bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of sound transmission through, and radiation from, panels using a wave and finite element method
Authors: Yang Yi , Mace Brian R. , Kingan Michael J.
Published: April 2017

This paper describes the extension of a wave and finite element (WFE) method to the prediction of noise transmission through, and radiation from, infinite panels. The WFE method starts with a conventional finite element model of a small segment of the panel. For a given frequency, the mass and stiffness matrices of the segment are used to form the structural dynamic stiffness matrix. The acoustic responses of the fluids surrounding the structure are modelled analytically. The dynamic stiffness matrix of the segment is post-processed using periodic structure theory, and coupled with those of the fluids. The total dynamic stiffness matrix is used to obtain the response of the medium to an incident acoustic pressure. Excitation of the structure by oblique plane waves and a diffuse sound field are considered. The response to structural excitation and the consequent radiation are determined. Since the size of the WFE model is small, computational times are small. Various example applications are presented to illustrate the approach, including a thin isotropic panel, an antisymmetric, cross-ply sandwich panel and a symmetric panel with an orthotropic core.
Norway seeks to stamp out prion disease
Authors: Stokstad Erik
Published: April 2017

Hunters will cull reindeer in an attempt to contain outbreak of chronic wasting disease.
Deconstructing behavioral neuropharmacology with cellular specificity
Authors: Shields Brenda C. , Kahuno Elizabeth , Kim Charles , Apostolides Pierre F. , Brown Jennifer , Lindo Sarah , Mensh Brett D. , Dudman Joshua T. , Lavis Luke D. , Tadross Michael R.
Published: April 2017

A tailored look at behavioral pharmacology

It is important to understand how animal behavior is mediated by molecular, cellular, and circuit components of the brain. However, it has been difficult to link the activity of specific molecules in defined cells to behavioral roles. Shields
et al.
developed an approach to deconstruct behavioral neuropharmacology with cellular specificity. The technique, termed DART (drugs acutely restricted by tethering), uses enzymatic capture to restrict standard drugs to the surface of genetically specified cells without prior modification of the native pharmacological target. The method provides cell-type specificity, endogenous-protein specificity, acute onset, and utility in behaving animals. This enables the activity of specific molecules in defined circuit elements to be causally linked to behavior.

Science
, this issue p.
eaaj2161
Femtosecond x-ray spectroscopy of an electrocyclic ring-opening reaction
Authors: Attar Andrew R. , Bhattacherjee Aditi , Pemmaraju C. D. , Schnorr Kirsten , Closser Kristina D. , Prendergast David , Leone Stephen R.
Published: April 2017

X-ray vision catches Woodward-Hoffmann

The celebrated Woodward-Hoffmann (W-H) rules rationalize a variety of rapid bond rearrangements in organic molecules. The key insight involved symmetry conservation in the electronic journey from reactant to product. Attar
et al.
now report femtosecond x-ray absorption spectra and accompanying simulation studies that track shifts in carbon electronic states during one such reaction: the photochemical ring opening of cyclohexadiene to hexatriene (see the Perspective by Sension). The smooth evolution that occurs in the vicinity of the pericyclic minimum provides direct affirmation of the W-H framework. Moreover, the use of a convenient tabletop apparatus bodes well for future x-ray studies of ultrafast electronic dynamics.

Science
, this issue p.
54
; see also p.
31
Sensitivity and Kinetics of an NS1-Based Zika Virus Enzyme-Linked Immunosorbent Assay in Zika Virus-Infected Travelers from Israel, the Czech Republic, Italy, Belgium, Germany, and Chile
Authors: Lustig Yaniv , Zelena Hana , Venturi Giulietta , Van Esbroeck Marjan , Rothe Camilla , Perret Cecilia , Koren Ravit , Katz-Likvornik Shiri , Mendelson Ella , Schwartz Eli
Published: April 2017

Serological diagnosis of Zika virus is challenging due to high cross-reactivity of Zika virus with other flavivirus antibodies. Recently, a Zika NS1-based enzyme-linked immunosorbent assay (ELISA) was developed and shown to be highly specific for Zika antibody detection; however, sensitivity was evaluated for only a small number of confirmed Zika-infected patients. In this study, we measured the sensitivity and kinetics of Zika IgM and IgG antibodies using the Zika NS1-based ELISA in 105 samples from 63 returning travelers infected with Zika virus (proven by PCR or neutralization assay) from Israel, Czech Republic, Italy, Belgium, Germany, and Chile. Zika virus IgM was detected from 2 to 42 days post-symptom onset (PSO) with an overall sensitivity of 79% in the first month and 68% until 2 months PSO, while IgG antibodies were detected from 5 days to 3 years PSO with 79% sensitivity. Interestingly, significant differences in IgM sensitivity and IgM detection period were observed between Israeli and European/Chilean Zika-infected travelers, adding to the complexity of Zika infection diagnosis and suggesting that other diagnostic methods should be complemented to reduce false-negative results.
Transient Oral Human Cytomegalovirus Infections Indicate Inefficient Viral Spread from Very Few Initially Infected Cells
Authors: Mayer Bryan T. , Krantz Elizabeth M. , Swan David , Ferrenberg James , Simmons Karen , Selke Stacy , Huang Meei-Li , Casper Corey , Corey Lawrence , Wald Anna , Schiffer Joshua T. , Gantt Soren
Published: April 2017

Cytomegalovirus (CMV) is acquired by the oral route in children, and primary infection is associated with abundant mucosal replication, as well as the establishment of latency in myeloid cells that results in lifelong infection. The efficiency of primary CMV infection in humans following oral exposure, however, is unknown. We consistently detected self-limited, low-level oral CMV shedding events, which we termed transient CMV infections, in a prospective birth cohort of 30 highly exposed CMV-uninfected infants. We estimated the likelihood of transient oral CMV infections by comparing their observed frequency to that of established primary infections, characterized by persistent high-level shedding, viremia, and seroconversion. We developed mathematical models of viral dynamics upon initial oral CMV infection and validated them using clinical shedding data. Transient infections comprised 76 to 88% of oral CMV shedding events. For this high percentage of transient infections to occur, we identified two mathematical prerequisites: a very small number of initially infected oral cells (1 to 4) and low viral infectivity (<1.5 new cells infected/cell). These observations indicate that oral CMV infection in infants typically begins with a single virus that spreads inefficiently to neighboring cells. Thus, although the incidence of CMV infection is high during infancy, our data provide a mechanistic framework to explain why multiple CMV exposures are typically required before infection is successfully established. These findings imply that a sufficiently primed immune response could prevent CMV from establishing latent infection in humans and support the achievability of a prophylactic CMV vaccine.

IMPORTANCE
CMV infects the majority of the world's population and is a major cause of birth defects. Developing a vaccine to prevent CMV infection would be extremely valuable but would be facilitated by a better understanding of how natural human CMV infection is acquired. We studied CMV acquisition in infants and found that infections are usually brief and self-limited and are successfully established relatively rarely. Thus, although most people eventually acquire CMV infection, it usually requires numerous exposures. Our analyses indicate that this is because the virus is surprisingly inefficient, barely replicating well enough to spread to neighboring cells in the mouth. Greater knowledge of why CMV infection usually fails may provide insight into how to prevent it from succeeding.
Group A Rotaviruses in Chinese Bats: Genetic Composition, Serology, and Evidence for Bat-to-Human Transmission and Reassortment
Authors: He Biao , Huang Xiaohong , Zhang Fuqiang , Tan Weilong , Matthijnssens Jelle , Qin Shaomin , Xu Lin , Zhao Zihan , Yang Ling'en , Wang Quanxi , Hu Tingsong , Bao Xiaolei , Wu Jianmin , Tu Changchun
Published: April 2017

Bats are natural reservoirs for many pathogenic viruses, and increasing evidence supports the notion that bats can also harbor group A rotaviruses (RVAs), important causative agents of diarrhea in children and young animals. Currently, 8 RVA strains possessing completely novel genotype constellations or genotypes possibly originating from other mammals have been identified from African and Chinese bats. However, all the data were mainly based on detection of RVA RNA, present only during acute infections, which does not permit assessment of the true exposure of a bat population to RVA. To systematically investigate the genetic diversity of RVAs, 547 bat anal swabs or gut samples along with 448 bat sera were collected from five South Chinese provinces. Specific reverse transcription-PCR (RT-PCR) screening found four RVA strains. Strain GLRL1 possessed a completely novel genotype constellation, whereas the other three possessed a constellation consistent with the MSLH14-like genotype, a newly characterized group of viruses widely prevalent in Chinese insectivorous bats. Among the latter, strain LZHP2 provided strong evidence of cross-species transmission of RVAs from bats to humans, whereas strains YSSK5 and BSTM70 were likely reassortants between typical MSLH14-like RVAs and human RVAs. RVA-specific antibodies were detected in 10.7% (48/448) of bat sera by an indirect immunofluorescence assay (IIFA). Bats in Guangxi and Yunnan had a higher RVA-specific antibody prevalence than those from Fujian and Zhejiang provinces. These observations provide evidence for cross-species transmission of MSLH14-like bat RVAs to humans, highlighting the impact of bats as reservoirs of RVAs on public health.

IMPORTANCE
Bat viruses, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), Ebola, Hendra, and Nipah viruses, are important pathogens causing outbreaks of severe emerging infectious diseases. However, little is known about bat viruses capable of causing gastroenteritis in humans, even though 8 group A viruses (RVAs) have been identified from bats so far. In this study, another 4 RVA strains were identified, with one providing strong evidence for zoonotic transmission from bats to humans. Serological investigation has also indicated that RVA infection in bats is far more prevalent than expected based on the detection of viral RNA.
Electric Cell-Substrate Impedance Sensing To Monitor Viral Growth and Study Cellular Responses to Infection with Alphaherpesviruses in Real Time
Authors: Pennington Matthew R. , Van de Walle Gerlinde R.
Published: April 2017

Alphaherpesviruses, including those that commonly infect humans, such as HSV-1 and HSV-2, typically infect and cause cellular damage to epithelial cells at mucosal surfaces, leading to disease. The development of novel technologies to study the cellular responses to infection may allow a more complete understanding of virus replication and the creation of novel antiviral therapies. This study demonstrates the use of ECIS to study various aspects of herpesvirus biology, with a specific focus on changes in cellular morphology as a result of infection. We conclude that ECIS represents a valuable new tool with which to study alphaherpesvirus infections in real time and in an objective and reproducible manner.
Isolated brachydactyly type E and idiopathic pancreatitis in a patient presenting to a lipid disorders clinic
Authors: Page Michael M , Hooper Amanda J , Glendenning Paul , Burnett John R
Published: April 2017

An 18-year-old female tertiary student was referred to a lipid clinic with hypertriglyceridaemia discovered after presentation with acute pancreatitis. The patient’s only medication was l-thyroxine for treatment of hypothyroidism. She was overweight, normotensive, with unremarkable facies. However, she had hypermobile hand joints and brachydactyly resulting in loss of left 3–5 and right 4 and 5 knuckle definitions. Radiography revealed shortening of metacarpals 3–5 on the left and 4 and 5 on the right. Her mother had similar skeletal changes, consistent with a dominant mode of inheritance. Abnormally short digits involving the metacarpals, classified as brachydactyly type E, can be isolated or occur as part of a syndrome. Turner syndrome, Albright hereditary osteodystrophy, hypertension with brachydactyly, chromosome 2q37 microdeletion andPTHLHmutations were excluded following clinical, biochemical and genetic testing. No specific treatment was required. Genetic testing for isolated and syndromic forms of brachydactyly facilitates family screening and prepregnancy counselling.
Effect of β-blockade on lung function, exercise performance and dynamic hyperinflation in people with arterial vascular disease with and without COPD
Authors: Key Angela , Parry Matthew , West Malcolm A , Asher Rebecca , Jack Sandy , Duffy Nick , Torella Francesco , Walker Paul P
Published: April 2017

Introduction

β Blockers are important treatment for ischaemic heart disease and heart failure; however, there has long been concern about their use in people with chronic obstructive pulmonary disease (COPD) due to fear of symptomatic worsening of breathlessness. Despite growing evidence of safety and efficacy, they remain underused. We examined the effect of β-blockade on lung function, exercise performance and dynamic hyperinflation in a group of vascular surgical patients, a high proportion of who were expected to have COPD.

Methods

People undergoing routine abdominal aortic aneurysm (AAA) surveillance were sequentially recruited from vascular surgery clinic. They completed plethysmographically measured lung function and incremental cardiopulmonary exercise testing with dynamic measurement of inspiratory capacity while taking and not taking β blocker.

Results

48 participants completed tests while taking and not taking β blockers with 38 completing all assessments successfully. 15 participants (39%) were found to have, predominantly mild and undiagnosed, COPD. People with COPD had airflow obstruction, increased airway resistance (Raw) and specific conductance (sGaw), static hyperinflation and dynamically hyperinflated during exercise. In the whole group, β-blockade led to a small fall in FEV1 (0.1 L/2.8% predicted) but did not affect Raw, sGaw, static or dynamic hyperinflation. No difference in response to β-blockade was seen in those with and without COPD.

Conclusions

In people with AAA, β-blockade has little effect on lung function and dynamic hyperinflation in those with and without COPD. In this population, the prevalence of COPD is high and consideration should be given to case finding with spirometry.

Trial registration number

NCT02106286.
Ankle syndesmosis repair and rehabilitation in professional rugby league players: a case series report
Authors: Latham Alex James , Goodwin Peter Charles , Stirling Ben , Budgen Adam
Published: April 2017

Background/aim

The distal tibiofibular joint is described as a syndesmosis. Traditionally, severe syndesmotic injuries with diastasis have been treated surgically with screw fixation. This case series details an ankle syndesmosis tightrope repair and an accelerated rehabilitation protocol that reduces the amount of time to return to professional rugby league in the UK. The aim of this study was to describe players’ journey from injury, through diagnosis to surgery, rehabilitation and return to participation, detailing time scales and methods used at each stage to highlight the change in current practice.

Methods

Players were identified via a single orthopaedic surgeon in the UK who specialises in ankle syndesmosis repair. Between January 2010 and September 2015, adult men playing full-time professional rugby league in the UK Super League with ankle syndesmosis injuries were identified.

Results

Eighteen players from six different clubs were included. The most common mechanism of injury was forced dorsiflexion/eversion. The average return to participation was 64 days (SD 17.2, range 38–108). This compares favourably to reports of between 120 and 180 days following screw fixation.

Conclusion

Ankle syndesmosis tightrope repair and an accelerated rehabilitation protocol is as safe as traditional methods. The accelerated rehabilitation protocol promotes early weight-bearing and has shown to expedite the return to sport for professional Rugby League players. It is possible to return to sport 2 months after a tightrope repair and accelerated rehabilitation, compared with 3–6 months post screw fixation. This is extremely encouraging for the professional sporting population.
Rare Genetic Variants in Gata Transcription Factors in Patients with Hypertrophic Cardiomyopathy
Authors: Alonso-Montes Cristina , Rodríguez-Reguero Julián , Martín María , Gómez Juan , Coto Eliecer , Naves-Díaz Manuel , Morís César , Cannata-Andía Jorge B , Rodríguez Isabel
Published: April 2017

Hypertrophic cardiomyopathy (HCM) is a very heterogeneous disease. Although primarily caused by mutations in genes encoding sarcomeric proteins, other genes might explain that heterogeneity. Potential candidate genes are GATA transcription factors that regulate the expression of proteins associated with HCM. Exons of GATA2, GATA4, and GATA6 genes were sequenced in 212 patients with unrelated HCM previously analyzed for genes encoding the most frequently mutated sarcomeric proteins. Functional effects of variants were predicted by in silico analyses. 3 potentially pathogenic variants were identified: c.-77G>A in GATA2, p.Ala343Thr (rs370588269) in GATA4, and p.Pro555Ala (rs146243018) in GATA6. Multivariate analyses showed that angina was more frequent in patients carrying sarcomeric and GATA rare variants (55% vs 23.2% in non-carriers of GATA rare variants, OR (95% CI) 7.12 (1.23 to 41.27), p=0.029). Among patients without a known causal mutation, GATA rare variants were associated with a greater maximum posterior wall thickness (16.4±4.4 vs 14.0±3.1 mm in non-carriers, p=0.021). Thus, variants having a putative effect on GATA genes would alter the expression of their target genes and could modify the hypertrophic response. Therefore, although relatively infrequent in patients with HCM, they may represent a novel insight into the molecular mechanisms related to the pathogenesis of HCM.
Gauge invariant gluon spin operator for spinless nonlinear wave solutions
Authors: Lee Bum-Hoon , Kim Youngman , Pak D. G. , Tsukioka Takuya , Zhang P. M.
Published: April 2017

We consider nonlinear wave type solutions with intrinsic mass scale parameter and zero spin in a pure SU(2) quantum chromodynamics (QCD). A new stationary solution which can be treated as a system of static Wu–Yang monopole dressed in off-diagonal gluon field is proposed. A remarkable feature of such a solution is that it possesses a finite energy density everywhere. All considered nonlinear wave type solutions have common features: presence of the mass scale parameter, nonvanishing projection of the color fields along the propagation direction and zero spin. The last property requires revision of the gauge invariant definition of the spin density operator which is supposed to produce spin one states for the massless vector gluon field. We construct a gauge invariant definition of the classical gluon spin density operator which is unique and Lorentz frame independent.
Serious limitations of the strong equivalence principle
Authors: Dai De-Chang
Published: April 2017

It is well known that an accelerated charged particle radiates away energy. However, whether an accelerated neutral composite particle radiates away energy is unclear. We study decoherent Larmor radiation from an accelerated neutral composite object. We find that the neutral object’s long wavelength radiation is highly suppressed because radiation from different charges is canceled out. However, the neutral object radiates high energy or short wavelength radiation without any suppression. In that case, radiation from each particle can be treated independently, and it is called the decoherent radiation. We compare a hydrogen atom’s decoherent Larmor radiation with its gravitational radiation while the atom is in a circular orbit around a star. Gravitational radiation is stronger than the electromagnetic radiation if the orbital radius is larger than some critical radius. Since the decoherent radiation is related to the object’s structure, this implies that the strong equivalence principle which states that gravitational motion does not depend on an object’s constitution has severe limitations.
Bright–dark soliton solutions for the (2+1)-dimensional variable-coefficient coupled nonlinear Schrödinger system in a graded-index waveguide
Authors: Yuan Yu-Qiang , Tian Bo , Xie Xi-Yang , Chai Jun , Liu Lei
Published: April 2017

Under investigation in this paper is the (2[Formula: see text]+[Formula: see text]1)-dimensional coupled nonlinear Schrödinger (NLS) system with variable coefficients, which describes the propagation of an optical beam inside the two-dimensional graded-index waveguide amplifier with the polarization effects. Through a similarity transformation, we convert that system into a set of the integrable defocusing (1[Formula: see text]+[Formula: see text]1)-dimensional coupled NLS equations, and subsequently construct the bright–dark soliton solutions for the original system which are converted from the ones of the latter set. With the graphic analysis, we discuss the soliton propagation and collision with r(t), which is related to the nonlinear, profile and gain/loss coefficients. When r(t) is a constant, one soliton propagates with the amplitude, width and velocity unvaried, while velocity and width of the one soliton can be affected, and two solitons possess the elastic collision; When r(t) is a linear function, velocity and width of the one soliton varies with t increasing, and collision of the two solitons is altered. Besides, bound-state solitons are seen.
Numerical Studies of Vibration of Four-Span Continuous Plate with Rails Excited by Moving Car with Experimental Validation
Authors: Yang Jing , Ouyang Huajiang , Stancioiu Dan
Published: April 2017

The vibration of a four-span continuous plate with two rails on top and four extra elastic supports excited by a moving model car is studied through numerical simulations and experiments. Modal testing is carried out to identify the Young’s moduli of the plate material and the rail material. Shell elements and beam elements are adopted for the plate and the rails of their Finite Element (FE) model, respectively. An offset is required to connect the rails and the plate in the FE model and the offset ratio of the shell element is updated to bring the numerical frequencies of the structure (plate with rails) closest to its experimental frequencies. Modal Superposition (MS) method with numerical modes of the structure and an iterative method are combined to predict the vibration of the structure subjected to the moving car. The displacements of four points of the plate are measured during the crossing of the car and compared with predicted results. The two sets of results agree well, which validates the model of the system. Parametric analysis is then made using the validated system model.
Pullback attractors for a strongly damped delay wave equation in ℝn
Authors: Wang Yejuan , Qin Yizhao , Wang Jingyu
Published: April 2017

In this paper, we prove the existence of a pullback attractor for a strongly damped delay wave equation in [Formula: see text]. We do not assume any Lipschitz condition on the nonlinear term, just a continuity assumption together with growth conditions, so that some new methods to obtain the existence of pullback attractors for multi-valued processes on an unbounded domain are introduced.
Decentralised Detection of Emergence in Complex Adaptive Systems
Authors: O'toole Eamonn , Nallur Vivek , Clarke Siobhán
Published: April 2017

This article describes Decentralised Emergence Detection (DETect), a novel distributed algorithm that enables agents to collaboratively detect emergent events in Complex Adaptive Systems (CAS). Non-deterministic interactions between agents in CAS can give rise to emergent behaviour or properties at the system level. The nature, timing, and consequence of emergence is unpredictable and may be harmful to the system or individual agents. DETect relies on the feedback that occurs from the system level (macro) to the agent level (micro) when emergence occurs. This feedback constrains agents at the micro level and results in changes occurring in the relationship between an agent and its environment. DETect uses statistical methods to automatically select the properties of the agent and environment to monitor and tracks the relationship between these properties over time. When a significant change is detected, the algorithm uses distributed consensus to determine if a sufficient number of agents have simultaneously experienced a similar change. On agreement of emergence, DETect raises an event, which its agent or other interested observers can use to act appropriately. The approach is evaluated using a multi-agent case study.
Unifying Virtual and Physical Worlds
Authors: Wang Xiang , Nie Liqiang , Song Xuemeng , Zhang Dongxiang , Chua Tat-Seng
Published: April 2017

Event-based social networking services, such as Meetup, are capable of linking online virtual interactions to offline physical activities. Compared to mono online social networking services (e.g., Twitter and Google+), such dual networks provide a complete picture of users’ online and offline behaviors that more often than not are compatible and complementary. In the light of this, we argue that joint learning over dual networks offers us a better way to comprehensively understand user behaviors and their underlying organizational principles. Despite its value, few efforts have been dedicated to jointly considering the following factors within a unified model: (1) local user contextualization, (2) global structure coherence, and (3) effectiveness evaluation. Toward this end, we propose a novel dual clustering model for community detection over dual networks to jointly model local consistency for a specific user and global consistency of partitioning results across networks. We theoretically derived its solution. In addition, we verified our model regarding multiple metrics from different aspects and applied it to the application of event attendance prediction.
An Overview of Research and Evaluation Designs for Dissemination and Implementation
Authors: Brown C. Hendricks , Curran Geoffrey , Palinkas Lawrence A. , Aarons Gregory A. , Wells Kenneth B. , Jones Loretta , Collins Linda M. , Duan Naihua , Mittman Brian S. , Wallace Andrea , Tabak Rachel G. , Ducharme Lori , Chambers David A. , Neta Gila , Wiley Tisha , Landsverk John , Cheung Ken , Cruden Gracelyn
Published: April 2017

The wide variety of dissemination and implementation designs now being used to evaluate and improve health systems and outcomes warrants review of the scope, features, and limitations of these designs. This article is one product of a design workgroup that was formed in 2013 by the National Institutes of Health to address dissemination and implementation research, and whose members represented diverse methodologic backgrounds, content focus areas, and health sectors. These experts integrated their collective knowledge on dissemination and implementation designs with searches of published evaluations strategies. This article emphasizes randomized and nonrandomized designs for the traditional translational research continuum or pipeline, which builds on existing efficacy and effectiveness trials to examine how one or more evidence-based clinical/prevention interventions are adopted, scaled up, and sustained in community or service delivery systems. We also mention other designs, including hybrid designs that combine effectiveness and implementation research, quality improvement designs for local knowledge, and designs that use simulation modeling.
Countermarketing Alcohol and Unhealthy Food: An Effective Strategy for Preventing Noncommunicable Diseases? Lessons from Tobacco
Authors: Palmedo P. Christopher , Dorfman Lori , Garza Sarah , Murphy Eleni , Freudenberg Nicholas
Published: April 2017

Countermarketing campaigns use health communications to reduce the demand for unhealthy products by exposing motives and undermining marketing practices of producers. These campaigns can contribute to the prevention of noncommunicable diseases by denormalizing the marketing of tobacco, alcohol, and unhealthy food. By portraying these activities as outside the boundaries of civilized corporate behavior, countermarketing can reduce the demand for unhealthy products and lead to changes in industry marketing practices. Countermarketing blends consumer protection, media advocacy, and health education with the demand for corporate accountability. Countermarketing campaigns have been demonstrated to be an effective component of comprehensive tobacco control. This review describes common elements of tobacco countermarketing such as describing adverse health consequences, appealing to negative emotions, highlighting industry manipulation of consumers, and engaging users in the design or implementation of campaigns. It then assesses the potential for using these elements to reduce consumption of alcohol and unhealthy foods.
Balance between S-nitrosylation and denitrosylation modulates myoblast proliferation independently of soluble guanylyl cyclase activation
Authors: Yamashita Aline M. S. , Ancillotti Maryana T. C. , Rangel Luciana P. , Fontenele Marcio , Figueiredo-Freitas Cicero , Possidonio Ana C. , Soares Carolina P. , Sorenson Martha M. , Mermelstein Claudia , Nogueira Leonardo
Published: April 2017

Nitric oxide (NO) contributes to myogenesis by regulating the transition between myoblast proliferation and fusion through cGMP signaling. NO can form S-nitrosothiols (RSNO), which control signaling pathways in many different cell types. However, neither the role of RSNO content nor its regulation by the denitrosylase activity of S-nitrosoglutathione reductase (GSNOR) during myogenesis is understood. Here, we used primary cultures of chick embryonic skeletal muscle cells to investigate whether changes in intracellular RSNO alter proliferation and fusion of myoblasts in the presence and absence of cGMP. Cultures were grown to fuse most of the myoblasts into myotubes, with and without S-nitrosocysteine (CysNO), 8-Br-cGMP, DETA-NO, or inhibitors for NO synthase (NOS), GSNOR, soluble guanylyl cyclase (sGC), or a combination of these, followed by analysis of GSNOR activity, protein expression, RSNO, cGMP, and cell morphology. Although the activity of GSNOR increased progressively over 72 h, inhibiting GSNOR (by GSNOR inhibitor – GSNORi – or by knocking down GSNOR with siRNA) produced an increase in RSNO and in the number of myoblasts and fibroblasts, accompanied by a decrease in myoblast fusion index. This was also detected with CysNO supplementation. Enhanced myoblast number was proportional to GSNOR inhibition. Effects of the GSNORi and GSNOR knockdown were blunted by NOS inhibition, suggesting their dependence on NO synthesis. Interestingly, GSNORi and GSNOR knockdown reversed the attenuated proliferation obtained with sGC inhibition in myoblasts, but not in fibroblasts. Hence myoblast proliferation is enhanced by increasing RSNO, and regulated by GSNOR activity, independently of cGMP production and signaling.
Biphasic adaptation to osmotic stress in the C. elegans germ line
Authors: Davis Michael , Montalbano Andrea , Wood Megan P. , Schisa Jennifer A.
Published: April 2017

Cells respond to environmental stress in multiple ways. In the germ line, heat shock and nutritive stress trigger the assembly of large ribonucleoprotein (RNP) granules via liquid-liquid phase separation (LLPS). The RNP granules are hypothesized to maintain the quality of oocytes during stress. The goal of this study was to investigate the cellular response to glucose in the germ line and determine if it is an osmotic stress response. We found that exposure to 500 mM glucose induces the assembly of RNP granules in the germ line within 1 h. Interestingly, the RNP granules are maintained for up to 3 h; however, they dissociate after longer periods of stress. The RNP granules include processing body and stress granule proteins, suggesting shared functions. Based on several lines of evidence, the germ line response to glucose largely appears to be an osmotic stress response, thus identifying osmotic stress as a trigger of LLPS. Although RNP granules are not maintained beyond 3 h of osmotic stress, the quality of oocytes does not appear to decrease after longer periods of stress, suggesting a secondary adaptation in the germ line. We used an indirect marker of glycerol and observed high levels after 5 and 20 h of glucose exposure. Moreover, in gpdh-1;gpdh-2 germ lines, glycerol levels are reduced concomitant with RNP granules being maintained for an extended period. We speculate that increased glycerol levels may function as a secondary osmoregulatory adaptive response in the germ line, following a primary response of RNP granule assembly.
Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model
Authors: Huleihel Luai , Sellares Jacobo , Cardenes Nayra , Álvarez Diana , Faner Rosa , Sakamoto Koji , Yu Guoying , Kapetanaki Maria G. , Kaminski Naftali , Rojas Mauricio
Published: April 2017

Although different preclinical models have demonstrated a favorable role for bone marrow-derived mesenchymal stem cells (B-MSC) in preventing fibrosis, this protective effect is not observed with late administration of these cells, when fibrotic changes are consolidated. We sought to investigate whether the late administration of B-MSCs overexpressing microRNAs (miRNAs) let-7d (antifibrotic) or miR-154 (profibrotic) could alter lung fibrosis in a murine bleomycin model. Using lentiviral vectors, we transduced miRNAs (let-7d or miR-154) or a control sequence into human B-MSCs. Overexpression of let-7d or miR-154 was associated with changes in the mesenchymal properties of B-MSCs and in their cytokine expression. Modified B-MSCs were intravenously administered to mice at day 7 after bleomycin instillation, and the mice were euthanized at day 14. Bleomycin-injured animals that were treated with let-7d cells were found to recover quicker from the initial weight loss compared with the other treatment groups. Interestingly, animals treated with miR-154 cells had the lowest survival rate. Although a slight reduction in collagen mRNA levels was observed in lung tissue from let-7d mice, no significant differences were observed in Ashcroft score and OH-proline. However, the distinctive expression in cytokines and CD45-positive cells in the lung suggests that the differential effects observed in both miRNA mice groups were related to an effect on the immunomodulation function. Our results establish the use of miRNA-modified mesenchymal stem cells as a potential future research in lung fibrosis.
A novel biomarker associated with distress in humans: calcium-binding protein, spermatid-specific 1 (CABS1)
Authors: Ritz Thomas , Rosenfield David , St. Laurent Chris D. , Trueba Ana F. , Werchan Chelsey A. , Vogel Pia D. , Auchus Richard J. , Reyes-Serratos Eduardo , Befus A. Dean
Published: April 2017

Calcium-binding protein spermatid-specific 1 (CABS1) is expressed in the human submandibular gland and has an anti-inflammatory motif similar to that in submandibular rat 1 in rats. Here, we investigate CABS1 in human saliva and its association with psychological and physiological distress and inflammation in humans. Volunteers participated across three studies: 1) weekly baseline measures; 2) a psychosocial speech and mental arithmetic stressor under evaluative threat; and 3) during academic exam stress. Salivary samples were analyzed for CABS1 and cortisol. Additional measures included questionnaires of perceived stress and negative affect; exhaled nitric oxide; respiration and cardiac activity; lung function; and salivary and nasal inflammatory markers. We identified a CABS1 immunoreactive band at 27 kDa in all participants and additional molecular mass forms in some participants. One week temporal stability of the 27-kDa band was satisfactory (test–retest reliability estimate = 0.62–0.86). Acute stress increased intensity of 18, 27, and 55 kDa bands; 27-kDa increases were associated with more negative affect and lower heart rate, sympathetic activity, respiration rate, and minute ventilation. In both acute and academic stress, changes in 27 kDa were positively associated with salivary cortisol. The 27-kDa band was also positively associated with VEGF and salivary leukotriene B4 levels. Participants with low molecular weight CABS1 bands showed reduced habitual stress and negative affect in response to acute stress. CABS1 is readily detected in human saliva and is associated with psychological and physiological indicators of stress. The role of CABS1 in inflammatory processes, stress, and stress resilience requires careful study.
Chronic kidney disease induces autophagy leading to dysfunction of mitochondria in skeletal muscle
Authors: Su Zhen , Klein Janet D. , Du Jie , Franch Harold A. , Zhang Liping , Hassounah Faten , Hudson Matthew B. , Wang Xiaonan H.
Published: April 2017

Chronic kidney disease (CKD) causes loss of lean body mass by multiple mechanisms. This study examines whether autophagy-mediated proteolysis contributes to CKD-induced muscle wasting. We tested autophagy in the muscle of CKD mice with plantaris muscle overloading to mimic resistance exercise or with acupuncture plus low-frequency electrical stimulation (Acu/LFES) treatment. In CKD muscle, Bnip3, Beclin-1, and LC3II mRNAs and proteins were increased compared with those in control muscle, indicating autophagosome-lysosome formation induction. Acu/LFES suppressed the CKD-induced upregulation of autophagy. However, overloading increased autophagy-related proteins in normal and CKD muscle. Serum from uremic mice induces autophagy formation but did not increase the myosin degradation or actin break down in cultured muscle satellite cells. We examined mitochondrial biogenesis, copy number, and ATP production in cultured myotubes, and found all three aspects to be decreased by uremic serum. Inhibition of autophagy partially reversed this decline in cultured myotubes. In CKD mice, the mitochondrial copy number, biogenesis marker peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), mitochondrial transcription factor A (TFAM), and mitochondrial fusion marker Mitofusin-2 (Mfn2) are decreased. Both muscle overloading and Acu/LFES increased mitochondrial copy number, and reversed the CKD-induced decreases in PGC-1α, TFAM, and Mfn2. We conclude that the autophagy is activated in the muscle of CKD mice. However, myofibrillar protein is not directly broken down through autophagy. Instead, CKD-induced upregulation of autophagy leads to dysfunction of mitochondria and decrease of ATP production.
Sympathetic nervous system activation reduces contraction-induced rapid vasodilation in the leg of humans independent of age
Authors: Hughes William E. , Kruse Nicholas T. , Casey Darren P.
Published: April 2017

Contraction-induced rapid vasodilation is attenuated similarly in the upper and lower limbs of older adults. In the forearm, this attenuation is in part due to a greater sympathetic vasoconstriction. We examined whether the age-related reduction in contraction-induced vasodilation in the leg is also due to a sympathetic vasoconstrictive mechanism. Thirteen young (24 ± 1 yr) and twelve older adults (67 ± 1 yr) performed single-leg knee extension at 20 and 40% of work-rate maximum (WRmax) during control and cold-pressor test (CPT) conditions. Femoral artery diameter and blood velocity were measured using Doppler ultrasound. Vascular conductance (VC; ml·min−1·mmHg−1) was calculated using blood flow (ml/min) and mean arterial pressure (mmHg). Peak (ΔVC from baseline) and total VC were blunted in older adults during control conditions across exercise intensities ( P < 0.05). Peak and total VC were reduced during CPT in both age groups across exercise intensities ( P < 0.05). The relative change (i.e., %reduction; CPT vs. control) in peak (−25 ± 5 vs. −22 ± 4% at 20% WRmax; and −21 ± 6 vs. −27 ± 5% at 40% WRmax; P = 0.42–0.55) and total VC (−28 ± 5 vs. −36 ± 6% at 20% WRmax; and −22 ± 8 vs. −33 ± 5% at 40% WRmax; P = 0.23–0.34) were similar between young and older adults. When matched for absolute workload (~10 W), age differences persisted in peak VC ( P < 0.05) under both conditions, with similar relative changes in peak and total VC during CPT. Our data suggest that 1) sympathetic stimulation reduces contraction-induced rapid vasodilation in the leg of young and older adults similarly; and 2) enhanced sympathetic vasoconstriction does not fully explain age-related differences in contraction-induced vasodilation within the leg.

NEW & NOTEWORTHY Aging is associated with attenuated contraction-induced rapid onset vasodilation (ROV). Within the forearm, this attenuation is partially due to enhanced sympathetic vasoconstriction. In the current study, we found that sympathetic vasoconstriction reduces contraction-induced ROV within the leg of both young and older adults, with the magnitude of change being similar between age groups. Our current results suggest that age-related attenuations in contraction-induced ROV within the leg are not fully explained by a sympathetic vasoconstrictor mechanism.
Eight weeks of local vibration training increases dorsiflexor muscle cortical voluntary activation
Authors: Souron Robin , Farabet Adrien , Féasson Léonard , Belli Alain , Millet Guillaume Y. , Lapole Thomas
Published: April 2017

The aim of this study was to evaluate the effects of an 8-wk local vibration training (LVT) program on functional and corticospinal properties of dorsiflexor muscles. Forty-four young subjects were allocated to a training (VIB, n = 22) or control (CON, n = 22) group. The VIB group performed twenty-four 1-h sessions (3 sessions/wk) of 100-Hz vibration applied to the right tibialis anterior. Both legs were tested in each group before training (PRE), after 4 (MID) and 8 (POST) wk of training, and 2 wk after training (POST2W). Maximal voluntary contraction (MVC) torque was assessed, and transcranial magnetic stimulation (TMS) was used to evaluate cortical voluntary activation (VATMS), motor evoked potential (MEP), cortical silent period (CSP), and input-output curve parameters. MVC was significantly increased for VIB at MID for right and left legs [+7.4% ( P = 0.001) and +6.2% ( P < 0.01), respectively] and remained significantly greater than PRE at POST [+12.0% ( P < 0.001) and +10.1% ( P < 0.001), respectively]. VATMS was significantly increased for right and left legs at MID [+4.4% ( P < 0.01) and +4.7% ( P < 0.01), respectively] and at POST [+4.9% ( P = 0.001) and +6.2% ( P = 0.001), respectively]. These parameters remained enhanced in both legs at POST2W. MEP and CSP recorded during MVC and input-output curve parameters did not change at any time point for either leg. Despite no changes in excitability or inhibition being observed, LVT seems to be a promising method to improve strength through an increase of maximal voluntary activation, i.e., neural adaptations. Local vibration may thus be further considered for clinical or aging populations.

NEW & NOTEWORTHY The effects of a local vibration training program on cortical voluntary activation measured with transcranial magnetic stimulation were assessed for the first time in dorsiflexors, a functionally important muscle group. We observed that training increased maximal voluntary strength likely because of the strong and repeated activation of Ia spindle afferents during vibration training that led to changes in the cortico-motoneuronal pathway, as demonstrated by the increase in cortical voluntary activation.
The effects of physical exercise on nonmotor symptoms and on neuroimmune RAGE network in experimental parkinsonism
Authors: Viana Sofia D. , Pita Inês R. , Lemos Cristina , Rial Daniel , Couceiro Patrícia , Rodrigues-Santos Paulo , Caramelo Francisco , Carvalho Félix , Ali Syed F. , Prediger Rui D. , Fontes Ribeiro Carlos A. , Pereira Frederico C.
Published: April 2017

Parkinson's disease (PD) prodromal stages comprise neuropsychiatric perturbations that critically compromise a patient’s quality of life. These nonmotor symptoms (NMS) are associated with exacerbated innate immunity, a hallmark of overt PD. Physical exercise (PE) has the potential to improve neuropsychiatric deficits and to modulate immune network including receptor for advanced glycation end products (RAGE) and Toll-like receptors (TLRs) in distinct pathological settings. Accordingly, the present study aimed to test the hypothesis that PE 1) alleviates PD NMS and 2) modulates neuroimmune RAGE network in experimental PD. Adult Wistar rats subjected to long-term mild treadmill were administered intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probed for PD NMS before the onset of motor abnormalities. Twelve days after MPTP, neuroimmune RAGE network transcriptomics (real-time quantitative PCR) was analyzed in frontal cortex, hippocampus, and striatum. Untrained MPTP animals displayed habit-learning and motivational deficits without gross motor impairments (cued version of water-maze, splash, and open-field tests, respectively). A suppression of RAGE and neuroimmune-related genes was observed in frontal cortex on chemical and physical stressors (untrained MPTP: RAGE, TLR5 and -7, and p22 NADPH oxidase; saline-trained animals: RAGE, TLR1 and -5 to -11, TNF-α, IL-1β, and p22 NADPH oxidase), suggesting the recruitment of compensatory mechanisms to restrain innate inflammation. Notably, trained MPTP animals displayed normal cognitive/motivational performances. Additionally, these animals showed normal RAGE expression and neuroprotective PD-related DJ-1 gene upregulation in frontal cortex when compared with untrained MPTP animals. These findings corroborate PE efficacy in improving PD NMS and newly identify RAGE network as a neural substrate for exercise intervention. Additional research is warranted to unveil functional consequences of PE-induced modulation of RAGE/DJ-1 transcriptomics in PD premotor stages.

NEW & NOTEWORTHY This study newly shows that physical exercise (PE) corrects nonmotor symptoms of the intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of experimental parkinsonism. Additionally, we show that suppression of neuroimmune receptor for advanced glycation end products (RAGE) network occurs in frontal cortex on chemical (MPTP) and physical (PE) interventions. Finally, PE normalizes frontal cortical RAGE transcriptomics and upregulates the neuroprotective DJ-1 gene in the intranasal MPTP model of experimental parkinsonism.