bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlled Attachment of Pseudomonas aeruginosa with Binary Colloidal Crystal‐Based Topographies
Authors: Pingle Hitesh , Wang Peng‐Yuan , Thissen Helmut , Kingshott Peter
Published: February 2018

Micro‐ and nanotopographies can interfere with bacteria attachment, however, the interplay existing between surface chemistry and topography remains unclear. Here, self‐assembled spherical micrometer‐ silica and nanometer poly(methyl methacrylate) (PMMA)‐sized particles are used to make binary colloidal crystal (BCC) topographical patterns to study bacterial attachment. A uniform surface chemistry of allylamine plasma polymer (AAMpp) is coated on the top of the BCCs to study only the topography effects. The uncoated and coated BCCs are exposed to Pseudomonas aeruginosa, and the surfaces and bacteria are characterized using scanning electron microscopy (SEM), X‐ray photoelectron spectroscopy (XPS), and fluorescence microscopy. It is found that bacteria attachment to the uncoated BCCs is delayed and individual cells are attracted to the small particle regions of the patterns. Surprisingly, this phenomenon is also observed for the AAMpp‐coated BCCs, with bacteria attaching to the small particle regions of the pattern, in stark contrast to uniform flat films of AAMpp that are highly adhesive toward P. aeruginosa. Also, the overall levels of bacterial attachment are significantly reduced by the BCC patterns compared to controls. Thus, there is a trade‐off that exists between chemistry and topography that can be exploited to delay the onset of P. aeruginosa biofilm formation on surfaces.
Measuring trust: A reinvestigation
Authors: Aksoy Billur , Harwell Haley , Kovaliukaite Ada , Eckel Catherine
Published: February 2018

We reinvestigate the question first posed by Glaeser et al. (2000): Do survey measures about trust predict actual trusting behavior? This important study established that the behavior in an incentivized trust game is not correlated with the responses to the most widely used survey measures of trust. We conduct a replication and a reinvestigation of GLSS. In the replication, we use the GLSS protocol and we reproduce their results. In the reinvestigation, we introduce one major change: We replace their variation of the standard Berg, Dickhaut, and McCabe (1995) investment game with the original unmodified game. The standard game endows both players, while the modified version endows only the first mover. After endowing both movers in the reinvestigation experiment, we find a significant correlation between the two measures, suggesting that trust is a single construct, whether measured by the survey questions or by an incentivized trust game.
Fourth ventricle index: sonographic marker for severe fetal vermian dysgenesis/agenesis
Authors: Haratz K. K. , Shulevitz S. L. , Leibovitz Z. , Lev D. , Shalev J. , Tomarkin M. , Malinger G. , Lerman‐Sagie T. , Gindes L.
Published: February 2018

Objective

Prenatal diagnosis of midbrain‐hindbrain (MB‐HB) malformations relies primarily on abnormal size and shape of the cerebellum and retrocerebellar space, particularly ‘open fourth ventricle’ (4V), the most common indicator of MB‐HB malformations. The aim of this study was to present the fourth ventricle index (4VI), and to evaluate its role as a marker for severe vermian dysgenesis/agenesis in cases without open 4V.

Methods

This was a prospective cross‐sectional study of patients with singleton low‐risk pregnancy at 14 + 1 to 36 + 6 gestational weeks presenting between May 2016 and November 2017 for routine ultrasound examination. Axial images of the fetal 4V were obtained and the 4VI was calculated as the ratio between the laterolateral and the anteroposterior diameters. Reference ranges were constructed and retrospectively collected values from 44 fetuses with confirmed anomalies involving severe vermian dysgenesis/agenesis (Joubert syndrome and related disorders, rhombencephalosynapsis, cobblestone malformations and cerebellar hypoplasia) but without open 4V were compared with the normal values.

Results

In total, 384 healthy fetuses were enrolled into the study, from which reference ranges were produced, and 44 cases were collected retrospectively. The 4VI in the normal fetuses was always > 1. In affected fetuses, it was always below mean −2 SD and < 1.

Conclusions

The 4VI is a sonographic marker for severe fetal vermian dysgenesis/agenesis in the absence of an open 4V. It may be incorporated easily into the routine brain scan; 4VI < 1 indicates a need for dedicated fetal neuroimaging for diagnosis and prenatal counseling. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Systems analysis of dilated cardiomyopathy in the next generation sequencing era
Authors: Harakalova Magdalena , Asselbergs Folkert W.
Published: February 2018

Dilated cardiomyopathy (DCM) is a form of severe failure of cardiac muscle caused by a long list of etiologies ranging from myocardial infarction, DNA mutations in cardiac genes, to toxics. Systems analysis integrating next‐generation sequencing (NGS)‐based omics approaches, such as the sequencing of DNA, RNA, and chromatin, provide valuable insights into DCM mechanisms. The outcome and interpretation of NGS methods can be affected by the localization of cardiac biopsy, level of tissue degradation, and variable ratios of different cell populations, especially in the presence of fibrosis. Heart tissue composition may even differ between sexes, or siblings carrying the same disease causing mutation. Therefore, before planning any experiments, it is important to fully appreciate the complexities of DCM, and the selection of samples suitable for given research question should be an interdisciplinary effort involving clinicians and biologists. The list of NGS omics datasets in DCM to date is short. More studies have to be performed to contribute to public data repositories and facilitate systems analysis. In addition, proper data integration is a difficult task requiring complex computational approaches. Despite these complications, there are multiple promising implications of systems analysis in DCM. By combining various types of datasets, for example, RNA‐seq, ChIP‐seq, or 4C, deep insights into cardiac biology, and possible biomarkers and treatment targets, can be gained. Systems analysis can also facilitate the annotation of noncoding mutations in cardiac‐specific DNA regulatory regions that play a substantial role in maintaining the tissue‐ and cell‐specific transcriptional programs in the heart.

This article is categorized under:

Physiology > Mammalian Physiology in Health and Disease

Laboratory Methods and Technologies > Genetic/Genomic Methods

Laboratory Methods and Technologies > RNA Methods
Prophylactic Central Neck Dissection for Papillary Thyroid Carcinoma with Clinically Uninvolved Central Neck Lymph Nodes: A Systematic Review and Meta‐analysis
Authors: Chen Lawrence , Wu Yi‐Hsiu , Lee Chia‐Hwa , Chen Hsin‐An , Loh El‐Wui , Tam Ka‐Wai
Published: February 2018

Background

Central neck dissection and total thyroidectomy are standard treatments for patients with papillary thyroid carcinoma (PTC) with clinically involved central nodes. However, prophylactic central neck dissection (pCND) in patients with clinically uninvolved cN0 has been beneficial in some studies but ineffective in others. We conducted a meta‐analysis to evaluate the efficacy and safety of pCND in patients with central neck lymph nodes cN0 PTC.

Methods

The PubMed, EMBASE, Cochrane Library, and Scopus databases and the ClinicalTrials.gov registry were electronically searched for studies published until September 2017. The meta‐analysis was conducted to calculate the pooled effect size by using random‐effects model. Treatment efficacies were measured by determining locoregional recurrence (LRR). Secondary outcomes included transient recurrent laryngeal nerve (RLN) injury, permanent RLN injury, transient hypocalcemia, and permanent hypocalcemia.

Results

Twenty‐three retrospective and prospective cohort studies involving 18,376 patients were reviewed. Patients who underwent pCND had significantly lower LRR (odds ratio [OR] 0.65; 95% confidence interval [CI] 0.48–0.88) but significantly higher incidence rates of transient RLN injury (OR 2.03; 95% CI 1.32–3.13), transient hypocalcemia (OR 2.23; 95% CI 1.84–2.70), and permanent hypocalcemia (OR 2.22; 95% CI 1.58–3.13) than that of no pCND group.

Conclusion

Compared with no pCND, pCND significantly reduces LRR but is accompanied by numerous adverse effects. The clinical decision should be made after the shared decision‐making process of clinicians and patients.
The Spatial Structure of Farmland Values: A Semiparametric Approach
Authors: Wang Haoying
Published: February 2018

Controlling for spatial heterogeneity and spatial dependence in farmland valuation models has gained substantial attention in recent literature. This paper proposes to derive the spatial structure of farmland values endogenously and semiparametrically based on the spatial competition theory. The paper assembles panel data of Pennsylvania county level farmland values between 1982 and 2012. A spatial autoregressive panel data model with spatial weights matrix endogenously incorporated is estimated. Out of sample predictions and non-nested statistical tests for model selection suggest that the fit and the predictability of hedonic farmland valuation models can be greatly improved.
Outpatient Antibiotic Prescription Trends in the United States: A National Cohort Study
Authors: Durkin Michael J. , Jafarzadeh S. Reza , Hsueh Kevin , Sallah Ya Haddy , Munshi Kiraat D. , Henderson Rochelle R. , Fraser Victoria J.
Published: February 2018

OBJECTIVE

To characterize trends in outpatient antibiotic prescriptions in the United States

DESIGN

Retrospective ecological and temporal trend study evaluating outpatient antibiotic prescriptions from 2013 to 2015

SETTING

National administrative claims data from a pharmacy benefits manager PARTICIPANTS. Prescription pharmacy beneficiaries from Express Scripts Holding Company

MEASUREMENTS

Annual and seasonal percent change in antibiotic prescriptions

RESULTS

Approximately 98 million outpatient antibiotic prescriptions were filled by 39 million insurance beneficiaries during the 3-year study period. The most commonly prescribed antibiotics were azithromycin, amoxicillin, amoxicillin/clavulanate, ciprofloxacin, and cephalexin. No significant changes in individual or overall annual antibiotic prescribing rates were found during the study period. Significant seasonal variation was observed, with antibiotics being 42% more likely to be prescribed during February than September (peak-to-trough ratio [PTTR], 1.42; 95% confidence interval [CI], 1.39–1.61). Similar seasonal trends were found for azithromycin (PTTR, 2.46; 95% CI, 2.44–3.47), amoxicillin (PTTR, 1.52; 95% CI, 1.42–1.89), and amoxicillin/clavulanate (PTTR, 1.78; 95% CI, 1.68–2.29).

CONCLUSIONS

This study demonstrates that annual national outpatient antibiotic prescribing practices remained unchanged during our study period. Furthermore, seasonal peaks in antibiotics generally used to treat viral upper respiratory tract infections remained unchanged during cold and influenza season. These results suggest that inappropriate prescribing of antibiotics remains widespread, despite the concurrent release of several guideline-based best practices intended to reduce inappropriate antibiotic consumption; however, further research linking national outpatient antibiotic prescriptions to associated medical conditions is needed to confirm these findings.

Infect Control Hosp Epidemiol 2018;39:584–589
Impacts and Best Management Practices for Erect Veldtgrass (Ehrharta erecta)
Authors: Ray Courtenay A. , Sherman Joel J. , Godinho Anna L. , Hanson Nikki , Parker Ingrid M.
Published: February 2018

Erect veldtgrass (Ehrharta erecta Lam.) is an invasive grass actively spreading in California that is capable of invading multiple habitats. Our objective is to contribute to a better understanding of the ecology, impacts, and potential for control of E. erecta in order to guide management practices. In a mixed-evergreen forest in Santa Cruz County, we measured impacts of E. erecta on native plant species richness and abundance in an observational comparison across 11 sites. Strikingly, we measured nearly four times greater total vegetation cover in plots invaded by E. erecta. However, native plants were not significantly less abundant in invaded plots than in reference plots, and native cover was not significantly predicted by E. erecta cover within invaded plots. We did, however, find evidence of change in community composition in response to E. erecta abundance. Our findings demonstrate that native species can persist in the presence of E. erecta, although the long-term impacts on populations of the perennial plants that dominate this forest understory are still unknown.

We also compared the effectiveness of mechanical (hand pulling with volunteers) and chemical (glyphosate) management methods. Twenty-two months following management treatments, we found substantial reductions in E. erecta using both mechanical and herbicide treatments, but herbicide application also produced greater reductions in native species cover and species richness. Transplanting native yerba buena [Clinopodium douglasii (Benth.) Kuntze] into management plots following treatment did not slow regrowth of E. erecta. It did, however, increase total native plant percent cover in herbicide and pull treatments, although largely by increasing C. douglasii cover. Effective management is possible using either manual or chemical removal methods; the optimal method may depend on the availability of manual labor and the sensitivity of the habitat to non-target effects on native plants.
Phloroglucinol derivatives fromHypericumspecies trigger mitochondrial dysfunction inLeishmania amazonensis
Authors: Dagnino Ana Paula Aquistapase , Mesquita Camila Saporiti , Dorneles Gilson Pires , Teixeira Vivian de Oliveira Nunes , de Barros Francisco Maikon Corrêa , Vidal Ccana-Ccapatinta Gari , Fonseca Simone Gonçalves , Monteiro Marta Chagas , Júnior Luiz Carlos Rodrigues , Peres Alessandra , von Poser Gilsane Lino , Romão Pedro Roosevelt Torres
Published: February 2018

Bioactive molecules isolated from plants are promising sources for the development of new therapies against leishmaniasis. We investigated the leishmanicidal activity of cariphenone A (1), isouliginosin B (2) and uliginosin B (3) isolated fromHypericumspecies. Promastigotes and amastigotes ofLeishmania amazonensiswere incubated with compounds 1–3 at concentrations 1–100µmfor 48 h. The anti-promastigote effect of compounds was also tested in combinations. The cytotoxicity against macrophages and human erythrocytes were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method and hemolysis assay, respectively. The compounds 1–3 showed high leishmanicidal activity against promastigotes, IC50values of 10.5, 17.5 and 11.3µm, respectively. Synergistic interactions were found to the associations of compounds 1 and 2 [Σ fractional inhibitory concentration (FIC) = 0.41], and 2 and 3 (ΣFIC = 0.28) on promastigotes. AllHypericumcompounds induced mitochondrial hyperpolarization and reactive oxygen species production in promastigotes. The compounds showed low cytotoxicity toward mammalian cells, high selectivity index and killed intracellular amastigotes probably mediated by oxidative stress. These results indicate that these compounds are promising candidates for the development of drugs against leishmaniasis.
King Lear: A Psychological Study
Authors: J. C. B.
Published: February 2018

Aye, every inch a King, in all his pompous vanity, his reckless passion, his unstable judgment, a thorough king, whom even madness could not dethrone from the royal habits of authority, of strenuous will, and of proud predominance. As the highest mountain summit becomes the fearful beacon of volcanic flame, testifying in lurid characters to the world's deep heart-throes, so this kingliest of minds—he who in his little world has been the summit and the cope of things—becomes, in the creative hand of the poet, the visible outlet of those forces which devastate the soul. We stand by in reverential awe, despairing, with our small gauge of criticism, to estimate the forces of this human Etna. Oppressed by the power and magnitude of the passions, as depicted in this most sublime and awful of poetic creations, it is only after the senses have become accustomed to the roar and turmoil that we throw off the stupor, and dare to look down upon the throes of the Titan, and begin to recognize the distinctive features of the fierce commotion. Even then we must stand afar off; for not in Lear, as in others of the poet's great characters, can one for a single moment perform the act of mental transmutation. In Hamlet, for instance, the most complex of all, many a man may see reflected the depths of his own soul. But Lear is more and less than human in its isolated grandeur, in the force and depths of its passions, in its abstraction from accidental qualities. In the breadth of his strength and weakness he is painted like one of those old gods, older and greater than the heathen representatives of small virtues and vices—the usurping vulgarities of polytheism. The true divinities of Lear were old, like himself very old and kingly—Saturn and Rhea, the autochthones of the heavens; even as his qualities are laid upon the dark and far off, yet solid and deep foundations of moral personality. Well might this King of sorrows exclaim, in the words of the World-spirit, to those who attempt to tear his passions to tatters before the footlights; yea, even to the more reverent efforts of critics—
4.—French Retrospect
Authors: Geoghegan Edward G.
Published: February 2018

In an article of 50 pages the authors adduce 56 cases to confirm their former observations, and render their conclusion more precise. Many of these cases relate to patients in the Salpétrière during the past year, and the rest are gathered from the literature of the same period.
Continental Creatures: Animals and History in Contemporary Europe
Authors: FLACK ANDREW J. P.
Published: February 2018

In Norse mythology Fenrir, a wolf God born of the God of fire, possessed so much power that he horrified the other gods. Restrained by a chain forged from elements of the earth – such as the breath of fish and the roots of mountains – his power was held in check so that it could not be unleashed across the realms of gods and men. The chains of his captivity appeared to be fragile but were in fact supernaturally robust, though his eventual catastrophic escape was foretold by oracles of the age.
Bus Crashes in Iran
Authors: Parvaresh-Masoud Mohammad , Asayesh Hamid
Published: February 2018

Parvaresh-MasoudM, AsayeshH. Bus crashes in Iran. Prehosp Disaster Med. 2018;33(2):227–227.
Maternal Impression Management in the Assessment of Childhood Depressive Symptomatology
Authors: Lilly Megan , Davis Thompson E. , Castagna Peter J. , Marker Arwen , Davis Allison B.
Published: February 2018

Background:Self-report instruments are commonly used to assess for childhood depressive symptoms. Historically, clinicians have relied heavily on parent-reports due to concerns about childrens’ cognitive abilities to understand diagnostic questions. However, parents may also be unreliable reporters due to a lack of understanding of their child's symptomatology, overshadowing by their own problems, and tendencies to promote themselves more favourably in order to achieve desired assessment goals. One such variable that can lead to unreliable reporting is impression management, which is a goal-directed response in which an individual (e.g. mother or father) attempts to represent themselves, or their child, in a socially desirable way to the observer.Aims:This study examined the relationship between mothers who engage in impression management, as measured by the Parenting Stress Index-Short Form defensive responding subscale, and parent-/child-self-reports of depressive symptomatology in 106 mother–child dyads.Methods:106 clinic-referred children (mean child age = 10.06 years, range 7–16 years) were administered the Child Depression Inventory, and mothers (mean mother age = 40.80 years, range 27–57 years) were administered the Child-Behavior Checklist, Parenting Stress Index-Short Form, and Symptom Checklist-90-Revised.Results:As predicted, mothers who engaged in impression management under-reported their child's symptomatology on the anxious/depressed and withdrawn subscales of the Child Behavior Checklist. Moreover, the relationship between maternal-reported child depressive symptoms and child-reported depressive symptoms was moderated by impression management.Conclusions:These results suggest that children may be more reliable reporters of their own depressive symptomatology when mothers are highly defensive or stressed.
The Influence of Beam Broadening on the Spatial Resolution of Annular Dark Field Scanning Transmission Electron Microscopy
Authors: de Jonge Niels , Verch Andreas , Demers Hendrix
Published: February 2018

The spatial resolution of aberration-corrected annular dark field scanning transmission electron microscopy was studied as function of the vertical position z within a sample. The samples consisted of gold nanoparticles (AuNPs) positioned in different horizontal layers within aluminum matrices of 0.6 and 1.0 µm thickness. The highest resolution was achieved in the top layer, whereas the resolution was reduced by beam broadening for AuNPs deeper in the sample. To examine the influence of the beam broadening, the intensity profiles of line scans over nanoparticles at a certain vertical location were analyzed. The experimental data were compared with Monte Carlo simulations that accurately matched the data. The spatial resolution was also calculated using three different theoretical models of the beam blurring as function of the vertical position within the sample. One model considered beam blurring to occur as a single scattering event but was found to be inaccurate for larger depths of the AuNPs in the sample. Two models were adapted and evaluated that include estimates for multiple scattering, and these described the data with sufficient accuracy to be able to predict the resolution. The beam broadening depended on z1.5 in all three models.
Deep vein thrombosis and properties of the arterial wall
Authors: Jeraj Luka , Spirkoska Ana , Ježovnik Mateja Kaja , Poredoš Pavel
Published: February 2018

Abstract. Background: Deep vein thrombosis (DVT) affects more than one out of 1,000 people every year, of which 50 % develop post-thrombotic syndrome (PTS). Studies indicated that patients with DVT have deteriorated arterial wall function, while less is known about the association with PTS. We therefore investigated this relationship further. Patients and methods: A total of 120 patients treated for DVT of the lower extremity and a control group of 40 subjects without DVT were included. We assessed the presence of PTS using the Villalta scale. Flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) were calculated and reactive hyperaemia index (RHI) and augmentation index (AI) were obtained. Results: Patients with a history of DVT had lower FMD (4.0 % vs. 8.0 %, p < 0.001), lower NMD (12 % vs. 19 %, p = 0.001), and increased diameter of brachial artery (4.8 mm vs. 4.4 mm, p = 0.017). Peripheral arterial tonometry showed higher AI in patients with DVT (22.0 vs. 6.0, p = 0.004), while there was no difference in RHI. No differences in values between PTS-positive and PTS-negative patients were found. Conclusions: We confirmed the association between DVT and deteriorated functional properties of the arterial wall. Endothelial dysfunction of the large arteries, increased arterial stiffness, and increased diameter of the brachial artery were found in patients with DVT. However, there was no association between functional capability of the arterial wall and the incidence of PTS in DVT patients.
Lysine methyltransferase SMYD2 promotes triple negative breast cancer progression
Authors: Li Linda Xiaoyan , Zhou Julie Xia , Calvet James P. , Godwin Andrew K. , Jensen Roy A. , Li Xiaogang
Published: February 2018

We identified SMYD2, a SMYD (SET and MYND domain) family protein with lysine methyltransferase activity, as a novel breast cancer oncogene. SMYD2 was expressed at significantly higher levels in breast cancer cell lines and in breast tumor tissues. Silencing of SMYD2 by RNAi in triple-negative breast cancer (TNBC) cell lines or inhibition of SMYD2 with its specific inhibitor, AZ505, significantly reduced tumor growth in vivo. SMYD2 executes this activity via methylation and activation of its novel non-histone substrates, including STAT3 and the p65 subunit of NF-κB, leading to increased TNBC cell proliferation and survival. There are cross-talk and synergistic effects among SMYD2, STAT3, and NF-κB in TNBC cells, in that STAT3 can contribute to the modification of NF-κB p65 subunit post-translationally by recruitment of SMYD2, whereas the p65 subunit of NF-κB can also contribute to the modification of STAT3 post-translationally by recruitment of SMYD2, leading to methylation and activation of STAT3 and p65 in these cells. The expression of SMYD2 can be upregulated by IL-6-STAT3 and TNFα-NF-κB signaling, which integrates epigenetic regulation to inflammation in TNBC development. In addition, we have identified a novel SMYD2 transcriptional target gene, PTPN13, which links SMYD2 to other known breast cancer associated signaling pathways, including ERK, mTOR, and Akt signaling via PTPN13 mediated phosphorylation.
Reagent-controlled regiodivergent ring expansions of steroids
Authors: Charaschanya Manwika , Aubé Jeffrey
Published: February 2018

Ring expansion provides a powerful way of introducing a heteroatom substituent into a carbocyclic framework. However, such reactions are often limited by the tendency of a given substrate to afford only one of the two rearrangement products or fail to achieve high selectivity at all. These limitations are particularly acute when seeking to carry out late-stage functionalization of natural products as starting points in drug discovery. In this work, we present a stereoelectronically controlled ring expansion sequence towards selective and flexible access to complementary ring systems derived from common steroidal substrates. Chemical diversification of the reaction intermediate affords over 100 isomerically pure analogs with spatial and functional diversity. This regiodivergent rearrangement, and the concept of using chiral reagents to affect regiocontrol in chiral natural products, should be broadly applicable to late-stage natural product diversification programs.
Dissecting super-enhancer hierarchy based on chromatin interactions
Authors: Huang Jialiang , Li Kailong , Cai Wenqing , Liu Xin , Zhang Yuannyu , Orkin Stuart H. , Xu Jian , Yuan Guo-Cheng
Published: February 2018

Recent studies have highlighted super-enhancers (SEs) as important regulatory elements for gene expression, but their intrinsic properties remain incompletely characterized. Through an integrative analysis of Hi-C and ChIP-seq data, here we find that a significant fraction of SEs are hierarchically organized, containing both hub and non-hub enhancers. Hub enhancers share similar histone marks with non-hub enhancers, but are distinctly associated with cohesin and CTCF binding sites and disease-associated genetic variants. Genetic ablation of hub enhancers results in profound defects in gene activation and local chromatin landscape. As such, hub enhancers are the major constituents responsible for SE functional and structural organization.
A diminutive perinate European Enantiornithes reveals an asynchronous ossification pattern in early birds
Authors: Knoll Fabien , Chiappe Luis M. , Sanchez Sophie , Garwood Russell J. , Edwards Nicholas P. , Wogelius Roy A. , Sellers William I. , Manning Phillip L. , Ortega Francisco , Serrano Francisco J. , Marugán-Lobón Jesús , Cuesta Elena , Escaso Fernando , Sanz Jose Luis
Published: February 2018

Fossils of juvenile Mesozoic birds provide insight into the early evolution of avian development, however such fossils are rare. The analysis of the ossification sequence in these early-branching birds has the potential to address important questions about their comparative developmental biology and to help understand their morphological evolution and ecological differentiation. Here we report on an early juvenile enantiornithine specimen from the Early Cretaceous of Europe, which sheds new light on the osteogenesis in this most species-rich clade of Mesozoic birds. Consisting of a nearly complete skeleton, it is amongst the smallest known Mesozoic avian fossils representing post-hatching stages of development. Comparisons between this new specimen and other known early juvenile enantiornithines support a clade-wide asynchronous pattern of osteogenesis in the sternum and the vertebral column, and strongly indicate that the hatchlings of these phylogenetically basal birds varied greatly in size and tempo of skeletal maturation.
A browser-based tool for visualization and analysis of diffusion MRI data
Authors: Yeatman Jason D. , Richie-Halford Adam , Smith Josh K. , Keshavan Anisha , Rokem Ariel
Published: February 2018

Human neuroscience research faces several challenges with regards to reproducibility. While scientists are generally aware that data sharing is important, it is not always clear how to share data in a manner that allows other labs to understand and reproduce published findings. Here we report a new open source tool, AFQ-Browser, that builds an interactive website as a companion to a diffusion MRI study. Because AFQ-Browser is portable—it runs in any web-browser—it can facilitate transparency and data sharing. Moreover, by leveraging new web-visualization technologies to create linked views between different dimensions of the dataset (anatomy, diffusion metrics, subject metadata), AFQ-Browser facilitates exploratory data analysis, fueling new discoveries based on previously published datasets. In an era where Big Data is playing an increasingly prominent role in scientific discovery, so will browser-based tools for exploring high-dimensional datasets, communicating scientific discoveries, aggregating data across labs, and publishing data alongside manuscripts.
Cancer-associated fibroblasts induce antigen-specific deletion of CD8 + T Cells to protect tumour cells
Authors: Lakins Matthew A. , Ghorani Ehsan , Munir Hafsa , Martins Carla P. , Shields Jacqueline D.
Published: February 2018

Tumours have developed strategies to interfere with most steps required for anti-tumour immune responses. Although many populations contribute to anti-tumour responses, tumour-infiltrating cytotoxic T cells dominate, hence, many suppressive strategies act to inhibit these. Tumour-associated T cells are frequently restricted to stromal zones rather than tumour islands, raising the possibility that the tumour microenvironment, where crosstalk between malignant and “normal” stromal cells exists, may be critical for T cell suppression. We provide evidence of direct interactions between stroma and T cells driving suppression, showing that cancer-associated fibroblasts (CAFs) sample, process and cross-present antigen, killing CD8+T cells in an antigen-specific, antigen-dependent manner via PD-L2 and FASL. Inhibitory ligand expression is observed in CAFs from human tumours, and neutralisation of PD-L2 or FASL reactivates T cell cytotoxic capacity in vitro and in vivo. Thus, CAFs support T cell suppression within the tumour microenvironment by a mechanism dependent on immune checkpoint activation.
Convergent shifts in host-associated microbial communities across environmentally elicited phenotypes
Authors: Carrier Tyler J. , Reitzel Adam M.
Published: February 2018

Morphological plasticity is a genotype-by-environment interaction that enables organisms to increase fitness across varying environments. Symbioses with diverse microbiota may aid in acclimating to this variation, but whether the associated bacteria community is phenotype specific remains understudied. Here we induce morphological plasticity in three species of sea urchin larvae and measure changes in the associated bacterial community. While each host species has unique bacterial communities, the expression of plasticity results in the convergence on a phenotype-specific microbiome that is, in part, driven by differential association with α- and γ-proteobacteria. Furthermore, these results suggest that phenotype-specific signatures are the product of the environment and are correlated with ingestive and digestive structures. By manipulating diet quantity over time, we also show that differentially associating with microbiota along a phenotypic continuum is bidirectional. Taken together, our data support the idea of a phenotype-specific microbial community and that phenotypic plasticity extends beyond a genotype-by-environment interaction.
Elucidating anionic oxygen activity in lithium-rich layered oxides
Authors: Xu Jing , Sun Meiling , Qiao Ruimin , Renfrew Sara E. , Ma Lu , Wu Tianpin , Hwang Sooyeon , Nordlund Dennis , Su Dong , Amine Khalil , Lu Jun , McCloskey Bryan D. , Yang Wanli , Tong Wei
Published: February 2018

Recent research has explored combining conventional transition-metal redox with anionic lattice oxygen redox as a new and exciting direction to search for high-capacity lithium-ion cathodes. Here, we probe the poorly understood electrochemical activity of anionic oxygen from a material perspective by elucidating the effect of the transition metal on oxygen redox activity. We study two lithium-rich layered oxides, specifically lithium nickel metal oxides where metal is either manganese or ruthenium, which possess a similar structure and discharge characteristics, but exhibit distinctly different charge profiles. By combining X-ray spectroscopy with operando differential electrochemical mass spectrometry, we reveal completely different oxygen redox activity in each material, likely resulting from the different interaction between the lattice oxygen and transition metals. This work provides additional insights into the complex mechanism of oxygen redox and development of advanced high-capacity lithium-ion cathodes.
The Seasonality of Acute Attack of Primary Angle-Closure Glaucoma in Beijing, China
Authors: Zhu Jingyuan , Xu Yang , Wang Hongyuan , Liu Dongjing , Zhu Jingbo , Wu Huijuan
Published: February 2018

In this study, the seasonality of acute attack of primary angle-closure glaucoma (PACG) was analysed. This retrospective case series included 283 patients (200 women, 83 men; mean age, 68.2 ± 10.3 years; range, 37–96 years) with acute attack of PACG from a university-based clinic over 4 years. Patients’ age and sex, and the date and season of onset of PACG attack, were analysed. Descriptive analysis and von Mises distribution were used for statistical analysis. The highest incidence of acute attack of PACG was observed in those aged 60–69 years (34.6%). Descriptive analysis showed that the incidence was greater in June and July for men, November for women, and November for the entire sample. An angular plot (using von Mises distribution) of the individual dates of onset revealed the estimated peak onset on September 11, November 8, and October 28 for men, women, and both, respectively. Integration of the results from the two analyses revealed the incidence to be higher in the summer and winter for men, and in the winter for women and for the entire sample. More females than males were affected. Monthly and seasonal variations in onset were observed, which might be related to weather changes.
A retrospective study of community-acquired Clostridium difficile infection in southwest China
Authors: Liao Feng , Li Wenge , Gu Wenpeng , Zhang Wenzhu , Liu Xiaoshu , Fu Xiaoqing , Xu Wen , Wu Yuan , Lu Jinxing
Published: February 2018

To identify the prevalence and characteristics of community-acquiredClostridium difficileinfection (CA-CDI) in southwest China, we conducted a cross-sectional study. 978 diarrhea patients were enrolled and stool specimens’ DNA was screened for virulence genes. Bacterial culture was performed and isolates were characterized by PCR ribotyping and multilocus sequence typing. Toxin genestcdAand/ortcdBwere found in 138/978 (14.11%) cases for fecal samples. A total of 55 C. difficilestrains were isolated (5.62%). The positive rate of toxin genes and isolation results had no statistical significance between children and adults groups. However, some clinical features, such as fecal property, diarrhea times before hospital treatment shown difference between two groups. The watery stool was more likely found in children, while the blood stool for adults; most of children cases diarrhea ≤3 times before hospital treatment, and adults diarrhea >3 times. Independent risk factor associated with CA-CDI was patients with fever. ST35/RT046 (18.18%), ST54/RT012 (14.55%), ST3/RT001 (14.55%) and ST3/RT009 (12.73%) were the most distributed genotype profiles. ST35/RT046, ST3/RT001 and ST3/RT009 were the commonly found in children patients but ST54/RT012 for adults. The prevalence of CA-CDI in Yunnan province was relatively high, and isolates displayed heterogeneity between children and adults groups.
Circuit-specific and neuronal subcellular-wide E-I balance in cortical pyramidal cells
Authors: Yang Weiguo , Sun Qian-Quan
Published: February 2018

We used ChR2-assisted circuit mapping (CRACM) to examine neuronal/compartmental excitatory and inhibitory synaptic balance (E-I balance) in pyramidal cells (PCs) located in several brain regions (including both neocortices and paleocortices). Within the vS1, different inputs on the same neurons, or the same inputs formed on different targets, induced different E/I ratios. E/I ratios in PCs from different regions were largely different. Chemogenetic silencing of somatostatin (SOM)- or parvalbumin (PV)-containing interneurons (INs) while optogenetically activating long-range M1 inputs demonstrated differential contribution of PV and SOM INs to the E/I ratios in a layer-specific manner in S1. Our results thus demonstrate that there are both universal subcellular-wide E-I balance within single PC and high specificity in the value of E/I ratios across different circuits (i.e. visual, somatosensory, piriform and hippocampal). Specificity of E/I balance are likely caused by unique glutamatergic innervation of interneurons. The dichotomy of high specificity and generalization of subcellular E-I balance in different circuits forms the basis for further understanding of neuronal computation under physiological conditions and various neuro-psychiatric disease-states.
Recombinant RNA-Dependent RNA Polymerase Complex of Ebola Virus
Authors: Tchesnokov Egor P. , Raeisimakiani Parisa , Ngure Marianne , Marchant David , Götte Matthias
Published: February 2018

Here we report on the expression, purification and characterization of recombinant ebola virus RNA-dependent RNA polymerase (EBOV RdRp). Active protein complexes composed of the large L protein and viral protein VP35 were isolated from insect cells and analyzed using a short primer/template substrate that allowed benchmarking against related enzymes. RNA synthesis by multiprotein complexes of EBOV, influenza B, respiratory syncytial virus (RSV) and monomeric enzymes of hepatitis C and Zika (ZIKV) viruses required a 5′-phosporylated primer. The minimum length of the primer varied between two and three nucleotides in this system. The EBOV enzyme utilizes Mg2+ as a co-factor and the D742A substitution provides an active site mutant that likely affects binding of the catalytic metal ions. Selectivity measurements with nucleotide analogues translate our assay into quantitative terms and facilitate drug discovery efforts. The related EBOV and RSV enzymes are not able to efficiently discriminate against ara-cytidine-5′-triphosphate. We demonstrate that this compound acts like a non-obligate chain-terminator.
Changes in global translation elongation or initiation rates shape the proteome via the Kozak sequence
Authors: Acevedo Julieta M. , Hoermann Bernhard , Schlimbach Tilo , Teleman Aurelio A.
Published: February 2018

The sequence context surrounding the AUG start codon of an open reading frame - the ‘Kozak sequence’ - affects the probability with which a scanning ribosome will recognize the start codon and start translating there. A significant number of transcripts in animals such as Drosophila contain weak Kozak sequences. This is predicted to cause constitutively low translation of these transcripts. We study here the additional possibility that these mRNAs have weak Kozak sequences to allow for the regulation of their translation in response to stress or altered cellular signaling. We find that transcripts with weak Kozak sequences are less sensitive to drops in global elongation rates and more sensitive to drops in global initiation rates compared to transcripts with strong Kozak sequences. This provides a mechanism by which changes in these global translation parameters differentially affect different pools of mRNAs depending on their Kozak sequence, thereby shaping the proteome. Interestingly, mRNAs with weak Kozak sequences are enriched for genes involved in neurobiology, suggesting that they constitute a functional group that can be translationally co-regulated.
Prediction of pKa Values for Neutral and Basic Drugs based on Hybrid Artificial Intelligence Methods
Authors: Li Mengshan , Zhang Huaijing , Chen Bingsheng , Wu Yan , Guan Lixin
Published: February 2018

The pKa value of drugs is an important parameter in drug design and pharmacology. In this paper, an improved particle swarm optimization (PSO) algorithm was proposed based on the population entropy diversity. In the improved algorithm, when the population entropy was higher than the set maximum threshold, the convergence strategy was adopted; when the population entropy was lower than the set minimum threshold the divergence strategy was adopted; when the population entropy was between the maximum and minimum threshold, the self-adaptive adjustment strategy was maintained. The improved PSO algorithm was applied in the training of radial basis function artificial neural network (RBF ANN) model and the selection of molecular descriptors. A quantitative structure-activity relationship model based on RBF ANN trained by the improved PSO algorithm was proposed to predict the pKa values of 74 kinds of neutral and basic drugs and then validated by another database containing 20 molecules. The validation results showed that the model had a good prediction performance. The absolute average relative error, root mean square error, and squared correlation coefficient were 0.3105, 0.0411, and 0.9685, respectively. The model can be used as a reference for exploring other quantitative structure-activity relationships.
Low intensity repetitive transcranial magnetic stimulation modulates skilled motor learning in adult mice
Authors: Tang Alexander D. , Bennett William , Hadrill Claire , Collins Jessica , Fulopova Barbora , Wills Karen , Bindoff Aidan , Puri Rohan , Garry Michael I. , Hinder Mark R. , Summers Jeffery J. , Rodger Jennifer , Canty Alison J.
Published: February 2018

Repetitive transcranial magnetic stimulation (rTMS) is commonly used to modulate cortical plasticity in clinical and non-clinical populations. Clinically, rTMS is delivered to targeted regions of the cortex at high intensities (>1 T). We have previously shown that even at low intensities, rTMS induces structural and molecular plasticity in the rodent cortex. To determine whether low intensity rTMS (LI-rTMS) alters behavioural performance, daily intermittent theta burst LI-rTMS (120 mT) or sham was delivered as a priming or consolidating stimulus to mice completing 10 consecutive days of skilled reaching training. Relative to sham, priming LI-rTMS (before each training session), increased skill accuracy (~9%) but did not alter the rate of learning over time. In contrast, consolidating LI-rTMS (after each training session), resulted in a small increase in the rate of learning (an additional ~1.6% each day) but did not alter the daily skill accuracy. Changes in behaviour with LI-rTMS were not accompanied with long lasting changes in brain-derived neurotrophic factor (BDNF) expression or in the expression of plasticity markers at excitatory and inhibitory synapses for either priming or consolidation groups. These results suggest that LI-rTMS can alter specific aspects of skilled motor learning in a manner dependent on the timing of intervention.
Cedratvirus getuliensis replication cycle: an in-depth morphological analysis
Authors: Silva Ludmila Karen dos Santos , Andrade Ana Cláudia dos Santos Pereira , Dornas Fábio Pio , Rodrigues Rodrigo Araújo Lima , Arantes Thalita , Kroon Erna Geessien , Bonjardim Cláudio Antônio , Abrahão Jônatas Santos
Published: February 2018

The giant viruses are the largest and most complex viruses in the virosphere. In the last decade, new members have constantly been added to this group. Here, we provide an in-depth descriptive analysis of the replication cycle of Cedratvirus getuliensis, one of the largest viruses known to date. We tracked the virion entry, the early steps of virus factory and particles morphogenesis, and during this phase, we observed a complex and unique sequential organization of immature particle elements, including horseshoe and rectangular compartments, revealed by transverse and longitudinal sections, respectively, until the formation of the final ovoid-shaped striped virion. The genome and virion proteins are incorporated through a longitudinal opening in the immature virion, followed by the incorporation of the second cork and thickening of the capsid well. Moreover, many cell modifications occur during viral infection, including intense membrane trafficking important to viral morphogenesis and release, as evidenced by treatment using brefeldin A. Finally, we observed that Cedratvirus getuliensis particles are released after cellular lysis, although we obtained microscopic evidence that some particles are released by exocytosis. The present study provides new information on the unexplored steps in the life cycle of cedratviruses.
Comparative efficacy of corticosteroid injection and non-invasive treatments for plantar fasciitis: a systematic review and meta-analysis
Authors: Chen Chien-Min , Lee Meng , Lin Chia-Hung , Chang Chia-Hao , Lin Chu-Hsu
Published: February 2018

The first choice of treatment for patients with plantar fasciitis is non-invasive treatment, rather than corticosteroid injection (CSI). However, no comprehensive study has compared the effectiveness of CSI with non-invasive treatments for plantar fasciitis. We conducted a meta-analysis comparing CSI and non-invasive treatment effects on plantar fasciitis. The primary outcome was pain reduction. Nine randomized controlled trials comparing CSI with 4 non-invasive treatment types were included. A trend favoring CSI over non-invasive treatments was indicated regarding reduction in the visual analogue scale (VAS) score at 1–1.5 (mean difference (MD), 1.70; 95% confidence interval (CI) = 0.39–3.01; P = 0.01) and 2–3 months (MD, 1.67; 95% CI = 0.58–2.76; P = 0.003). At 1.5-month follow-up, CSI was associated with improved VAS score compared with physical therapy (PT) (MD, 2.5; 95% CI = 0.1–4.9; P = 0.04). No significant differences in the VAS score reduction were observed between CSI and shock wave therapy within 3 months. In summary, CSI tends to be more effective for pain reduction than non-invasive treatments within 3 months. Moreover, CSI provides significant pain relief at 1.5 months after treatment compared with PT. This study provides important clinical information for selecting therapeutics.