bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human platelet antigen antibody induction in uncomplicated pregnancy is associated with HLA sensitization
Authors: Reiher Viktoria S.A. , Hönger Gideon , Infanti Laura , Passweg Jakob R. , Hösli Irene , Frey Beat M. , Gassner Christoph , Meyer Stefan , Buser Andreas S. , Holbro Andreas , Schaub Stefan 
Published: March 2017

BACKGROUNDAlloimmunization against human platelet antigens (HPAs) during pregnancy is rare but can lead to severe bleeding disorders, such as fetal and neonatal alloimmune thrombocytopenia.STUDY DESIGN AND METHODSIn a cohort of 241 uncomplicated pregnancies, we investigated the immunogenicity of HPA mismatches and correlated HLA sensitization with HPA antibody formation. HPA antibodies were measured with a Luminex‐based multiplex assay.RESULTSHPA mismatches were observed in 109 of 241 pregnancies (45%), but child‐specific HPA antibodies were only found in two of 109 cases (2%), indicating a low immunogenicity. Only nine of 241 women (4%) had detectable HPA antibodies. HLA sensitization was identified as a strong and independent predictor for HPA antibody formation (hazard ratio, 10.2; 95% confidence interval, 1.8‐193; p = 0.006), whereas the number of pregnancies was not.CONCLUSIONOur observational data indicated a low immunogenicity of HPA and suggest that a broader immune response—inferred by HLA sensitization—is probably associated with HPA antibody induction.
STAT3 potentiates the ability of airway smooth muscle cells to promote angiogenesis by regulating VEGF signalling
Authors: Lv Jing , Sun Baohua , Mai Zhitao , Jiang Mingming , Du Junfeng 
Published: March 2017

New Findings
What is the central question of this study?
Airway angiogenesis occurs in asthma, and airway smooth muscle (ASM) cells have been reported to be capable of promoting airway angiogenesis. What is the potential mechanism by which ASM cells harvested from patients with asthma are capable of promoting airway angiogenesis?

What is the main finding and its importance?
Endogenous STAT3 mediated the pro‐angiogenic ability of ASM cells by directly activating VEGF signalling. These findings contribute to the understanding of airway angiogenesis in pathology and could represent a possible therapeutic target for asthma.

Airway angiogenesis indicates the specific vascular structure remodelling that occurs in asthma. Airway smooth muscle (ASM) cells have been reported to be capable of promoting airway angiogenesis; however, the potential mechanism is not yet fully defined. Herein, we investigated the role of signal transducer and activator of transcription 3 (STAT3) in the progress of airway angiogenesis. Western blot analysis showed that STAT3 activation was aberrantly upregulated in ASM tissues of patients with asthma and ASM cells that were exposed to cytokines to imitate the airway conditions in patients with asthma. Compared with the control group, both the inhibition of STAT3 activation and the silencing of endogenous STAT3 in ASM cells significantly reduced the proliferation, migration and tube‐forming ability of human lung microvascular endothelial cells induced by the conditioned medium (CM) of ASM cells. The increased proliferation and migration of human aortic vascular smooth muscle cells were also repressed by inhibition of STAT3 in ASM cells. Besides, the increased activity of VEGF signalling was observed in ASM cells and the CM by RT‐PCR and Western blotting assay, whereas this increased activity was reduced by STAT3 silencing. Further studies indicated that STAT3 regulated VEGF activation by directly interacting with the binding site on the 5′ region of the VEGF gene. The increase in STAT3‐induced pro‐angiogenic activity of ASM cells was significantly decreased by administration of VEGF neutralizing antibody. In conclusion, we provided evidence that endogenous STAT3 mediates the pro‐angiogenic ability of ASM cells by directly activating VEGF signalling, which could represent a possible therapeutic target for asthma.
Evidence for a functional vasoconstrictor role for ATP in the human cutaneous microvasculature
Authors: Lang James A. , Krajek Alex C. , Smaller Kevin A. 
Published: March 2017

New Findings
What is the central question of this study?
In young adults, about half of the cold‐related reduction in skin blood flow during cold exposure is mediated by noradrenaline, while the remainder is attributable to other substances co‐released with noradrenaline that have yet to be identified.
What is the main finding and its importance?
Purinergic receptor blockade blunted the vasoconstriction response to whole‐body cooling and to intradermal administration of tyramine. These results indicate that ATP is necessary to vasoconstrict blood vessels in the skin adequately and prevent heat loss in a cold environment.
Noradrenaline is responsible for eliciting ∼60% of the reflex cutaneous vasoconstriction (VC) response in young adults, while the remainder is attributable to one or more unidentified co‐released sympathetic adrenergic neurotransmitter(s). Inconsistent evidence has placed neuropeptide Y in this role; however, other putative cotransmitters have yet to be tested. We hypothesize that ATP contributes to the reflex cutaneous VC response. Two protocols were conducted in young adults (n = 10); both involved the placement of three microdialysis probes in forearm skin and whole‐body cooling (skin temperature = 30.5°C). In protocol 1, the following solutions were infused: (i) lactated Ringer solution (control); (ii) 10 mm l‐NAME; and (iii) purinergic receptor blockade with 1 mm suramin plus l‐NAME. In protocol 2, the following solutions were infused: (i) lactated Ringer solution; (ii) suramin plus l‐NAME; and (iii) suramin plus l‐NAME plus adrenoreceptor blockade with 5 mm yohimbine plus 1 mm propranolol. Laser Doppler flux (LDF) was measured over each microdialysis site, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP) and expressed as percentage changes from baseline (%ΔCVCBASELINE). l‐NAME was used to block the vasodilatory influence of ATP and unmask the P2X‐mediated VC response to exogenous ATP infusion (−21 ± 6%ΔCVCBASELINE). During cooling, the VC response (control, −39 ± 8%ΔCVCBASELINE) was attenuated at the suramin site (−21 ± 4%ΔCVCBASELINE) and further blunted with combined adrenoreceptor blockade (−9 ± 3%ΔCVCBASELINE; P < 0.05). Compared with the control site (−22 ± 5%ΔCVCBASELINE), suramin inhibited pharmacologically induced VC to tyramine (−12 ± 6%ΔCVCBASELINE; P < 0.05), which displaces adrenergic neurotransmitters from axon terminals. These data indicate that ATP contributes to the cutaneous VC response in humans.
Remuscularization of the failing heart
Authors: Zimmermann Wolfram‐Hubertus 
Published: March 2017

AbstractMyocardial remuscularization can be achieved by cardiomyocyte implantation. Electromechanical integration and long‐term survival of cardiomyocyte grafts are essential for maximal therapeutic impact. Cardiomyocyte application with support material has been instrumental in enhancing cell retention. Co‐administration of pro‐survival factors and immunological matching are additional strategies for increased cell graft survival. Finally, larger cardiomyocyte grafts, although therapeutically desirable, will increase the risk for arrhythmias and, if pluripotent stem cells are used to derive cardiomyocytes, tumour formation. This review introduces major challenges pertaining to myocardial remuscularization (cardiomyocyte retention, arrhythmogenicity and tumourigenicity), discusses studies addressing these challenges, and suggests strategies to overcome remaining challenges for the translation of myocardial remuscularization.
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Mechano‐chemo‐transduction in cardiac myocytes
Authors: Chen‐Izu Ye , Izu Leighton T. 
Published: March 2017

AbstractThe heart has the ability to adjust to changing mechanical loads. The Frank–Starling law and the Anrep effect describe exquisite intrinsic mechanisms the heart has for autoregulating the force of contraction to maintain cardiac output under changes of preload and afterload. Although these mechanisms have been known for more than a century, their cellular and molecular underpinnings are still debated. How does the cardiac myocyte sense changes in preload or afterload? How does the myocyte adjust its response to compensate for such changes? In cardiac myocytes Ca2+ is a crucial regulator of contractile force and in this review we compare and contrast recent studies from different labs that address these two important questions. The ‘dimensionality’ of the mechanical milieu under which experiments are carried out provide important clues to the location of the mechanosensors and the kinds of mechanical forces they can sense and respond to. As a first approximation, sensors inside the myocyte appear to modulate reactive oxygen species while sensors on the cell surface appear to also modulate nitric oxide signalling; both signalling pathways affect Ca2+ handling. Undoubtedly, further studies will add layers to this simplified picture. Clarifying the intimate links from cellular mechanics to reactive oxygen species and nitric oxide signalling and to Ca2+ handling will deepen our understanding of the Frank–Starling law and the Anrep effect, and also provide a unified view on how arrhythmias may arise in seemingly disparate diseases that have in common altered myocyte mechanics.
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Top down control of spinal sensorimotor circuits essential for survival
Authors: Koutsikou Stella , Apps Richard , Lumb Bridget M. 
Published: March 2017

AbstractThe ability to interact with challenging environments requires coordination of sensory and motor systems that underpin appropriate survival behaviours. All animals, including humans, use active and passive coping strategies to react to escapable or inescapable threats, respectively. Across species the neural pathways involved in survival behaviours are highly conserved and there is a consensus that knowledge of such pathways is a fundamental step towards understanding the neural circuits underpinning emotion in humans and treating anxiety or other prevalent emotional disorders. The midbrain periaqueductal grey (PAG) lies at the heart of the defence‐arousal system and its integrity is paramount to the expression of survival behaviours. To date, studies of ‘top down control’ components of defence behaviours have focused largely on the sensory and autonomic consequences of PAG activation. In this context, effects on motor activity have received comparatively little attention, despite overwhelming evidence of a pivotal role for the PAG in coordinating motor responses essential to survival (e.g. such as freezing in response to fear). In this article we provide an overview of top down control of sensory functions from the PAG, including selective control of different modalities of sensory, including proprioceptive, information forwarded to a major supsraspinal motor control centre, the cerebellum. Next, evidence from our own and other laboratories of PAG control of motor outflow is also discussed. Finally, the integration of sensorimotor functions by the PAG is considered, as part of coordinated defence behaviours that prepare an animal to be ready and able to react to danger.
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Complete Genome Sequence of a Staphylococcus epidermidis Strain with Exceptional Antimicrobial Activity
Authors: Lassen Simon B. , Lomholt Hans B. , Brüggemann Holger 
Published: March 2017

ABSTRACT

Staphylococcus epidermidis
is a Gram-positive bacterium that is prevalent on human skin. The species is associated with skin health, as well as with opportunistic infections. Here, we report the complete genome sequence of
S. epidermidis
14.1.R1, isolated from human skin. In bacterial interference assays, the strain showed exceptional antimicrobial activity.
Draft Genome Sequence of
Pseudoalteromonas
sp. Strain PAB 2.2 Isolated from Abrolhos Bank (Brazil)
Authors: Silva Bruno S. O. , Nobrega Maria S. , Leomil Luciana , Tschoeke Diogo A. , Garcia Gizele D. , Dias Graciela , Thompson Cristiane C. , Thompson Fabiano L. 
Published: March 2017

ABSTRACT

We present here the draft genome sequence of
Pseudoalteromonas
sp. strain PAB 2.2, isolated from water of Parcel de Abrolhos coral reef (17°57′32.7″; 38°30′20.3″), on Abrolhos Bank, at a depth of 12 m. The assembly consists of 4,434,635 bp and contains 40 contigs, with a G+C content of 41.60%.
Draft Genome Sequence of Lactobacillus reuteri 121, a Source of α-Glucan and β-Fructan Exopolysaccharides
Authors: Gangoiti Joana , Meng Xiangfeng , Lammerts van Bueren Alicia , Dijkhuizen Lubbert 
Published: March 2017

ABSTRACT

The probiotic bacterium
Lactobacillus reuteri
121 is a well-known producer of diverse homoexopolysaccharides (α-glucans and β-fructans) from sucrose and maltodextrins/starches of interest for food applications. Here, we report the draft genome sequence of this strain, with a focus on carbohydrate-active enzymes.
The risk of injury associated with body checking among Pee Wee ice hockey players: an evaluation of Hockey Canada’s national body checking policy change
Authors: Black Amanda M , Hagel Brent E , Palacios-Derflingher Luz , Schneider Kathryn J , Emery Carolyn A 
Published: March 2017

BackgroundIn 2013, Hockey Canada introduced an evidence-informed policy change delaying the earliest age of introduction to body checking in ice hockey until Bantam (ages 13–14) nationwide.ObjectiveTo determine if the risk of injury, including concussions, changes for Pee Wee (11–12 years) ice hockey players in the season following a national policy change disallowing body checking.MethodsIn a historical cohort study, Pee Wee players were recruited from teams in all divisions of play in 2011–2012 prior to the rule change and in 2013–2014 following the change. Baseline information, injury and exposure data for both cohorts were collected using validated injury surveillance.ResultsPee Wee players were recruited from 59 teams in Calgary, Alberta (n=883) in 2011–2012 and from 73 teams in 2013–2014 (n=618). There were 163 game-related injuries (incidence rate (IR)=4.37/1000 game-hours) and 104 concussions (IR=2.79/1000 game-hours) in Alberta prior to the rule change, and 48 injuries (IR=2.16/1000 game-hours) and 25 concussions (IR=1.12/1000 game-hours) after the rule change. Based on multivariable Poisson regression with exposure hours as an offset, the adjusted incidence rate ratio associated with the national policy change disallowing body checking was 0.50 for all game-related injuries (95% CI 0.33 to 0.75) and 0.36 for concussion specifically (95% CI 0.22 to 0.58).ConclusionsIntroduction of the 2013 national body checking policy change disallowing body checking in Pee Wee resulted in a 50% relative reduction in injury rate and a 64% reduction in concussion rate in 11-year-old and 12-year-old hockey players in Alberta.
Development of a high resolution MRI intracranial atherosclerosis imaging phantom
Authors: Chueh Ju-Yu , van der Marel Kajo , Gounis Matthew J , LeMatty Todd , Brown Truman R , Ansari Sameer A , Carroll Timothy J , Buck Amanda K , Zhou Xiaohong Joe , Chatterjee A Rano , King Robert M , Mao Hui , Zheng Shaokuan , Brooks Olivia W , Rappleye Jeff W , Swartz Richard H , Feldmann Edward , Turan Tanya N 
Published: March 2017

Background and purposeCurrently, there is neither a standard protocol for vessel wall MR imaging of intracranial atherosclerotic disease (ICAD) nor a gold standard phantom to compare MR sequences. In this study, a plaque phantom is developed and characterized that provides a platform for establishing a uniform imaging approach for ICAD.Materials and methodsA patient specific injection mold was 3D printed to construct a geometrically accurate ICAD phantom. Polyvinyl alcohol hydrogel was infused into the core shell mold to form the stenotic artery. The ICAD phantom incorporated materials mimicking a stenotic vessel and plaque components, including fibrous cap and lipid core. Two phantoms were scanned using high resolution cone beam CT and compared with four different 3 T MRI systems across eight different sites over a period of 18 months. Inter-phantom variability was assessed by lumen dimensions and contrast to noise ratio (CNR).ResultsQuantitative evaluation of the minimum lumen radius in the stenosis showed that the radius was on average 0.80 mm (95% CI 0.77 to 0.82 mm) in model 1 and 0.77 mm (95% CI 0.74 to 0.81 mm) in model 2. The highest CNRs were observed for comparisons between lipid and vessel wall. To evaluate manufacturing reproducibility, the CNR variability between the two models had an average absolute difference of 4.31 (95% CI 3.82 to 5.78). Variation in CNR between the images from the same scanner separated by 7 months was 2.5–6.2, showing reproducible phantom durability.ConclusionsA plaque phantom composed of a stenotic vessel wall and plaque components was successfully constructed for multicenter high resolution MRI standardization.
Attendance of MSM at Genitourinary Medicine services in England: implications for selective HPV vaccination programme (a short communication)
Authors: Bayley Jake , Mesher David , Nadarzynski Tom , Hughes Gwenda , Soldan Kate 
Published: March 2017

BackgroundHuman papillomaviruses (HPV) immunisation programmes for female adolescents in the UK offer relatively little benefit to men who have sex with men (MSM). Targeted HPV vaccination for MSM may reduce the high incidence of HPV-related disease among MSM. We used national data from sexual health clinics to calculate the number of MSM attending these clinics throughout England from 2009 to 2014 and to identify their characteristics, to inform the implementation of a targeted HPV vaccination programme in MSM.MethodsWe used the Genitourinary Medicine Clinic Activity Dataset (GUMCADv2) to obtain data for men aged 15–70 years who had attended a GUM clinic in England from 2009 to 2014. We analysed both numbers of MSM attending and number of GUM attendances, age at first attendance, ethnicity and geographical area of the clinic in England.ResultsA total of 374 983 MSM attended sexual health services in England between 2009 and 2014. Median age of presentation was 32 years (IQR 25–41) and showed regional geographical variation. Of all men attending sexual health clinics in England, the highest proportion of those identifying as MSM was in London (21%). Excluding visits within 1 month of an initial attendance, 49% of all MSM re-attended within 12 months and 58% within 24 months. MSM aged ≥36 years reattended more frequently than younger MSM. 51% reattended at least twice within 24 months of initial visit.ConclusionsThe majority of MSM reattend clinic at least once within a 24-month period, potentially facilitating the delivery of a three-dose HPV vaccination programme. This would reduce the burden on sexual health clinics and cost to local authorities due to extra visits if HPV vaccination were to be delivered through these services.
Reforming in a Difficult Macroeconomic Context: A Review of Issues and Recent Literature
Authors: Sánchez Aida Caldera , de Serres Alain , Yashiro Naomitsu 
Published: March 2017

This paper reviews the main issues related to the short-term impact of structural reforms in different macroeconomic contexts and takes stock of existing theoretical and empirical studies. Taking reforms introduced in “normal” times as a benchmark, it reviews the available evidence on the impact of reforms that are implemented in “bad” times — defined as the presence of a sizeable negative output gap and persistently weak demand — as well as under different assumptions regarding the availability or effectiveness of macroeconomic policies in supporting the reforms. In doing so, the paper focuses on the key channels through which different reforms influence short-term activity via the main components of demand and discusses how these channels operate under different macro conditions.
Effects of β-adrenergic receptor drugs on embryonic ventricular cell proliferation and differentiation and their impact on donor cell transplantation
Authors: Feridooni Tiam , Hotchkiss Adam , Baguma-Nibasheka Mark , Zhang Feixiong , Allen Brittney , Chinni Sarita , Pasumarthi Kishore B. S. 
Published: March 2017

β-Adrenergic receptors (β-ARs) and catecholamines are present in rodents as early as embryonic day (E)10.5. However, it is not known whether β-AR signaling plays any role in the proliferation and differentiation of ventricular cells in the embryonic heart. Here, we characterized expression profiles of β-AR subtypes and established dose-response curves for the nonselective β-AR agonist isoproterenol (ISO) in the developing mouse ventricular cells. Furthermore, we investigated the effects of ISO on cell cycle activity and differentiation of cultured E11.5 ventricular cells. ISO treatment significantly reduced tritiated thymidine incorporation and cell proliferation rates in both cardiac progenitor cell and cardiomyocyte populations. The ISO-mediated effects on DNA synthesis could be abolished by cotreatment of E11.5 cultures with either metoprolol (a β1-AR antagonist) or ICI-118,551 (a β2-AR antagonist). In contrast, ISO-mediated effects on cell proliferation could be abolished only by metoprolol. Furthermore, ISO treatment significantly increased the percentage of differentiated cardiomyocytes compared with that in control cultures. Additional experiments revealed that β-AR stimulation leads to downregulation of Erk and Akt phosphorylation followed by significant decreases in cyclin D1 and cyclin-dependent kinase 4 levels in E11.5 ventricular cells. Consistent with in vitro results, we found that chronic stimulation of recipient mice with ISO after intracardiac cell transplantation significantly decreased graft size, whereas metoprolol protected grafts from the inhibitory effects of systemic catecholamines. Collectively, these results underscore the effects of β-AR signaling in cardiac development as well as graft expansion after cell transplantation. NEW & NOTEWORTHY β-Adrenergic receptor (β-AR) stimulation can decrease the proliferation of embryonic ventricular cells in vitro and reduce the graft size after intracardiac cell transplantation. In contrast, β1-AR antagonists can abrogate the antiproliferative effects mediated by β-AR stimulation and increase graft size. These results highlight potential interactions between adrenergic drugs and cell transplantation.