bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Mandatory Helmet-Use Legislation on the Frequency of Cycling to School and Helmet Use Among Adolescents
Authors: Molina-García Javier , Queralt Ana
Published: January 2016

Background:

This paper analyzes changes in the frequency of cycling to school and helmet wearing after the introduction of a mandatory helmet law, and attempts to identify factors associated with the acceptance of helmet use.

Methods:

A mixed-method study was designed with a 7-month follow-up period (April 2014 to November 2014). The initial sample included 262 students (aged 12 to 16 years) from Valencia, Spain. The data were collected by questionnaire and 2 focus-group interviews were conducted.

Results:

No significant changes in cyclingto-school behavior were found during the study period. Cycle helmet use improved, especially among boys, those who used their own bike, and among adolescents who lived within 2 km of school (P < .05 in all cases). The most common reasons given for not using a helmet were social factors. Peer-group pressure had a negative influence on helmet use among adolescents. Participants also indicated that helmet use is inconvenient, in particular among students who used the public bicycle-sharing program.

Conclusions:

The implementation of the helmet-use law did not have a negative impact on the frequency of cycling to school. Our findings provide an empirical basis for designing educational interventions and programs to increase helmet use among adolescents.
Enhanced seasonal CO
2
exchange caused by amplified plant productivity in northern ecosystems
Authors: Forkel Matthias , Carvalhais Nuno , Rödenbeck Christian , Keeling Ralph , Heimann Martin , Thonicke Kirsten , Zaehle Sönke , Reichstein Markus
Published: January 2016

Warming making bigger CO
2
swings

The combined effects of climate change and vegetation dynamics at high northern latitudes have amplified the seasonal variation of atmospheric CO
2
concentrations over the past half century. Forkel
et al.
combined observations and models to show that climate warming has caused the photosynthetic uptake of carbon to increase faster than its respiratory release from the terrestrial biosphere. This has increased the difference from summer to winter, as well as the latitudinal gradient. Because of the physiological limitations to carbon uptake by terrestrial vegetation, this negative feedback to warming in the boreal north and Arctic cannot continue indefinitely.

Science
, this issue p.
696
Broadly targeted CD8
+
T cell responses restricted by major histocompatibility complex E
Authors: Hansen Scott G. , Wu Helen L. , Burwitz Benjamin J. , Hughes Colette M. , Hammond Katherine B. , Ventura Abigail B. , Reed Jason S. , Gilbride Roxanne M. , Ainslie Emily , Morrow David W. , Ford Julia C. , Selseth Andrea N. , Pathak Reesab , Malouli Daniel , Legasse Alfred W. , Axthelm Michael K. , Nelson Jay A. , Gillespie Geraldine M. , Walters Lucy C. , Brackenridge Simon , Sharpe Hannah R. , López César A. , Früh Klaus , Korber Bette T. , McMichael Andrew J. , Gnanakaran S. , Sacha Jonah B. , Picker Louis J.
Published: January 2016

An unconventional route to protection

One promising approach toward an HIV-1 vaccine involves infecting people with cytomegalovirus engineered to express proteins from HIV-1. This approach, which works by eliciting virus-killing CD8
+
T cells, provides robust protection in nonhuman primate models. Hansen
et al.
have found out why this approach is so effective. Normally, peptide antigens presented by major histocompatibility complex-1a (MHC-Ia) activate CD8
+
T cells. In vaccinated monkeys, however, CD8
+
T cells reacted to peptide antigens presented by MHC-E molecules instead. Moreover, MHC-E could present a much wider range of peptides than MHC-Ia.

Science
, this issue p.
714
Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells
Authors: Soucie Erinn L. , Weng Ziming , Geirsdóttir Laufey , Molawi Kaaweh , Maurizio Julien , Fenouil Romain , Mossadegh-Keller Noushine , Gimenez Gregory , VanHille Laurent , Beniazza Meryam , Favret Jeremy , Berruyer Carole , Perrin Pierre , Hacohen Nir , Andrau J.-C. , Ferrier Pierre , Dubreuil Patrice , Sidow Arend , Sieweke Michael H.
Published: January 2016

Genetic programming for self-renewal

Instead of repopulating themselves from tissue-resident stem cell pools like most types of differentiated cells, tissue macrophages maintain themselves by self-renewing. The underlying genetic programs that allow for this, however, are unknown. Soucie
et al.
now report that in macrophages at homeostasis, a pair of transcription factors (MafB and c-Maf) bind to and repress the enhancers of genes regulating self-renewal. When macrophages need to replenish their stocks, for example in response to injury, they transiently decrease MafB and c-Maf expression so they can self-renew. A parallel pathway also operates to control the self-renewal of embryonic stem cells.

Science
, this issue p.
10.1126/science.aad5510
Ubiquitinated Fancd2 recruits Fan1 to stalled replication forks to prevent genome instability
Authors: Lachaud Christophe , Moreno Alberto , Marchesi Francesco , Toth Rachel , Blow J. Julian , Rouse John
Published: January 2016

A key player in cancer prevention

Obstacles that block DNA replication can lead to chromosomal abnormalities and ultimately cancer. Fanconi anemia, for example, is caused by defects in the repair of DNA interstrand cross-links. The Fan1 nuclease was originally identified as a protein essential for this cross-link repair. Lachaud
et al
. now show that it does much more. It is recruited to stalled replication forks by ubiquitinated Fancd2 enabling the processing of these structures, thereby preventing chromosomal abnormalities and acting more broadly in cancer prevention.

Science
, this issue p.
846
Complete Genome Sequence of Lysinibacillus sphaericus B1-CDA, a Bacterium That Accumulates Arsenic
Authors: Rahman Aminur , Nahar Noor , Jass Jana , Olsson Björn , Mandal Abul
Published: January 2016

Here, we report the genomic sequence and genetic composition of an arsenic-resistant bacterium,
Lysinibacillus sphaericus
B1-CDA. Assembly of the sequencing reads revealed that the genome size is ~4.5 Mb, encompassing ~80% of the chromosomal DNA.
Inhangapi Virus: Genome Sequencing of a Brazilian Ungrouped Rhabdovirus Isolated in the Amazon Region
Authors: Wanzeller Ana Lucia M. , Nunes Márcio R. T. , Tavares Fernando N. , Pinto Walber V. M. , Júnior Edivaldo C. , de Lima Clayton P. S. , de Oliveira Layanna F. , Júnior João Lídio S. G. V. , Cardoso Jedson F. , Vasconcelos Pedro F. C.
Published: January 2016

We report here nearly complete genome sequence of Inhangapi virus (INHV) strain BEAR177325, which was isolated from a pool of sandflies (
Lutzomyia flaviscutellata
) in the Utinga neighborhood, Belém (01º28´S 48°27′W), State of Pará, Brazil, in 1969. The genome of this virus showed similarity with members belonging to the family
Rhabdoviridae
.
Draft Genome Sequence of Streptomyces vitaminophilus ATCC 31673, a Producer of Pyrrolomycin Antibiotics, Some of Which Contain a Nitro Group
Authors: Mahan Kristina M. , Klingeman Dawn M. , Hettich Robert L. , Parry Ronald J. , Graham David E.
Published: January 2016

Streptomyces vitaminophilus
produces pyrrolomycins, which are halogenated polyketide antibiotics. Some of the pyrrolomycins contain a rare nitro group located on the pyrrole ring. The 6.5-Mbp genome encodes 5,941 predicted protein-coding sequences in 39 contigs with a 71.9% G+C content.
Draft Genome Sequence of
Janthinobacterium
sp. Ant5-2-1, Isolated from Proglacial Lake Podprudnoye in the Schirmacher Oasis of East Antarctica
Authors: Koo Hyunmin , Strope Bailey M. , Kim Eddy H. , Shabani Adel M. , Kumar Ranjit , Crowley Michael R. , Andersen Dale T. , Bej Asim K.
Published: January 2016

Janthinobacterium
sp. Ant5-2-1, isolated from the Schirmacher Oasis of East Antarctica, produces a purple-violet pigment, manifests diverse energy metabolism abilities, and tolerates cold, ultraviolet radiation, and other environmental stressors. We report here the 6.19-Mb draft genome of strain Ant5-2-1, which will help understand its survival mechanisms in extreme Antarctic ecosystems.
Complete Genome Sequences of the Obligate Symbionts “
Candidatus
Sulcia muelleri” and “
Ca.
Nasuia deltocephalinicola” from the Pestiferous Leafhopper
Macrosteles quadripunctulatus
(Hemiptera: Cicadellidae)
Authors: Bennett Gordon M. , Abbà Simona , Kube Michael , Marzachì Cristina
Published: January 2016

Two bacterial symbionts of the European pest leafhopper,
Macrosteles quadripunctulatus
(Hemiptera: Cicadellidae), were fully sequenced. “
Candidatus
Sulcia muelleri” and “
Ca
. Nasuia deltocephalinicola” represent two of the smallest known bacterial genomes at 190 kb and 112 kb, respectively. Genome sequences are nearly identical to strains reported from the closely related host species,
M. quadrilineatus
.
Injury prevention strategies, coach compliance and player adherence of 33 of the UEFA Elite Club Injury Study teams: a survey of teams’ head medical officers
Authors: McCall Alan , Dupont Gregory , Ekstrand Jan
Published: January 2016

Purpose

(1) To quantify current practice at the most elite level of professional club football in Europe with regard to injury prevention strategy; (2) to describe player adherence and coach compliance to the overall injury prevention programme.

Methods

A structured online survey was administered to the Head medical officers of 34 elite European teams currently participating in the UEFA Elite Club Injury Study. The survey had 4 sections; (1) risk factors for injury, (2) assessment and monitoring of injury risk, (3) prevention strategies and (4) coach compliance and player adherence to the injury prevention process.

Results

33 (97%) Medical officers of the teams responded. The most important perceived injury risk factor was previous injury. Four of the top 6 risk factors—physical fitness, accumulated fatigue, reduced recovery time between matches and training load—were related to player workload. The top 3 preventative exercises were eccentric, balance/proprioception and core training. Regarding monitoring, the top 3 tools implemented were measurement of workload, subjective wellness and a general medical screen. The subjectively rated level of coach compliance in UEFA teams was perceived as ‘high’, while the player adherence varied from none at all to perfect.

Summary and conclusion

Medical officers place importance on workload-related variables as risk factors for injury in elite European football players. A lack of consistently high player adherence may limit the effects of contemporary injury prevention programmes in elite European footballers.
Initial experience in setting up a medical student first responder scheme in South Central England
Authors: Seligman William H , Ganatra Sameer , England David , Black John J M
Published: January 2016

Prehospital emergency medicine (PHEM) is a recently recognised subspecialty of emergency medicine, and anaesthetics, intensive care and acute medicine, in the UK, and yet it receives little to no mention in many undergraduate medical curricula. However, there is growing interest in PHEM among medical students and junior doctors. Several programmes are in existence across the UK that serve to provide teaching and exposure of prehospital care to medical students and junior doctors. However, relatively few students are able to gain significant first-hand experience of treating patients in the prehospital phase. In this short report, we discuss our experience of launching the student first responder (SFR) scheme across three counties in the Thames Valley. Medical students are trained by the regional ambulance service and respond to life-threatening medical emergencies in an ambulance response vehicle. The scheme is likely to benefit the ambulance service by providing a wider pool of trained volunteer first responders able to attend to emergency calls, to benefit patients by providing a quick response at their time of need, and to benefit medical students by providing first-hand experience of medical emergencies in the community. In its first 15 months of operation, SFRs were dispatched to 343 incidents. This scheme can serve as a training model for other ambulance services and medical schools across the UK.
Delays to initial reduction attempt are associated with higher failure rates in anterior shoulder dislocation: a retrospective analysis of factors affecting reduction failure
Authors: Kanji Avinash , Atkinson Paul , Fraser Jacqueline , Lewis David , Benjamin Susan
Published: January 2016

Introduction

Little is understood about the relationship between delay to treatment and initial reduction success for anterior shoulder dislocation. Our study examines whether delays to initial treatment, from injury and hospital presentation, are associated with higher reduction failure rates for anterior shoulder dislocation.

Methods

A retrospective database and chart review was performed for patients undergoing intravenous sedation for attempted reduction of anterior shoulder dislocation in the emergency department (ED). Stepwise regression analysis was performed to identify predictors of reduction failure. Key variables analysed were the duration of the wait in the ED, the interval between the time of injury and first intervention and the interval from time of injury to arrival at the ED. Possible confounding variables analysed included age, gender, dose of sedative agent, qualifications of the reducing physician and whether the dislocated shoulder was recurrent.

Results

The duration of the intervals from injury to first reduction attempt and from arrival at the ED to first reduction attempt were both independent predictors of a higher reduction failure rate (OR=1.07, 95% CI 1.02 to 1.13; OR=1.19, 95% CI 1.05 to 1.34). Every interval of 10 min increased the odds of a failed reduction attempt by 7% and 19%, respectively. Overall, shoulder reduction was successful during the initial sedation event in 97 cases (92%) and unsuccessful in nine cases (8%).

Conclusions

Delays to first reduction attempt either from the time of injury or within the ED are associated with a lower reduction success rate for anterior shoulder dislocations.
Less frequently mutated genes in colorectal cancer: evidences from next-generation sequencing of 653 routine cases
Authors: Malapelle Umberto , Pisapia Pasquale , Sgariglia Roberta , Vigliar Elena , Biglietto Maria , Carlomagno Chiara , Giuffrè Giuseppe , Bellevicine Claudio , Troncone Giancarlo
Published: January 2016

Aims

The incidence ofRAS/RAF/PI3KAandTP53gene mutations in colorectal cancer (CRC) is well established. Less information, however, is available on other components of the CRC genomic landscape, which are potential CRC prognostic/predictive markers.

Methods

Following a previous validation study, ion-semiconductor next-generation sequencing (NGS) was employed to process 653 routine CRC samples by a multiplex PCR targeting 91 hotspot regions in 22 CRC significant genes.

Results

A total of 796 somatic mutations in 499 (76.4%) tumours were detected. BesidesRAS/RAF/PI3KAandTP53,other 12 genes showed at least one mutation includingFBXW7(6%),PTEN(2.8%),SMAD4(2.1%),EGFR(1.2%),CTNNB1(1.1%),AKT1(0.9%),STK11(0.8%),ERBB2(0.6%),ERBB4(0.6%),ALK(0.2%),MAP2K1(0.2%) andNOTCH1(0.2%).

Conclusions

In a routine diagnostic setting, NGS had the potential to generate robust and comprehensive genetic information also including less frequently mutated genes potentially relevant for prognostic assessments or for actionable treatments.
Optical coherence tomography versus intravascular ultrasound to evaluate stent implantation in patients with calcific coronary artery disease
Authors: Gudmundsdottir Ingibjorg , Adamson Philip , Gray Calum , Spratt James C , Behan Miles W , Henriksen Peter , Newby David E , Mills Nicholas , Uren Neal G , Cruden Nicholas L
Published: January 2016

Aims

Stent underexpansion and malapposition are associated with adverse outcomes following percutaneous coronary intervention, but detection and treatment can be challenging in the presence of extensive coronary artery calcification. Frequency domain optical coherence tomography (FD-OCT) is a novel intravascular imaging technique with greater spatial resolution than intravascular ultrasound (IVUS) but its role in the presence of extensive coronary calcification remains unclear. We sought to determine the utility of FD-OCT compared to IVUS imaging to guide percutaneous coronary intervention in patients with severe calcific coronary artery disease.

Methods

18 matched IVUS and FD-OCT examinations were evaluated following coronary stent implantation in 12 patients (10 male; mean age 70±7 years) undergoing rotational atherectomy for symptomatic calcific coronary artery disease.

Results

In-stent luminal areas were smaller (minimum in-stent area 6.77±2.18 vs 7.19±2.62 mm2, p<0.05), while reference lumen dimensions were similar with FD-OCT compared with IVUS. Stent malapposition was detected in all patients by FD-OCT and in 10 patients by IVUS. The extent of stent malapposition detected was greater (20% vs 6%, p<0.001) with FD-OCT compared to IVUS. Postdilation increased the in-stent luminal area (minimum in-stent area: 8.15±1.90 vs 7.30±1.62 mm2, p<0.05) and reduced the extent of stent malapposition (19% vs 34%, p<0.005) when assessed by FD-OCT, but not IVUS.

Conclusions

Acute stent malapposition occurs frequently in patients with calcific coronary disease undergoing rotational atherectomy and stent implantation. In the presence of extensive coronary artery calcification, FD-OCT affords enhanced stent visualisation and detection of malapposition, facilitating improved postdilation stent apposition and minimal luminal areas.

Trial Registration number

NCT02065102.
Structural, electronic and optical properties of hexagonal TaN compound
Authors: Chen Zhongjun , Yan Jungan , Kuang Zhong , Chen Taihong , Li Dehua
Published: January 2016

Structural and electronic properties of hexagonal Tantalum nitride (TaN) in CoSn and WC structures are studied using the first-principle calculations. Lattice constants and electronic band structures are in an excellent agreement with the available experimental and other theoretical values. TaN in both structures studied has a metallic nature and a strong hybridization of Ta 5d and N 2p are found from the spin density of states (DOS). Meanwhile, our LSDA+U calculations predicted a strong ferromagnetic state for CoSn-type structure and an obvious paramagnetic nature for WC-type structure. No phase transition are observed within cubic and hexagonal CoSn and WC structures under high pressures. Our results show WC-type TaN is the calculated ground-state structure among the three crystallographic structures studied under 120 GPa. Optical properties show that TaN in CoSn-type structure is a better dielectric material.
A First-Order Fully Cascadable Current-Mode Universal Filter Composed of Dual Output CCIIs and a Grounded Capacitor
Authors: Yuce Erkan , Minaei Shahram
Published: January 2016

In this paper, a new first-order current-mode (CM) universal filter employing two dual output second-generation current conveyors (DO-CCIIs), one resistor and a grounded capacitor is proposed. The proposed filter has low input and high output impedances; thus, it can be easily connected with other CM circuits. It can simultaneously realize first-order low-pass (LP) and all-pass (AP) responses and can provide high-pass (HP) response with interconnection of LP and AP responses. It can be tuned electronically by replacing with dual output second-generation current controlled conveyors (DO-CCCIIs) instead of DO-CCIIs and removing the resistor. It has only a resistor but no capacitor connected in series to X terminal of DO-CCII; accordingly, it can be operated at high frequencies. Also, it does not need any critical passive component matching conditions and cancellation constraints. A number of simulation results based on SPICE program are included to exhibit performance, workability and effectiveness of the proposed filter configuration.
Hybrid Approach of Within-Clock Power Gating and Normal Power Gating to Reduce Power
Authors: Nath Debanjali , Choudhury Priyanka , Pradhan Sambhu Nath
Published: January 2016

Power gating (PG) is used to reduce leakage power by shutting down the power supply of the inactive block of the circuit. PG technique for finite state machine (FSM) is used to reduce not only leakage power but also the switching power of circuit. One FSM is partitioned into two sub-FSMs and encoded for minimizing total power for the power-gated design of the circuit. Depending on the state of the machine, at a time one sub-FSM is power gated by shutting off the power supply. There is a complete eradication of power in power-gated sub-FSM, but another one is in an active mode that continues to dissipate power. There is a scope to reduce leakage in active sub-FSM if the clock period is larger than the critical path delay of the combinational part of this sub-FSM. In this condition, there is a certain portion of the clock period which is idle and in this period PG may be used. The objective of this paper is to reduce power by applying PG at circuit level to the active sub-FSM, whereas, inactive sub-FSM is still power gated. This paper presents a new technique, called WCPG_IN_PG, which reduces the power of active sub-FSM (within the clock period) and power-gated FSM. By varying the frequency, power results are reported for different input combinations.
Searching for Cooperative Security 2.0
Authors: Evans Paul
Published: January 2016

At a moment of strategic transition in Asia Pacific security, views differ widely on the inevitability of conflict and the prospects of a managed accommodation of great power relations. There is widespread agreement that economic integration is deep and valuable, that a power shift is underway, and that the new array of multilateral institutions are welcome but merely formative. At the end of the Cold War period, there was a creative moment in which key concepts like cooperative and comprehensive security underpinned an era of institution building. The essay argues that it is time to revisit these ideas and look at the fundamental elements of a security order appropriate to a diverse and increasingly interconnected region in the midst of a power transition. It examines some of the key ideas offered by security thinkers from several countries and pays particular attention to the concept of a consociational security order as an entree to constructive discussion. As important as the U.S.-China relationship is to a future security order, a G2 is neither likely nor desirable. The conclusion poses a series of questions that will need to be answered as a new version of cooperative security with 21st century characteristics is developed.
Pioglitazone attenuates hepatic inflammation and fibrosis in phosphatidylethanolamineN-methyltransferase-deficient mice
Authors: van der Veen Jelske N. , Lingrell Susanne , Gao Xia , Quiroga Ariel D. , Takawale Abhijit , Armstrong Edward A. , Yager Jerome Y. , Kassiri Zamaneh , Lehner Richard , Vance Dennis E. , Jacobs René L.
Published: January 2016

Phosphatidylethanolamine N-methyltransferase (PEMT) is an important enzyme in hepatic phosphatidylcholine (PC) biosynthesis. Pemt−/−mice are protected against high-fat diet (HFD)-induced obesity and insulin resistance; however, these mice develop nonalcoholic fatty liver disease (NAFLD). We hypothesized that peroxisomal proliferator-activated receptor-γ (PPARγ) activation by pioglitazone might stimulate adipocyte proliferation, thereby directing lipids from the liver toward white adipose tissue. Pioglitazone might also act directly on PPARγ in the liver to improve NAFLD. Pemt+/+and Pemt−/−mice were fed a HFD with or without pioglitazone (20 mg·kg−1·day−1) for 10 wk. Pemt−/−mice were protected from HFD-induced obesity but developed NAFLD. Treatment with pioglitazone caused an increase in body weight gain in Pemt−/−mice that was mainly due to increased adiposity. Moreover, pioglitazone improved NAFLD in Pemt−/−mice, as indicated by a 35% reduction in liver weight and a 57% decrease in plasma alanine transaminase levels. Livers from HFD-fed Pemt−/−mice were steatotic, inflamed, and fibrotic. Hepatic steatosis was still evident in pioglitazone-treated Pemt−/−mice; however, treatment with pioglitazone reduced hepatic fibrosis, as evidenced by reduced Sirius red staining and lowered mRNA levels of collagen type Iα1( Col1a1), tissue inhibitor of metalloproteinases 1 ( Timp1), α-smooth muscle actin ( Acta2), and transforming growth factor-β ( Tgf-β). Similarly, oxidative stress and inflammation were reduced in livers from Pemt−/−mice upon treatment with pioglitazone. Together, these data show that activation of PPARγ in HFD-fed Pemt−/−mice improved liver function, while these mice were still protected against diet-induced obesity and insulin resistance.
Targeted delivery of human iPS-ECs overexpressing IL-8 receptors inhibits neointimal and inflammatory responses to vascular injury in the rat
Authors: Giordano Samantha , Zhao Xiangmin , Xing Daisy , Hage Fadi , Oparil Suzanne , Cooke John P. , Lee Jieun , Nakayama Karina H. , Huang Ngan F. , Chen Yiu-Fai
Published: January 2016

Interleukin-8 (IL8) is highly expressed by injured arteries in a variety of diseases and is a chemoattractant for neutrophils which express IL8 receptors IL8RA and RB (IL8RA/B) on their membranes. Neutrophils interact with the damaged endothelium and initiate an inflammatory cascade at the site of injury. We have generated a novel translational targeted cell therapy for acute vascular injury using adenoviral vectors to overexpress IL8RA/B and green fluorescent protein (GFP) on the surface of endothelial cells (ECs) derived from human induced pluripotent stem cells (HiPS-IL8RA/B-ECs). We hypothesize that HiPS-IL8RA/B-ECs transfused intravenously into rats with balloon injury of the carotid artery will target to the injured site and compete with neutrophils, thus inhibiting inflammation and neointima formation. Young adult male Sprague-Dawley rats underwent balloon injury of the right carotid artery and received intravenous transfusion of saline vehicle, 1.5 × 106 HiPS-ECs, 1.5 × 106 HiPS-Null-ECs, or 1.5 × 106 HiPS-IL8RA/B-ECs immediately after endoluminal injury. Tissue distribution of HiPS-IL8RA/B-ECs was analyzed by a novel GFP DNA qPCR method. Cytokine and chemokine expression and leukocyte infiltration were measured in injured and uninjured arteries at 24 h postinjury by ELISA and immunohistochemistry, respectively. Neointimal, medial areas, and reendothelialization were measured 14 days postinjury. HiPS-IL8RA/B-ECs homed to injured arteries, inhibited inflammatory mediator expression and inflammatory cell infiltration, accelerated reendothelialization, and attenuated neointima formation after endoluminal injury while control HiPS-ECs and HiPS-Null-ECs did not. HiPS-IL8RA/B-ECs transfused into rats with endoluminal carotid artery injury target to the injured artery and provide a novel strategy to treat vascular injury.
ERK1/2 MAPK signaling in hypothalamic paraventricular nucleus contributes to sympathetic excitation in rats with heart failure after myocardial infarction
Authors: Yu Yang , Wei Shun-Guang , Zhang Zhi-Hua , Weiss Robert M. , Felder Robert B.
Published: January 2016

Brain MAPK signaling pathways are activated in heart failure (HF) induced by myocardial infarction and contribute to augmented sympathetic nerve activity. We tested whether decreasing ERK1/2 (also known as p44/42 MAPK) signaling in the hypothalamic paraventricular nucleus (PVN), a forebrain source of presympathetic neurons, would reduce the upregulation of sympathoexcitatory mediators in the PVN and augmented sympathetic nerve activity in rats with HF. Sprague-Dawley rats underwent left anterior descending coronary artery ligation to induce HF, with left ventricular dysfunction confirmed by echocardiography. One week after coronary artery ligation or sham operation, small interfering (si)RNAs targeting ERK1/2 or a nontargeting control siRNA was microinjected bilaterally into the PVN. Experiments were conducted 5–7 days later. Confocal images revealed reduced phosphorylated ERK1/2 immunofluorescence in the PVN of HF rats treated with ERK1/2 siRNAs compared with HF rats treated with control siRNA. Western blot analysis confirmed significant reductions in both total and phosphorylated ERK1/2 in the PVN of HF rats treated with ERK1/2 siRNAs along with reduced expression of renin-angiotensin system components and inflammatory mediators. HF rats treated with ERK1/2 siRNAs also had reduced PVN neuronal excitation (fewer Fos-related antigen-like-immunoreactive neurons), lower plasma norepinephrine levels, and improved peripheral manifestations of HF compared with HF rats treated with control siRNAs. These results demonstrate that ERK1/2 signaling in the PVN plays a pivotal role in mediating sympathetic drive in HF induced by myocardial infarction and may be a novel target for therapeutic intervention.
Oscillatory lower body negative pressure impairs task related functional hyperemia in healthy volunteers
Authors: Stewart Julian M. , Balakrishnan Keshawadhana , Visintainer Paul , Del Pozzi Andrew T. , Messer Zachary R. , Terilli Courtney , Medow Marvin S.
Published: January 2016

Neurovascular coupling refers to the link between an increase in neural activity in response to a task and an increase in cerebral blood flow denoted “functional hyperemia.” Recent work on postural tachycardia syndrome indicated that increased oscillatory cerebral blood flow velocity (CBFv) was associated with reduced functional hyperemia. We hypothesized that a reduction in functional hyperemia could be causally produced in healthy volunteers by using oscillations in lower body negative pressure (OLBNP) to force oscillations in CBFv. CBFv was measured by transcranial Doppler ultrasound of the left middle cerebral artery. We used passive arm flexion applied during eight periodic 60-s flexion/60-s relaxation epochs to produce 120-s periodic changes in functional hyperemia (at 0.0083 Hz). We used −30 mmHg of OLBNP at 0.03, 0.05, and 0.10 Hz, the range for cerebral autoregulation, and measured spectral power of CBFv at all frequencies. Arm flexion power performed without OLBNP was compared with arm flexion power during OLBNP. OLBNP power performed in isolation was compared with power during OLBNP plus arm flexion. Cerebral flow velocity oscillations at 0.05 Hz reduced and at 0.10 Hz eliminated functional hyperemia, while 0.03 Hz did not reach significance. In contrast, arm flexion reduced OLBNP-induced oscillatory power at all frequencies. The interactions between OLBNP-driven CBFv oscillations and arm flexion-driven CBFv oscillations are reciprocal. Thus induced cerebral blood flow oscillations suppress functional hyperemia, and functional hyperemia suppresses cerebral blood flow oscillations. We conclude that oscillatory cerebral blood flow produces a causal reduction of functional hyperemia.
Ascorbic acid improves brachial artery vasodilation during progressive handgrip exercise in the elderly through a nitric oxide-mediated mechanism
Authors: Trinity Joel D. , Wray D. Walter , Witman Melissa A. H. , Layec Gwenael , Barrett-O'Keefe Zachary , Ives Stephen J. , Conklin Jamie D. , Reese Van , Zhao Jia , Richardson Russell S.
Published: January 2016

The proposed mechanistic link between the age-related attenuation in vascular function and free radicals is an attractive hypothesis; however, direct evidence of free radical attenuation and a concomitant improvement in vascular function in the elderly is lacking. Therefore, this study sought to test the hypothesis that ascorbic acid (AA), administered intra-arterially during progressive handgrip exercise, improves brachial artery (BA) vasodilation in a nitric oxide (NO)-dependent manner, by mitigating free radical production. BA vasodilation (Doppler ultrasound) and free radical outflow [electron paramagnetic resonance (EPR) spectroscopy] were measured in seven healthy older adults (69 ± 2 yr) during handgrip exercise at 3, 6, 9, and 12 kg (∼13–52% of maximal voluntary contraction) during the control condition and nitric oxide synthase (NOS) inhibition via NG-monomethyl-l-arginine (l-NMMA), AA, and coinfusion of l-NMMA + AA. Baseline BA diameter was not altered by any of the treatments, while l-NMMA and l-NMMA + AA diminished baseline BA blood flow and shear rate. AA improved BA dilation compared with control at 9 kg (control: 6.5 ± 2.2%, AA: 10.9 ± 2.5%, P = 0.01) and 12 kg (control: 9.5 ± 2.7%, AA: 15.9 ± 3.7%, P < 0.01). NOS inhibition blunted BA vasodilation compared with control and when combined with AA eliminated the AA-induced improvement in BA vasodilation. Free radical outflow increased with exercise intensity but, interestingly, was not attenuated by AA. Collectively, these results indicate that AA improves BA vasodilation in the elderly during handgrip exercise through an NO-dependent mechanism; however, this improvement appears not to be the direct consequence of attenuated free radical outflow from the forearm.
Electrolyte transport properties in distal small airways from cystic fibrosis pigs with implications for host defense
Authors: Li Xiaopeng , Tang Xiao Xiao , Vargas Buonfiglio Luis G. , Comellas Alejandro P. , Thornell Ian M. , Ramachandran Shyam , Karp Philip H. , Taft Peter J. , Sheets Kelsey , Abou Alaiwa Mahmoud H. , Welsh Michael J. , Meyerholz David K. , Stoltz David A. , Zabner Joseph
Published: January 2016

While pathological and clinical data suggest that small airways are involved in early cystic fibrosis (CF) lung disease development, little is known about how the lack of cystic fibrosis transmembrane conductance regulator (CFTR) function contributes to disease pathogenesis in these small airways. Large and small airway epithelia are exposed to different airflow velocities, temperatures, humidity, and CO2 concentrations. The cellular composition of these two regions is different, and small airways lack submucosal glands. To better understand the ion transport properties and impacts of lack of CFTR function on host defense function in small airways, we adapted a novel protocol to isolate small airway epithelial cells from CF and non-CF pigs and established an organotypic culture model. Compared with non-CF large airways, non-CF small airway epithelia cultures had higher Cl− and bicarbonate (HCO3−) short-circuit currents and higher airway surface liquid (ASL) pH under 5% CO2 conditions. CF small airway epithelia were characterized by minimal Cl− and HCO3− transport and decreased ASL pH, and had impaired bacterial killing compared with non-CF small airways. In addition, CF small airway epithelia had a higher ASL viscosity than non-CF small airways. Thus, the activity of CFTR is higher in the small airways, where it plays a role in alkalinization of ASL, enhancement of antimicrobial activity, and lowering of mucus viscosity. These data provide insight to explain why the small airways are a susceptible site for the bacterial colonization.
miR-155 Drives Metabolic Reprogramming of ER+ Breast Cancer Cells Following Long-Term Estrogen Deprivation and Predicts Clinical Response to Aromatase Inhibitors
Authors: Bacci Marina , Giannoni Elisa , Fearns Antony , Ribas Ricardo , Gao Qiong , Taddei Maria Letizia , Pintus Gianfranco , Dowsett Mitch , Isacke Clare M. , Martin Lesley-Ann , Chiarugi Paola , Morandi Andrea
Published: January 2016

Aromatase inhibitors (AI) have become the first-line endocrine treatment of choice for postmenopausal estrogen receptor–positive (ER+) breast cancer patients, but resistance remains a major challenge. Metabolic reprogramming is a hallmark of cancer and may contribute to drug resistance. Here, we investigated the link between altered breast cancer metabolism and AI resistance using AI-resistant and sensitive breast cancer cells, patient tumor samples, and AI-sensitive human xenografts. We found that long-term estrogen deprivation (LTED), a model of AI resistance, was associated with increased glycolysis dependency. Targeting the glycolysis-priming enzyme hexokinase-2 (HK2) in combination with the AI, letrozole, synergistically reduced cell viability in AI-sensitive models. Conversely, MCF7-LTED cells, which displayed a high degree of metabolic plasticity, switched to oxidative phosphorylation when glycolysis was impaired. This effect was ER dependent as breast cancer cells with undetectable levels of ER failed to exhibit metabolic plasticity. MCF7-LTED cells were also more motile than their parental counterparts and assumed amoeboid-like invasive abilities upon glycolysis inhibition with 2-deoxyglucose (2-DG). Mechanistic investigations further revealed an important role for miR-155 in metabolic reprogramming. Suppression of miR-155 resulted in sensitization of MCF7-LTED cells to metformin treatment and impairment of 2-DG–induced motility. Notably, high baseline miR-155 expression correlated with poor response to AI therapy in a cohort of ER+ breast cancers treated with neoadjuvant anastrozole. These findings suggest that miR-155 represents a biomarker potentially capable of identifying the subset of breast cancers most likely to adapt to and relapse on AI therapy. Cancer Res; 76(6); 1615–26. ©2016 AACR.
Influence of Topical, Systemic and Combined Application of Antioxidants on the Barrier Properties of the Human Skin
Authors: Lademann Juergen , Vergou Theognosia , Darvin Maxim E. , Patzelt Alexa , Meinke Martina C. , Voit Christiane , Papakostas Dimitrios , Zastrow Leonhard , Sterry Wolfram , Doucet Olivier
Published: January 2016

Background: The formation of free radicals in human skin by solar ultraviolet radiation is considered to be the main reason for extrinsic skin aging. The antioxidants in human tissue represent an efficient protection system against the destructive action of these reactive free radicals. In this study, the parameters of the skin, epidermal thickness, stratum corneum moisture, elasticity and wrinkle volume, were determined before and after the treatment with antioxidant- or placebo-containing tablets and creams. Methods: The study included 5 groups of 15 volunteers each, who were treated for 2 months with antioxidant-containing or placebo tablets, creams or a combination of antioxidant-containing tablets and cream. The skin parameters were measured at time point 0 and at week 8 utilizing ultrasound for the determination of epidermal thickness, a corneometer for stratum corneum moisture measurements, skin profilometry for quantifying the wrinkle volume and a cutometer for determining the elasticity. Results: The verum cream had a positive influence on epidermal thickness, elasticity and skin moisture, but the verum tablets improved the epidermal thickness only. The combined application of verum tablets and creams led to a significant improvement of all investigated skin parameters, whereas the application of placebo tablets or cream did not influence any parameters. Conclusion: The topical and oral supplementation of antioxidants can be an instrument to improve several skin parameters and potentially counteract or decelerate the process of extrinsic skin aging.
A Ética da Voz
Authors: Dolar Mladen
Published: January 2016

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Vozes negras na cantoria (1870-1925) O caso de Severino Perigo
Authors: Iumatti Paulo Teixeira
Published: January 2016

Trata-se de investigar a formação de um espaço ritual de interseção entre negros e “brancos”, em meio à sociedade escravista, no âmbito do universo da cantoria em províncias do chamado Norte do Brasil a partir de meados do século XIX. Tal espaço se constituiu em meio à crise da escravidão como instituição, e se articulou, a partir da Abolição, de forma a não favorecer a presença dos cantadores negros – que, no entanto, continuaram, em parte, atuantes.  Aspectos desse processo de exclusão, que envolveu, dentre outros fatores, disputas acirradas pela memória na sociedade, nas obras dos folcloristas e nos folhetos de cordel, são estudados pela análise dos rastros da trajetória e da performance do cantador “não profissional” paraibano Severino Perigo, registrado em 1925 por Leonardo Mota. Argumentamos que, na leitura crítica da relação folclorista/informante, o estudo das construções simbólicas em torno do corpo e da voz é particularmente profícuo.

 
Escritas de ouvido na literatura brasileira
Authors: Rocha Marília Librandi
Published: January 2016

Este texto propõe que no coração da literatura brasileira encontra-se o pulsar de uma escrita auditiva, elaborada por autores que “escrevem de ouvido”. O objetivo é conceituar o termo “escrita de ouvido”, e descrever a forma que assume na prosa de ficção, em especial no romance. Machado de Assis, Clarice Lispector e Guimarães Rosa são os escritores centrais dessa pesquisa, que também se aplica a outros escritores-chave como Oswald de Andrade, Mário de Andrade e Graciliano Ramos. Pensa-se pois o ouvido como um terceiro termo para além da dicotomia entre a fala e a escrita, o romance, como um espaço de escuta, e a autoria, como um lugar de recepção mais do que de producão. Busca-se assim contribuir para uma poética da ressonância e uma história aural da literatura escrita em português com acentos multilíngues.
ORALIDADE, CORPO E GESTO Das teorias a Mart´nália
Authors: Ferreira Jerusa Pires
Published: January 2016

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Bucalidade
Authors: Guyer Sara
Published: January 2016

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Literatura vs história: uma questão anacrônica?
Authors: Riaudel Michel
Published: January 2016

O ensaio dispõe-se a revisitar a relação entre literatura e história sob o prisma do anacronismo. Seria leviano considerar que o crítico literário está livre de respeitar a cronologia. Porém, o tempo da obra não se limita apenas à linearidade cronológica, mas se projeta, em parte pela incompletude da arte, fora de seu contexto de produção. Portanto, considerando nossa concepção histórica da literatura, qualquer leitura que tenha em vista essa condição artística haverá de levar em consideração esses dois corpos da obra.
Dossiê Figuras do estranhamento
Authors: Passos Cleusa Rios , Riaudel Michel , Rosenbaum Yudith
Published: January 2016

Apresentação
 
Primeiras reflexões
“Figuras do estranhamento” pretende ser um território de múltiplas faces, abrindo-se para estudos de saberes diversos – literários, sociais, políticos, psicanalíticos, entre outros –, articulados em torno de...
Discoidin Domain Receptor-1 Regulates Calcific Extracellular Vesicle Release in Vascular Smooth Muscle Cell Fibrocalcific Response via Transforming Growth Factor-β Signaling
Authors: Krohn Jona B. , Hutcheson Joshua D. , Martínez-Martínez Eduardo , Irvin Whitney S. , Bouten Carlijn V.C. , Bertazzo Sergio , Bendeck Michelle P. , Aikawa Elena
Published: January 2016

Objective—

Collagen accumulation and calcification are major determinants of atherosclerotic plaque stability. Extracellular vesicle (EV)–derived microcalcifications in the collagen-poor fibrous cap may promote plaque rupture. In this study, we hypothesize that the collagen receptor discoidin domain receptor-1 (DDR-1) regulates collagen deposition and release of calcifying EVs by vascular smooth muscle cells (SMCs) through the transforming growth factor-β (TGF-β) pathway.

Approach and Results—

SMCs from the carotid arteries of DDR-1
−/−
mice and wild-type littermates (n=5–10 per group) were cultured in normal or calcifying media. At days 14 and 21, SMCs were harvested and EVs isolated for analysis. Compared with wild-type, DDR-1
−/−
SMCs exhibited a 4-fold increase in EV release (
P
<0.001) with concomitantly elevated alkaline phosphatase activity (
P
<0.0001) as a hallmark of EV calcifying potential. The DDR-1
−/−
phenotype was characterized by increased mineralization (Alizarin Red S and Osteosense,
P
<0.001 and
P
=0.002, respectively) and amorphous collagen deposition (
P
<0.001). We further identified a novel link between DDR-1 and the TGF-β pathway previously implicated in both fibrotic and calcific responses. An increase in TGF-β1 release by DDR-1
−/−
SMCs in calcifying media (
P
<0.001) stimulated p38 phosphorylation (
P
=0.02) and suppressed activation of Smad3. Inhibition of either TGF-β receptor-I or phospho-p38 reversed the fibrocalcific DDR-1
−/−
phenotype, corroborating a causal relationship between DDR-1 and TGF-β in EV-mediated vascular calcification.

Conclusions—

DDR-1 interacts with the TGF-β pathway to restrict calcifying EV-mediated mineralization and fibrosis by SMCs. We therefore establish a novel mechanism of cell-matrix homeostasis in atherosclerotic plaque formation.
Programmed Ventricular Stimulation for Risk Stratification in the Brugada Syndrome
Authors: Sroubek Jakub , Probst Vincent , Mazzanti Andrea , Delise Pietro , Hevia Jesus Castro , Ohkubo Kimie , Zorzi Alessandro , Champagne Jean , Kostopoulou Anna , Yin Xiaoyan , Napolitano Carlo , Milan David J. , Wilde Arthur , Sacher Frederic , Borggrefe Martin , Ellinor Patrick T. , Theodorakis George , Nault Isabelle , Corrado Domenico , Watanabe Ichiro , Antzelevitch Charles , Allocca Giuseppe , Priori Silvia G. , Lubitz Steven A.
Published: January 2016

Background—

The role of programmed ventricular stimulation in identifying patients with Brugada syndrome at the highest risk for sudden death is uncertain.

Methods and Results—

We performed a systematic review and pooled analysis of prospective, observational studies of patients with Brugada syndrome without a history of sudden cardiac arrest who underwent programmed ventricular stimulation. We estimated incidence rates and relative hazards of cardiac arrest or implantable cardioverter-defibrillator shock. We analyzed individual-level data from 8 studies comprising 1312 patients who experienced 65 cardiac events (median follow-up, 38.3 months). A total of 527 patients were induced into arrhythmias with up to triple extrastimuli. Induction was associated with cardiac events during follow-up (hazard ratio, 2.66; 95% confidence interval [CI], 1.44–4.92,
P
<0.001), with the greatest risk observed among those induced with single or double extrastimuli. Annual event rates varied substantially by syncope history, presence of spontaneous type 1 ECG pattern, and arrhythmia induction. The lowest risk occurred in individuals without syncope and with drug-induced type 1 patterns (0.23%, 95% CI, 0.05–0.68 for no induced arrhythmia with up to double extrastimuli; 0.45%, 95% CI, 0.01–2.49 for induced arrhythmia), and the highest risk occurred in individuals with syncope and spontaneous type 1 patterns (2.55%, 95% CI, 1.58–3.89 for no induced arrhythmia; 5.60%, 95% CI, 2.98–9.58 for induced arrhythmia).

Conclusions—

In patients with Brugada syndrome, arrhythmias induced with programmed ventricular stimulation are associated with future ventricular arrhythmia risk. Induction with fewer extrastimuli is associated with higher risk. However, clinical risk factors are important determinants of arrhythmia risk, and lack of induction does not necessarily portend low ventricular arrhythmia risk, particularly in patients with high-risk clinical features.