bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity
Authors: Pigeyre Marie , Yazdi Fereshteh T. , Kaur Yuvreet , Meyre David
Published: May 2016

In high-, middle- and low-income countries, the rising prevalence of obesity is the underlying cause of numerous health complications and increased mortality. Being a complex and heritable disorder, obesity results from the interplay between genetic susceptibility, epigenetics, metagenomics and the environment. Attempts at understanding the genetic basis of obesity have identified numerous genes associated with syndromic monogenic, non-syndromic monogenic, oligogenic and polygenic obesity. The genetics of leanness are also considered relevant as it mirrors some of obesity's aetiologies. In this report, we summarize ten genetically elucidated obesity syndromes, some of which are involved in ciliary functioning. We comprehensively review 11 monogenic obesity genes identified to date and their role in energy maintenance as part of the leptin–melanocortin pathway. With the emergence of genome-wide association studies over the last decade, 227 genetic variants involved in different biological pathways (central nervous system, food sensing and digestion, adipocyte differentiation, insulin signalling, lipid metabolism, muscle and liver biology, gut microbiota) have been associated with polygenic obesity. Advances in obligatory and facilitated epigenetic variation, and gene–environment interaction studies have partly accounted for the missing heritability of obesity and provided additional insight into its aetiology. The role of gut microbiota in obesity pathophysiology, as well as the 12 genes associated with lipodystrophies is discussed. Furthermore, in an attempt to improve future studies and merge the gap between research and clinical practice, we provide suggestions on how high-throughput ‘-omic’ data can be integrated in order to get closer to the new age of personalized medicine.
Solitonic and chaotic behaviors for the nonlinear dust-acoustic waves in a magnetized dusty plasma
Authors: Zhen Hui-Ling , Tian Bo , Xie Xi-Yang , Wu Xiao-Yu , Wen Xiao-Yong
Published: May 2016

A model for the nonlinear dust-ion-acoustic waves in a two-ion-temperature, magnetized dusty plasma is studied in this paper. Via the symbolic computation, one-, two- and N-soliton solutions are obtained. It is found that when μeμi<2Ti2Te2+TiTe, the soliton amplitude is positively related to μe, μi, Ti, Zd, and B0, but inversely related to Te and md, with Te, Ti, μe, and μi as the temperature of an electron, temperature of a positive ion, normalized initial density of electrons, and normalized initial density of positive ions, respectively, Zd, B0, and md as the charge number of a dust particle, strength of the static magnetic field, and mass of a dust particle, respectively. It is also found that the two solitons are always parallel during the propagation on the x − y, x − t, and y − t planes, where x, y, and z are the scaled spacial coordinates, and t is the retarded time. Upon the introduction of the driving force Γ(t), both the developed and weak chaotic motions as well as the effect of Γ(t) are explored. Via the phase projections and power spectra, we find the difference between the two chaotic motions roots in the relative magnitude of nonlinearity and external force. Increasing the frequency of the external force or the strength of the damped term can weaken the chaotic motions of such a forced model.
The Kelvin-Helmholtz instability in National Ignition Facility hohlraums as a source of gold-gas mixing
Authors: Vandenboomgaerde M. , Bonnefille M. , Gauthier P.
Published: May 2016

Highly resolved radiation-hydrodynamics FCI2 simulations have been performed to model laser experiments on the National Ignition Facility. In these experiments, cylindrical gas-filled hohlraums with gold walls are driven by a 20 ns laser pulse. For the first time, simulations show the appearance of Kelvin-Helmholtz (KH) vortices at the interface between the expanding wall material and the gas fill. In this paper, we determine the mechanisms which generate this instability: the increase of the gas pressure around the expanding gold plasma leads to the aggregation of an over-dense gold layer simultaneously with shear flows. At the surface of this layer, all the conditions are met for a KH instability to grow. Later on, as the interface decelerates, the Rayleigh-Taylor instability also comes into play. A potential scenario for the generation of a mixing zone at the gold-gas interface due to the KH instability is presented. Our estimates of the Reynolds number and the plasma diffusion width at the interface support the possibility of such a mix. The key role of the first nanosecond of the laser pulse in the instability occurrence is also underlined.
Measurements of the parallel wavenumber of lower hybrid waves in the scrape-off layer of a high-density tokamak
Authors: Baek S. G. , Wallace G. M. , Shinya T. , Parker R. R. , Shiraiwa S. , Bonoli P. T. , Brunner D. , Faust I. , LaBombard B. L. , Takase Y. , Wukitch S.
Published: May 2016

In lower hybrid current drive (LHCD) experiments on tokamaks, the parallel wavenumber of lower hybrid waves is an important physics parameter that governs the wave propagation and absorption physics. However, this parameter has not been experimentally well-characterized in the present-day high density tokamaks, despite the advances in the wave physics modeling. In this paper, we present the first measurement of the dominant parallel wavenumber of lower hybrid waves in the scrape-off layer (SOL) of the Alcator C-Mod tokamak with an array of magnetic loop probes. The electric field strength measured with the probe in typical C-Mod plasmas is about one-fifth of that of the electric field at the mouth of the grill antenna. The amplitude and phase responses of the measured signals on the applied power spectrum are consistent with the expected wave energy propagation. At higher density, the observed k|| increases for the fixed launched k||, and the wave amplitude decreases rapidly. This decrease is correlated with the loss of LHCD efficiency at high density, suggesting the presence of loss mechanisms. Evidence of the spectral broadening mechanisms is observed in the frequency spectra. However, no clear modifications in the dominant k|| are observed in the spectrally broadened wave components, as compared to the measured k|| at the applied frequency. It could be due to (1) the probe being in the SOL and (2) the limited k|| resolution of the diagnostic. Future experiments are planned to investigate the roles of the observed spectral broadening mechanisms on the LH density limit problem in the strong single pass damping regime.
Optical properties of the atmospheric pressure helium plasma jet generated by alternative current (a.c.) power supply
Authors: Ilik Erkan , Akan Tamer
Published: May 2016

In this work, an atmospheric pressure plasma jet (APPJ) was produced to generate cold flowing post-discharge plasma of pure helium gas. The main aim of this study was to generate cold flowing APPJ of pure helium gas and to determine how their optical emission spectrum change influences varying different flow rates. Lengths of early, middle, and late post-discharge plasma (jet) regions and their fluctuations were determined, respectively. Then, ignition condition dependence of the post-discharge plasma for flow rate was specified at a constant voltage. Spectroscopic studies of an atmospheric pressure plasma jet of helium were presented via analyzing OH, N2, N2+, oxygen, and helium intensities for various flow rates.
Plasma and cyclotron frequency effects on output power of the plasma wave-pumped free-electron lasers
Authors: Zolghadr S. H. , Jafari S. , Raghavi A.
Published: May 2016

Significant progress has been made employing plasmas in the free-electron lasers (FELs) interaction region. In this regard, we study the output power and saturation length of the plasma whistler wave-pumped FEL in a magnetized plasma channel. The small wavelength of the whistler wave (in sub-μm range) in plasma allows obtaining higher radiation frequency than conventional wiggler FELs. This configuration has a higher tunability by adjusting the plasma density relative to the conventional ones. A set of coupled nonlinear differential equations is employed which governs on the self-consistent evolution of an electromagnetic wave. The electron bunching process of the whistler-pumped FEL has been investigated numerically. The result reveals that for a long wiggler length, the bunching factor can appreciably change as the electron beam propagates through the wiggler. The effects of plasma frequency (or plasma density) and cyclotron frequency on the output power and saturation length have been studied. Simulation results indicate that with increasing the plasma frequency, the power increases and the saturation length decreases. In addition, when density of background plasma is higher than the electron beam density (i.e., for a dense plasma channel), the plasma effects are more pronounced and the FEL-power is significantly high. It is also found that with increasing the strength of the external magnetic field frequency, the power decreases and the saturation length increases, noticeably.
Changes in oxidative patterns during dormancy break by warm and cold stratification in seeds of an edible fruit tree
Authors: Shalimu Dilinuer , Sun Jia , Baskin Carol C. , Baskin Jerry M. , Sun Liwei , Liu Yujun
Published: May 2016

The transition from seed dormancy to germination is triggered by environmental factors, and in pomegranate ( Punica granatum ) seeds higher germination percentages are achieved by warm + cold stratification rather than by cold stratification alone. Our objective was to define the pattern of internal oxidative changes in pomegranate seeds as dormancy was being broken by warm + cold stratification and by cold stratification alone. Embryos isolated from seeds after 1–42 days of warm stratification, after 56 days of warm stratification + 7, 28 or 56 days of cold stratification, and after 1–84 days of cold stratification alone, were used in biochemical tests. Hydrogen peroxide (H 2 O 2 ), nitric oxide (NO), proline, lipid peroxidation, protein carbonylation, and activities of the scavenging enzymes superoxide dismutase (SOD), hydrogen peroxide enzyme and peroxidase in the embryos were assessed by colorimetric methods. Our results indicated that warm + cold stratification had a stronger dormancy-breaking effect than cold stratification (85% versus 50% germination), which may be attributed to a higher yield of H 2 O 2 , NO, lipid peroxidation and protein carbonylation in warm + cold stratification. Furthermore, warm + cold stratification-induced H 2 O 2 change led to greater changes (elevation followed by attenuation) in activities of the scavenging enzymes than that induced by cold stratification alone. These results indicated that restriction of the level of reactive oxygen species change within a positive and safe range by such enzymes promoted seed germination. In addition, a relatively strong elevation of proline during warm + cold stratification also contributed to dormancy breakage and subsequent germination. In conclusion, the strong dormancy alleviating effect of warm + cold stratification on pomegranate seeds may be attributed to the corresponding active oxidative change via H 2 O 2 , NO, proline, malondialdehyde, protein carbonylation and scavenging enzymes.
Dark bubbles around high-redshift radio-loud active galactic nucleus
Authors: Ghisellini G. , Sbarrato T.
Published: May 2016

At redshift larger than 3 there is a disagreement between the number of blazars (whose jet is pointing at us) and the number of expected parents (whose jet is pointing elsewhere). Now we strengthen this claim because (i) the number of blazars identified within the Sloan Digital Sky Survey (SDSS)+Faint Images of the Radio Sky at Twenty-cm (FIRST) survey footprint increased, demanding a more numerous parent population, and (ii) the detected blazars have a radio flux large enough to be above the FIRST flux limit even if the jet is slightly misaligned. The foreseen number of these slightly misaligned jets, in principle detectable, is much larger than the radio-detected sources in the FIRST+SDSS survey (at redshift larger than 4). This argument is independent of the presence of an isotropic radio component, such as the hotspot or the radio lobe, and does not depend on the bulk Lorentz factor Γ. We propose a scenario that ascribes the lack of slightly misaligned sources to an overobscuration of the nucleus by a ‘bubble’ of dust, possibly typical of the first high-redshift quasars.
Inference of maternal allele inheritance via Bayesian hierarchical model in noninvasive prenatal diagnosis
Authors: Shao Chunxuan
Published: May 2016

Noninvasive prenatal diagnosis (NIPD) poses a promising solution for detecting genetic alterations in fetus genome. However, the inference of the maternal allele inheritance in monogenic autosomal recessive disease is still challenging. Here the Bayesian hierarchical model is proposed to deduce the allele inheritance basing on haplotype frequency. The Bayesian approach, which does not depend on the knowledge of fetus DNA proportion in maternal plasma, provides accurate estimations on both real and simulated data; moreover, it is most robust than current methods in analyzing noisy or even erroneous data.
GEFs and Rac GTPases control directional specificity of neurite extension along the anterior-posterior axis
Authors: Zheng Chaogu , Diaz-Cuadros Margarete , Chalfie Martin
Published: May 2016

Although previous studies have identified many extracellular guidance molecules and intracellular signaling proteins that regulate axonal outgrowth and extension, most were conducted in the context of unidirectional neurite growth, in which the guidance cues either attract or repel growth cones. Very few studies addressed how intracellular signaling molecules differentially specify bidirectional outgrowth. Here, using the bipolar PLM neurons inC. elegans, we show that the guanine nucleotide exchange factors (GEFs) UNC-73/Trio and TIAM-1 promote anterior and posterior neurite extension, respectively. The Rac subfamily GTPases act downstream of the GEFs; CED-10/Rac1 is activated by TIAM-1, whereas CED-10 and MIG-2/RhoG act redundantly downstream of UNC-73. Moreover, these two pathways antagonize each other and, thus, regulate the directional bias of neuritogenesis. Our study suggests that directional specificity of neurite extension is conferred through the intracellular activation of distinct GEFs and Rac GTPases.

Significance Statement

Most previous studies on intracellular signaling during neurite guidance were performed in the context of unidirectional neurite growth. They could not address the molecular basis of directional outgrowth of multiple neurites mainly because of the lack of a good model system. Using a pair of bipolar neurons in the nematodeCaenorhabditis elegans, we found that distinct sets of intracellular molecules are required for neurite extension towards the anterior and the posterior. Moreover, signaling pathways that promote neurite extension in different directions antagonize each other to achieve balanced growth. Therefore, our study offers anin vivoexample for a long-standing concept that spatially selective activation of intracellular signaling molecules could enable a diverse range of neuronal growth patterns.
Synthetic lipid-containing scaffolds enhance production by co-localizing enzymes
Authors: Myhrvold Cameron , Polka Jessica K. , Silver Pamela A.
Published: May 2016

Subcellular organization is critical for isolating, concentrating, and protecting biological activities. Natural subcellular organization is often achieved using co-localization of proteins on scaffold molecules, thereby enhancing metabolic fluxes and enabling co-regulation. Synthetic scaffolds extend these benefits to new biological processes, and are typically constructed from proteins or nucleic acids. To expand the range of available building materials, we use a minimal set of components from the lipid-encapsulated bacteriophage Φ6 to form synthetic lipid-containing scaffolds (SLSs) inE. coli. Analysis of diffusive behavior by tracking particles in live cells indicates that SLSs are >20 nm in diameter; furthermore, density measurements demonstrate that SLSs contain a mixture of lipids and proteins. The fluorescent proteins mCitrine and mCerulean can be co-localized to SLSs. To test for effects on enzymatic production, we localized two enzymes involved in indigo biosynthesis to SLSs. We observed a scaffold-dependent increase in indigo production, showing that SLSs can enhance metabolic reactions.
A novel nuclear genetic code alteration in yeasts and the evolution of codon reassignment in eukaryotes
Authors: Mühlhausen Stefanie , Findeisen Peggy , Plessmann Uwe , Urlaub Henning , Kollmar Martin
Published: May 2016

The genetic code is the cellular translation table for the conversion of nucleotide sequences into amino acid sequences. Changes to the meaning of sense codons would introduce errors into almost every translated message and are expected to be highly detrimental. However, reassignment of single or multiple codons in mitochondria and nuclear genomes, although extremely rare, demonstrates that the code can evolve. Several models for the mechanism of alteration of nuclear genetic codes have been proposed (including “codon capture,” “genome streamlining,” and “ambiguous intermediate” theories), but with little resolution. Here, we report a novel sense codon reassignment in Pachysolen tannophilus, a yeast related to the Pichiaceae. By generating proteomics data and using tRNA sequence comparisons, we show that Pachysolen translates CUG codons as alanine and not as the more usual leucine. The Pachysolen tRNACAG is an anticodon-mutated tRNAAla containing all major alanine tRNA recognition sites. The polyphyly of the CUG-decoding tRNAs in yeasts is best explained by a tRNA loss driven codon reassignment mechanism. Loss of the CUG-tRNA in the ancient yeast is followed by gradual decrease of respective codons and subsequent codon capture by tRNAs whose anticodon is not part of the aminoacyl-tRNA synthetase recognition region. Our hypothesis applies to all nuclear genetic code alterations and provides several testable predictions. We anticipate more codon reassignments to be uncovered in existing and upcoming genome projects.
Alternative prey use affects helminth parasite infections in grey wolves
Authors: Friesen Olwyn C. , Roth James D.
Published: May 2016

Predators affect prey populations not only through direct predation, but also by acting as definitive hosts for their parasites and completing parasite life cycles. Understanding the affects of parasitism on prey population dynamics requires knowing how their predators’ parasite community is affected by diet and prey availability. Ungulates, such as moose (Alces americanus) and white‐tailed deer (Odocoileus virginianus), are often important prey for wolves (Canis lupus), but wolves also consume a variety of alternative prey, including beaver (Castor canadensis) and snowshoe hare (Lepus americanus).

The use of alternative prey, which may host different or fewer parasites than ungulates, could potentially reduce overall abundance of ungulate parasites within the ecosystem, benefiting both wolves and ungulate hosts.

We examined parasites in wolf carcasses from eastern Manitoba and estimated wolf diet using stable isotope analysis. Taeniidae cestodes were present in most wolves (75%), reflecting a diet primarily comprised of ungulates, but nematodes were unexpectedly rare.

Cestode abundance was negatively related to the wolf's δ13C value, indicating diet affects parasite abundance. Wolves that consumed a higher proportion of beaver and caribou (Rangifer tarandus), estimated using Bayesian mixing models, had lower cestode abundance, suggesting the use of these alternative prey can reduce parasite loads.

Long‐term consumption of beavers may lower the abundance of adult parasites in wolves, eventually lowering parasite density in the region and ultimately benefiting ungulates that serve as intermediate hosts. Thus, alternative prey can affect both predator–prey and host–parasite interactions and potentially affect food web dynamics.
Coupled range dynamics of brood parasites and their hosts responding to climate and vegetation changes
Authors: Péron Guillaume , Altwegg Res , Jamie Gabriel A. , Spottiswoode Claire N.
Published: May 2016

As populations shift their ranges in response to global change, local species assemblages can change, setting the stage for new ecological interactions, community equilibria and evolutionary responses.

Here, we focus on the range dynamics of four avian brood parasite species and their hosts in southern Africa, in a context of bush encroachment (increase in woody vegetation density in places previously occupied by savanna–grassland mosaics) favouring some species at the expense of others. We first tested whether hosts and parasites constrained each other's ability to expand or maintain their ranges. Secondly, we investigated whether range shifts represented an opportunity for new host–parasite and parasite–parasite interactions.

We used multispecies dynamic occupancy models with interactions, fitted to citizen science data, to estimate the contribution of interspecific interactions to range shifts and to quantify the change in species co‐occurrence probability over a 25‐year period.

Parasites were able to track their hosts’ range shifts. We detected no deleterious effect of the parasites’ presence on either the local population viability of host species or the hosts’ ability to colonize newly suitable areas. In the recently diversified indigobird radiation (Vidua spp.), following bush encroachment, the new assemblages presented more potential opportunities for speciation via host switch, but also more potential for hybridization between extant lineages, also via host switch.

Multispecies dynamic occupancy models with interactions brought new insights into the feedbacks between range shifts, biotic interactions and local demography: brood parasitism had little detected impact on extinction or colonization processes, but inversely the latter processes affected biotic interactions via the modification of co‐occurrence patterns.
Family factors associated with adolescent self‐harm: a narrative review
Authors: Fortune Sarah , Cottrell David , Fife Sarah
Published: May 2016

This narrative literature review focuses on family factors that might be amenable to intervention using family therapy (n=126). Domains of interest include parent/child interactions, inter‐parental relationships, child characteristics, parental characteristics, wider system factors, treatment needs and moderators. The focus of family‐orientated treatment with this population should focus on maximizing cohesion, attachment, adaptability, family support, parental warmth while reducing maltreatment, scapegoating and moderating parental control. Close working relationships with child protection services and schools represent additional opportunities.

Practitioner points

Over and above any inherited risk, a range of family interactional factors are strongly associated with self‐harming behaviours in young people

Therapy has the potential to make a positive difference by focusing on enhancing family cohesion and adaptability, whilst reducing discord and violence. Discussions that enhance perceived parental support and warmth may be particularly helpful

Therapists should attend to issues of perceived difference and potential victimization (bullying, gender orientation and identity, ethnic minority status) as these may play an important role in self‐harm
Gentrification, Social Justice and Personal Ethics
Authors: Marcuse Peter
Published: May 2016

Gentrification, leading to displacement, is an increasingly recognized social problem. Individuals who are confronted with tight housing possibilities but have adequate incomes confront personal ethical issues on whether to act in ways that may contribute to displacement of lower‐income residents, and researchers working on housing issues may be particularly concerned. In order to work out an ethical position, clarity is first needed on the differences among the various aspects of gentrification. The working definition used here is that gentrification includes the danger of displacement. A public policy response is thus required to deal with its social injustices. Specific steps are suggested for the development of such policy. Secondly, the suggestion is made that the individual choice of whether to move in or not is, importantly, a personal ethical choice and should take into account both the economic and political impact of the move itself but also the contribution that can be made through collective and political action by an in‐mover to deal with the injustices of gentrification. However, it is also an ethical choice for the professions involved and their associations.
Audit Fee Differential, Audit Effort, and Litigation Risk: An Examination of ADR Firms
Authors: Bronson Scott N. , Ghosh Aloke (Al) , Hogan Chris E.
Published: May 2016

Prior studies find that audit fees are higher for cross‐listed firms, and these studies primarily attribute the incremental fees to added litigation costs. In this study, we investigate whether the higher audit fees that foreign firms cross‐listed in the United States pay are also attributable to incremental audit effort associated with U.S. disclosure requirements and a more stringent U.S. auditing environment. By comparing audit fees of foreign cross‐listed firms to U.S. domiciled firms and to non‐cross‐listed foreign firms, we are able to decompose incremental audit fees into portions attributable to added audit effort and to added litigation costs. We find that, on average, foreign firms cross‐listed in the United States pay significantly higher fees than domestic U.S. firms and foreign firms that do not cross‐list. Furthermore, we find that audit effort is almost as important as litigation costs in explaining the higher fees associated with foreign cross‐listed firms; our estimates suggest that between 29 percent and 48 percent of the incremental fees are attributable to incremental audit effort. In addition, the total cross‐listing premium is increasing in the difference between the U.S. auditing regulatory environment and that of the home country of the cross‐listed firm. Our study improves our understanding of the role of audit effort in explaining the added fees charged by auditors when foreign firms cross‐list in the United States.
Patient and Process Factors Associated With Type of First Neuroimaging and Delayed Diagnosis in Childhood Arterial Ischemic Stroke
Authors: Daverio Marco , Bressan Silvia , Gregori Dario , Babl Franz E. , Mackay Mark T.
Published: May 2016

Objectives

In‐hospital factors contribute more to delayed diagnosis of childhood arterial ischemic stroke (AIS) than prehospital factors. We aimed to explore process and patient factors associated with type of and timing to neuroimaging in childhood AIS in the emergency department (ED).

Methods

This was a retrospective hospital registry–based study of children with AIS, presenting to an Australian tertiary pediatric ED between January 2003 and December 2012. Neuroimaging data and timelines of care were also collected from referring hospitals for transferred patients.

Results

Seventy‐one AIS episodes and 19 transient ischemic attacks were recorded. The majority (56%) were initially seen at a referring hospital. Patients underwent computed tomography (CT) as first scan more frequently than magnetic resonance imaging (MRI) as first scan (61% vs. 32%) at both the referring and the tertiary hospitals. Time to first scan as CT was significantly shorter compared with MRI (median = 1.5 hours vs. 10.9 hours, p < 0.001). MRI was performed more often at the tertiary hospital (92.5% vs. 26%, p = 0.001). Median time to performance of diagnostic MRI was 15.1 hours (interquartile range = 7.1–23.5), with no significant difference between patients first presenting to a referring hospital and those directly accessing the tertiary center. Patient characteristics including age, past medical history, conscious state, focal symptoms, and signs on arrival were not associated with the type of first neuroimaging or time to diagnostic MRI. Patients presenting during weekends were less likely to receive an MRI as first scan (odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.1–0.8), while time to MRI was significantly longer for children presenting after hours (5 pm–8 am; median = 17.6 hours vs. 8.4 hours, p = 0.026). MRI overall and as first scan was associated with a higher use of sedation than CT (OR = 6.5, 95% CI = 1.3–32.9; and OR = 3.9, 95% CI = 1.3–11.8), particularly for children younger than 5 years of age (OR = 12.5, 95% CI = 3–52.4).

Conclusions

Strategies to improve rapid diagnosis of pediatric stroke should include shared regional hospital networks protocols to optimize local imaging strategies and where possible rapid transfer to the tertiary center. Future priorities should include development of pediatric ED physician decision support tools to differentiate stroke from mimics and the development and implementation of rapid ED imaging stroke protocols to improve access to confirmatory MRI scanning.
Accuracy of Point‐of‐care Lung Ultrasonography for Diagnosis of Acute Chest Syndrome in Pediatric Patients with Sickle Cell Disease and Fever
Authors: Daswani Dina D. , Shah Vaishali P. , Avner Jeffrey R. , Manwani Deepa G. , Kurian Jessica , Rabiner Joni E.
Published: May 2016

Objectives

The objective was to determine the test performance characteristics for point‐of‐care lung ultrasonography (LUS) performed by pediatric emergency medicine (PEM) physicians compared with radiographic diagnosis of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) and fever.

Methods

This was a prospective study of patients up to 21 years with SCD and fever requiring chest X‐ray (CXR) evaluation for ACS. Before obtaining CXR, a blinded PEM physician performed LUS using a standardized scanning protocol. Positive LUS for ACS was defined as lung consolidation. All patients received CXR and follow‐up. The criterion standard for ACS was consolidation on CXR as determined by a blinded radiologist. LUS clips were reviewed by a blinded expert PEM sonologist.

Results

A total of 116 febrile events from 91 patients with a median age of 5.7 years were enrolled by 15 PEM sonologists. CXR was positive for ACS in 15 (13%) patients, and LUS was positive for ACS in 19 (16%) patients. Positive LUS had a sensitivity of 87% (95% confidence interval [CI] = 62% to 96%), specificity of 94% (95% CI = 88% to 97%), positive likelihood ratio of 14.6 (95% CI = 6.5 to 32.5), and negative likelihood ratio of 0.14 (95% CI = 0.04 to 0.52) for ACS. The interobserver agreement (kappa) was 0.77. There were two missed cases of ACS on LUS.

Conclusions

LUS may be sensitive and specific for diagnosis of ACS in pediatric patients with SCD and fever. LUS may reduce the need for routine CXR and associated ionizing radiation exposure in this population.
Comparative Trends and Downstream Outcomes of Coronary Computed Tomography Angiography and Cardiac Stress Testing in Emergency Department Patients With Chest Pain: An Administrative Claims Analysis
Authors: Morris Jacob R. , Bellolio M. Fernanda , Sangaralingham Lindsey R. , Schilz Stephanie R. , Shah Nilay D. , Goyal Deepi G. , Bell Malcolm R. , Kopecky Stephen L. , Gilani Waqas I. , Hess Erik P.
Published: May 2016

Objectives

Coronary computerized tomography angiography (CCTA) is a rapidly emerging technology for the evaluation of chest pain in the emergency department (ED). We assessed trends in CCTA use and compared downstream healthcare utilization between CCTA and cardiac stress testing modalities.

Methods

Using administrative claims data (Optum Labs Data Warehouse) from over 100 million geographically diverse privately insured and Medicare Advantage enrollees across the United States, we identified 2,047,799 ED patients from January 2006 to December 2013 who presented with chest pain and had a CCTA or cardiac stress test within 72 hours. Cohorts were established based on CCTA or functional stress testing (myocardial perfusion scintigraphy [MPS], stress echocardiogram [SE], or treadmill exercise electrocardiogram [TMET]) performed within 72 hours of the ED visit. We tracked subsequent invasive cardiac procedures (invasive coronary angiography [ICA], percutaneous coronary intervention [PCI], and coronary artery bypass grafting [CABG]), repeat noninvasive testing, return ED visits, hospitalization, and the rate of acute myocardial infarction (AMI) within 30 days. We used propensity‐score matching to adjust for coronary artery disease (CAD) risk factors, Charlson‐Deyo comorbidity index, and baseline differences between patients selected for CCTA or cardiac stress testing. Logistic regression was used to measure adjusted associations between testing modality and outcomes.

Results

During the study period, CCTA use increased from 0.8% to 4.5% of all cardiac testing within 72 hours, a change of 434% (p‐value for trend < 0.001), while rates of other cardiac stress testing modalities decreased (–22% for TMET [p < 0.001]; –11% for SE [p = 0.11]; –6% for MPS [p = 0.04]. After matching, there was no difference in the 30‐day rate of AMI between testing modalities. Compared to MPS, CCTA was associated with higher rates of PCI (odds ratio [OR] = 1.25, 95% confidence interval [CI] = 1.04 to 1.51), and CABG (OR = 1.47; 95% CI = 1.03 to 2.13). Compared to SE and treadmill stress testing, CCTA was associated with more invasive procedures, hospitalizations, return ED visits, and repeat noninvasive testing.

Conclusions

CCTA use increased fourfold during the study period and was associated with higher rates of PCI, CABG, repeat noninvasive testing, hospitalization, and return ED visits.

The authors have no relevant financial information or potential conflicts to disclose.
Associations Between Gestational Age at Birth and Alcohol Use in the Avon Longitudinal Study of Parents and Children
Authors: Do Elizabeth K. , Latendresse Shawn J. , Edwards Alexis C. , Kendler Kenneth S. , Dick Danielle M. , York Timothy P.
Published: May 2016

Background

The relationship between gestational age at birth (GA) and alcohol use measures in early adulthood was examined in a large U.K. community‐based birth cohort (Avon Longitudinal Study of Parents and Children).

Methods

A series of linear and logistic regression models were used to test for main effects of a continuous measure of GA on a range of alcohol use measures, and moderation of these associations by sex. In addition, mediation analyses assessed the extent to which significant associations between GA and alcohol use operated indirectly, through influences of the parental environment and/or childhood measures of emotional and behavioral health (EBH).

Results

Earlier GA significantly predicted never drinking by age 18, but was not associated with other measures of alcohol use behavior among young adult drinkers (i.e., Self‐Rating of the Effects of Alcohol, Alcohol Use Disorders Identification Test, or DSM‐IV‐TR Criteria for Alcohol Dependence). The association between earlier GA and never drinking by age 18 was moderated by sex, such that females born early were less likely to have ever had a drink by age 18. In the full sample, childhood measures of EBH were found to mediate the association between earlier GA and never drinking by age 18. This association was not mediated by parenting factors.

Conclusions

Earlier GA is associated with never drinking alcohol in early adulthood, in females. Emotional and behavioral difficulties experienced in early childhood may mediate the relationship between earlier GA and never drinking by age 18.
Psoriasin (S100A7) promotes stress-induced angiogenesis
Authors: Vegfors J. , Ekman A.-K. , Stoll S.W. , Bivik Eding C. , Enerbäck C.
Published: May 2016

Background

Vascular modifications occur early in the development of psoriasis, and angiogenesis is one of the key features in the pathogenesis of the disease.

Objectives

To identify the role of the S100 protein psoriasin in psoriasis-associated angiogenesis.

Methods

The role of psoriasin in mediating angiogenesis was investigated by silencing psoriasin with small interfering RNA (siRNA) and measuring psoriasis-associated angiogenic factors in human epidermal keratinocytes. The secretion of psoriasin and the effect of psoriasin on general regulators of angiogenesis in keratinocytes, and on endothelial cell migration, proliferation, tube formation and production of angiogenic mediators, was evaluated.

Results

Reactive oxygen species (ROS) and hypoxia induced the expression of psoriasin. Downregulation of psoriasin in keratinocytes using siRNA altered the ROS-induced expression of the psoriasis-associated angiogenic factors vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor-like growth factor, matrix metalloproteinase 1 and thrombospondin 1. Overexpression of psoriasin altered several regulators of angiogenesis and led to the secretion of psoriasin. Treatment with extracellular psoriasin induced proliferation, migration and tube formation in dermal-derived endothelial cells to a similar extent as VEGF and interleukin-17, and induced the expression and release of proangiogenic mediators. These effects were suggested to be mediated by the PI3K and nuclear factor kappa B pathways.

Conclusions

These findings suggest that psoriasin expression is promoted by oxidative stress in keratinocytes and amplifies the ROS-induced expression of angiogenic factors relevant to psoriasis. Moreover, extracellularly secreted psoriasin may act on dermal endothelial cells to contribute to key features angiogenesis.
Exploring students’ acceptance of team messaging services: The roles of social presence and motivation
Authors: Huang Yong‐Ming
Published: May 2016

Team messaging services represent a type of cloud computing applications that support not only the messaging among users but also the collaboration in a team. Accordingly, team messaging services have great potential to facilitate students’ collaboration. However, only few studies utilized such services to support students’ collaboration and further investigated the factors that influence students’ acceptance of these services. To remedy this deficiency, this research not only employed a team messaging service to support the subjects’ collaboration but also conducted a survey with a questionnaire designed for identifying the factors that influenced their intention to use the service. The research findings demonstrated that (1) social presence not only played an important role in influencing the subjects’ intention to use the service, but also significantly affected their motivation in using it; (2) the subjects’ intrinsic motivation played a more significant role than their extrinsic motivation did in influencing their attitude toward using and behavioral intention; (3) the subjects’ attitude toward using the service exerted no influence on their intention to use it. These findings suggested that, when students collaborate through a team messaging service, their awareness of others’ presence will significantly influence their motivation and intention to use the service.
Genetic variation in neuronal glutamate transport genes and associations with posttraumatic seizure
Authors: Ritter Anne C. , Kammerer Candace M. , Brooks Maria M. , Conley Yvette P. , Wagner Amy K.
Published: May 2016

Objective

Posttraumatic seizures (PTS) commonly occur following severe traumatic brain injury (sTBI). Risk factors for PTS have been identified, but variability in who develops PTS remains. Excitotoxicity may influence epileptogenesis following sTBI. Glutamate transporters manage glutamate levels and excitatory neurotransmission, and they have been associated with both epilepsy and TBI. Therefore, we aimed to determine if genetic variation in neuronal glutamate transporter genes is associated with accelerated epileptogenesis and increased PTS risk after sTBI.

Methods

Individuals (N = 253) 18–75 years of age with sTBI were assessed for genetic relationships with PTS. Single nucleotide polymorphisms (SNPs) within SLC1A1 and SLC1A6 were assayed. Kaplan‐Meier estimates and log‐rank statistics were used to compare seizure rates from injury to 3 years postinjury for SNPs by genotype. Hazard ratios (HRs) were estimated using Cox proportional hazards regression for SNPs significant in Kaplan‐Meier analyses adjusting for known PTS risk factors.

Results

Thirty‐two tagging SNPs were examined (SLC1A1: n = 28, SLC1A6: n = 4). Forty‐nine subjects (19.37%) had PTS. Of these, 18 (36.7%) seized within 7 days, and 31 (63.3%) seized between 8 days and 3 years post‐TBI. With correction for multiple comparisons, genotypes at SNP rs10974620 (SLC1A1) were significantly associated with time to first seizure across the full 3‐year follow‐up (seizure rates: 77.1% minor allele homozygotes, 24.8% heterozygotes, 16.6% major allele homozygotes; p = 0.001). When seizure follow‐up began day 2 postinjury, genotypes at SNP rs7858819 (SLC1A1) were significantly associated with PTS risk (seizure rates: 52.7% minor allele homozygotes, 11.8% heterozygotes, 21.1% major allele homozygotes; p = 0.002). After adjusting for covariates, we found that rs10974620 remained significant (p = 0.017, minor allele versus major allele homozygotes HR 3.4, 95% confidence interval [CI] 1.3–9.3). rs7858819 also remained significant in adjusted models (p = 0.023, minor allele versus major allele homozygotes HR 3.4, 95%CI 1.1–10.5).

Significance

Variations within SLC1A1 are associated with risk of epileptogenesis following sTBI. Future studies need to confirm findings, but variation within neuronal glutamate transporter genes may represent a possible pharmaceutical target for PTS prevention and treatment.
Magnetic resonance imaging of presumptive neonatal encephalopathy in a foal
Authors: Wong D. M. , Jeffery N. , Hepworth‐Warren K. L. , Wiechert S. A. , Miles K.
Published: May 2016

A 10‐h‐old Thoroughbred foal presented with clinical signs consistent with neonatal encephalopathy including absent suckling behaviour, lack of affinity for the mare and seizures. The foal was provided supportive care and treated with broad‐spectrum antimicrobials and fed via naso‐oesophageal tube. In addition, magnetic resonance imaging (MRI) was performed to investigate for structural changes that might be evident with equine neonatal encephalopathy. Notable findings on MRI included hyperintensity of the basal nuclei and superficial layers of the ventral cerebral hemispheres as well as the ventral thalamic nuclei and rostral aspect of the ventral midbrain. These imaging changes were consistent with the counterpart disease in infants and are the first to document MRI changes in a foal with neonatal encephalopathy. This report serves as an initial description of MRI findings associated with the presumed diagnosis of equine neonatal encephalopathy and also serves to solicit future diagnostic imaging studies that may help elucidate the pathophysiology and prognosis of equine neonatal encephalopathy.
NMR in structural genomics to increase structural coverage of the protein universe
Authors: Serrano Pedro , Dutta Samit K. , Proudfoot Andrew , Mohanty Biswaranjan , Susac Lukas , Martin Bryan , Geralt Michael , Jaroszewski Lukasz , Godzik Adam , Elsliger Marc , Wilson Ian A. , Wüthrich Kurt
Published: May 2016

For more than a decade, the Joint Center for Structural Genomics (JCSG; www.jcsg.org) worked toward increased three‐dimensional structure coverage of the protein universe. This coordinated quest was one of the main goals of the four high‐throughput (HT) structure determination centers of the Protein Structure Initiative (PSI; www.nigms.nih.gov/Research/specificareas/PSI). To achieve the goals of the PSI, the JCSG made use of the complementarity of structure determination by X‐ray crystallography and nuclear magnetic resonance (NMR) spectroscopy to increase and diversify the range of targets entering the HT structure determination pipeline. The overall strategy, for both techniques, was to determine atomic resolution structures for representatives of large protein families, as defined by the Pfam database, which had no structural coverage and could make significant contributions to biological and biomedical research. Furthermore, the experimental structures could be leveraged by homology modeling to further expand the structural coverage of the protein universe and increase biological insights. Here, we describe what could be achieved by this structural genomics approach, using as an illustration the contributions from 20 NMR structure determinations out of a total of 98 JCSG NMR structures, which were selected because they are the first three‐dimensional structure representations of the respective Pfam protein families. The information from this small sample is representative for the overall results from crystal and NMR structure determination in the JCSG. There are five new folds, which were classified as domains of unknown functions (DUF), three of the proteins could be functionally annotated based on three‐dimensional structure similarity with previously characterized proteins, and 12 proteins showed only limited similarity with previous deposits in the Protein Data Bank (PDB) and were classified as DUFs.
Improved microstructure and properties of the gelatin film produced through prior cross‐linking induced by horseradish peroxidase, glucose oxidase and glucose
Authors: Han Yan‐Ping , Zhao Xin‐Huai
Published: May 2016

The effects of prior enzymatic cross‐linking of bovine gelatin via horseradish peroxidase, glucose oxidase and glucose on microstructure and properties of the target film (cross‐linked gelatin film) were assessed. The cross‐linked gelatin film exhibited similar film thickness and moisture content, lower water solubility and higher opacity than the gelatin film directly prepared with bovine gelatin. The cross‐linked gelatin film also demonstrated improved thermal stability and mechanical properties, characterised by higher melting point and glass transition temperature, enhanced tensile strength and elongation at break and greater storage modulus. Prior gelatin cross‐linking resulted in 30.2% and 68.6% reductions in water vapour and CO2 permeability of the cross‐linked gelatin film, respectively, but did not affect oil permeability. Furthermore, the cross‐linked gelatin film possessed smaller cross‐sectional voids (diameter 100−360 nm vs. 200−595 nm) than the bovine gelatin film. This study shows that cross‐linking can efficiently improve film microstructure and properties of the gelatin‐like products.
Lipid rafts in immune signalling: current progress and future perspective
Authors: Varshney Pallavi , Yadav Vikas , Saini Neeru
Published: May 2016

Lipid rafts are dynamic assemblies of proteins and lipids that harbour many receptors and regulatory molecules and so act as a platform for signal transduction. They float freely within the liquid‐disordered bilayer of cellular membranes and can cluster to form larger ordered domains. Alterations in lipid rafts are commonly found to be associated with the pathogenesis of several human diseases and recent reports have shown that the raft domains can also be perturbed by targeting raft proteins through microRNAs. Over the last few years, the importance of lipid rafts in modulating both innate and acquired immune responses has been elucidated. Various receptors present on immune cells like B cells, T cells, basophils and mast cells associate with lipid rafts on ligand binding and initiate signalling cascades leading to inflammation. Furthermore, disrupting lipid raft integrity alters lipopolysaccharide‐induced cytokine secretion, IgE signalling, and B‐cell and T‐cell activation. The objective of this review is to summarize the recent progress in understanding the role of lipid rafts in the modulation of immune signalling and its related therapeutic potential for autoimmune diseases and inflammatory disorders.