bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unravelling the folding and stability of an ABC (ATP-binding cassette) transporter
Authors: DiBartolo Natalie , Booth Paula J. 
Published: August 2015

Prokaryotic importers from the large family of ABC (ATP-binding cassette) transporters comprise four separate subunits: two membrane-embedded and two cytoplasmic ATP-binding subunits. This modular construction makes them ideal candidates for studies of the intersubunit interactions of membrane protein complexes that contain both hydrophobic and hydrophilic subunits. In the present paper, we focus on the vitamin B12 importer of Escherichia coli, BtuCD, that contains two transmembrane BtuC subunits and two ATP-binding BtuD subunits. We have studied the factors that induce subunit dissociation and unfolding in vitro. The BtuCD complex remains intact in alcohol and mild detergents, but urea or SDS separate the BtuC and BtuD subunits, with 6 M urea causing 80% of BtuD to be removed from BtuCD. ATP is found to stabilize the complex as a result of its binding to the BtuD subunits. In the absence of ATP, low concentrations of urea (0.5–3 M) also induce some unfolding, with approximately 14% reduction in helicity in 3 M urea, whereas, in the presence of ATP, no changes are observed. Disassembly at the BtuD–BtuD dimeric interface in BtuCD can be achieved with smaller concentrations of urea (0.5–3 M) than that required to cause disassembly at the BtuC–BtuD transmission interface (3–8 M), suggesting a stronger interaction of the latter. The results also suggest that unfolding and disassociation of subunits appear to be coupled processes. Our work provides insights into the subunit interactions of an ABC transporter and lays the foundation for studies of the reassembly of BtuCD.
Biochemical properties of the kinase PINK1 as sensor protein for mitochondrial damage signalling
Authors: Rüb Cornelia , Schröder Nadja , Voos Wolfgang 
Published: August 2015

Defects of mitochondrial functions have been implicated in many different human diseases, in particular neurodegenerative diseases. The kinase PINK1 [phosphatase and tensin homologue (PTEN)-induced kinase 1] has been identified as a crucial player in a specific damage signalling pathway, eliminating defective mitochondria by an autophagic process. Mutations in PINK1 have been shown to cause familial cases of Parkinson's disease. In this review, we summarize the biochemical mechanisms that underlie the association of PINK1 with mitochondria under normal and pathological conditions. This unconventional mitochondrial localization pathway is discussed in the context of the role of PINK1 as a sensor of mitochondrial damage and a causative factor in Parkinson's disease.
Random bursts determine dynamics of active filaments
Authors: Weber Christoph A. , Suzuki Ryo , Schaller Volker , Aranson Igor S. , Bausch Andreas R. , Frey Erwin 
Published: August 2015

Significance
Biological active systems like swimming bacteria or molecular motors in the cell cytoskeleton consume energy locally to create movements or stresses. Although the surrounding fluid gives rise to thermal fluctuations of the system’s dynamic variables, the corresponding statistics can deviate significantly from a thermal Boltzmann distribution. To quantify these differences, we compare the statistics and dynamics of actin filaments driven by molecular motors with Brownian filaments. In both cases, energy injection is local and random; however, for active filaments, motors can generate sudden jump-like changes in the system’s dynamic variables, leading to nonequilibrium energy dissipation. Motor activity results in a nonthermal distribution of filament curvatures and a faster relaxation of filament bends than in the thermal case.
Third generation behavioural therapy for neurodevelopmental disorders: review and trajectories
Authors: Leoni Mauro , Corti Serafino , Cavagnola Roberto 
Published: August 2015

Purpose– The purpose of this paper is mainly to present a general review of third generation cognitive-behavioural therapies (CBTs), and to debate whether these approaches are applicable to persons with neurodevelopmental disorders (NDD).Design/methodology/approach– Despite the lack of consistent literature focused on this population, the authors have considered the available general literature on the third generation of CBTs and analysed core issues of the processes within the context of intellectual disabilities and Autism spectrum disorder.Findings– The evidence from typical developing population studies and the emerging literature specific to people with NDD is convincing, but there is a need for studies exploring how and when these therapeutic approaches can be applicable. Two behavioural approaches of third generation therapies – acceptance and commitment therapy and mindfulness-based CBT – appear to have the most potential to be adapted for robust intervention for the broad spectrum of persons with NDD.Research limitations/implications– The number of studies and methodologies applied are a clear limitation and the present paper is only exploratory.Originality/value– The paper supports clinicians to use the emerging protocols, and to replicate and implement procedures and techniques.
Effect fracture resistance on retardation of crack growth
Authors: Behal Jirí , Homola Petr , Ružek Roman 
Published: August 2015

Purpose
– The prediction of fatigue crack growth behaviour is an important part of damage tolerance analyses. Recently, the author’s work has focused on evaluating the FASTRAN retardation model. This model is implemented in the AFGROW code, which allows different retardation models to be compared. The primary advantage of the model is that all input parameters, including those for an initial plane-strain state and its transition to a plane-stress-state, are objectively measured using standard middle-crack-tension M(T) specimens. The purpose of this paper is to evaluate the ability of the FASTRAN model to predict correct retardation effects due to high loading peaks that occur during variable amplitude loading in sequences representative of an aircraft service.

Design/methodology/approach
– This paper addresses pre-setting of the fracture toughness K

R
(based on J-integral J

Q
according to ASTM1820) in the FASTRAN retardation model. A set of experiments were performed using specimens made from a 7475-T7351 aluminium alloy plate. Loading sequences with peaks ordered in ascending-descending blocks were used. The effect of truncating and clipping selected load levels on crack propagation behaviour was evaluated using both experimental data and numerical analyses. The findings were supported by the results of a fractographic analysis.

Findings
– Fatigue crack propagation data defined using M(T) specimens made from Al 7475-T7351 alloy indicate the difficulty of evaluating the following two events simultaneously: fatigue crack increments after application of loads with maximum amplitudes that exceeded J

Q
and subcritical crack increments caused by loads at high stress intensity factors. An effect of overloading peaks with a maximum that exceeds J

Q
should be assessed using a special analysis beyond the scope of the FASTRAN retardation model.

Originality/value
– Measurements of fatigue crack growth on specimens made from 7475 T7351 aluminium alloy were carried out. The results indicated that simultaneously evaluating fatigue crack increments after application of the load amplitude above J

Q
and subcritical increments caused by the loads at high stress intensity factors is difficult. Experiments demonstrated that if the fatigue crack reaches a specific length, the maximal amplitude load induces considerable crack growth retardation.
Does the presence of placental basal plate myometrial fibres increase the risk of subsequent morbidly adherent placenta: a case–control study
Authors: Miller ES , Linn RL , Ernst LM 
Published: August 2015

ObjectiveAntenatal diagnosis of morbidly adherent placenta has been shown to improve outcomes, but existing predictors lack sensitivity. Our objective was to determine whether the presence of myometrial fibres attached to the placental basal plate (BPMYO) in an antecedent pregnancy is associated with subsequent morbidly adherent placenta.DesignA case–control study.SettingDepartments of Obstetrics and Gynecology and Pathology, Northwestern University, Chicago, IL, USA.SampleWomen who had at least two pregnancies with placental pathological evaluation.MethodsCases were defined as women with evidence of morbidly adherent placenta (both clinically and pathologically) in their most recent pregnancy whereas women without evidence of morbidly adherent placenta served as controls. Pathological specimens of placentas from previous pregnancies were evaluated for BPMYO. The presence of BPMYO on a previous placenta was evaluated to determine whether it could be used to improve the antenatal diagnosis of morbidly adherent placenta.ResultsOf the 25 cases of morbidly adherent placenta, 19 (76%) had BPMYO present on their previous placenta compared with 41 (41%) of controls (odds ratio 4.8, 95% CI 1.8–13.0). Adding BPMYO to a regression including other risk factors for morbidly adherent placenta (i.e. maternal age, number of previous caesarean sections, placenta praevia, previous multiple gestation, any previous curettage, and ultrasonographic suspicion of placenta accreta) significantly improved the sensitivity of antenatal diagnosis of morbidly adherent placenta (61% versus 39%, P < 0.001) without a change in specificity (97% versus 97%, P = 1.00).ConclusionBPMYO on previous placental pathology is associated with an increased risk of morbidly adherent placenta in a subsequent pregnancy. These findings may shed light on the pathophysiology of accreta and inform future research on predictors of accreta.Tweetable abstractPrevious basal plate myometrium improves the ability to detect subsequent morbidly adherent placenta.
Biomarkers associated with severe hypoglycaemia and death in ACCORD
Authors: Chow L. S. , Chen H. , Miller M. E. , Marcovina S. M. , Seaquist E. R. 
Published: August 2015

AbstractAims and hypothesisIn patients with Type 2 diabetes, intensive glycaemic control is associated with hypoglycaemia and possibly increased mortality. However, no blood biomarkers exist to predict these outcomes. Using participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, we hypothesized that insulin deficiency and islet autoantibodies in patients with clinically diagnosed Type 2 diabetes would be associated with severe hypoglycaemia and death.MethodsA nested case–control study design was used. A case (n = 86) was a participant who died with at least one episode of severe hypoglycaemia, defined as hypoglycaemia requiring assistance, at any point during ACCORD follow‐up. A control (n = 344) was a participant who did not die and did not have severe hypoglycaemia during follow‐up. Each case was matched to four controls (glycaemic intervention arm, race, age and BMI). Baseline insulin deficiency (fasting C–peptide ≤ 0.15 nmol/l) and islet autoantibodies [glutamic acid decarboxylase (GAD), tyrosine phosphatase‐related islet antigen 2 (IA2), insulin (IAA) and zinc transporter (ZnT8)] were measured. Conditional logistic regression with and without adjustment for age, BMI and diabetes duration was used.ResultsDeath during ACCORD in those who experienced at least one episode of severe hypoglycaemia was associated with insulin deficiency [OR 4.8 (2.1, 11.1): P < 0.0001], GAD antibodies [OR 2.3 (1.1, 5.1): P = 0.04], the presence of IAA or baseline insulin use [OR 6.1 (3.5,10.7): P < 0.0001], which remained significant after adjusting for age, BMI, and diabetes duration. There was no significant association with IA2 or ZnT8 antibodies.ConclusionsIn patients with Type 2 diabetes, C–peptide or GAD antibodies may serve as blood biomarkers predicting higher odds of subsequent severe hypoglycaemia and death. (Clinical Trial Registry No: NCT00000620, www.clinicaltrials.gov for original ACCORD study)
Polyketide synthases from poison hemlock (Conium maculatum L.)
Authors: Hotti Hannu , Seppänen‐Laakso Tuulikki , Arvas Mikko , Teeri Teemu H. , Rischer Heiko 
Published: August 2015

Coniine is a toxic alkaloid, the biosynthesis of which is not well understood. A possible route, supported by evidence from labelling experiments, involves a polyketide formed by the condensation of one acetyl‐CoA and three malonyl‐CoAs catalysed by a polyketide synthase (PKS). We isolated PKS genes or their fragments from poison hemlock (Conium maculatum L.) by using random amplification of cDNA ends (RACE) and transcriptome analysis, and characterized three full‐length enzymes by feeding different starter‐CoAs in vitro. On the basis of our in vitro experiments, two of the three characterized PKS genes in poison hemlock encode chalcone synthases (CPKS1 and CPKS2), and one encodes a novel type of PKS (CPKS5). We show that CPKS5 kinetically favours butyryl‐CoA as a starter‐CoA in vitro. Our results suggest that CPKS5 is responsible for the initiation of coniine biosynthesis by catalysing the synthesis of the carbon backbone from one butyryl‐CoA and two malonyl‐CoAs.DatabaseNucleotide sequence data are available in GenBank/EMBL/DDBJ under the accession numbers KP726914, KP726915, KP726916, KP726917, KP726918, and KP726919
Sunscreen remanence on the skin: a noninvasive real time in vivo spectral analysis assessing the quenching of specular ultraviolet A light reflectance
Authors: Piérard Gérald E. , Khazaka Diana , Khazaka Gabriel 
Published: August 2015

SummaryBackgroundUnder specific light illumination, particularly ultraviolet radiation (UVR), the skin produces both specular light reflectance and, possibly, specific fluorescent emission. A quenching effect of fluorescence is observed following the application of sunscreens active against UVA radiations.AimsTo assess noninvasively in a real‐time process, the potential sunscreen remanence/substantivity after application on the skin.MethodsThe Visiopor® device was used in a real‐time procedure after application of sunscreens to the skin. A quenching effect of follicular fluorescence due to bacterial porphyrins was evaluated at 30‐min intervals. The Visioscan® device was used as a distinct UVA emitter in a control procedure of spectral analysis of specular UVR emission and reflectance by dermal fibers.ResultsUnder UVA‐1 irradiations, facial skin produced different patterns of specular UVR reflectance and fluorescent emission as well. The porphyrin‐related follicular fluorescence was instantly abated by UVA blockers present in suncare products. The potential sunscreen remanence/substantivity was assessed by the follicular and interfollicular fluorescence recurrence all along the next hours.ConclusionsAll UVA blocker‐containing suncare products exhibited a similar overall quenching effect on porphyrin‐enriched facial hair follicles and dermal fibers. This effect lasted for a few hours. Differences in the fluorescence recovery were likely related to the amount in suncare application and the nature of the formulation components.
Perceived discrimination and youths' adjustment: sleep as a moderator
Authors: El‐Sheikh Mona , Tu Kelly M. , Saini Ekjyot K. , Fuller‐Rowell Thomas E. , Buckhalt Joseph A. 
Published: August 2015

SummaryAdolescents' sleep duration was examined as a moderator of the association between perceived discrimination and internalizing (anxiety, depression) and externalizing symptoms. Participants were 252 adolescents (mean: 15.79 years; 66% European American, 34% African American) who reported on their perceived discrimination (racial and general) and adjustment. Sleep duration was measured using actigraphy. Moderation effects were evident. The lowest levels of internalizing symptoms were observed for adolescents with longer sleep duration in conjunction with lower levels of perceived racial discrimination. Further, general perceived discrimination was associated more strongly with externalizing behaviours for youth with shorter versus longer sleep. Findings highlight the importance of sleep as a bioregulatory system that can ameliorate or exacerbate the effects of discrimination on youths' adjustment.
Phospholipase Dε enhances Braasca napus growth and seed production in response to nitrogen availability
Authors: Lu Shaoping , Yao Shuaibing , Wang Geliang , Guo Liang , Zhou Yongming , Hong Yueyun , Wang Xuemin 
Published: August 2015

SummaryPhospholipase D (PLD), which hydrolyses phospholipids to produce phosphatidic acid, has been implicated in plant response to macronutrient availability in Arabidopsis. This study investigated the effect of increased PLDε expression on nitrogen utilization in Brassica napus to explore the application of PLDε manipulation to crop improvement. In addition, changes in membrane lipid species in response to nitrogen availability were determined in the oil seed crop. Multiple PLDε over expression (PLDε‐OE) lines displayed enhanced biomass accumulation under nitrogen‐deficient and nitrogen‐replete conditions. PLDε‐OE plants in the field produced more seeds than wild‐type plants but have no impact on seed oil content. Compared with wild‐type plants, PLDε‐OE plants were enhanced in nitrate transporter expression, uptake and reduction, whereas the activity of nitrite reductase was higher under nitrogen‐depleted, but not at nitrogen‐replete conditions. The level of nitrogen altered membrane glycerolipid metabolism, with greater impacts on young than mature leaves. The data indicate increased expression of PLDε has the potential to improve crop plant growth and production under nitrogen‐depleted and nitrogen‐replete conditions.
Use of designer nucleases for targeted gene and genome editing in plants
Authors: Weeks Donald P. , Spalding Martin H. , Yang Bing 
Published: August 2015

SummaryThe ability to efficiently inactivate or replace genes in model organisms allowed a rapid expansion of our understanding of many of the genetic, biochemical, molecular and cellular mechanisms that support life. With the advent of new techniques for manipulating genes and genomes that are applicable not only to single‐celled organisms, but also to more complex organisms such as animals and plants, the speed with which scientists and biotechnologists can expand fundamental knowledge and apply that knowledge to improvements in medicine, industry and agriculture is set to expand in an exponential fashion. At the heart of these advancements will be the use of gene editing tools such as zinc finger nucleases, modified meganucleases, hybrid DNA/RNA oligonucleotides, TAL effector nucleases and modified CRISPR/Cas9. Each of these tools has the ability to precisely target one specific DNA sequence within a genome and (except for DNA/RNA oligonucleotides) to create a double‐stranded DNA break. DNA repair to such breaks sometimes leads to gene knockouts or gene replacement by homologous recombination if exogenously supplied homologous DNA fragments are made available. Genome rearrangements are also possible to engineer. Creation and use of such genome rearrangements, gene knockouts and gene replacements by the plant science community is gaining significant momentum. To document some of this progress and to explore the technology's longer term potential, this review highlights present and future uses of designer nucleases to greatly expedite research with model plant systems and to engineer genes and genomes in major and minor crop species for enhanced food production.
Diagnostic endoscopy of the navicular bursa using a needle endoscope by direct or transthecal approach: A comparative cadaver study
Authors: Mählmann Kathrin , Koch Christoph , Bodó Gábor 
Published: August 2015

ObjectivesTo compare the practicability, visualization of structures, and iatrogenic damage of direct and transthecal approaches to the navicular bursa for diagnostic needle endoscopy.Study designDescriptive study.Sample PopulationEquine cadaver forelimbs (n = 30).MethodsDirect and transthecal approaches for insertion of a needle endoscope into the navicular bursa were performed. Video recordings of endoscopic procedures were assessed to determine all structures visualized within the navicular bursa. Number of attempts to gain access to the navicular bursa and total time for insertion and examination were recorded. Distribution and severity of iatrogenic lesions were assessed and scored after dissection.ResultsThere were no statistical differences for number of attempts or time needed for insertion and examination between direct and transthecal approaches. The direct approach offered significantly increased visibility of the ipsilateral abaxial and proximal margins of the navicular bone, and ipsilateral collateral sesamoidean ligament. Iatrogenic lesions were superficial and focal, regardless of approach taken, or whether a blunt or sharp trocar tip was used.ConclusionsThe direct approach provided significantly better visualization of the ipsilateral structures within the navicular bursa compared to the transthecal approach. Needle endoscopy offers a reliable technique to evaluate the navicular bursa and may complement or replace other diagnostic modalities in horses with lameness localized to the navicular region.
Caveolae regulate vasoconstriction of conduit arteries to angiotensin II in hindlimb unweighted rats
Authors: Wang Zhongchao , Bai Yungang , Yu Jinwen , Liu Huan , Cheng Yaoping , Liu Yonghong , Xie Xiaoping , Ma Jin , Bao Junxiang 
Published: August 2015

Key points
Exposure to microgravity induces postflight orthostatic intolerance on re‐exposure to 1 G gravity which is second to the structural and functional remodelling of arteries.
We found the maximal developed force (Emax) of angiotensin II‐elicited vasoconstriction was decreased in abdominal aorta, unchanged in thoracic aorta and increased in carotid artery by simulated weightlessness. However, the sensitivity of the response (EC50) was decreased in all of the arteries as was the desensitization of angiotensin II type I receptor (AT1) upon angiotensin II stimulation.
We demonstrate that caveolae on vascular smooth muscle cells play a key role in the adaptation of EC50 and AT1 desensitization, but not Emax of the response to simulated weightlessness.
This study gives insight into the mechanism underlying the arterial functional remodelling during weightlessness. Further, the findings might stimulate new ideas for research into countermeasures to postflight orthostatic intolerance upon astronauts returning to the earth.
AbstractWeightlessness induces the functional remodelling of arteries, but the changes to angiotensin II (Ang II)‐elicited vasoconstriction and the underlying mechanism have never been reported. Caveolae are invaginations of the cell membrane crucial for the contraction of vascular smooth muscle cells, so we investigated the adaptation of Ang II‐elicited vasoconstriction to simulated weightlessness and the role of caveolae in it. The 4 week hindlimb unweighted (HU) rat was used to simulate the effects of weightlessness. Ang II‐elicited vasoconstriction was measured by isometric force recording. The morphology of caveolae was examined by transmission electron microscope. The binding of the angiotensin II type 1 receptor (AT1) and caveolin‐1 (cav‐1) was examined by coimmunoprecipitation and Western blot. We found that the maximal developing force (Emax) of Ang II‐elicited vasoconstriction was decreased in abdominal aorta by 30.6%, unchanged in thoracic aorta and increased in carotid artery by 17.9% after HU, while EC50 of the response was increased in all three arteries (P < 0.05). AT1 desensitization upon activation was significantly reduced by HU in all three arteries, as was the number of caveolae (P < 0.05). Furthermore, Ang II promoted the binding of AT1 and cav‐1 significantly in control but not HU arteries. Both the number of caveolae and the binding of AT1 and cav‐1 in HU arteries were restored by cholesterol pretreatment which also reinstated the change in EC50 as well as the level of AT1 desensitization. These results indicate that modified caveolae in vascular smooth muscle cells could interfere with the binding of AT1 and cav‐1 mediating the adaptation of Ang II‐elicited vasoconstriction to HU.