susceptibility to ME1111 were selected in our laboratory, and genome sequences were determined for 3 resistant mutants. The inhibitory effect on a candidate target was evaluated by a spectrophotometric enzyme assay using mitochondrial fractions. Point mutations were introduced into candidate genes by a reverse genetics approach. Whole-genome analysis of the 3 selected mutants revealed point mutations in the structural regions of genes encoding subunits of succinate dehydrogenase (complex II). All of the laboratory-generated resistant mutants tested harbored a mutation in one of the subunits of succinate dehydrogenase (SdhB, SdhC, or SdhD). Most of the mutants showed cross-resistance to carboxin and boscalid, which are succinate dehydrogenase inhibitors. ME1111 strongly inhibited the succinate-2,6-dichlorophenolindophenol reductase reaction in
Trichophyton rubrum
and
T. mentagrophytes
(50% inhibitory concentrations [IC
50
s] of 0.029 and 0.025 μg/ml, respectively) but demonstrated only moderate inhibition of the same reaction in human cell lines. Furthermore, the target protein of ME1111 was confirmed by the introduction of point mutations causing the amino acid substitutions in SdhB, SdhC, and SdhD found in the laboratory-generated resistant mutants, which resulted in reduced susceptibility to ME1111. Thus, ME1111 is a novel inhibitor of the succinate dehydrogenase of
Trichophyton
species, and its mechanism of action indicates its selective profile.
Evaluating 5-Nitrothiazoles as Trypanocidal Agents
Authors: O'Shea Ivan P. , Shahed Mohammed , Aguilera-Venegas Benjamín , Wilkinson Shane R. 
Published: November 2015

ABSTRACT

The growth-inhibitory properties of a 5-nitrothiazole series were evaluated against
Trypanosoma brucei
. A subset of related compounds displayed the greatest potency toward the parasite while exhibiting little cytotoxic effect on mammalian cells, with this antiparasitic activity dependent on expression of a type I nitroreductase by the trypanosome. We conclude that the 5-nitrothiazole class of nitroheterocyclic drugs may represent a new lead in the treatment of human African trypanosomiasis.
Antagonism of Fluconazole and a Proton Pump Inhibitor against Candida albicans
Authors: Liu Ning-Ning , Köhler Julia R. 
Published: November 2015

ABSTRACT

Hospitalized ill patients, at risk for invasive candidiasis, often receive multiple medications, including proton pump inhibitors (PPIs). The antifungal fluconazole perturbs the vacuolar proton ATPase. The PPI omeprazole antagonized
Candida albicans
growth inhibition by fluconazole. A
C. albicans
codon-adapted pHluorin, Ca.pHluorin, was generated to measure cytosolic pH. The fungal cytosol was acidified by omeprazole and realkalinized by coexposure to fluconazole. Vacuolar pH was alkalinized by fluconazole. Off-target effects of any medication on fungal pathogens may occur.
Exposing a β-Lactamase “Twist”: the Mechanistic Basis for the High Level of Ceftazidime Resistance in the C69F Variant of the Burkholderia pseudomallei PenI β-Lactamase
Authors: Papp-Wallace Krisztina M. , Becka Scott A. , Taracila Magdalena A. , Winkler Marisa L. , Gatta Julian A. , Rholl Drew A. , Schweizer Herbert P. , Bonomo Robert A. 
Published: November 2015

ABSTRACT

Around the world,
Burkholderia
spp. are emerging as pathogens highly resistant to β-lactam antibiotics, especially ceftazidime. Clinical variants of
Burkholderia pseudomallei
possessing the class A β-lactamase PenI with substitutions at positions C69 and P167 are known to demonstrate ceftazidime resistance. However, the biochemical basis for ceftazidime resistance in class A β-lactamases in
B. pseudomallei
is largely undefined. Here, we performed site saturation mutagenesis of the C69 position and investigated the kinetic properties of the C69F variant of PenI from
B. pseudomallei
that results in a high level of ceftazidime resistance (2 to 64 mg/liter) when expressed in
Escherichia coli
. Surprisingly, quantitative immunoblotting showed that the steady-state protein levels of the C69F variant β-lactamase were ∼4-fold lower than those of wild-type PenI (0.76 fg of protein/cell versus 4.1 fg of protein/cell, respectively). However, growth in the presence of ceftazidime increases the relative amount of the C69F variant to greater than wild-type PenI levels. The C69F variant exhibits a branched kinetic mechanism for ceftazidime hydrolysis, suggesting there are two different conformations of the enzyme. When incubated with an anti-PenI antibody, one conformation of the C69F variant rapidly hydrolyzes ceftazidime and most likely contributes to the higher levels of ceftazidime resistance observed in cell-based assays. Molecular dynamics simulations suggest that the electrostatic characteristics of the oxyanion hole are altered in the C69F variant. When ceftazidime was positioned in the active site, the C69F variant is predicted to form a greater number of hydrogen-bonding interactions than PenI with ceftazidime. In conclusion, we propose “a new twist” for enhanced ceftazidime resistance mediated by the C69F variant of the PenI β-lactamase based on conformational changes in the C69F variant. Our findings explain the biochemical basis of ceftazidime resistance in
B. pseudomallei
, a pathogen of considerable importance, and suggest that the full repertoire of conformational states of a β-lactamase profoundly affects β-lactam resistance.
Potential of Tetracycline Resistance Proteins To Evolve Tigecycline Resistance
Authors: Linkevicius Marius , Sandegren Linus , Andersson Dan I. 
Published: November 2015

ABSTRACT

Tigecycline is a glycylcycline antibiotic active against multidrug-resistant bacterial pathogens. The objectives of our study were to examine the potential of the Tet(A), Tet(K), Tet(M), and Tet(X) tetracycline resistance proteins to acquire mutations causing tigecycline resistance and to determine how this affects resistance to earlier classes of tetracyclines. Mutations in all four
tet
genes caused a significant increase in the tigecycline MIC in
Escherichia coli
, and strains expressing mutant Tet(A) and Tet(X) variants reached clinically relevant MICs (2 mg/liter and 3 mg/liter, respectively). Mutations predominantly accumulated in transmembrane domains of the efflux pumps, most likely increasing the accommodation of tigecycline as a substrate. All selected Tet(M) mutants contained at least one mutation in the functionally most important loop III of domain IV. Deletion of leucine 505 of this loop led to the highest increase of the tigecycline MIC (0.5 mg/liter) among Tet(M) mutants. It also caused collateral sensitivity to earlier classes of tetracyclines. A majority of the Tet(X) mutants showed increased activity against all three classes of tetracylines. All tested Tet proteins have the potential to acquire mutations leading to increased MICs of tigecycline. As
tet
genes are widely found in pathogenic bacteria and spread easily by horizontal gene transfer, resistance development by alteration of existing Tet proteins might compromise the future medical use of tigecycline. We predict that Tet(X) might become the most problematic future Tet determinant, since its weak intrinsic tigecycline activity can be mutationally improved to reach clinically relevant levels without collateral loss in activity to other tetracyclines.