bluuebunny/crossref_metadata_2025 huggingface dataset:
Intranasal packs and haemostatic agents for the management of adult epistaxis: systematic review
Authors: Iqbal I Z , Jones G H , Dawe N , Mamais C , Smith M E , Williams R J , Kuhn I , Carrie S
Published: December 2017

Background:

The mainstay of management of epistaxis refractory to first aid and cautery is intranasal packing. This review aimed to identify evidence surrounding nasal pack use.

Method:

A systematic review of the literature was performed using standardised methodology.

Results:

Twenty-seven eligible articles were identified relating to non-dissolvable packs and nine to dissolvable packs. Nasal packing appears to be more effective when applied by trained professionals. For non-dissolvable packs, the re-bleed rates for Rapid Rhino and Merocel were similar, but were higher with bismuth iodoform paraffin paste packing. Rapid Rhino packs were the most tolerated non-dissolvable packs. Evidence indicates that 96 per cent of re-bleeding occurs within the first 4 hours after nasal pack removal. Limited evidence suggests that dissolvable packs are effective and well tolerated by patients. There was a lack of evidence relating to: the duration of pack use, the economic effects of pack choice and the appropriate care setting for non-dissolvable packs.

Conclusion:

Rapid Rhino packs are the best tolerated, with efficacy equivalent to nasal tampons. FloSeal is easy to use, causes less discomfort and may be superior to Merocel in anterior epistaxis cases. There is no strong evidence to support prophylactic antibiotic use.
Haematological factors in the management of adult epistaxis: systematic review
Authors: Williams A , Biffen A , Pilkington N , Arrick L , Williams R J , Smith M E , Smith M , Birchall J
Published: December 2017

Background:

The management of epistaxis requires an understanding of haematological factors that may complicate its treatment. This systematic review includes six distinct reviews examining the evidence supporting epistaxis-specific management strategies relating to warfarin, direct oral anticoagulants, heparin, antiplatelet agents, tranexamic acid and transfusion.

Method:

A systematic review of the literature was performed using a standardised methodology and search strategy.

Results:

Limited numbers of articles were identified in each systematic review, with level 1 evidence only regarding the use of tranexamic acid. No studies met the inclusion criteria within the heparin, direct oral anticoagulants or transfusion systematic reviews. Many studies were limited by small sample sizes and significant risk of bias.

Conclusion:

The management of major bleeding and transfusion practice is well documented in national guidance from multiple sources. The guidelines include advice on anticoagulants, antiplatelet agents and tranexamic acid. In the absence of more specific evidence, these guidelines should be applied in the management of epistaxis.
International Trade and Coordination
Authors: Carter David B. , Goemans H. E.
Published: December 2017

This article examines how the institutional design of borders affects international trade. The authors explore variation in the effects of borders by comparing new international borders that follow precedent and thus have a prior institutional history with new international borders that lack such an institutional history. The former minimally disrupt—or restore—previous economic networks, while the latter fundamentally disrupt existing economic networks. A variety of empirical tests show that, consistent with this institutional perspective on borders, new international boundaries that follow precedent are associated with significantly faster recovery and greater increase in subsequent trade flows. By contrast, when new international borders are truly new, they disrupt local economic networks, introduce new transaction costs, and impose higher adjustment costs on states, which the authors show to have long-term deleterious effects on trade.
Human Rights in the Paris Agreement: Too Little, Too Late?
Authors: Adelman Sam
Published: December 2017

This article examines the impact of the Paris Agreement on the human rights of communities who are particularly vulnerable to the impacts of anthropogenic warming because of their geographical location, their spiritual and cultural connections with land and the wider environment, and their histories of colonialism, dispossession and other forms of exploitation. It focuses on two groups: forest dwellers, and inhabitants of small island developing states who are in danger of inundation as a result of rising sea levels. The Paris Agreement on climate change includes stand-alone articles on reducing emissions from deforestation and forest degradation (REDD+), and loss and damage. The main argument in this article is that the inclusion of human rights in the Preamble to the Paris Agreement is a step forward, but is incommensurate with the scale and urgency of climate change.
Vetting New Models of Climate Responses to Geoengineering
Authors: Kravitz Ben , Robock Alan
Published: December 2017

The Seventh Meeting of the Geoengineering Model Intercomparison Project; Newry, Maine, 26 July 2017
Risk factors for arterial versus venous thrombosis in polycythemia vera: a single center experience in 587 patients
Authors: Cerquozzi S. , Barraco D. , Lasho T. , Finke C. , Hanson C. A. , Ketterling R. P. , Pardanani A. , Gangat N. , Tefferi A.
Published: December 2017

In a recent International Working Group on Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) study, prior arterial events and hypertension were predictors of subsequent arterial thrombosis whereas prior venous events and age ≥65 years predicted venous thrombosis in polycythemia vera (PV). In the current study, we sought to validate the above findings and identify additional predictors of arterial versus venous thrombosis. At a median follow up of 109 months, thrombosis after diagnosis occurred in 128 (22%) patients; 82 (14%) arterial and 57 (10%) venous events. On multivariate analysis, prior arterial events (<0.0001), hyperlipidemia (p = 0.03), and hypertension (p = 0.02) predicted subsequent arterial events. In comparison, prior venous events (p = 0.05), leukocytosis ≥11 × 109/L (p = 0.002), and major hemorrhage (p = 0.02) were predictors of subsequent venous events. Salient associations with arterial thrombosis included age ≥ 60 years, hypertension, diabetes, hyperlipidemia and normal karyotype whereas age ≤ 60 years, females, palpable splenomegaly and history of major hemorrhage were associated with venous thrombosis. TET2 or ASXL1 mutations did not impact arterial nor venous thrombosis. In conclusion, we identify distinct associations for arterial versus venous thrombosis in PV and confirm that a prior arterial or venous thrombotic event is the most reliable predictor of subsequent events.
Obligatory and facilitative allelic variation in the DNA methylome within common disease-associated loci
Authors: Bell Christopher G. , Gao Fei , Yuan Wei , Roos Leonie , Acton Richard J. , Xia Yudong , Bell Jordana , Ward Kirsten , Mangino Massimo , Hysi Pirro G. , Wang Jun , Spector Timothy D.
Published: December 2017

Integrating epigenetic data with genome-wide association study (GWAS) results can reveal disease mechanisms. The genome sequence itself also shapes the epigenome, with CpG density and transcription factor binding sites (TFBSs) strongly encoding the DNA methylome. Therefore, genetic polymorphism impacts on the observed epigenome. Furthermore, large genetic variants alter epigenetic signal dosage. Here, we identify DNA methylation variability between GWAS-SNP risk and non-risk haplotypes. In three subsets comprising 3128 MeDIP-seq peripheral-blood DNA methylomes, we find 7173 consistent and functionally enriched Differentially Methylated Regions. 36.8% can be attributed to common non-SNP genetic variants. CpG-SNPs, as well as facilitative TFBS-motifs, are also enriched. Highlighting their functional potential, CpG-SNPs strongly associate with allele-specific DNase-I hypersensitivity sites. Our results demonstrate strong DNA methylation allelic differences driven by obligatory or facilitative genetic effects, with potential direct or regional disease-related repercussions. These allelic variations require disentangling from pure tissue-specific modifications, may influence array studies, and imply underestimated population variability in current reference epigenomes.
Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine
Authors: Calipari Erin S. , Godino Arthur , Peck Emily G. , Salery Marine , Mervosh Nicholas L. , Landry Joseph A. , Russo Scott J. , Hurd Yasmin L. , Nestler Eric J. , Kiraly Drew D.
Published: December 2017

Cocaine addiction is characterized by dysfunction in reward-related brain circuits, leading to maladaptive motivation to seek and take the drug. There are currently no clinically available pharmacotherapies to treat cocaine addiction. Through a broad screen of innate immune mediators, we identify granulocyte-colony stimulating factor (G-CSF) as a potent mediator of cocaine-induced adaptations. Here we report that G-CSF potentiates cocaine-induced increases in neural activity in the nucleus accumbens (NAc) and prefrontal cortex. In addition, G-CSF injections potentiate cocaine place preference and enhance motivation to self-administer cocaine, while not affecting responses to natural rewards. Infusion of G-CSF neutralizing antibody into NAc blocks the ability of G-CSF to modulate cocaine’s behavioral effects, providing a direct link between central G-CSF action in NAc and cocaine reward. These results demonstrate that manipulating G-CSF is sufficient to alter the motivation for cocaine, but not natural rewards, providing a pharmacotherapeutic avenue to manipulate addictive behaviors without abuse potential.
Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling
Authors: Elia Josephine , Ungal Grace , Kao Charlly , Ambrosini Alexander , De Jesus-Rosario Nilsa , Larsen Lene , Chiavacci Rosetta , Wang Tiancheng , Kurian Christine , Titchen Kanani , Sykes Brian , Hwang Sharon , Kumar Bhumi , Potts Jacqueline , Davis Joshua , Malatack Jeffrey , Slattery Emma , Moorthy Ganesh , Zuppa Athena , Weller Andrew , Byrne Enda , Li Yun R. , Kraft Walter K. , Hakonarson Hakon
Published: December 2017

The glutamatergic neurotransmitter system may play an important role in attention-deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind, placebo-controlled study reports the safety, pharmacokinetics and responsiveness of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in 30 adolescents, age 12–17 years with ADHD, harboring mutations in mGluR network genes. Mutation status was double-blinded. A single-dose pharmacokinetic profiling from 50–800 mg was followed by a single-blind placebo at week 1 and subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks. NFC-1 treatment resulted in significant improvement. Mean Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scores were, respectively, 3.79 at baseline vs. 2.33 at week 5 (P < 0.001) and 4.83 at baseline vs. 3.86 at week 5 (P < 0.001). Parental Vanderbilt scores showed significant improvement for subjects with mGluR Tier 1 variants (P < 0.035). There were no differences in the incidence of adverse events between placebo week and weeks on active drug. The trial is registered at https://clinicaltrials.gov/ct2/show/study/NCT02286817.
Trapping IgE in a closed conformation by mimicking CD23 binding prevents and disrupts FcεRI interaction
Authors: Jabs Frederic , Plum Melanie , Laursen Nick S. , Jensen Rasmus K. , Mølgaard Brian , Miehe Michaela , Mandolesi Marco , Rauber Michèle M. , Pfützner Wolfgang , Jakob Thilo , Möbs Christian , Andersen Gregers R. , Spillner Edzard
Published: December 2017

Anti-IgE therapeutics interfere with the ability of IgE to bind to its receptors on effector cells. Here we report the crystal structure of an anti-IgE single-domain antibody in complex with an IgE Fc fragment, revealing how the antibody inhibits interactions between IgE and the two receptors FcεRI and CD23. The epitope overlaps only slightly with the FcεRI-binding site but significantly with the CD23-binding site. Solution scattering studies of the IgE Fc reveal that antibody binding induces a half-bent conformation in between the well-known bent and extended IgE Fc conformations. The antibody acts as functional homolog of CD23 and induces a closed conformation of IgE Fc incompatible with FcεRI binding. Notably the antibody displaces IgE from both CD23 and FcεRI, and abrogates allergen-mediated basophil activation and facilitated allergen binding. The inhibitory mechanism might facilitate strategies for the future development of anti-IgE therapeutics for treatment of allergic diseases.
VAMPnets for deep learning of molecular kinetics
Authors: Mardt Andreas , Pasquali Luca , Wu Hao , Noé Frank
Published: December 2017

There is an increasing demand for computing the relevant structures, equilibria, and long-timescale kinetics of biomolecular processes, such as protein-drug binding, from high-throughput molecular dynamics simulations. Current methods employ transformation of simulated coordinates into structural features, dimension reduction, clustering the dimension-reduced data, and estimation of a Markov state model or related model of the interconversion rates between molecular structures. This handcrafted approach demands a substantial amount of modeling expertise, as poor decisions at any step will lead to large modeling errors. Here we employ the variational approach for Markov processes (VAMP) to develop a deep learning framework for molecular kinetics using neural networks, dubbed VAMPnets. A VAMPnet encodes the entire mapping from molecular coordinates to Markov states, thus combining the whole data processing pipeline in a single end-to-end framework. Our method performs equally or better than state-of-the-art Markov modeling methods and provides easily interpretable few-state kinetic models.
Perturbation-response genes reveal signaling footprints in cancer gene expression
Authors: Schubert Michael , Klinger Bertram , Klünemann Martina , Sieber Anja , Uhlitz Florian , Sauer Sascha , Garnett Mathew J. , Blüthgen Nils , Saez-Rodriguez Julio
Published: December 2017

Aberrant cell signaling can cause cancer and other diseases and is a focal point of drug research. A common approach is to infer signaling activity of pathways from gene expression. However, mapping gene expression to pathway components disregards the effect of post-translational modifications, and downstream signatures represent very specific experimental conditions. Here we present PROGENy, a method that overcomes both limitations by leveraging a large compendium of publicly available perturbation experiments to yield a common core of Pathway RespOnsive GENes. Unlike pathway mapping methods, PROGENy can (i) recover the effect of known driver mutations, (ii) provide or improve strong markers for drug indications, and (iii) distinguish between oncogenic and tumor suppressor pathways for patient survival. Collectively, these results show that PROGENy accurately infers pathway activity from gene expression in a wide range of conditions.
Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury
Authors: Li Tuoyi , Yu Bing , Liu Zhixin , Li Jingyuan , Ma Mingliang , Wang Yingbao , Zhu Mingjiang , Yin Huiyong , Wang Xiaofeng , Fu Yi , Yu Fang , Wang Xian , Fang Xiaohong , Sun Jinpeng , Kong Wei
Published: December 2017

Hyperhomocysteinemia (HHcy) is a risk factor for various cardiovascular diseases. However, the mechanism underlying HHcy-aggravated vascular injury remains unclear. Here we show that the aggravation of abdominal aortic aneurysm by HHcy is abolished in mice with genetic deletion of the angiotensin II type 1 (AT1) receptor and in mice treated with an AT1 blocker. We find that homocysteine directly activates AT1 receptor signalling. Homocysteine displaces angiotensin II and limits its binding to AT1 receptor. Bioluminescence resonance energy transfer analysis reveals distinct conformational changes of AT1 receptor upon binding to angiotensin II and homocysteine. Molecular dynamics and site-directed mutagenesis experiments suggest that homocysteine regulates the conformation of the AT1 receptor both orthosterically and allosterically by forming a salt bridge and a disulfide bond with its Arg167 and Cys289 residues, respectively. Together, these findings suggest that strategies aimed at blocking the AT1 receptor may mitigate HHcy-associated aneurysmal vascular injuries.
Network connectivity determines cortical thinning in early Parkinson’s disease progression
Authors: Yau Y. , Zeighami Y. , Baker T. E. , Larcher K. , Vainik U. , Dadar M. , Fonov V. S. , Hagmann P. , Griffa A. , Mišić B. , Collins D. L. , Dagher A.
Published: December 2017

Here we test the hypothesis that the neurodegenerative process in Parkinson’s disease (PD) moves stereotypically along neural networks, possibly reflecting the spread of toxic alpha-synuclein molecules. PD patients (n = 105) and matched controls (n = 57) underwent T1-MRI at entry and 1 year later as part of the Parkinson’s Progression Markers Initiative. Over this period, PD patients demonstrate significantly greater cortical thinning than controls in parts of the left occipital and bilateral frontal lobes and right somatomotor-sensory cortex. Cortical thinning is correlated to connectivity (measured functionally or structurally) to a “disease reservoir” evaluated by MRI at baseline. The atrophy pattern in the ventral frontal lobes resembles one described in certain cases of Alzheimer’s disease. Our findings suggest that disease propagation to the cortex in PD follows neuronal connectivity and that disease spread to the cortex may herald the onset of cognitive impairment.
Cooperative interactions between seed-borne bacterial and air-borne fungal pathogens on rice
Authors: Jung Boknam , Park Jungwook , Kim Namgyu , Li Taiying , Kim Soyeon , Bartley Laura E. , Kim Jinnyun , Kim Inyoung , Kang Yoonhee , Yun Kihoon , Choi Younghae , Lee Hyun-Hee , Ji Sungyeon , Lee Kwang Sik , Kim Bo Yeon , Shon Jong Cheol , Kim Won Cheol , Liu Kwang-Hyeon , Yoon Dahye , Kim Suhkman , Seo Young-Su , Lee Jungkwan
Published: December 2017

Bacterial-fungal interactions are widely found in distinct environments and contribute to ecosystem processes. Previous studies of these interactions have mostly been performed in soil, and only limited studies of aerial plant tissues have been conducted. Here we show that a seed-borne plant pathogenic bacterium, Burkholderia glumae (Bg), and an air-borne plant pathogenic fungus, Fusarium graminearum (Fg), interact to promote bacterial survival, bacterial and fungal dispersal, and disease progression on rice plants, despite the production of antifungal toxoflavin by Bg. We perform assays of toxoflavin sensitivity, RNA-seq analyses, lipid staining and measures of triacylglyceride content to show that triacylglycerides containing linolenic acid mediate resistance to reactive oxygen species that are generated in response to toxoflavin in Fg. As a result, Bg is able to physically attach to Fg to achieve rapid and expansive dispersal to enhance disease severity.
Development of a genetically encodable FRET system using fluorescent RNA aptamers
Authors: Jepsen Mette D. E. , Sparvath Steffen M. , Nielsen Thorbjørn B. , Langvad Ane H. , Grossi Guido , Gothelf Kurt V. , Andersen Ebbe S.
Published: December 2017

Fluorescent RNA aptamers are useful as markers for tracking RNA molecules inside cells and for creating biosensor devices. Förster resonance energy transfer (FRET) based on fluorescent proteins has been used to detect conformational changes, however, such FRET devices have not yet been produced using fluorescent RNA aptamers. Here we develop an RNA aptamer-based FRET (apta-FRET) system using single-stranded RNA origami scaffolds. To obtain FRET, the fluorescent aptamers Spinach and Mango are placed in close proximity on the RNA scaffolds and a new fluorophore is synthesized to increase spectral overlap. RNA devices that respond to conformational changes are developed, and finally, apta-FRET constructs are expressed in E. coli where FRET is observed, demonstrating that the apta-FRET system is genetically encodable and that the RNA nanostructures fold correctly in bacteria. We anticipate that the RNA apta-FRET system could have applications as ratiometric sensors for real-time studies in cell and synthetic biology.
Structural characterisation reveals insights into substrate recognition by the glutamine transporter ASCT2/SLC1A5
Authors: Scopelliti Amanda J , Font Josep , Vandenberg Robert J , Boudker Olga , Ryan Renae M
Published: December 2017

Cancer cells undergo a shift in metabolism where they become reliant on nutrients such as the amino-acid glutamine. Glutamine enters the cell via the alanine/serine/cysteine transporter 2 (ASCT2) that is upregulated in several cancers to maintain an increased supply of this nutrient and are therefore an attractive target in cancer therapeutic development. ASCT2 belongs to the glutamate transporter (SLC1A) family but is the only transporter in this family able to transport glutamine. The structural basis for glutamine selectivity of ASCT2 is unknown. Here, we identify two amino-acid residues in the substrate-binding site that are responsible for conferring glutamine selectivity. We introduce corresponding mutations into a prokaryotic homologue of ASCT2 and solve four crystal structures, which reveal the structural basis for neutral amino acid and inhibitor binding in this family. This structural model of ASCT2 may provide a basis for future development of selective ASCT2 inhibitors to treat glutamine-dependent cancers.
Inhibition of Poly(A)-binding protein with a synthetic RNA mimic reduces pain sensitization in mice
Authors: Barragán-Iglesias Paulino , Lou Tzu-Fang , Bhat Vandita D. , Megat Salim , Burton Michael D. , Price Theodore J. , Campbell Zachary T.
Published: December 2017

Nociceptors rely on cap-dependent translation to rapidly induce protein synthesis in response to pro-inflammatory signals. Comparatively little is known regarding the role of the regulatory factors bound to the 3′ end of mRNA in nociceptor sensitization. Poly(A)-binding protein (PABP) stimulates translation initiation by bridging the Poly(A) tail to the eukaryotic initiation factor 4F complex associated with the mRNA cap. Here, we use unbiased assessment of PABP binding specificity to generate a chemically modified RNA-based competitive inhibitor of PABP. The resulting RNA mimic, which we designated as the Poly(A) SPOT-ON, is more stable than unmodified RNA and binds PABP with high affinity and selectivity in vitro. We show that injection of the Poly(A) SPOT-ON at the site of an injury can attenuate behavioral response to pain. Collectively, these results suggest that PABP is integral for nociceptive plasticity. The general strategy described here provides a broad new source of mechanism-based inhibitors for RNA-binding proteins and is applicable for in vivo studies.
A unifying theory for top-heavy ecosystem structure in the ocean
Authors: Woodson C. Brock , Schramski John R. , Joye Samantha B.
Published: December 2017

Size generally dictates metabolic requirements, trophic level, and consequently, ecosystem structure, where inefficient energy transfer leads to bottom-heavy ecosystem structure and biomass decreases as individual size (or trophic level) increases. However, many animals deviate from simple size-based predictions by either adopting generalist predatory behavior, or feeding lower in the trophic web than predicted from their size. Here we show that generalist predatory behavior and lower trophic feeding at large body size increase overall biomass and shift ecosystems from a bottom-heavy pyramid to a top-heavy hourglass shape, with the most biomass accounted for by the largest animals. These effects could be especially dramatic in the ocean, where primary producers are the smallest components of the ecosystem. This approach makes it possible to explore and predict, in the past and in the future, the structure of ocean ecosystems without biomass extraction and other impacts.
TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis
Authors: Conrad Curdin , Di Domizio Jeremy , Mylonas Alessio , Belkhodja Cyrine , Demaria Olivier , Navarini Alexander A. , Lapointe Anne-Karine , French Lars E. , Vernez Maxime , Gilliet Michel
Published: December 2017

Although anti-tumor necrosis factor (TNF) agents are highly effective in the treatment of psoriasis, 2–5% of treated patients develop psoriasis-like skin lesions called paradoxical psoriasis. The pathogenesis of this side effect and its distinction from classical psoriasis remain unknown. Here we show that skin lesions from patients with paradoxical psoriasis are characterized by a selective overexpression of type I interferons, dermal accumulation of plasmacytoid dendritic cells (pDC), and reduced T-cell numbers, when compared to classical psoriasis. Anti-TNF treatment prolongs type I interferon production by pDCs through inhibition of their maturation. The resulting type I interferon overexpression is responsible for the skin phenotype of paradoxical psoriasis, which, unlike classical psoriasis, is independent of T cells. These findings indicate that paradoxical psoriasis represents an ongoing overactive innate inflammatory process, driven by pDC-derived type I interferon that does not lead to T-cell autoimmunity.
Discovery of human cell selective effector molecules using single cell multiplexed activity metabolomics
Authors: Earl David C. , Ferrell P. Brent , Leelatian Nalin , Froese Jordan T. , Reisman Benjamin J. , Irish Jonathan M. , Bachmann Brian O.
Published: December 2017

Discovering bioactive metabolites within a metabolome is challenging because there is generally little foreknowledge of metabolite molecular and cell-targeting activities. Here, single-cell response profiles and primary human tissue comprise a response platform used to discover novel microbial metabolites with cell-type-selective effector properties in untargeted metabolomic inventories. Metabolites display diverse effector mechanisms, including targeting protein synthesis, cell cycle status, DNA damage repair, necrosis, apoptosis, or phosphoprotein signaling. Arrayed metabolites are tested against acute myeloid leukemia patient bone marrow and molecules that specifically targeted blast cells or nonleukemic immune cell subsets within the same tissue biopsy are revealed. Cell-targeting polyketides are identified in extracts from biosynthetically prolific bacteria, including a previously unreported leukemia blast-targeting anthracycline and a polyene macrolactam that alternates between targeting blasts or nonmalignant cells by way of light-triggered photochemical isomerization. High-resolution cell profiling with mass cytometry confirms response mechanisms and is used to validate initial observations.
Macrophages orchestrate breast cancer early dissemination and metastasis
Authors: Linde Nina , Casanova-Acebes Maria , Sosa Maria Soledad , Mortha Arthur , Rahman Adeeb , Farias Eduardo , Harper Kathryn , Tardio Ethan , Reyes Torres Ivan , Jones Joan , Condeelis John , Merad Miriam , Aguirre-Ghiso Julio A.
Published: December 2017

Cancer cell dissemination during very early stages of breast cancer proceeds through poorly understood mechanisms. Here we show, in a mouse model of HER2+ breast cancer, that a previously described sub-population of early-evolved cancer cells requires macrophages for early dissemination. Depletion of macrophages specifically during pre-malignant stages reduces early dissemination and also results in reduced metastatic burden at end stages of cancer progression. Mechanistically, we show that, in pre-malignant lesions, CCL2 produced by cancer cells and myeloid cells attracts CD206+/Tie2+ macrophages and induces Wnt-1 upregulation that in turn downregulates E-cadherin junctions in the HER2+ early cancer cells. We also observe macrophage-containing tumor microenvironments of metastasis structures in the pre-malignant lesions that can operate as portals for intravasation. These data support a causal role for macrophages in early dissemination that affects long-term metastasis development much later in cancer progression. A pilot analysis on human specimens revealed intra-epithelial macrophages and loss of E-cadherin junctions in ductal carcinoma in situ, supporting a potential clinical relevance.
RAD54 N-terminal domain is a DNA sensor that couples ATP hydrolysis with branch migration of Holliday junctions
Authors: Goyal Nadish , Rossi Matthew J. , Mazina Olga M. , Chi Yong , Moritz Robert L. , Clurman Bruce E. , Mazin Alexander V.
Published: December 2017

In eukaryotes, RAD54 catalyzes branch migration (BM) of Holliday junctions, a basic process during DNA repair, replication, and recombination. RAD54 also stimulates RAD51 recombinase and has other activities. Here, we investigate the structural determinants for different RAD54 activities. We find that the RAD54 N-terminal domain (NTD) is responsible for initiation of BM through two coupled, but distinct steps; specific binding to Holliday junctions and RAD54 oligomerization. Furthermore, we find that the RAD54 oligomeric state can be controlled by NTD phosphorylation at S49, a CDK2 consensus site, which inhibits RAD54 oligomerization and, consequently, BM. Importantly, the effect of phosphorylation on RAD54 oligomerization is specific for BM, as it does not affect stimulation of RAD51 recombinase by RAD54. Thus, the transition of the oligomeric states provides an important control of the biological functions of RAD54 and, likely, other multifunctional proteins.
Extreme haplotype variation in the desiccation-tolerant clubmoss Selaginella lepidophylla
Authors: VanBuren Robert , Wai Ching Man , Ou Shujun , Pardo Jeremy , Bryant Doug , Jiang Ning , Mockler Todd C. , Edger Patrick , Michael Todd P.
Published: December 2017

Plant genome size varies by four orders of magnitude, and most of this variation stems from dynamic changes in repetitive DNA content. Here we report the small 109 Mb genome of Selaginella lepidophylla, a clubmoss with extreme desiccation tolerance. Single-molecule sequencing enables accurate haplotype assembly of a single heterozygous S. lepidophylla plant, revealing extensive structural variation. We observe numerous haplotype-specific deletions consisting of largely repetitive and heavily methylated sequences, with enrichment in young Gypsy LTR retrotransposons. Such elements are active but rapidly deleted, suggesting “bloat and purge” to maintain a small genome size. Unlike all other land plant lineages, Selaginella has no evidence of a whole-genome duplication event in its evolutionary history, but instead shows unique tandem gene duplication patterns reflecting adaptation to extreme drying. Gene expression changes during desiccation in S. lepidophylla mirror patterns observed across angiosperm resurrection plants.
Incorporating cuprous-halide clusters and lanthanide clusters to construct Heterometallic cluster organic frameworks with luminescence and gas adsorption properties
Authors: Liu Jin-Hua , Gu Ya-Nan , Chen Yi , Qi Yan-Jie , Li Xin-Xiong , Zheng Shou-Tian
Published: December 2017

A series of heterometallic cluster organic frameworks based on cuprous-halide Cu4I4 clusters and lanthanide clusters have been successfully synthesized under solvothermal conditions.
Protective effects of a Ganoderma atrum polysaccharide against acrylamide induced oxidative damage via a mitochondria mediated intrinsic apoptotic pathway in IEC-6 cells
Authors: Jiang Guoyong , Zhang Lulu , Wang Hui , Chen Qian , Wu Xiaolin , Yan Xiaoli , Chen Yi , Xie Mingyong
Published: December 2017

PSG-1-F2 is an effective and natural compound that could prevent ACR-induced apoptotic damage via a ROS triggered mitochondria associated pathway.
Design, synthesis and biological evaluation of 3′,4′,5′-trimethoxy flavonoid benzimidazole derivatives as potential anti-tumor agents
Authors: Wang Zhe , Deng Xiangping , Xiong Runde , Xiong Shujuan , Liu Juan , Cao Xuan , Lei Xiaoyong , Chen Yanming , Zheng Xing , Tang Guotao
Published: December 2017

A series of 3′,4′,5′-trimethoxy flavonoids with benzimidazole linked by different chain alkanes have been designed and synthesized.
Cu(i) complexes of dihydrobis(2-mercapto-benzimidazolyl)borate and dihydrobis(2-mercapto-benzothiazolyl)borate ligands: structural, photophysical and computational studies
Authors: Neshat Abdollah , Varestan Solmaz , Halvagar Mohammad Reza
Published: December 2017

Thermochromic behavior of complex 3 at 77 K.
Surface glycopolymer-modified functional macroporous polyHIPE obtained by ATRP for the removal of boron in water
Authors: Chen Xiangnan , Yuan Weizhong , Jiang Miao , Xie Xiaoyun
Published: December 2017

Macroporous polymeric monoliths PHIPE-PGAMA were obtained from polyHIPE with surface modification of PGAMA and used for boron removal.
Enhanced activity of trinuclear Zn(ii) complexes towards phosphate ester bond cleavage by introducing three-metal cooperativity
Authors: Joshi Pooja , Hussain Navid , Ali Shah Raj , Rishu Rishu , Bhardwaj Vimal K.
Published: December 2017

The catalytic efficiency (DNA binding followed by phosphate ester bond cleavage) of Zn(ii) complexes has been tuned by variation in the nuclearity, flexibility and coordination environment to explore the structure activity correlation.
High performing smart hyperbranched polyurethane nanocomposites with efficient self-healing, self-cleaning and photocatalytic attributes
Authors: Duarah Rituparna , Karak Niranjan
Published: December 2017

Tough smart starch modified hyperbranched polyurethane/reduced graphene oxide–silver–reduced carbon nanodot nanocomposites with self-healing and self-cleaning attributes under a sustainable energy source.
Kinetics and mechanistic studies on the formation and reactivity of high valent MnO porphyrin species: mono-ortho or para-substituted porphyrins versus a di-ortho-substituted one
Authors: Nasrollahi Rahele , Zakavi Saeed
Published: December 2017

High valent Mn(O) species of a series of electron-rich and -deficient meso-tetra(aryl)porphyrins (aryl = phenyl, 2-Cl-phenyl, 2-nitrophenyl, 2-Me-phenyl, 2-Br-phenyl, 2,6-di-Cl-phenyl 4-OMe-phenyl, 4-Me-phenyl, 4-Cl-phenyl and 4-pyridyl) were prepared at 273 K.
A novel carbon quantum dot-based fluorescent nanosensor for selective detection of flumioxazin in real samples
Authors: Panda Snigdharani , Jadav Arpita , Panda Niranjan , Mohapatra Sasmita
Published: December 2017

Herein, a carbon quantum dot-based highly selective luminescent probe has been designed for the detection of the pesticide flumioxazinviathe alkyne azide click reaction.
Hierarchically structured multi-shell nanotube arrays by self-assembly for efficient water oxidation
Authors: Czioska Steffen , Wang Jianying , Teng Xue , Zuo Shangshang , Xie Songhai , Chen Zuofeng
Published: December 2017

A novel structure of nickel hydroxide nanosheets on iron copper hydroxide nanotubes for OER was prepared by a simple self-assembling growth approach in solution.
Probing transcription factor binding activity and downstream gene silencing in living cells with a DNA nanoswitch
Authors: Bertucci Alessandro , Guo Junling , Oppmann Nicolas , Glab Agata , Ricci Francesco , Caruso Frank , Cavalieri Francesca
Published: December 2017

A dynamic DNA nanoswitch is used to probe NF-κB binding activity and its expression level directly in living cells.
Expanding pore sizes of ZIF-8-derived nitrogen-doped microporous carbon via C60 embedding: toward improved anode performance for the lithium-ion battery
Authors: Guan Jian , Zhong Xiongwu , Chen Xiang , Zhu Xianjun , Li Panlong , Wu Jianhua , Lu Yalin , Yu Yan , Yang Shangfeng
Published: December 2017

A novel C60-embedded nitrogen-doped microporous carbon material (C60@N-MPC) was prepared and applied as a superior anode material for lithium-ion battery (LIB).
pH-Responsible fluorescent carbon nanoparticles for tumor selective theranostics via pH-turn on/off fluorescence and photothermal effect in vivo and in vitro
Authors: Kang Eun Bi , Lee Jung Eun , Mazrad Zihnil Adha Islamy , In Insik , Jeong Ji Hoon , Park Sung Young
Published: December 2017

Here we designed the functionalized FNP as “switch-on” fluorescence probes to sense intracellular cancer cells and controllable photothermal therapy (PTT) in vivo and in vitro.
Porous layered stacked MnCo2O4 cubes with enhanced electrochemical capacitive performance
Authors: Li Menggang , Yang Weiwei , Li Ji , Feng Ming , Li Weili , Li Haibo , Yu Yongsheng
Published: December 2017

The porous layered stacked MnCo2O4 cubes have more excellent electrochemical capacitive performance compared with the other morphologies of MnCo2O4.
The effect of linker length on ConA and DC-SIGN binding of S-glucosyl functionalized poly(2-oxazoline)s
Authors: Yilmaz Gokhan , Uzunova Veselina , Hartweg Manuel , Beyer Valentin , Napier Richard , Becer C. Remzi
Published: December 2017

A series of poly(2-oxazoline) based glycopolymers with different linkers were prepared via thiol–ene click reaction and cationic ring opening reaction. The binding of these polymers to lectins were studied.
High-yield bottom-up synthesis of 2D metal–organic frameworks and their derived ultrathin carbon nanosheets for energy storage
Authors: Zhao Kuangmin , Liu Suqin , Ye Guanying , Gan Qingmeng , Zhou Zhi , He Zhen
Published: December 2017

We report a facile and low-cost bottom-up synthesis of ultrathin Zn(bim)(OAc) MOF nanosheets (with thicknesses of ∼5 nm and a high yield of ∼65%) and their derived N-doped porous ultrathin (2.5 ± 0.8 nm) carbon nanosheets (UT-CNSs) for energy storage.
Gold nanoparticles confined in imidazolium-based porous organic polymers to assemble a microfluidic reactor: controllable growth and enhanced catalytic activity
Authors: Fang Haobin , Sun Shujian , Liao Peisen , Hu Ya , Zhang Jianyong
Published: December 2017

Gold nanoparticles confined in imidazolium-based porous organic polymers show high activity in a microfluidic reactor.
Borophene and defective borophene as potential anchoring materials for lithium–sulfur batteries: a first-principles study
Authors: Jiang H. R. , Shyy W. , Liu M. , Ren Y. X. , Zhao T. S.
Published: December 2017

Lacking effective anchoring materials to suppress the severe shuttle effect is a longstanding issue hindering the development of lithium–sulfur (Li–S) batteries.
High-efficiency vertical-structure GaN-based light-emitting diodes on Si substrates
Authors: Wang Wenliang , Lin Yunhao , Li Yuan , Li Xiaochan , Huang Liegen , Zheng Yulin , Lin Zhiting , Wang Haiyan , Li Guoqiang
Published: December 2017

High-quality GaN-based light-emitting diode (LED) wafers have been grown on Si substrates by metal–organic chemical vapor deposition by designing epitaxial structures with AlN/Al0.24Ga0.76N buffer layers and a three-dimensional (3D) GaN layer.
Spirobi[dibenzo[b,e][1,4]azasiline]: a novel platform for host materials in highly efficient organic light-emitting diodes
Authors: Liu Xiang-Yang , Tang Xun , Zhao Yue , Zhao Danli , Fan Jian , Liao Liang-Sheng
Published: December 2017

Spirobi[dibenzo[b,e][1,4]azasiline] molecular platform was used as a building block to construct host materials for highly efficient RGB phosphorescent OLEDs.
Circularly polarized electroluminescence by controlling the emission zone in a twisted mesogenic conjugate polymer
Authors: Jung Jin-Hyung , Lee Dong-Myung , Kim Jae-Hoon , Yu Chang-Jae
Published: December 2017

The measuredgfactor and the corresponding emission zone were evaluated by theoretical analysis based on the Müller matrix method by increasing the thickness of the hole transport layer (TPBi) in the twisted configuration of conjugate polymer (F8BT).
Tutorial: Assessment and Analysis of Polysyllables in Young Children
Authors: Masso Sarah , McLeod Sharynne , Baker Elise
Published: December 2017

Purpose

Polysyllables, words of 3 or more syllables, represent almost 30% of words used in American English. The purpose of this tutorial is to support speech-language pathologists' (SLPs') assessment and analysis of polysyllables, extending the focus of published assessment tools that focus on sampling and analyzing children's segmental accuracy and/or the presence of phonological error patterns.

Method

This tutorial will guide SLPs through a review of 53 research papers that have explored the use of polysyllables in assessment, including the sampling and analysis procedures used in different research studies. The tutorial will also introduce two new tools to analyze and interpret polysyllable speech samples: the Word-Level Analysis of Polysyllables (WAP; Masso, 2016b) and the Framework of Polysyllable Maturity (Framework; Masso, 2016a).

Results

Connected speech and single-word sampling tasks were used across the 53 studies to elicit polysyllables, and a number of analysis methods were reported, including measures of segmental accuracy and measures of structural and suprasegmental accuracy. The WAP and the Framework extend SLPs' depth of analysis of polysyllables.

Conclusion

SLPs need a range of clinical tools to support the assessment and analysis of polysyllables. A case study comparing different speech analysis methods demonstrates the clinical value in utilizing the WAP and the Framework to interpret children's polysyllable productions in addition to traditional methods of speech sampling and analysis.
Liver Injury in Hemolysis, Elevated Liver Enzymes, and Low Platelets Syndrome Measured by Diffusion-Weighted Magnetic Resonance Imaging
Authors: Khan Ambereen , Bailey April , Yokoo Takeshi , Pedrosa Ivan , McIntire Donald , Cunningham F. , Nelson David
Published: December 2017

Objective The objective of this study was to evaluate acute liver injury (ALI) detected by diffusion-weighted magnetic resonance imaging (MRI) and the associated laboratory findings in women with hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome.

Study Design This was a retrospective, observational study of women with HELLP syndrome defined by serum aspartate aminotransferase (AST) levels ≥100 U/L and thrombocytopenia with platelets ≤100,000/µL. All women underwent MRI postpartum including diffusion-weighted imaging to estimate the volume of ALI with reconstructed apparent diffusion coefficient (ADC) maps. The ADC map and the volume of ALI were compared with laboratory abnormalities by Spearman's correlation analysis.

Results From March 2013 through August 2015, 16 women with HELLP syndrome underwent MRI, and of these, 14 (88%) women had areas of increased signal intensity suggestive of ALI. Their median (range) maximum AST level was 262 (140–1,958) IU/L, and at the time of MRI, AST was 103 (36–1,426) IU/L. Both of these AST levels significantly correlated with ADC map as well as the volume of ALI (both p-values <0.001).

Conclusion Women with HELLP syndrome frequently exhibited areas of abnormal diffusion in the liver on diffusion-weighted MRI, suggestive of ALI. The extent of liver injury was significantly correlated with serum AST.
ICF und der Begriff „wesentliche Behinderung“ im Bundesteilhabegesetz (BTHG)
Authors: Wagener Wolfgang
Published: December 2017

Bisher ist nur klar, dass noch vieles unklar ist. Das Ende letzten Jahres noch schnell verabschiedete Bundesteilhabegesetz sollte den Perspektivwechsel vom Fürsorge-System zum Teilhabe-Recht unterstreichen. Darum soll die Eingliederungshilfe von existenzsichernden Leistungen der Sozialhilfe getrennt werden. Manches in diesem Gesetz ist hilfreich, vielleicht sogar wegweisend. Aber es bleibt viel Interpretationsspielraum. Aus (amts-)ärztlicher Sicht besonders kritisch ist die Bestimmung „wesentlicher Behinderung“. Im Gesetzentwurf wurden die in der ICF definierten neun Lebensbereiche unzulässig instrumentalisiert. Eine „fünf aus neun“-Festsetzung ist gescheitert. Bis Ende 2019 ist eine Definition zu finden. Dabei muss klar sein, dass jeder Arzt nach bestem Wissen und Gewissen auf der Gesetzesgrundlage eine gutachterliche Bewertung vornimmt, aber keine mathematische Gleichung löst. Dies entspräche weder der Menschenwürde, noch wäre damit jemandem geholfen. Es bleibt aufmerksam zu beobachten, was sich bis 2023 in der Umsetzung des BTHG tut, um Fehlentwicklungen, die primär finanzielle Interessen vertritt, ggf. frühzeitig entgegen treten zu können. Hier sind alle (Amts-)Ärzte nicht nur sozialmedizinisch, sondern sehr wohl auch sozialpolitisch gefordert.
Dekolonisation bei Nachweis von Methicillin-sensiblen Staphylococcus aureus bei Mitarbeitern einer neonatologischen Intensivstation
Authors: Richter Annika , Eder Ines , König Brigitte , Lutze Bettina , Rodloff Arne , Thome Ulrich , Weiss Melanie , Chaberny Iris
Published: December 2017

Hintergrund Auf einer neonatologischen Intensivstation am Universitätsklinikum Leipzig wurden im Jahr 2016 vermehrt Kolonisationen mit Methicillin-sensiblen Staphylococcus aureus Stämmen festgestellt. Typisierungsergebnisse zeigten einen prädominierenden spa-Typ t091. Aufgrund der nosokomialen Häufungen wurden verschiedene Maßnahmen zur Infektionsprävention etabliert, z. B. intensive Barrieremaßnahmen, Einzelzimmer, Kohortierung, Umgebungsuntersuchungen auf S. aureus, Schulungen. Ein Teil dieses Maßnahmenbündels war die Durchführung eines Mitarbeiterscreenings, um kolonisierte Mitarbeiter als mögliches Reservoir zu sanieren.

Methodik Mitarbeiter mit S. aureus-Nachweis führten in der eigenen Häuslichkeit eine 5-tägige Sanierung durch. Hierfür wurden Produkte mit dem Wirkstoff Octenidin verwendet. Kontrollabstriche erfolgten frühestens 48 Stunden nach Beendigung des Sanierungsintervalls (3 im Abstand von mind. 24 Stunden). Mitarbeiter mit 2 erfolglosen Sanierungsversuchen erhielten anstelle von Octenidin-, Mupirocin-haltige Nasensalbe.

Ergebnisse Bei 128 untersuchten Mitarbeitern wurde in 43 Fällen (33,6%) S. aureus nachgewiesen, der in 9 Fällen (20,9%; 9/43) dem Typ t091 entsprach. Unter den S. aureus-positiven Mitarbeitern waren 2 MRSA-Nachweise (4,7%; 2/43) als Zufallsbefund zu verzeichnen. Die Erfolgsquote nach dem ersten Sanierungsversuch von t091 und MRSA lag bei 0%. In 3 Fällen lagen nach dem zweiten Versuch 3 negative Kontrollabstriche vor und 8 Mitarbeiter konnten erst unter Einsatz von Mupirocin-haltiger Nasensalbe saniert werden.

Schlussfolgerungen Ursachen für die erschwerte Sanierung können vielfältig sein: Schwer umzusetzende Sanierung im eigenen Haushalt, Vorhandensein von dekolonisierungshemmenden Faktoren, nicht konsequente Durchführung aller Sanierungsmaßnahmen und eine mögliche Rekolonisation während der Arbeitszeit oder durch Familienangehörige. Weiterhin ist zu diskutieren, ob der Erfolg der Sanierung bei Verwendung von Mupirocin-Nasensalbe in der besseren Wirksamkeit von Mupirocin im Vergleich zu Octenidin begründet ist oder ob die unterschiedliche Konsistenz der Präparate ausschlaggebend ist.
BaTiO3-based piezoelectrics: Fundamentals, current status, and perspectives
Authors: Acosta M. , Novak N. , Rojas V. , Patel S. , Vaish R. , Koruza J. , Rossetti G. A. , Rödel J.
Published: December 2017

We present a critical review that encompasses the fundamentals and state-of-the-art knowledge of barium titanate-based piezoelectrics. First, the essential crystallography, thermodynamic relations, and concepts necessary to understand piezoelectricity and ferroelectricity in barium titanate are discussed. Strategies to optimize piezoelectric properties through microstructure control and chemical modification are also introduced. Thereafter, we systematically review the synthesis, microstructure, and phase diagrams of barium titanate-based piezoelectrics and provide a detailed compilation of their functional and mechanical properties. The most salient materials treated include the (Ba,Ca)(Zr,Ti)O3, (Ba,Ca)(Sn,Ti)O3, and (Ba,Ca)(Hf,Ti)O3 solid solution systems. The technological relevance of barium titanate-based piezoelectrics is also discussed and some potential market indicators are outlined. Finally, perspectives on productive lines of future research and promising areas for the applications of these materials are presented.