bluuebunny/crossref_metadata_2025 huggingface dataset:
BRCA1 interacts with Nrf2 to regulate antioxidant signaling and cell survival
Authors: Gorrini Chiara , Baniasadi Pegah S. , Harris Isaac S. , Silvester Jennifer , Inoue Satoshi , Snow Bryan , Joshi Purna A. , Wakeham Andrew , Molyneux Sam D. , Martin Bernard , Bouwman Peter , Cescon David W. , Elia Andrew J. , Winterton-Perks Zoe , Cruickshank Jennifer , Brenner Dirk , Tseng Alan , Musgrave Melinda , Berman Hal K. , Khokha Rama , Jonkers Jos , Mak Tak W. , Gauthier Mona L.
Published: July 2013

Oxidative stress plays an important role in cancer development and treatment. Recent data implicate the tumor suppressor BRCA1 in regulating oxidative stress, but the molecular mechanism and the impact in BRCA1-associated tumorigenesis remain unclear. Here, we show that BRCA1 regulates Nrf2-dependent antioxidant signaling by physically interacting with Nrf2 and promoting its stability and activation. BRCA1-deficient mouse primary mammary epithelial cells show low expression of Nrf2-regulated antioxidant enzymes and accumulate reactive oxygen species (ROS) that impair survival in vivo. Increased Nrf2 activation rescues survival and ROS levels in BRCA1-null cells. Interestingly, 53BP1 inactivation, which has been shown to alleviate several defects associated with BRCA1 loss, rescues survival of BRCA1-null cells without restoring ROS levels. We demonstrate that estrogen treatment partially restores Nrf2 levels in the absence of BRCA1. Our data suggest that Nrf2-regulated antioxidant response plays a crucial role in controlling survival downstream of BRCA1 loss. The ability of estrogen to induce Nrf2 posits an involvement of an estrogen-Nrf2 connection in BRCA1 tumor suppression. Lastly, BRCA1-mutated tumors retain a defective antioxidant response that increases the sensitivity to oxidative stress. In conclusion, the role of BRCA1 in regulating Nrf2 activity suggests important implications for both the etiology and treatment of BRCA1-related cancers.
Ca2+ and K+ channels of normal human adrenal zona fasciculata cells: Properties and modulation by ACTH and AngII
Authors: Enyeart John J. , Enyeart Judith A.
Published: July 2013

In whole cell patch clamp recordings, we found that normal human adrenal zona fasciculata (AZF) cells express voltage-gated, rapidly inactivating Ca2+ and K+ currents and a noninactivating, leak-type K+ current. Characterization of these currents with respect to voltage-dependent gating and kinetic properties, pharmacology, and modulation by the peptide hormones adrenocorticotropic hormone (ACTH) and AngII, in conjunction with Northern blot analysis, identified these channels as Cav3.2 (encoded by CACNA1H), Kv1.4 (KCNA4), and TREK-1 (KCNK2). In particular, the low voltage–activated, rapidly inactivating and slowly deactivating Ca2+ current (Cav3.2) was potently blocked by Ni2+ with an IC50 of 3 µM. The voltage-gated, rapidly inactivating K+ current (Kv1.4) was robustly expressed in nearly every cell, with a current density of 95.0 ± 7.2 pA/pF (n = 64). The noninactivating, outwardly rectifying K+ current (TREK-1) grew to a stable maximum over a period of minutes when recording at a holding potential of −80 mV. This noninactivating K+ current was markedly activated by cinnamyl 1-3,4-dihydroxy-α-cyanocinnamate (CDC) and arachidonic acid (AA) and inhibited almost completely by forskolin, properties which are specific to TREK-1 among the K2P family of K+ channels. The activation of TREK-1 by AA and inhibition by forskolin were closely linked to membrane hyperpolarization and depolarization, respectively. ACTH and AngII selectively inhibited the noninactivating K+ current in human AZF cells at concentrations that stimulated cortisol secretion. Accordingly, mibefradil and CDC at concentrations that, respectively, blocked Cav3.2 and activated TREK-1, each inhibited both ACTH- and AngII-stimulated cortisol secretion. These results characterize the major Ca2+ and K+ channels expressed by normal human AZF cells and identify TREK-1 as the primary leak-type channel involved in establishing the membrane potential. These findings also suggest a model for cortisol secretion in human AZF cells wherein ACTH and AngII receptor activation is coupled to membrane depolarization and the activation of Cav3.2 channels through inhibition of hTREK-1.
The G-protein–gated K+ channel, IKACh, is required for regulation of pacemaker activity and recovery of resting heart rate after sympathetic stimulation
Authors: Mesirca Pietro , Marger Laurine , Toyoda Futoshi , Rizzetto Riccardo , Audoubert Matthieu , Dubel Stefan , Torrente Angelo G. , DiFrancesco Mattia L. , Muller Jana Christina , Leoni Anne-Laure , Couette Brigitte , Nargeot Joël , Clapham David E. , Wickman Kevin , Mangoni Matteo E.
Published: July 2013

Parasympathetic regulation of sinoatrial node (SAN) pacemaker activity modulates multiple ion channels to temper heart rate. The functional role of the G-protein–activated K+ current (IKACh) in the control of SAN pacemaking and heart rate is not completely understood. We have investigated the functional consequences of loss of IKACh in cholinergic regulation of pacemaker activity of SAN cells and in heart rate control under physiological situations mimicking the fight or flight response. We used knockout mice with loss of function of the Girk4 (Kir3.4) gene (Girk4−/− mice), which codes for an integral subunit of the cardiac IKACh channel. SAN pacemaker cells from Girk4−/− mice completely lacked IKACh. Loss of IKACh strongly reduced cholinergic regulation of pacemaker activity of SAN cells and isolated intact hearts. Telemetric recordings of electrocardiograms of freely moving mice showed that heart rate measured over a 24-h recording period was moderately increased (10%) in Girk4−/− animals. Although the relative extent of heart rate regulation of Girk4−/− mice was similar to that of wild-type animals, recovery of resting heart rate after stress, physical exercise, or pharmacological β-adrenergic stimulation of SAN pacemaking was significantly delayed in Girk4−/− animals. We conclude that IKACh plays a critical role in the kinetics of heart rate recovery to resting levels after sympathetic stimulation or after direct β-adrenergic stimulation of pacemaker activity. Our study thus uncovers a novel role for IKACh in SAN physiology and heart rate regulation.
Mechanism of calsequestrin regulation of single cardiac ryanodine receptor in normal and pathological conditions
Authors: Chen Haiyan , Valle Giorgia , Furlan Sandra , Nani Alma , Gyorke Sandor , Fill Michael , Volpe Pompeo
Published: July 2013

Release of Ca2+ from the sarcoplasmic reticulum (SR) drives contractile function of cardiac myocytes. Luminal Ca2+ regulation of SR Ca2+ release is fundamental not only in physiology but also in physiopathology because abnormal luminal Ca2+ regulation is known to lead to arrhythmias, catecholaminergic polymorphic ventricular tachycardia (CPVT), and/or sudden cardiac arrest, as inferred from animal model studies. Luminal Ca2+ regulates ryanodine receptor (RyR)2-mediated SR Ca2+ release through mechanisms localized inside the SR; one of these involves luminal Ca2+ interacting with calsequestrin (CASQ), triadin, and/or junctin to regulate RyR2 function.

CASQ2-RyR2 regulation was examined at the single RyR2 channel level. Single RyR2s were incorporated into planar lipid bilayers by the fusion of native SR vesicles isolated from either wild-type (WT), CASQ2 knockout (KO), or R33Q-CASQ2 knock-in (KI) mice. KO and KI mice have CPVT-like phenotypes. We show that CASQ2(WT) action on RyR2 function (either activation or inhibition) was strongly influenced by the presence of cytosolic MgATP. Function of the reconstituted CASQ2(WT)–RyR2 complex was unaffected by changes in luminal free [Ca2+] (from 0.1 to 1 mM). The inhibition exerted by CASQ2(WT) association with the RyR2 determined a reduction in cytosolic Ca2+ activation sensitivity. RyR2s from KO mice were significantly more sensitive to cytosolic Ca2+ activation and had significantly longer mean open times than RyR2s from WT mice. Sensitivity of RyR2s from KI mice was in between that of RyR2 channels from KO and WT mice. Enhanced cytosolic RyR2 Ca2+ sensitivity and longer RyR2 open times likely explain the CPVT-like phenotype of both KO and KI mice.
On extremal even unimodular 72-dimensional lattices
Authors: Nebe Gabriele , Parker Richard
Published: July 2013

By computer search we show that the lattice

Γ
\Gamma

of Nebe (2012) is the unique extremal even unimodular 72-dimensional lattices that can be constructed as proposed by Griess (2010).
Association of low body temperature and poor outcomes in patients admitted with worsening heart failure: a substudy of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial
Authors: Payvar Saeed , Spertus John A. , Miller Alan B. , Casscells S. Ward , Pang Peter S. , Zannad Faiez , Swedberg Karl , Maggioni Aldo P. , Reid Kimberly J. , Gheorghiade Mihai ,   for the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) Investigators
Published: July 2013

Aims

Risk stratification in patients admitted with worsening heart failure (HF) is essential for tailoring therapy and counselling. Risk models are available but rarely used, in part because many require laboratory and imaging results that are not routinely available. Body temperature is associated with prognosis in other illnesses, and we hypothesized that low body temperature would be associated with worse outcomes in patients admitted with worsening HF.

Methods and results

The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial was an event‐driven, randomized, double‐blind, placebo‐controlled study of tolvaptan in 4133 patients hospitalized for worsening HF with an EF <40%. Co‐primary endpoints were all‐cause mortality and cardiovascular (CV) death or HF rehospitalization. Body temperature was measured orally at randomization and entered in analyses both as a continuous variable and categorized into three groups (<36°C, 36–36.5°C, and >36.5°C) using Cox regression models. The composite of CV death or HF rehospitalization occurred in 1544 patients within 1 year. For every 1°C decrease in body temperature, the risk of adverse outcomes increased by 16% [hazard raio (HR) 1.16, 95% confidence interval (CI) 1.04–1.28], after adjustment for age, gender, race, systolic blood pressure, EF, blood urea nitrogen, and serum sodium. In fully adjusted analysis, the risk of adverse outcomes in the lowest body temperature group (<36°C) was 51% higher than that of the index group (>36.5°C) (HR 1.35, 95% CI 1.15–1.58).

Conclusions

Low body temperature is an independent marker of poor cardiovascular outcomes in patients admitted with worsening HF and reduced EF.
Detailed Composition Analyses of Diverse Oat Genotype Kernels Grown in Different Environments in North Dakota
Authors: Doehlert Douglas C. , Simsek Senay , Thavarajah Dil , Thavarajah Pushparajah , Ohm Jae‐Bom
Published: July 2013

Nutritional composition of oat kernels from 18 genotypes grown in six environments in North Dakota, U.S.A., was analyzed by chemical means. Of the macronutrients, mean starch concentration was 56.5%, protein was 18.1%, oil was 7.9%, neutral detergent fiber (insoluble fiber) was 6.0%, β‐glucan (soluble fiber) was 5.2%, ash was 1.9%, and soluble carbohydrate was 0.6%. These add up to 96.2%, which appears to account for most of the mass of the oat kernel. Protein amino acid analysis indicated 4.5% lysine and 1.8% methionine. Free amino acid analysis indicated 1,129 μg of asparagine per gram of flour. The 18:1 and 18:2 fatty acids were the most abundant in oat lipids. Mean micronutrient concentrations in oat kernels included potassium (3,419 ppm), magnesium (1,416 ppm), calcium (441 ppm), iron (52 ppm), zinc (26 ppm), and selenium (0.38 ppm). Analysis of variance indicated significant genotypic and environmental variation, as well as significant genotype × environmental interaction for most of the nutritional components. In general, protein was higher in drier, hotter environments, whereas oil, β‐glucan, and starch were higher in wetter, cooler environments. The results provide a unique database of a collection of compositional components for specific oat genotypes in diverse environments.
First Molecular Detection of Ramularia Leaf Spot (Ramularia collo-cygni) in Seeds and Leaves of Barley in Argentina
Authors: Havis N. D. , Gorniak K. , Carmona M. A. , Formento A. N. , Luque A. G. , Scandiani M. M.
Published: July 2013

The fungus Ramularia collo-cygni B. Sutton & J. M. Waller (Rcc) was identified as the causal agent of this emerging disease on barley (Hordeum vulgare L.) based on symptoms and signs on leaves and attributes of the fungus. The common name given to the disease was “necrotic sprinkling.” This disease was found for the first time on barley in fields of Buenos Aires Province, Argentina, in 2001, with severities ranging from 60 to 100% (2). During the spring of 2012, the disease spread throughout most barley growing areas of the Pampean region, affecting almost all varieties of barley in the Buenos Aires, Entre Ríos, and Santa Fe provinces. The disease showed typical symptoms of small, brown spots on leaves, sheaths, and awns, and caused rapid loss of green leaf area and significant economic damage. The diagnosis of this disease is difficult by conventional techniques and has caused some confusion. In order to obtain appropriate information about the incidence of this pathogen in the most important barley growing region of Argentina, as well as to confirm its presence on seed, 39 seed samples containing 200 seeds each and eight leaf samples were analyzed using a real-time PCR diagnostic test (4). Thirty-five of the 37 seed samples had Rcc DNA levels above the minimum detection level (0.13 pg DNA). Ramularia has been described as a seedborne fungus previously (1) and seed infection could hasten the spread of the fungus to new geographically distinct areas. Moreover, leaf samples were microscopically assessed for conidophore presence and then ground for DNA extraction. Rcc DNA was detected by PCR in all eight leaf samples. To our knowledge, this is the first report about molecular detection of R. collo-cygni in barley seed of harvested samples from Argentina. Seeds infected/infested may also lead to new strains of the fungus arriving in barley fields and provide a source of inoculum for future epidemics (3).

References: (1) N. D. Havis et al. FEMS Microbiol. Lett. 256:217, 2006. (2) M. Khier et al. Salpicado necrótico, nueva enfermedad de la cebada en Argentina causada por Ramularia collo-cygni. Page 47 in: Resúmenes XI Jornadas Fitosanitarias Argentinas, 26–29 June 2002, Río Cuarto, Córdoba, 2002. (3) P. Matusinsky et al. J. Plant Pathol. 3:679, 2011. (4) J. M. G. Taylor et al. Lett. Appl. Microbiol. 50:493, 2010.
Distribution of QoI Resistance in Populations of Tangerine-Infecting Alternaria alternata in Florida
Authors: Vega Byron , Dewdney Megan M.
Published: July 2013

Chemical control, based on copper and quinone outside inhibitor (QoI) fungicides, has been essential for the management of brown spot of citrus, caused by Alternaria alternata. However, QoI control failures were detected recently in Florida. From 2008 to 2012, 817 monoconidial isolates of A. alternata from 46 citrus orchards were examined for sensitivity to azoxystrobin (AZ) and pyraclostrobin (PYR). Of the isolates, 57.6% were resistant to both fungicides, with effective concentration to inhibit 50% growth (EC50) values greater than 5 μg/ml for AZ and 1 μg/ml for PYR. The mean EC50 values for sensitive isolates were 0.139 and 0.020 μg/ml for AZ and PYR, respectively. The EC50 values of both fungicides were highly correlated (P < 0.0001), indicating cross resistance. The proportion of resistant isolates differed significantly (P < 0.0001) among cultivars and with QoI application frequency (P < 0.0001). However, resistance was not significantly related (P = 0.364) to disease severity in the field (low, moderate, and high) or isolate virulence (P = 0.397). The molecular basis for QoI resistance was determined for a subset of 235 isolates using polymerase chain reaction restriction fragment length polymorphism of the cytochrome b gene. All resistant isolates showed the point mutation G143A. Based on the presence of one or two introns, isolates were classified as profile I and profile II, respectively. The resistance frequency was significantly higher (P < 0.0001) in isolate profile II, suggesting a higher selection pressure for resistant population profile II.
Optimal Fungicide Application Timings for Disease Control Are Also an Effective Anti-Resistance Strategy: A Case Study for Zymoseptoria tritici (Mycosphaerella graminicola) on Wheat
Authors: van den Berg F. , van den Bosch F. , Paveley N. D.
Published: July 2013

Strategies to slow fungicide resistance evolution often advocate early “prophylactic” fungicide application and avoidance of “curative” treatments where possible. There is little evidence to support such guidance. Fungicide applications are usually timed to maximize the efficiency of disease control during the yield-forming period. This article reports mathematical modeling to explore whether earlier timings might be more beneficial for fungicide resistance management compared with the timings that are optimal for efficacy. There are two key timings for fungicide treatment of winter wheat in the United Kingdom: full emergence of leaf three (counting down the canopy) and full emergence of the flag leaf (leaf 1). These timings (referred to as T1 and T2, respectively) maximize disease control on the upper leaves of the crop canopy that are crucial to yield. A differential equation model was developed to track the dynamics of leaf emergence and senescence, epidemic growth, fungicide efficacy, and selection for a resistant strain. The model represented Zymoseptoria tritici on wheat treated twice at varying spray timings. At all fungicide doses tested, moving one or both of the two sprays earlier than the normal T1 and T2 timings reduced selection but also reduced efficacy. Despite these opposing effects, at a fungicide dose just sufficient to obtain effective control, the T1 and T2 timings optimized fungicide effective life (the number of years that effective control can be maintained). At a higher dose, earlier spray timings maximized effective life but caused some reduction in efficacy, whereas the T1 and T2 timings maximized efficacy but resulted in an effective life 1 year shorter than the maximum achievable.
Lactobacillus rhamnosus GG on Rotavirus‐Induced Injury of Ileal Epithelium in Gnotobiotic Pigs
Authors: Liu Fangning , Li Guohua , Wen Ke , Wu Shaoping , Zhang Yongguo , Bui Tammy , Yang Xingdong , Kocher Jacob , Sun Jun , Jortner Bernard , Yuan Lijuan
Published: July 2013

Objective:

The aim of this study was to study the effect of continued Lactobacillus rhamnosus GG strain (LGG) feeding on rotavirus gastroenteritis in the gnotobiotic (Gn) pig model of virulent human rotavirus (HRV) infection.

Methods:

Gn pigs were assigned to treatment groups: mock control, LGG only, HRV only, or LGG plus HRV. Nine days before HRV inoculation (3 days of age), pigs were fed LGG with a daily dose increase of 10‐fold from 103 to 1012 colony‐forming units (CFU). The 1012 CFU/dose of LGG feeding continued until post‐HRV inoculation day (PID) 6. Clinical sign (diarrhea), rotavirus fecal shedding, histopathology of the ileum, adherent junction and tight junction protein expression in the ileal epithelial cells, mucin production in the large and small intestinal contents, and serum cytokine responses from PID 2 to 6 were examined and compared among the treatment groups.

Results:

Clinically, the percentage of pigs developing diarrhea, the mean duration of diarrhea, and the mean cumulative fecal scores were lower in the LGG fed pigs compared to the nonfed pigs after HRV inoculation. LGG partially protected ileal epithelium against HRV‐induced compensatory increases of the adherent junction protein α‐catenin and β‐catenin, tight junction protein occludin, claudin‐3 and claudin‐4, and leak protein claudin‐2. LGG promoted mucin production because the mucin levels in the large intestinal contents of the LGG+HRV pigs were significantly higher than the HRV‐only pigs on PID 2. Additionally, LGG maintained the anti‐inflammatory cytokine transforming growth factor‐β level in serum after HRV infection.

Conclusions:

LGG is moderately effective for ameliorating rotavirus diarrhea by partially preventing injuries to the epithelium.
Multivariate Granger causality: an estimation framework based on factorization of the spectral density matrix
Authors: Wen Xiaotong , Rangarajan Govindan , Ding Mingzhou
Published: July 2013

Granger causality is increasingly being applied to multi-electrode neurophysiological and functional imaging data to characterize directional interactions between neurons and brain regions. For a multivariate dataset, one might be interested in different subsets of the recorded neurons or brain regions. According to the current estimation framework, for each subset, one conducts a separate autoregressive model fitting process, introducing the potential for unwanted variability and uncertainty. In this paper, we propose a multivariate framework for estimating Granger causality. It is based on spectral density matrix factorization and offers the advantage that the estimation of such a matrix needs to be done only once for the entire multivariate dataset. For any subset of recorded data, Granger causality can be calculated through factorizing the appropriate submatrix of the overall spectral density matrix.
Causal inference with multiple time series: principles and problems
Authors: Eichler Michael
Published: July 2013

I review the use of the concept of Granger causality for causal inference from time-series data. First, I give a theoretical justification by relating the concept to other theoretical causality measures. Second, I outline possible problems with spurious causality and approaches to tackle these problems. Finally, I sketch an identification algorithm that learns causal time-series structures in the presence of latent variables. The description of the algorithm is non-technical and thus accessible to applied scientists who are interested in adopting the method.
Classification of cardiovascular time series based on different coupling structures using recurrence networks analysis
Authors: Ramírez Ávila Gonzalo Marcelo , Gapelyuk Andrej , Marwan Norbert , Walther Thomas , Stepan Holger , Kurths Jürgen , Wessel Niels
Published: July 2013

We analyse cardiovascular time series with the aim of performing early prediction of preeclampsia (PE), a pregnancy-specific disorder causing maternal and foetal morbidity and mortality. The analysis is made using a novel approach, namely the
ε
-recurrence networks applied to a phase space constructed by means of the time series of the variabilities of the heart rate and the blood pressure (systolic and diastolic). All the possible coupling structures among these variables are considered for the analysis. Network measures such as average path length, mean coreness, global clustering coefficient and scale-local transitivity dimension are computed and constitute the parameters for the subsequent quadratic discriminant analysis. This allows us to predict PE with a sensitivity of 91.7 per cent and a specificity of 68.1 per cent, thus validating the use of this method for classifying healthy and preeclamptic patients.
Case of chromoblastomycosis with pulmonary involvement
Authors: Camara‐Lemarroy Carlos R. , Soto‐Garcia Anally J. , Preciado‐Yepez Cesar I. , Moreno‐Hoyos Francisco , Hernandez‐Rodriguez Pedro A. , Galarza‐Delgado Dionicio A.
Published: July 2013

Chromoblastomycosis is a slowly growing chronic cutaneous mycosis associated with a variety of cutaneous lesions. Extra‐dermal involvement is rare. A 58‐year‐old man was admitted to the hospital with nausea, vomiting, weakness and a history of weight loss. On inspection, he had a large verrucous mass in the sacral region, and two large subcutaneous nodules in the anterior thoracic wall. He claimed the lesions were several years old. Biopsy and histological studies were positive for chromoblastomycosis. Routine chest radiography showed hilar enlargement, and a chest computed tomography was ordered. Pulmonary nodules were evident, and endoscopically acquired samples were also positive for chromoblastomycosis. Extra‐dermal and systemic involvement in chromoblastomycosis is exceedingly rare and often associated with immunosuppression. There is only one other case of pulmonary chromoblastomycosis reported in the published work.
Density‐dependent life history and the dynamics of small populations
Authors: Mugabo Marianne , Perret Samuel , Legendre Stéphane , Le Galliard Jean‐François
Published: July 2013

Small population dynamics depend importantly on the strength and shape of density dependence. Unfortunately, the lack of reliable life‐history data often prevents to make accurate demographic predictions for populations regulated by density dependence.

We created a gradient from low to high densities in small experimental populations of common lizards (Zootoca vivipara) and investigated the shape and strength of the density dependence of life‐history traits during a yearly cycle. We then analysed stochastic population dynamics using one‐sex and two‐sex age‐structured matrix models.

Body growth and reproductive performances decreased with density, yearling and adult survival and body size at birth were density‐independent, and juvenile survival increased with density. The density dependence of reproduction was partly explained by positive effects of body size on age at first reproduction and clutch size.

Parturition date decreased with density in sparse populations and then increased, providing one of the first empirical evidence of a component Allee effect in the phenology of reproduction.

Population growth rate (λ) was most affected by variations in juvenile and yearling survival. However, density at equilibrium was most affected by juvenile access to reproduction and yearling clutch size.

Stochastic simulations revealed that negative density dependence buffers the effects of initial density on extinction probability, has positive effects on the persistence of sparse populations and interacts with sex ratio fluctuations to shape extinction dynamics.

This study demonstrates that negative density dependence modifies the dynamics of small populations and should be investigated together with Allee effects to predict extinction risks.
Paralogous metabolism: S‐alkyl‐cysteine degradation in Bacillus subtilis
Authors: Chan Che‐Man , Danchin Antoine , Marlière Philippe , Sekowska Agnieszka
Published: July 2013

Metabolism is prone to produce analogs of essential building blocks in the cell (here named paralogous metabolism). The variants result from lack of absolute accuracy in enzyme‐templated reactions as well as from molecular aging. If variants were left to accumulate, the earth would be covered by chemical waste. The way bacteria cope with this situation is essentially unexplored. To gain a comprehensive understanding of Bacillus subtilis sulphur paralogous metabolism, we used expression profiling with DNA arrays to investigate the changes in gene expression in the presence of S‐methyl‐cysteine (SMeC) and its close analog, methionine, as sole sulphur source. Altogether, more than 200 genes whose relative strength of induction was significantly different depending on the sulphur source used were identified. This allowed us to pinpoint operon ytmItcyJKLMNytmO_ytnIJ_rbfK_ytnLM as controlling the pathway cycling SMeC directly to cysteine, without requiring sulphur oxygenation. Combining genetic and physiological experiments, we deciphered the corresponding pathway that begins with protection of the metabolite by acetylation. Oxygenation of the methyl group then follows, and after deprotection (deacetylation), N‐formyl cysteine is produced. This molecule is deformylated by the second deformylase present in B. subtilis DefB, yielding cysteine. This pathway appears to be present in plant‐associated microbes.
American crows as carriers of vancomycin‐resistant enterococci with vanA gene
Authors: Oravcova Veronika , Zurek Ludek , Townsend Andrea , Clark Anne B. , Ellis Julie C. , Cizek Alois , Literak Ivan
Published: July 2013

We studied the vanA‐carrying vancomycin‐resistant enterococci (VRE) isolated from American crows in the United States during the winter 2011/2012. Faecal samples from crows were cultured selectively for VRE and characterized. Pulsed‐field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to examine epidemiological relationships of vanA‐containing VRE. Isolates were tested in vitro for their ability to horizontally transfer the vancomycin resistance trait. VRE with the vanA gene were found in 15 (2.5%) of 590 crows samples, from which we obtained 22 different isolates. Enterococcal species were Enterococcus faecium (14) and E. faecalis (8). One, two and 19 isolates originated from Kansas, New York State and Massachusetts, respectively. Based on MLST analysis, E. faecium isolates were grouped as ST18 (6 isolates), ST555 (2), and novel types ST749 (1), ST750 (3), ST751 (1), ST752 (1). Enterococcus faecalis isolates belonged to ST6 (1), ST16 (3) and ST179 (4). All isolates were able to transfer the vancomycin resistance trait via filter mating with very high transfer range. Clinically important enterococci with the vanA gene occur in faeces of wild American crows throughout the United States. These migrating birds may contribute to the dissemination of VRE in environment over large distances. [Correction added after first online publication on 06 August 2013: The number of E. faecium ST752 isolate is now amended to ‘1’, consistent with that shown in the ‘Results’ section and Figure 2.]
Revealing underlying vulnerable emotion in couple therapy: impact on session and final outcome
Authors: McKinnon Jacqueline M. , Greenberg Leslie S.
Published: July 2013

This study examined how the revealing of underlying vulnerable emotion relates to session and final outcome in the context of emotion‐focused therapy for couples. Segments of videotaped therapy sessions were rated on a measure of underlying vulnerable emotional expression for twenty‐five couples. Results indicated that partners rated sessions in which underlying vulnerable emotion was expressed significantly more positively than control sessions on a measure of session outcome. Moreover, from pre to post, couples who were found to have expressed underlying vulnerable emotion at least once improved significantly more on a measure of trust, and marginally significantly more on a measure of unfinished business, than couples who were not found to have expressed underlying vulnerable emotion. Recommendations for treatment are provided in light of the findings.

Practitioner points

It is recommended that couple therapists help partners to access and express underlying vulnerable emotion, because this appears to be associated with better session and final outcomes.

When an underlying vulnerable emotion begins to emerge, it is recommended that the therapist maintain the focus on this emotion and help to facilitate its full expression.
Using the Bayesian Improved Surname Geocoding Method (BISG) to Create a Working Classification of Race and Ethnicity in a Diverse Managed Care Population: A Validation Study
Authors: Adjaye‐Gbewonyo Dzifa , Bednarczyk Robert A. , Davis Robert L. , Omer Saad B.
Published: July 2013

Objective

To validate classification of race/ethnicity based on the Bayesian Improved Surname Geocoding method (BISG) and assess variations in validity by gender and age.

Data Sources/Study Setting

Secondary data on members of Kaiser Permanente Georgia, an integrated managed care organization, through 2010.

Study Design

For 191,494 members with self‐reported race/ethnicity, probabilities for belonging to each of six race/ethnicity categories predicted from the BISG algorithm were used to assign individuals to a race/ethnicity category over a range of cutoffs greater than a probability of 0.50. Overall as well as gender‐ and age‐stratified sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Receiver operating characteristic (ROC) curves were generated and used to identify optimal cutoffs for race/ethnicity assignment.

Principal Findings

The overall cutoffs for assignment that optimized sensitivity and specificity ranged from 0.50 to 0.57 for the four main racial/ethnic categories (White, Black, Asian/Pacific Islander, Hispanic). Corresponding sensitivity, specificity, PPV, and NPV ranged from 64.4 to 81.4 percent, 80.8 to 99.7 percent, 75.0 to 91.6 percent, and 79.4 to 98.0 percent, respectively. Accuracy of assignment was better among males and individuals of 65 years or older.

Conclusions

BISG may be useful for classifying race/ethnicity of health plan members when needed for health care studies.
HIV Testing in the Nation's Opioid Treatment Programs, 2005–2011: The Role of State Regulations
Authors: D'Aunno Thomas , Pollack Harold A. , Jiang Lan , Metsch Lisa R. , Friedmann Peter D.
Published: July 2013

Objective

To identify the extent to which clients in a national sample of opioid treatment programs (OTPs) received HIV testing in 2005 and 2011; to examine relationships between state laws for informed consent and pretest counseling and rates of HIV testing among OTP clients.

Data Source

Data were collected from a nationally representative sample of OTPs in 2005 (n = 171) and 2011 (n = 200).

Study Design

Random‐effects logit and interval regression analyses were used to examine changes in HIV testing rates and the relationship of state laws to HIV testing among OTPs.

Data Collection

Data on OTP provision of HIV testing were collected in phone surveys from OTP managers; data also were collected on state laws for HIV testing.

Principal Findings

The percentage of OTPs offering HIV testing decreased significantly from 93 percent in 2005 to 64 percent in 2011. Similarly, the percentage of clients tested decreased from an average of 41 percent in 2005 to 17 percent in 2011. OTPs located in states whose laws do not require pretest counseling and that use opt‐out consent were more likely to provide HIV testing and to test higher percentages of clients.

Conclusions

The results show the need to increase HIV testing among OTP clients; the results also underscore the beneficial possibilities of dropping pretest counseling as a requirement for HIV testing and of using the opt‐out approach to informed consent for testing.
Report ofAkabosia matsudoensis Kinoshita (Collembola;Paronellidae) fromKorea, with notes on theKorean aquatic springtail fauna
Authors: Kang Sangkyu , Park Kyung‐Hwa
Published: July 2013

A hygrophilous collembolan species,Akabosia matsudoensisis redescribed and illustrated with a list and key to other aquatic fauna belonging toEntomobryoidea fromKorea. Specimens inhabiting the damp area near a creek were collected with hand net and aspirator. This species is characterized by the absence of scale, having 2 + 2 macrosetae on the vertex of the head, 2 feathered prelabial setae, dens crenulated and the base of mucro with bladder like appendage. GenusAkabosiareported only one species,A. matsudoensis, that was originally recorded inJapan;Korea is the second recorded country and it is the onlyParonellidae fromKorea.
Microbial production and chemical transformation of poly‐γ‐glutamate
Authors: Ashiuchi Makoto
Published: July 2013

Poly‐γ‐glutamate (PGA), a novel polyamide material with industrial applications, possesses a nylon‐like backbone, is structurally similar to polyacrylic acid, is biodegradable and is safe for human consumption. PGA is frequently found in the mucilage of natto, a Japanese traditional fermented food. To date, three different types of PGA, namely a homo polymer of d‐glutamate (D‐PGA), a homo polymer of l‐glutamate (L‐PGA), and a random copolymer consisting of d‐ and l‐glutamate (DL‐PGA), are known. This review will detail the occurrence and physiology of PGA. The proposed reaction mechanism of PGA synthesis including its localization and the structure of the involved enzyme, PGA synthetase, are described. The occurrence of multiple carboxyl residues in PGA likely plays a role in its relative unsuitability for the development of bio‐nylon plastics and thus, establishment of an efficient PGA‐reforming strategy is of great importance. Aside from the potential applications of PGA proposed to date, a new technique for chemical transformation of PGA is also discussed. Finally, some techniques for PGA and its derivatives in advanced material technology are presented.
Magnetic resonance imaging appearances in primary and secondary angiosarcoma of the breast
Authors: O'Neill Ailbhe C , D'Arcy Clare , McDermott Enda , O'Doherty Ann , Quinn Cecily , McNally Sorcha
Published: July 2013

Angiosarcomas are malignant tumours of endovascular origin. They are rare tumours accounting for 0.04–1% of all breast malignancies. Two different forms are described: primary, occurring in young women, and secondary angiosarcoma, which occurs in older women with a history of breast‐conserving surgery and radiation therapy. Imaging findings on mammography and ultrasound are non‐specific, but magnetic resonance imaging with dynamic contrast enhancement is more informative. We present two cases – one of primary and one of secondary angiosarcoma – and review the imaging findings.
Mass production of SNP markers in a nonmodel passerine bird through RAD sequencing and contig mapping to the zebra finch genome
Authors: Bourgeois Yann X. C. , Lhuillier Emeline , Cézard Timothée , Bertrand Joris A. M. , Delahaie Boris , Cornuault Josselin , Duval Thomas , Bouchez Olivier , Milá Borja , Thébaud Christophe
Published: July 2013

Here, we present an adaptation of restriction‐site‐associated DNA sequencing (RAD‐seq) to the Illumina HiSeq2000 technology that we used to produce SNP markers in very large quantities at low cost per unit in the Réunion grey white‐eye (Zosterops borbonicus), a nonmodel passerine bird species with no reference genome. We sequenced a set of six pools of 18–25 individuals using a single sequencing lane. This allowed us to build around 600 000 contigs, among which at least 386 000 could be mapped to the zebra finch (Taeniopygia guttata) genome. This yielded more than 80 000 SNPs that could be mapped unambiguously and are evenly distributed across the genome. Thus, our approach provides a good illustration of the high potential of paired‐end RAD sequencing of pooled DNA samples combined with comparative assembly to the zebra finch genome to build large contigs and characterize vast numbers of informative SNPs in nonmodel passerine bird species in a very efficient and cost‐effective way.
Minor impact of ocean acidification to the composition of the active microbial community in an Arctic sediment
Authors: Tait Karen , Laverock Bonnie , Shaw Jennifer , Somerfield Paul J. , Widdicombe Steve
Published: July 2013

Effects of ocean acidification on the composition of the active bacterial and archaeal community within Arctic surface sediment was analysed in detail using 16S rRNA 454 pyrosequencing. Intact sediment cores were collected and exposed to one of five different pCO2 concentrations [380 (present day), 540, 750, 1120 and 3000 μatm] and RNA extracted after a period of 14 days exposure. Measurements of diversity and multivariate similarity indicated very little difference between pCO2 treatments. Only when the highest and lowest pCO2 treatments were compared were significant differences evident, namely increases in the abundance of operational taxonomic units most closely related to the Halobacteria and differences to the presence/absence structure of the Planctomycetes. The relative abundance of members of the classes Planctomycetacia and Nitrospira increased with increasing pCO2 concentration, indicating that these groups may be able to take advantage of changing pH or pCO2 conditions. The modest response of the active microbial communities associated with these sediments may be due to the low and fluctuating pore‐water pH already experienced by sediment microbes, a result of the pH buffering capacity of marine sediments, or due to currently unknown factors. Further research is required to fully understand the impact of elevated CO2 on sediment physicochemical parameters, biogeochemistry and microbial community dynamics.
Stigma Toward Individuals Engaged in Consensual Nonmonogamy: Robust and Worthy of Additional Research
Authors: Moors Amy C. , Matsick Jes L. , Ziegler Ali , Rubin Jennifer D. , Conley Terri D.
Published: July 2013

In our target article, “The Fewer the Merrier: Assessing Stigma Surrounding Consensual Nonmonogamous Relationships,” we documented a robust stigma toward consensual nonmonogamous relationships and a halo surrounding monogamous relationships. In the present piece, we respond to six commentaries of our target article with the aim of promoting future research and policy change. First, we address questions and concerns raised by commentators using existing data and found that regardless of perceived relationship happiness, sexual orientation, or gender (of experimental targets), individuals in consensual nonmonogamous relationships were more negatively viewed on a variety of qualities (both relationship‐specific and nonrelationship specific) compared to those in monogamous relationships. Second, we suggest productive future research avenues with regards to implications for social change, and strengthening methodology used in consensual nonmonogamous research. Finally, we consider common ground among the commentators as an avenue to promote coalition building through the examinations of prejudice toward individuals in nonnormative romantic relationships. We conclude that this is only the beginning of a fruitful line of research and argue that the stigma toward departures from monogamy is robust and, of course, worthy of additional research.
Asian monsoon climate during the Last Glacial Maximum: palaeo‐data–model comparisons
Authors: Chabangborn Akkaneewut , Brandefelt Jenny , Wohlfarth Barbara
Published: July 2013

The Last Glacial Maximum (LGM) (23–19 ka BP) in the Asian monsoon region is generally described as cool and dry, due to a strong winter monsoon. More recently, however, palaeo‐data and climate model simulations have argued for a more variable LGM Asian monsoon climate with distinct regional differences. We compiled, evaluated, and partly re‐assessed proxy records for the Asian monsoon region in terms of wet/dry climatic conditions based on precipitation and effective moisture, and of sea surface temperatures. The comparison of the palaeo‐data set to LGM simulations by the Climate Community System Model version 3 (CCSM3) shows fairly good agreement: a dry LGM climate in the western and northern part due to a strengthened winter monsoon and/or strengthened westerly winds and wetter conditions in equatorial areas, due to a stronger summer monsoon. Data–model discrepancies are seen in some areas and are ascribed to the fairly coarse resolution of CCSM3 and/or to uncertainties in the reconstructions. Differences are also observed between the reconstructed and simulated northern boundaries of the Intertropical Convergence Zone (ITCZ). The reconstructions estimate a more southern position over southern India and the Bay of Bengal, whereas CCSM3 simulates a more northern position. In Indochina, the opposite is the case. The palaeo‐data indicate that climatic conditions changed around 20–19 ka BP, with some regions receiving higher precipitation and some experiencing drier conditions, which would imply a distinct shift in summer monsoon intensity. This shift was probably triggered by the late LGM sea‐level rise, which led to changes in atmosphere–ocean interactions in the Indian Ocean. The overall good correspondence between reconstructions and CCSM3 suggests that CCSM3 simulates LGM climate conditions over subtropical and tropical areas fairly well. The few high‐resolution qualitative and quantitative palaeo‐records available for the large Asian monsoon region make reconstructions however still uncertain.
Delayed post-injury administration of C5a improves regeneration and functional recovery after spinal cord injury in mice
Authors: Guo Q , Cheng J , Zhang J , Su B , Bian C , Lin S , Zhong C
Published: July 2013

The activation of a complement system can aggravate the secondary injury after spinal cord injury (SCI). However, it was reported recently that the activation of a complement could have both a secondary injury and a neuroprotective effect, in which C5a is the most important factor, but there is no direct evidence for this dual effect of C5a after SCI. In order to investigate the potential neuroprotective effect of C5a after SCI, in this study ectogenic C5a was injected intraperitoneally before/after SCI in vivo, or administrated to mechanically injured neurones in vitro; following this, neurone apoptosis, neurite outgrowth, axonal regeneration and functional recovery were investigated. The in-vivo experiments indicated that, following treatment with C5a 24 h before or immediately after injury, locomotor function was impaired significantly. However, when treatment with C5a took place 24 h after injury, locomotor function improved significantly. In-vitro experiments indicated that a certain concentration of C5a (50–100 nM) could inhibit caspase-3-mediated neurone apoptosis by binding to its receptor CD88, and that it could even promote the neurite outgrowth of uninjured neurones. In conclusion, delayed post-injury administration of C5a within a certain concentration could exert its neuroprotective effect through inhibiting caspase-3-mediated neurone apoptosis and promoting neurite outgrowth of uninjured neurones as well. These data suggest that C5a may have opposite functions in a time- and concentration-dependent manner after SCI. The dual roles of C5a have to be taken into account when measures are taken to inhibit complement activation in order to promote regeneration after SCI.
Health care provider recommendations for reducing cancer risks among women with a BRCA1 or BRCA2 mutation
Authors: Metcalfe KA , Kim‐Sing C , Ghadirian P , Sun P , Narod SA
Published: July 2013

There is a significant variation in the uptake of cancer risk reducing options by women with a BRCA1 or BRCA2 mutation. It is currently unclear why these differences exist and it is possible that recommendations vary between providers and these influence patient decisions. Eligible health care providers who provide genetic counseling for hereditary breast and ovarian cancer families in Canada were identified. Each provider was asked to complete a study specific questionnaire that included their opinion of various cancer risk reduction options and their recommendations for specific cases. Respondents recommended prophylactic oophorectomy more often than prophylactic mastectomy or tamoxifen for women with a BRCA1 or BRCA2 mutation (p < 0.0001). Fewer than half of the respondents agreed with the recommendation for prophylactic mastectomy, and a minority of the respondents supported the recommendation for tamoxifen for chemoprevention. The majority of Canadian genetics health care providers adhere to the National Comprehensive Cancer Network (NCCN) Guideline of recommending prophylactic oophorectomy to mutation carriers, however, the minority of genetics health care providers recommend either prophylactic mastectomy or tamoxifen.