bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of phylogenetic signal in the germination ability of Phelipanche ramosa on Brassicaceae hosts
Authors: Gibot‐Leclerc S , Perronne R , Dessaint F , Reibel C , Le corre V 
Published: August 2016

SummaryPhelipanche ramosa is a generalist parasitic weed known to cause yield losses in various crops, especially in winter oilseed rape, its new preferred host in France. This parasitic plant is also able to complete its life cycle on many Brassicaceae weeds, which are thus important alternative hosts. We studied a set of 14 common Brassicaceae weeds and characterised their ability to induce the germination of three genetically distinct pathovars of P. ramosa, based on in vitro experiments. We then investigated whether phylogenetic relatedness among Brassicaceae weeds could inform on their ability to induce germination of P. ramosa by testing for a phylogenetic signal in the germination rate of the parasite. In the presence of some phylogenetic signal, phylogenetic distances among species might be used as a surrogate to predict the ability to induce germination of potential additional Brassicaceae hosts. The three pathovars studied showed different germination patterns. Moreover, we found substantial variation in the germination rate of P. ramosa among the different Brassicaceae species, with a significant effect of the clustering of species into two ancient phylogenetic lineages. However, no significant phylogenetic signal was detected overall, that is we could not exclude that germination rates were randomly distributed over the phylogeny. We suggest that further analyses should be conducted across wider sets of potential hosts to better characterise the existence of a phylogenetic signal of the ability of weeds to induce the germination of P. ramosa.
Weed species composition of conventional soyabean crops in Hungary is determined by environmental, cultural, weed management and site variables
Authors: Pinke G , Blazsek K , Magyar L , Nagy K , Karácsony P , Czúcz B , Botta‐Dukát Z 
Published: August 2016

SummaryThe goal of this study was to identify factors determining weed species composition in soyabean crops in Hungary, where its expanding production faces difficult weed problems. The abundance of weed flora was measured in 262 fields across the country, along with 38 background variables. Using a minimal adequate model containing 24 terms with significant net effects, 21.6% of the total variation in weed species data could be explained. Plot location (edge vs core position, the single site variable in our analysis) was found to be the most important explanatory variable that was followed by a set of environmental (temperature, precipitation, altitude, soil texture, pH, Ca, K, Na and humus content), cultural (cultivar maturity, organic manure, fertiliser P and N, row spacing) and weed management (flumioxazin, pendimethalin, dimethenamid, propaquizafop, bentazone, quizalofop‐p‐ethyl, quizalofop‐p‐tefuril, linuron, thifensulfuron) factors. Variation partitioning revealed that environmental variables accounted for about four times more variance than cultural and about two and half times more than weed management variables. Chenopodium album, Ambrosia artemisiifolia, Hibiscus trionum, Echinochloa crus‐galli and Convolvulus arvensis were the most dominant and frequent weeds, but their abundance was influenced by different factors. The responses of weed species to the studied variables provide new information about their ecological behaviour, and our findings also can be used to develop better weed management strategies.
The relative contributions of store‐operated and voltage‐gated Ca2+ channels to the control of Ca2+ oscillations in airway smooth muscle
Authors: Boie Sebastian , Chen Jun , Sanderson Michael J. , Sneyd James 
Published: August 2016

Key points
Agonist‐dependent oscillations in the concentration of free cytosolic calcium are a vital mechanism for the control of airway smooth muscle contraction and thus are a critical factor in airway hyper‐responsiveness.
Using a mathematical model, closely tied to experimental work, we show that the oscillations in membrane potential accompanying the calcium oscillations have no significant effect on the properties of the calcium oscillations.
In addition, the model shows that calcium entry through store‐operated calcium channels is critical for calcium oscillations, but calcium entry through voltage‐gated channels has much less effect.
The model predicts that voltage‐gated channels are less important than store‐operated channels in the control of airway smooth muscle tone.
AbstractAirway smooth muscle contraction is typically the key mechanism underlying airway hyper‐responsiveness, and the strength of muscle contraction is determined by the frequency of oscillations of intracellular calcium (Ca2+) concentration. In airway smooth muscle cells, these Ca2+ oscillations are caused by cyclic Ca2+ release from the sarcoplasmic reticulum, although Ca2+ influx via plasma membrane channels is also necessary to sustain the oscillations over longer times. To assess the relative contributions of store‐operated and voltage‐gated Ca2+ channels to this Ca2+ influx, we generated a comprehensive mathematical model, based on experimental Ca2+ measurements in mouse precision‐cut lung slices, to simulate Ca2+ oscillations and changes in membrane potential. Agonist‐induced Ca2+ oscillations are accompanied by oscillations in membrane potential, although the membrane potential oscillations are too small to generate large Ca2+ currents through voltage‐gated Ca2+ channels, and thus have little effect on the Ca2+ oscillations. Ca2+ entry through voltage‐gated channels only becomes important when the cell is depolarized (e.g. by a high external K+ concentration). As a result, agonist‐induced Ca2+ oscillations are critically dependent on Ca2+ entry through store‐operated channels but do not depend strongly on Ca2+ entry though voltage‐gated channels.
Effects of Lipid-Lowering Drugs on Vancomycin Susceptibility of Mycobacteria
Authors: Rens Céline , Laval Françoise , Daffé Mamadou , Denis Olivier , Frita Rosangela , Baulard Alain , Wattiez Ruddy , Lefèvre Philippe , Fontaine Véronique 
Published: August 2016

ABSTRACT

Tuberculosis is still a cause of major concern, partly due to the emergence of multidrug-resistant strains. New drugs are therefore needed. Vancomycin can target mycobacteria with cell envelope deficiency. In this study, we used a vancomycin susceptibility assay to detect drugs hampering lipid synthesis in
Mycobacterium bovis
BCG and in
Mycobacterium tuberculosis
. We tested three drugs already used to treat human obesity: tetrahydrolipstatin (THL), simvastatin, and fenofibrate. Only vancomycin and THL were able to synergize on
M. bovis
BCG and on
M. tuberculosis
, although mycobacteria could also be inhibited by simvastatin alone. Lipid analysis allowed us to identify several lipid modifications in
M. tuberculosis
H37Rv treated with those drugs. THL treatment mainly reduced the phthiocerol dimycocerosate (PDIM) content in the mycobacterial cell wall, providing an explanation for the synergy, since PDIM deficiency has been related to vancomycin susceptibility. Proteomic analysis suggested that bacteria treated with THL, in contrast to bacteria treated with simvastatin, tried to recover, inducing, among other reactions, lipid synthesis. The combination of THL and vancomycin should be considered a promising solution in developing new strategies to treat multidrug-resistant tuberculosis.
Emergence of
ileS2
-Carrying, Multidrug-Resistant Plasmids in Staphylococcus lugdunensis
Authors: Ho Pak-Leung , Liu Melissa Chun-Jiao , Chow Kin-Hung , Tse Cindy Wing-Sze , Lo Wai-U , Mak Siu-Ka , Lo Wai-Kei 
Published: August 2016

ABSTRACT

Of 137
Staphylococcus lugdunensis
isolates collected from two nephrology centers in Hong Kong, 10 (7.3%) and 3 (2.2%) isolates had high-level and low-level mupirocin resistance, respectively. Isolates with high-level resistance contained the plasmid-mediated
ileS2
gene, while isolates with low-level resistance contained the mutation V588F within the chromosomal
ileS
gene. All but one of the
ileS2
-positive isolates belong to the predominating clone HKU1. Plasmids carrying the
ileS2
gene were mosaic and also cocarry multiple other resistance determinants.
Multiple Drug Transporters Are Involved in Renal Secretion of Entecavir
Authors: Yang Xi , Ma Zhiyuan , Zhou Sisi , Weng Yayun , Lei Hongmei , Zeng Su , Li Liping , Jiang Huidi 
Published: August 2016

ABSTRACT
Entecavir (ETV) is a first-line antiviral agent for the treatment of chronic hepatitis B virus infection. Renal excretion is the major elimination path of ETV, in which tubular secretion plays the key role. However, the secretion mechanism has not been clarified. We speculated that renal transporters mediated the secretion of ETV. Therefore, the aim of our study was to elucidate which transporters contribute to the renal disposition of ETV. Our results revealed that ETV (50 μM) remarkably reduced the accumulation of probe substrates in MDCK cells stably expressing human multidrug and toxin efflux extrusion proteins (hMATE1/2-K), organic cation transporter 2 (hOCT2), and carnitine/organic cation transporters (hOCTNs) and increased the substrate accumulation in cells transfected with multidrug resistance-associated protein 2 (hMRP2) or multidrug resistance protein 1 (hMDR1). Moreover, ETV was proved to be a substrate of the above-described transporters. In transwell studies, the transport of ETV in MDCK-hOCT2-hMATE1 showed a distinct directionality from BL (hOCT2) to AP (hMATE1), and the cellular accumulation of ETV in cells expressing hMATE1 was dramatically lower than that of the mock-treated cells. The accumulation of ETV in mouse primary renal tubular cells was obviously affected by inhibitors of organic anion transporter 1/3 (Oat1/3), Oct2, Octn1/2, and Mrp2. Therefore, the renal uptake of ETV is likely mediated by OAT1/3 and OCT2 while the efflux is mediated by MATEs, MDR1, and MRP2, and OCTN1/2 may participate in both renal secretion and reabsorption.
In Vitro
Activity of 3-Triazeneindoles against Mycobacterium tuberculosis and Mycobacterium avium
Authors: Nikonenko Boris V. , Kornienko Albert , Majorov Konstantin , Ivanov Pavel , Kondratieva Tatiana , Korotetskaya Maria , Apt Alexander S. , Salina Elena , Velezheva Valeriya 
Published: August 2016

ABSTRACT

Among 230 target-synthesized indole-based compounds, seven 3-triazenoindoles showed MICs of 0.2 to 0.5 μg/ml against
Mycobacterium tuberculosis
strain H37Rv and isoniazid-resistant human isolate CN-40. The TU112 compound was active also against a dormant form of
M. tuberculosis
. Some of these triazenoindoles were active against
Mycobacterium avium
, with MICs of 0.05 to 0.5 μg/ml. The selectivity indices (SI) for
M. tuberculosis
and
M. avium
were significantly higher than 10, making these compounds acceptable for the next testing step.
A Synonymous Mutation Upstream of the Gene Encoding a Weak-Link Enzyme Causes an Ultrasensitive Response in Growth Rate
Authors: Kershner Jamie P. , Yu McLoughlin Sean , Kim Juhan , Morgenthaler Andrew , Ebmeier Christopher C. , Old William M. , Copley Shelley D. 
Published: August 2016

ABSTRACT

When microbes are faced with an environmental challenge or opportunity, preexisting enzymes with promiscuous secondary activities can be recruited to provide newly important functions. Mutations that increase the efficiency of a new activity often compromise the original activity, resulting in an inefficient bifunctional enzyme. We have investigated the mechanisms by which growth of
Escherichia coli
can be improved when fitness is limited by such an enzyme, E383A ProA (ProA*). ProA* can serve the functions of both ProA (required for synthesis of proline) and ArgC (required for synthesis of arginine), albeit poorly. We identified four genetic changes that improve the growth rate by up to 6.2-fold. Two point mutations in the promoter of the
proBA*
operon increase expression of the entire operon. Massive amplification of a genomic segment around the
proBA*
operon also increases expression of the entire operon. Finally, a synonymous point mutation in the coding region of
proB
creates a new promoter for
proA*
. This synonymous mutation increases the level of ProA* by 2-fold but increases the growth rate by 5-fold, an ultrasensitive response likely arising from competition between two substrates for the active site of the inefficient bifunctional ProA*.

IMPORTANCE
The high-impact synonymous mutation we discovered in
proB
is remarkable for two reasons. First, most polar effects documented in the literature are detrimental. This finding demonstrates that polar effect mutations can have strongly beneficial effects, especially when an organism is facing a difficult environmental challenge for which it is poorly adapted. Furthermore, the consequence of the synonymous mutation in
proB
is a 2-fold increase in the level of ProA* but a disproportionately large 5.1-fold increase in growth rate. While ultrasensitive responses are often found in signaling networks and genetic circuits, an ultrasensitive response to an adaptive mutation has not been previously reported.
Evidence that Oxidative Stress Induces
spxA2
Transcription in Bacillus anthracis Sterne through a Mechanism Requiring SpxA1 and Positive Autoregulation
Authors: Barendt Skye , Birch Cierra , Mbengi Lea , Zuber Peter 
Published: August 2016

ABSTRACT

Bacillus anthracis
possesses two paralogs of the transcriptional regulator, Spx. SpxA1 and SpxA2 interact with RNA polymerase (RNAP) to activate the transcription of genes implicated in the prevention and alleviation of oxidative protein damage. The
spxA2
gene is highly upregulated in infected macrophages, but how this is achieved is unknown. Previous studies have shown that the
spxA2
gene was under negative control by the Rrf2 family repressor protein, SaiR, whose activity is sensitive to oxidative stress. These studies also suggested that
spxA2
was under positive autoregulation. In the present study, we show by
in vivo
and
in vitro
analyses that
spxA2
is under direct autoregulation but is also dependent on the SpxA1 paralogous protein. The deletion of either
spxA1
or
spxA2
reduced the diamide-inducible expression of an
spxA2-lacZ
construct.
In vitro
transcription reactions using purified
B. anthracis
RNAP showed that SpxA1 and SpxA2 protein stimulates transcription from a DNA fragment containing the
spxA2
promoter. Ectopically positioned
spxA2-lacZ
fusion requires both SpxA1 and SpxA2 for expression, but the requirement for SpxA1 is partially overcome when
saiR
is deleted. Electrophoretic mobility shift assays showed that SpxA1 and SpxA2 enhance the affinity of RNAP for
spxA2
promoter DNA and that this activity is sensitive to reductant. We hypothesize that the previously observed upregulation of
spxA2
in the oxidative environment of the macrophage is at least partly due to SpxA1-mediated SaiR repressor inactivation and the positive autoregulation of
spxA2
transcription.

IMPORTANCE
Regulators of transcription initiation are known to govern the expression of genes required for virulence in pathogenic bacterial species. Members of the Spx family of transcription factors function in control of genes required for virulence and viability in low-GC Gram-positive bacteria. In
Bacillus anthracis
, the
spxA2
gene is highly induced in infected macrophages, which suggests an important role in the control of virulence gene expression during the anthrax disease state. We provide evidence that elevated concentrations of oxidized, active SpxA2 result from an autoregulatory positive-feedback loop driving
spxA2
transcription.
Association between home birth and breast feeding outcomes: a cross-sectional study in 28 125 mother–infant pairs from Ireland and the UK
Authors: Quigley Clare , Taut Cristina , Zigman Tamara , Gallagher Louise , Campbell Harry , Zgaga Lina 
Published: August 2016

ObjectivesTo examine the association between breast feeding outcomes and place of birth (home vs hospital birth).DesignPopulation-based cross-sectional study.SettingIreland and UK.Participants10 604 mother–infant pairs from theGrowing Up in Irelandstudy (GUI, 2008–2009) and 17 521 pairs from theUK Millennium Cohort Study(UKMCS, 2001–2002) at low risk of delivery complications were included in the study.Primary and secondary outcome measuresBreast feeding initiation, exclusivity and duration.ResultsHome birth was found to be significantly associated with breast feeding at all examined time points, including at birth, 8 weeks, 6 months and breast feeding exclusively at 6 months. In GUI, adjusted OR was 1.90 (95% CI 1.19 to 3.02), 1.78 (1.18 to 2.69), 1.85 (1.23 to 2.77) and 2.77 (1.78 to 4.33), respectively, and in UKMCS it was 2.49 (1.84 to 3.44), 2.49 (1.92 to 3.26), 2.90 (2.25 to 3.73) and 2.24 (1.14 to 4.03).ConclusionsHome birth was strongly associated with improved breast feeding outcomes in low-risk deliveries. While the association between home birth and breast feeding is unlikely to be directly causal, further research is needed to determine which factor(s) drive the observed differences, to facilitate development of perinatal care that supports breast feeding.
Prospective, observational study comparing automated and visual point-of-care urinalysis in general practice
Authors: van Delft Sanne , Goedhart Annelijn , Spigt Mark , van Pinxteren Bart , de Wit Niek , Hopstaken Rogier 
Published: August 2016

ObjectivePoint-of-care testing (POCT) urinalysis might reduce errors in (subjective) reading, registration and communication of test results, and might also improve diagnostic outcome and optimise patient management. Evidence is lacking. In the present study, we have studied the analytical performance of automated urinalysis and visual urinalysis compared with a reference standard in routine general practice.SettingThe study was performed in six general practitioner (GP) group practices in the Netherlands. Automated urinalysis was compared with visual urinalysis in these practices. Reference testing was performed in a primary care laboratory (Saltro, Utrecht, The Netherlands).Primary and secondary outcome measuresAnalytical performance of automated and visual urinalysis compared with the reference laboratory method was the primary outcome measure, analysed by calculating sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) and Cohen's κ coefficient for agreement. Secondary outcome measure was the user-friendliness of the POCT analyser.ResultsAutomated urinalysis by experienced and routinely trained practice assistants in general practice performs as good as visual urinalysis for nitrite, leucocytes and erythrocytes. Agreement for nitrite is high for automated and visual urinalysis. κ's are 0.824 and 0.803 (ranked as very good and good, respectively). Agreement with the central laboratory reference standard for automated and visual urinalysis for leucocytes is rather poor (0.256 for POCT and 0.197 for visual, respectively, ranked as fair and poor). κ's for erythrocytes are higher: 0.517 (automated) and 0.416 (visual), both ranked as moderate. The Urisys 1100 analyser was easy to use and considered to be not prone to flaws.ConclusionsAutomated urinalysis performed as good as traditional visual urinalysis on reading of nitrite, leucocytes and erythrocytes in routine general practice. Implementation of automated urinalysis in general practice is justified as automation is expected to reduce human errors in patient identification and transcribing of results.
Periodontitis is an independent risk indicator for atherosclerotic cardiovascular diseases among 60 174 participants in a large dental school in the Netherlands
Authors: Beukers Nicky G F M , van der Heijden Geert J M G , van Wijk Arjen J , Loos Bruno G 
Published: August 2016

BackgroundThe association between periodontitis and atherosclerotic cardiovascular diseases (ACVD) has been established in some modestly sized studies (<10 000). Rarely, however, periodontitis has been studied directly; often tooth loss or self-reported periodontitis has been used as a proxy measure for periodontitis. Our aim is to investigate the adjusted association between periodontitis and ACVD among all individuals registered in a large dental school in the Netherlands (Academic Centre for Dentistry Amsterdam (ACTA)).MethodsAnonymised data were extracted from the electronic health records for all registered patients aged >35 years (period 1998–2013). A participant was recorded as having periodontitis based on diagnostic and treatment codes. Any affirmative answer for cerebrovascular accidents, angina pectoris and/or myocardial infarction labelled a participant as having ACVD. Other risk factors for ACVD, notably age, sex, smoking, diabetes, hypertension, hypercholesterolaemia and social economic status, were also extracted. Logistic regression analyses were used to evaluate the adjusted associations between periodontitis and ACVD.Results60 174 individuals were identified; 4.7% of the periodontitis participants (455/9730) and 1.9% of the non-periodontitis participants (962/50 444) reported ACVD; periodontitis showed a significant association with ACVD (OR 2.52; 95% CI 2.3 to 2.8). After adjustment for the confounders, periodontitis remained independently associated with ACVD (OR 1.59; 95% CI 1.39 to 1.81). With subsequent stratification for age and sex, periodontitis remained independently associated with ACVD.ConclusionsThis cross-sectional analysis of a large cohort in the Netherlands of 60 174 participants shows the independent association of periodontitis with ACVD.
Endovascular treatment of previously clipped aneurysms: continued evolution of hybrid neurosurgery
Authors: Gross Bradley A , Albuquerque Felipe C , Moon Karam , Ducruet Andrew F , McDougall Cameron G 
Published: August 2016

Background/objectiveThe optimal management of residual or recurrent clipped aneurysms is infrequently addressed in the literature.MethodsWe reviewed our endovascular database from January 1998 to May 2016 to identify patients with clipped aneurysms undergoing subsequent endovascular treatment, evaluating treatment approach, and clinical and angiographic outcomes.Results60 patients underwent endovascular treatment of residual/recurrent clipped aneurysms; 7 rebled prior to endovascular therapy. Treatment was via coiling alone (n=25, 42%), stent assisted coiling (n=15, 25%), balloon assisted coiling (n=8, 13%), flow diversion (n=8, 13%), stenting alone (n=3, 5%), or flow diversion with coiling (n=1, 2%). The procedural permanent neurological morbidity and mortality rates were 3% and 2%, respectively. Over a clinical follow-up of 253.4 patient years (median 3.9 years), there was one rebleed in a patient who had declined further treatment. For 43 patients with at least 1 month of digital subtraction angiographic follow-up (median 3.4 years), complete aneurysm occlusion was seen in 79% of cases. Neck remnants were observed in 14%, and stable small dome remnants were observed in 7% of cases. In a subgroup of 18 patients with ‘clip induced’ narrow neck aneurysms, all domes were initially coil occluded (Raymond 1 or 2); there was no permanent procedural morbidity and no aneurysms required retreatment or recanalized over a median follow-up of 3.9 years.ConclusionsEndovascular treatment of residual or recurrent clipped aneurysms is an excellent treatment approach in well selected patients; ‘clip induced’ narrow neck aneurysms fare particularly well after treatment both angiographically and clinically.