bluuebunny/crossref_metadata_2025 huggingface dataset:
International core curriculum for capsule endoscopy training courses
Authors: Fernandez-Urien Ignacio , Panter Simon , Carretero Cristina , Davison Carolyn , Dray Xavier , Fedorov Evgeny , Makins Richard , Mascarenhas Miguel , McAlindon Mark , McNamara Deirdre , Palmer Hansa , Rey Jean , Saurin Jean , Seitz Uwe , Spada Cristiano , Toth Ervin , Wiedbrauck Felix , Keuchel Martin
Published: June 2017

Capsule endoscopy (CE) has become a first-line noninvasive tool for visualisation of the small bowel (SB) and is being increasingly used for investigation of the colon. The European Society of Gastrointestinal Endoscopy (ESGE) guidelines have specified requirements for the clinical applications of CE. However, there are no standardized recommendations yet for CE training courses in Europe. The following suggestions in this curriculum are based on the experience of European CE training courses directors. It is suggested that 12 hours be dedicated for either a small bowel capsule endoscopy (SBCE) or a colon capsule endoscopy (CCE) course with 4 hours for an introductory CCE course delivered in conjunction with SBCE courses. SBCE courses should include state-of-the-art lectures on indications, contraindications, complications, patient management and hardware and software use. Procedural issues require approximately 2 hours. For CCE courses 2.5 hours for theoretical lessons and 3.5 hours for procedural issued are considered appropriate. Hands-on training on reading and interpretation of CE cases using a personal computer (PC) for 1 or 2 delegates is recommended for both SBCE and CCE courses. A total of 6 hours hands-on session- time should be allocated. Cases in a SBCE course should cover SB bleeding, inflammatory bowel diseases (IBD), tumors and variants of normal and cases with various types of polyps covered in CCE courses. Standardization of the description of findings and generation of high-quality reports should be essential parts of the training. Courses should be followed by an assessment of traineesʼ skills in order to certify readers’ competency.
Bewegung und körperliche Aktivität im ambulanten Setting bei Demenzerkrankungen
Authors: Deimel Hubertus , Dexel Monika , Schreckling Sibylle
Published: June 2017

Menschen mit Demenzerkrankungen werden oftmals im häuslichen Umfeld von Familienangehörigen betreut. Da pflegende Angehörige
umfassende Hilfe und Unterstützung bei dieser Aufgabe benötigen, spielen gemeindenahe Versorgungsangebote eine zunehmend
wichtigere Rolle. Hierbei finden primär nicht-pharmakologische Therapieansätze Anwendung. Sie sollen die verbliebenen
funktionellen und psychosozialen Fähigkeiten der Betroffenen möglichst lange erhalten oder ihren Abbau verlangsamen sowie
Entlastung für die pflegenden Angehörigen bieten. Bewegungsangebote können dazu beitragen, diese Ziele zu erreichen. Aufgrund der
heterogenen physischen, affektiven, kognitiven und psychosozialen Fähigkeiten von Menschen mit Demenz, ist es jedoch notwendig,
das Bewegungsangebot gut zu differenzieren und mit anderen Maßnahmen zu verknüpfen. Das lässt sich anhand der strukturellen
Rahmenbedingungen der „Arbeitsgemeinschaft für psychisch Kranke im Erftkreis e. V.“ sowie der angegliederten „Alzheimer
Gesellschaft Rhein-Erft-Kreis e. V.“ veranschaulichen. Als übergeordnetes Ziel der Maßnahmen gilt der Erhalt bzw. die Verbesserung
der Lebensqualität der betroffenen Teilnehmer sowie der pflegenden Angehörigen.
Privileg mit Tücken
Authors: Herz Mona
Published: June 2017

Läuft uns der Schweiß, ist das meist eine gesunde Reaktion auf Überwärmung. Die dabei entstehende Verdunstungskälte kühlt den Körper. Bei Hyperhidrose schwitzt man auch außerhalb von körperlicher Bewegung und Aufenthalt in Wärme übermäßig. Neben der idiopathischen Hyperhidrose kann übermäßiges Schwitzen auf ernsthafte Erkrankungen wie Tumoren und hormonelle Störungen hinweisen.
Die Notwendigkeit der psychosozialen Begleitung von Eltern in der Neonatologie
Authors: Schäfer Nicole , Karutz Harald , Schenk Olaf
Published: June 2017

Hintergrund Erhebliche Fortschritte in der neonatologischen Medizin haben in den letzten Jahren zu einer Verringerung der Mortalitätsrate und zu einem Anstieg der Morbiditätsrate unter den zu früh- und risikogeborenen Kindern geführt. Häufig ist diese Entwicklung jedoch mit einer zunehmenden Belastung für die gesamte Familie, insbesondere für die Eltern, verbunden. Anhand einer umfangreichen Literaturarbeit wird daher die Notwendigkeit der psychosozialen Begleitung von Eltern in der Neonatologie herausgestellt.

Methodik In den Datenbanken Pubmed, Psyndex, CINAHl und medpilot wurde zunächst eine systematische Literaturrecherche durchgeführt. Um weitere relevante Publikationen zu finden, wurden außerdem die Referenzlisten der gefundenen Artikel überprüft. Eine anschließende Freitextsuche hatte die Ergänzung der Schlagwortsuche zum Ziel. Insgesamt konnten auf diese Weise 78 Veröffentlichungen aus den Jahren von 1975 bis 2015 in die Studie einbezogen werden.

Ergebnisse Die Bedeutung der psychosozialen Begleitung von Eltern in der Neonatologie lässt sich anhand der ausgewerteten Fachliteratur eindrucksvoll belegen. Allerdings fällt auf, dass die Notwendigkeit eines Assessments als Grundlage einer den individuellen Bedürfnissen der Familie entsprechenden Begleitung zwar bekannt ist, die Verwendung von validierten Screeninginstrumenten offenbar jedoch noch nicht zum Standard gehört. Ferner wird deutlich, dass der Bedarf an psychosozialer Unterstützung seitens der Eltern nicht allein vom medizinischen Risiko des Kindes abhängt.

Schlussfolgerungen Die vorliegenden Erkenntnisse implizieren insbesondere die Herausforderung, unter Berücksichtigung der in der Entwicklung befindlichen Eltern-Kind-Einheit, in einem Gesundheitssystem mit eingeschränkten Ressourcen und vor dem Hintergrund gesundheitsökonomischer Vorgaben, dennoch eine hoch individuelle Betreuung betroffener Familien möglich zu machen. Mitunter intuitiv ausgebildete Konzepte sollten in Zukunft weiter wissenschaftlich fundiert werden. Beiträge aus den Bereichen der Psychologie und Bindungsforschung sind dabei zu berücksichtigen.
First-principles study on mechanical and elastic properties of BxAl1-xP alloys
Authors: Ma Huihui , Zhang Junqin , Zhao Bin , Wei Qun , Yang Yintang
Published: June 2017

Based on density functional theory calculations, systematic calculations of the structural properties, elastic anisotropy and mechanical properties of boron alloying aluminum phosphide (BxAl1-xP) ternary mixed crystal have been presented. The results of the lattice parameters, band gaps, elastic constants and elastic modulus accord with the experimental and others published data well. The band structure which is described by CASTEP method indicates they are direct gap semiconductors for the composition x = 0.25, 0.50 and 0.75. Beyond that, we studied the Debye temperatures together with the acoustic velocities for all the BxAl1-xP alloys using the obtained elastic modulus. Finally, we depicted the three dimensional surface constructions to explain the elastic anisotropy using several calculated different anisotropic indexes in our work.
Using the ALARP principle to significantly reduce offshore decommissioning costs
Authors: Goodwin Max J. , Muir Lucy D. , Piasentin Francesco
Published: June 2017

Lurking on the balance sheet of all offshore operators is a line item typically referred to as ‘abandonment costs’. Such costs are usually estimates made using assumptions of total removal and can run into the tens or hundreds of millions of dollars. In the next 25 years, it is estimated that 100 offshore oil-production installations will need to be decommissioned in Australia, with an anticipated cost in excess of AU$1.2 billion.
Most jurisdictions around the world ostensibly require total removal of all facilities post-production. In Australia and elsewhere, including the Gulf of Mexico and North Sea, there is an opportunity to propose deviations from total removal if there are good grounds for doing otherwise. The main alternative to removal, that is, in situ decommissioning, can offer many advantages including reduced cost, environmental impact and worker exposure to safety hazards.
Furthermore, the application of a stage-gate project approach – more traditionally used in oil and gas development stages (appraise, select, define, execute) – enables the effective integration of the inputs from the wide variety of stakeholders involved in a decommissioning project, as well as efficiently handling the potentially large volume of information and analysis that is involved.
Drawing on recent project experience, this paper describes the practical approaches needed to ensure a robust assessment and determination of ALARP.
Our energy future: the power of collaboration to transform Australia's energy resources sector
Authors: Taylor Miranda
Published: June 2017

After decades of sustained economic growth, Australia is experiencing declining productivity, accelerating technological change and disruption. At the same time, the energy sector is emerging from a massive investment phase, while facing its own perfect storm of disruptive challenges.
The industry must navigate these challenges to remain globally competitive. Continuing old practices is a sure pathway to stagnation and decline; we must urgently find different ways to do things.
Global benchmarking of the Australian energy resources sector, undertaken recently on behalf of NERA, indicated substantial room to improve the efficiency and productivity of the sector. The report outlines more than AU$5 billion of value through improvements across the following four key areas: supply chain, research and innovation, workforce and regulatory reform, and collaboration is the key.
Over the past 24 months, Australian energy-resource companies have focussed on lowering capital cost and improving profitability through efficiency, ensuring the industry has the fundamentals needed to be globally competitive.
However, transformational change is needed if the sector is to survive and thrive in this age of innovation and disruption. Further, Australia’s energy resources marketplace is too small to focus only internally. Industry, suppliers, innovators and knowledge experts must collaborate locally, forming connections to access the global marketplace.
The size of the prize is significant for everyone. The Australian energy resources sector has the potential to continue to meet the regions energy-resource needs for many years, generate substantial revenue for the nation and grow an export-orientated service and technology sector.
Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells
Authors: Zhu Xiaohua , Badawi Mohamed , Pomeroy Steven , Sutaria Dhruvitkumar S. , Xie Zhiliang , Baek Alice , Jiang Jinmai , Elgamal Ola A. , Mo Xiaokui , La Perle Krista , Chalmers Jeffrey , Schmittgen Thomas D. , Phelps Mitch A.
Published: June 2017

Extracellular vesicles (EVs) are under evaluation as therapeutics or as vehicles for drug delivery. Preclinical studies of EVs often use mice or other animal models to assess efficacy and disposition. However, as most EVs under evaluation are derived from human cells, they may elicit immune responses which may contribute to toxicities or enhanced EV clearance. Furthermore, EVs from different cell sources or EVs comprising various cargo may differ with respect to immunogenicity or toxicity. To assess EV‐induced immune response and toxicity, we dosed C57BL/6 mice with EVs intravenously and intraperitoneally for 3 weeks. EVs were harvested from wild type or engineered HEK293T cells which were modified to produce EVs loaded with miR‐199a‐3p and chimeric proteins. Blood was collected to assess hematology, blood chemistry, and immune markers. Spleen cells were immunophenotyped, and tissues were harvested for gross necropsy and histopathological examination. No signs of toxicity were observed, and minimal evidence of changes in immune markers were noted in mice dosed with engineered, but not with wild type EVs. This study provides a framework for assessment of immunogenicity and toxicity that will be required as EVs from varying cell sources are tested within numerous animal models and eventually in humans.
DNA base flipping analytical pipeline
Authors: Zhang Peng , Hastert Florian D. , Ludwig Anne K. , Breitwieser Kai , Hofstätter Maria , Cardoso M. Cristina
Published: June 2017

DNA base modifications and mutations are observed in all genomes throughout the kingdoms of life. Proteins involved in their establishment and removal were shown to use a base flipping mechanism to access their substrates. To better understand how proteins flip DNA bases to modify or remove them, we optimized and developed a pipeline of methods to step-by-step detect the process starting with protein–DNA interaction, base flipping itself and the ensuing DNA base modification or excision. As methylcytosine is the best-studied DNA modification, here we focus on the process of writing, modifying and reading this DNA base. Using multicolor electrophoretic mobility shift assays, we show that the methylcytosine modifier Tet1 exhibits little DNA sequence specificity with only a slight preference for methylated CpG containing DNA. A combination of chloroacetaldehyde treatment and high-resolution melting temperature analysis allowed us to detect base flipping induced by the methylcytosine modifier Tet1 as well as the methylcytosine writer M.HpaII. Finally, we show that high-resolution melting temperature analysis can be used to detect the activity of glycosylases, methyltransferases and dioxigenases on DNA substrates. Taken together, this DNA base flipping analytical pipeline (BaFAP) provide a complete toolbox for the fast and sensitive analysis of proteins that bind, flip and modify or excise DNA bases.
China's flourishing synthetic organofluorine chemistry: innovations in the new millennium
Authors: Liu Qinghe , Ni Chuanfa , Hu Jinbo
Published: June 2017

The new millennium has witnessed the rapid development of synthetic organofluorine chemistry all over the world, and chemists in China have made significant contributions in this field. This review aims to provide a brief introduction to China's primary innovations from 2000 to early 2017, covering fluorination, fluoroalkylation, fluoromethylthiolation, fluoroolefination and polyfluoroarylation, as well as synthesis with fluorinated building blocks. Recent advances in the chemistry of difluorocarbene and the chemistry of carbon–fluorine bond activation are also discussed. As a conclusion, the review ends with some personal perspectives on the future development of China's synthetic organofluorine chemistry.
Colonization of Durum Wheat (Triticum turgidum L. var. durum) Culms Exhibiting Premature Senescence (Dead Heads) Associated with Fusarium pseudograminearum Crown Rot
Authors: Knight Noel L. , Macdonald Bethany , Sutherland Mark W.
Published: June 2017

Fusarium crown rot is a significant disease of durum wheat (Triticum turgidum L. var. durum), which exhibits high levels of disease susceptibility. The most extreme symptom of crown rot is a prematurely senescing culm that typically fails to set grain. Individual crown rot-affected durum wheat plants displaying both nonsenescent and prematurely senescent culms were harvested to compare visual discoloration, Fusarium pseudograminearum biomass, and vascular colonization in culm sections sampled at three different heights above the crown. Field samples of EGA Bellaroi were collected at Wellcamp, QLD, in 2011, 2012, 2013, and 2014, and of Hyperno at Narrabri, NSW, in 2014. Prematurely senescent culms exhibited greater visual discoloration, F. pseudograminearum biomass, and vascular colonization than nonsenescent culms in each year they were examined. The extent of these differences varied between environments and timing of collection in each year. Vascular colonization initially occurred in xylem vessels and spread into phloem tissues as disease severity increased. The increased presence of hyphae in vascular bundles of prematurely senescing culms provides strong evidence for the hypothesis that restriction of water and nutrient movement in a diseased culm is a key factor in crown rot severity.
Wrist Arthroscopy in Children and Adolescent With Chronic Wrist Pain: Arthroscopic Findings Compared With MRI
Authors: Ramavath Ashok L. , Unnikrishnan P.N. , George Harvey L. , Sathyamoorthy Paramasivam , Bruce Colin E.
Published: June 2017

Background:

Wrist arthroscopy is a dynamic diagnostic procedure and its indications are growing as a treatment modality in the adult population. The aim of the study was to retrospectively report our series of pediatric and adolescence with chronic wrist pain, with or without wrist instability who underwent wrist arthroscopy after failing at least 4 months of conservative management. Our secondary aim was to report the sensitivity and specificity of clinical examination and magnetic resonance imaging evaluation for various injury subgroups against the gold standard of the arthroscopic findings. Technical challenges, complications, and outcomes are also discussed.

Methods:

A retrospective review of the medical records of 32 pediatric and adolescent patients who underwent wrist arthroscopy was conducted. Preoperative clinical diagnosis, radiographic, and intraoperative findings including classifications of triangular fibrocartilage complex (TFCC) and interosseous ligaments were obtained. Patients were followed up to 1 year postoperatively and were discharged if symptom free.

Results:

Thirty-three wrist arthroscopies in 32 patients were performed from 1996 to 2004. There were 2 male and 30 female patients. At arthroscopy 16 wrists were found to have TFCC injuries, 11 wrists had scapholunate injuries, and 8 had lunotriquetral (LT) injuries. Clinical examination for diagnosis of TFCC injury was too sensitive and nonspecific; however, clinical diagnosis of scapholunate injury was sensitive and specific. LT injury was under diagnosed clinically. Magnetic resonance imaging was found to have a low sensitivity for diagnosis of LT injury but diagnosis of TFCC was sensitive and specific.

Conclusions:

The sex ratio of 2 males:30 females was startling. Nevertheless, this therapeutic level 3 study supports a thorough search for pathology in any patient with persistent wrist symptoms because pathology was identified in 32 of the 33 wrists at arthroscopy.

Level of Evidence:

Level III—Therapeutic.
Minimally invasive surgery in pelvic floor repair
Authors: Zwain Omar , Aoun Joelle , Eisenstein David
Published: June 2017

Purpose of review

To review the use and efficacy of minimally invasive surgery in pelvic organ prolapse (POP) repair. This review summarizes surgical options for management of POP with special emphasis on minimally invasive surgical approach and discusses the recent experience and feasibility of integrating robot-assisted technology.

Recent findings

Minimally invasive approaches have equal efficacy and less morbidity than laparotomy for POP repair, particularly apical prolapse. Robotics may facilitate the rate of minimally invasive surgery for POP repair with greater cost and as yet no proven superiority for conventional laparoscopy.

Minimally invasive surgery is the preferred approach to POP repair. Conventional laparoscopic or robotic sacral colpopexy is recommended for apical defect and procidentia.
Fever and Pancytopenia in a Liver Transplant Recipient: Going Against the Rules of Occam's Razor
Authors: Lum Lionel Hon Wai , Chen Fei Wen , Jackett Louise , Strasser Simone I. , Davis Rebecca J.
Published: June 2017

The syndrome of fever and pancytopenia is not infrequently encountered postliver transplant, and a broad differential list of infectious and noninfectious aetiologies can be invoked. A transplant patient is susceptible to more than 1 opportunistic infection or disease process. We described the diagnostic conundrums in managing our patient who ran a complex protracted course postliver transplant. He was diagnosed to have both disseminated tuberculosis and graft-versus-host disease, a rare complication after solid organ transplantation.
Finite-element modelling of mechanobiological factors influencing sesamoid tissue morphology in the patellar tendon of an ostrich
Authors: Chadwick Kyle P. , Shefelbine Sandra J. , Pitsillides Andrew A. , Hutchinson John R.
Published: June 2017

The appearance and shape of sesamoid bones within a tendon or ligament wrapping around a joint are understood to be influenced by both genetic and epigenetic factors. Ostriches (
Struthio camelus
) possess two sesamoid patellae (kneecaps), one of which (the distal patella) is unique to their lineage, making them a good model for investigating sesamoid tissue development and evolution. Here we used finite-element modelling to test the hypothesis that specific mechanical cues in the ostrich patellar tendon favour the formation of multiple patellae. Using three-dimensional models that allow application of loading conditions in which all muscles, or only distal or only proximal muscles to be activated, we found that there were multiple regions within the tendon where transformation from soft tissue to fibrocartilage was favourable and therefore a potential for multiple patellae based solely upon mechanical stimuli. While more studies are needed to better understand universal mechanobiological principles as well as full developmental processes, our findings suggest that a tissue differentiation algorithm using shear strain and compressive strain as inputs may be a roughly effective predictor of the tissue differentiation required for sesamoid development.
Nonlinear evolution of a thin anodic film
Authors: McHugh J. P. , Barkey D.
Published: June 2017

The formation of pores in anodic aluminium oxide films is treated with a model equation. The model treats the oxide layer as a thin viscous liquid in two dimensions. Surface tension on the top boundary, electrostriction due to the external electric field and mass flow through the bottom boundary due to oxide formation are all included. Viscous flow is treated with the creeping flow assumption. The model equation is solved numerically using a Fourier spectral method in space and Adams–Bashforth/Adams–Moulton methods in time. Initial conditions include sinusoidal shapes as well as random shapes. The results show that pores form at the trough of the initial sinusoidal shape. Random shapes get smoothed before forming pore structures with spacing different than predicted by linear theory.
Biological interactions both facilitate and resist climate-related functional change in temperate reef communities
Authors: Bates Amanda E. , Stuart-Smith Rick D. , Barrett Neville S. , Edgar Graham J.
Published: June 2017

Shifts in the abundance and location of species are restructuring life on the Earth, presenting the need to build resilience into our natural systems. Here, we tested if protection from fishing promotes community resilience in temperate reef communities undergoing rapid warming in Tasmania. Regardless of protection status, we detected a signature of warming in the brown macroalgae, invertebrates and fishes, through increases in the local richness and abundance of warm-affinity species. Even so, responses in protected communities diverged from exploited communities. At the local scale, the number of cool-affinity fishes and canopy-forming algal species increased following protection, even though the observation window fell within a period of warming. At the same time, exploited communities gained turf algal and sessile invertebrate species. We further found that the recovery of predator populations following protection leads to marked declines in mobile invertebrates—this trend could be incorrectly attributed to warming without contextual data quantifying community change across trophic levels. By comparing long-term change in exploited and protected reefs, we empirically demonstrate the role of biological interactions in both facilitating and resisting climate-related biodiversity change. We further highlight the potential for trophic interactions to alter the progression of both range expansions and contractions.
First case of human peritoneal cysticercosis mimicking peritoneal carcinosis: necessity of laparoscopy and histologic assessment for the correct diagnosis
Authors: Rudelius Martina , Brehm Klaus , Poelcher Martin , Spinner Christoph , Rosenwald Andreas , Costa Clarissa Prazeres da
Published: June 2017

Introduction. Correct diagnosis of peritoneal infectious disease can be extremely difficult due to non-specific clinical features. Thus, careful assessment with thorough histopathological work-up is essential. Here, we report the first case of human peritoneal cysticercosis mimicking peritoneal carcinosis.

Case presentation. The patient presented with recurring ascites and a tumour in the Douglas cavity accompanied by elevated tumour markers. There were no signs of systemic infection. On laparoscopy, the tumour was resected completely. Histology revealed a granulomatous reaction and a diagnosis suspicious of tuberculosis was made. Only after additional sections, avital cestode-fragments were visible and Taenia martis DNA was detected. Further staging by computerized tomography scan of the lung and brain turned out negative and the patient recovered quickly.

Conclusion. Laparoscopy and histopathological examination can be extremely helpful for correct diagnosis and management in uncertain recurrent ascites. This case clearly demonstrates that orphan infectious diseases should also be considered. Only complete histopathological examination with serial sections and additional molecular testing can lead to the appropriate diagnosis.
RL-SKAT: An exact and efficient score test for heritability and set tests
Authors: Schweiger Regev , Weissbrod Omer , Rahmani Elior , Müller-Nurasyid Martina , Kunze Sonja , Gieger Christian , Waldenberger Melanie , Rosset Saharon , Halperin Eran
Published: June 2017

Testing for the existence of variance components in linear mixed models is a fundamental task in many applicative fields. In statistical genetics, the score test has recently become instrumental in the task of testing an association between a set of genetic markers and a phenotype. With few markers, this amounts to set-based variance component tests, which attempt to increase power in association studies by aggregating weak individual effects. When the entire genome is considered, it allows testing for the heritability of a phenotype, defined as the proportion of phenotypic variance explained by genetics. In the popular score-based Sequence Kernel Association Test (SKAT) method, the assumed distribution of the score test statistic is uncalibrated in small samples, with a correction being computationally expensive. This may cause severe inflation or deflation of p-values, even when the null hypothesis is true. Here, we characterize the conditions under which this discrepancy holds, and show it may occur also in large real datasets, such as a dataset from the Wellcome Trust Case Control Consortium 2 (n=13,950) study, and in particular when the individuals in the sample are unrelated. In these cases the SKAT approximation tends to be highly over-conservative and therefore underpowered. To address this limitation, we suggest an efficient method to calculate exact p-values for the score test in the case of a single variance component and a continuous response vector, which can speed up the analysis by orders of magnitude. Our results enable fast and accurate application of the score test in heritability and in set-based association tests. Our method is available inhttp://github.com/cozygene/RL-SKAT.
Parallel diversifications ofCremastospermaandMosannona(Annonaceae), tropical rainforest trees tracking Neogene upheaval of the South American continent
Authors: Pirie Michael D. , Maas Paul J. M. , Wilschut Rutger A. , Melchers-Sharrott Heleen , Chatrou Lars W.
Published: June 2017

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100033).Much of the immense present day biological diversity of Neotropical rainforests originated from the Miocene onwards, a period of geological and ecological upheaval in South America. We assess the impact of the Andean orogeny, drainage of lake Pebas, and closure of the Panama Isthmus on two clades of trees (Cremastosperma, c. 31 spp.; andMosannona, c. 14 spp.; both Annonaceae) found in humid forest distributed across the transition zones between the Andes and Western (lowland) Amazonia and between Central and South America. We inferred phylogenies based on c. 80% of recognised species of each clade using plastid and nuclear encoded sequence markers, revealing similar patterns of geographically restricted clades. Using molecular dating we showed that diversifications in the different areas occurred in parallel, with timing consistent with Andean vicariance and Central American geodispersal. In apparent contradiction of high dispersal abilities of rainforest trees,Cremastospermaclades within Amazonia are also geographically restricted, with a southern/montane clade that appears to have diversified along the foothills of the Andes sister to one of more northern/lowland species that diversified in a region once inundated by lake Pebas. Ecological niche modelling approaches show phylogenetically conserved niche differentiation, particularly withinCremastosperma. Niche similarity and recent common ancestry of Amazon and GuiananMosannonaspecies contrasts with dissimilar niches and more distant ancestry of Amazon, Venezuelan and Guianan species ofCremastospermasuggesting that this element of the similar patterns of disjunct distributions in the two genera is instead a biogeographic parallelism, with differing origins. The results provide further independent evidence for the importance of the Andean orogeny, the drainage of Lake Pebas, and the formation of links between South and Central America in the evolutionary history of Neotropical lowland rainforest trees.
ClassifyingDrosophilaOlfactory Projection Neuron Subtypes by Single-cell RNA Sequencing
Authors: Li Hongjie , Horns Felix , Wu Bing , Xie Qijing , Li Jiefu , Li Tongchao , Luginbuhl David , Quake Stephen R. , Luo Liqun
Published: June 2017

How a neuronal cell type is defined and how this relates to its transcriptome are still open questions. TheDrosophilaolfactory projection neurons (PNs) are among the best-characterized neuronal types: Different PN classes target dendrites to distinct olfactory glomeruli and PNs of the same class exhibit indistinguishable anatomical and physiological properties. Using single-cell RNA-sequencing, we comprehensively characterized the transcriptomes of 40 PN classes and unequivocally identified transcriptomes for 6 classes. We found a new lineage-specific transcription factor that instructs PN dendrite targeting. Transcriptomes of closely-related PN classes exhibit the largest difference during circuit assembly, but become indistinguishable in adults, suggesting that neuronal subtype diversity peaks during development. Genes encoding transcription factors and cell-surface molecules are the most differentially expressed, indicating their central roles in specifying neuronal identity. Finally, we show that PNs use highly redundant combinatorial molecular codes to distinguish subtypes, enabling robust specification of cell identity and circuit assembly.
Polyclonal HIV envelope-specific breast milk antibodies limit founder SHIV acquisition and cell-associated virus loads in infant rhesus monkeys
Authors: Himes Jonathon E. , Goswami Ria , Mangan Riley J. , Kumar Amit , Jeffries Thomas L. , Eudailey Joshua A. , Heimsath Holly , Nguyen Quang N. , Pollara Justin , LaBranche Celia , Chen Meng , Vandergrift Nathan A. , Peacock James W. , Schiro Faith , Midkiff Cecily , Ferrari Guido , Montefiori David C. , Alvarez-Hernandez Xavier , Aye Pyone Pyone , Permar Sallie R.
Published: June 2017

Vertical HIV-1 transmission via breastfeeding is the predominant contributor to pediatric infections that are ongoing in this era of highly effective antiretroviral therapy (ART). Remarkably, only ~10% of infants chronically exposed to the virus via breastfeeding from untreated HIV-infected mothers become infected, suggesting the presence of naturally protective factors in breast milk. HIV-specific maternal antibodies are obvious candidates as potential contributors to this protection. This study assessed the protective capacity of common HIV envelope-specific non-broadly neutralizing antibodies isolated from breast milk of HIV-infected women in an infant rhesus monkey (RM), tier 2 SHIV oral challenge model. Prior to oral SHIV challenge, infant RMs were i.v. infused with either a single weakly-neutralizing monoclonal antibody (mAb), a tri-mAb cocktail with neutralizing and ADCC functionalities, or an anti-influenza HA control mAb. Of these groups, the fewest tri-mAb-treated infants developed plasma viremia (2/6, 3/6, and 6/8 animals viremic in tri-mAb, single-mAb, and control mAb groups, respectively). Tri-mAb-treated infants demonstrated significantly fewer transmitted/founder SHIV variants in plasma and decreased peripheral CD4+ T cell proviral loads at 8 week post-challenge compared to control mAb-treated infants. Abortive infection was observed as detectable CD4+ T cell provirus in non-viremic control mAb- and single-mAb-, but not tri-mAb-treated animals. Taken together, these results support the potential viability of maternal or infant vaccine strategies that elicit non-broadly neutralizing antibodies to prevent vertical transmission of HIV through breastfeeding.
Discovery of the first genome-wide significant risk loci for ADHD
Authors: Demontis Ditte , Walters Raymond K. , Martin Joanna , Mattheisen Manuel , Als Thomas D. , Agerbo Esben , Belliveau Rich , Bybjerg-Grauholm Jonas , Bækvad-Hansen Marie , Cerrato Felecia , Chambert Kimberly , Churchhouse Claire , Dumont Ashley , Eriksson Nicholas , Gandal Michael , Goldstein Jacqueline , Grove Jakob , Hansen Christine S. , Hauberg Mads E. , Hollegaard Mads V. , Howrigan Daniel P. , Huang Hailiang , Maller Julian , Martin Alicia R. , Moran Jennifer , Pallesen Jonatan , Palmer Duncan S. , Pedersen Carsten B. , Pedersen Marianne G. , Poterba Timothy , Poulsen Jesper B. , Ripke Stephan , Robinson Elise B. , Satterstrom Kyle F. , Stevens Christine , Turley Patrick , Won Hyejung ,   ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team, Andreassen Ole A. , Burton Christie , Boomsma Dorret , Cormand Bru , Dalsgaard Søren , Franke Barbara , Gelernter Joel , Geschwind Daniel , Hakonarson Hakon , Haavik Jan , Kranzler Henry , Kuntsi Jonna , Langley Kate , Lesch Klaus-Peter , Middeldorp Christel , Reif Andreas , Rohde Luis A. , Roussos Panos , Schachar Russell , Sklar Pamela , Sonuga-Barke Edmund , Sullivan Patrick F. , Thapar Anita , Tung Joyce , Waldman Irwin , Nordentoft Merete , Hougaard David M. , Werge Thomas , Mors Ole , Mortensen Preben B. , Daly Mark J. , Faraone Stephen V. , Børglum Anders D. , Neale Benjamin M.
Published: June 2017

Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of school-age children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no individual variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 ADHD cases and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, revealing new and important information on the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes, as well as around brain-expressed regulatory marks. These findings, based on clinical interviews and/or medical records are supported by additional analyses of a self-reported ADHD sample and a study of quantitative measures of ADHD symptoms in the population. Meta-analyzing these data with our primary scan yielded a total of 16 genome-wide significant loci. The results support the hypothesis that clinical diagnosis of ADHD is an extreme expression of one or more continuous heritable traits.
Improving the value of public RNA-seq expression data by phenotype prediction
Authors: Ellis Shannon E. , Collado-Torres Leonardo , Leek Jeffrey T.
Published: June 2017

Background

Publicly available genomic data are a valuable resource for studying normal human variation and disease, but these data are often not well labeled or annotated. The lack of phenotype information for public genomic data severely limits their utility for addressing targeted biological questions.

Results

We develop anin silico phenotypingapproach for predicting critical missing annotation directly from genomic measurements using, well-annotated genomic and phenotypic data produced by consortia like TCGA and GTEx as training data. We applyin silico phenotypingto a set of 70,000 RNA-seq samples we recently processed on a common pipeline as part of therecount2project (https://jhubiostatistics.shinyapps.io/recount/). We use gene expression data to build and evaluate predictors for both biological phenotypes (sex, tissue, sample source) and experimental conditions (sequencing strategy). We demonstrate how these predictions can be used to study cross-sample properties of public genomic data, select genomic projects with specific characteristics, and perform downstream analyses using predicted phenotypes. The methods to perform phenotype prediction are available in thephenopredictR package (https://github.com/leekgroup/phenopredict) and the predictions forrecount2are available from therecountR package (https://bioconductor.org/packages/release/bioc/html/recount.html)

Conclusion

Having leveraging massive public data sets to generate a well-phenotyped set of expression data for more than 70,000 human samples, expression data is available for use on a scale that was not previously feasible.
Chondroitin Sulfate Flourishes Gut Sulfatase-Secreting Bacteria To Damage Mucus Layers, Leak Bacterial Debris, And Trigger Inflammatory Lesions In Mice
Authors: Liao Tao , Chen Yan-Ping , Tan Li-Li , Li Chang-Qing , Wang Qi , Huang Shui-Qing , Huang Xin-An , Xu Qin , Zeng Qing-Ping
Published: June 2017

Background

An interaction of the food types with the gut microbiota changes is deeply implicated in human health and disease. To verify whether animal-based diets would lead to gut dysbiosis, systemic inflammation and inflammatory pathogenesis, we fed mice with chondroitin sulfate (CS), a sulfate-containingO-glycan naturally occurring in livestock and poultry products, and monitored the dynamic changes of microbial flores, inflammatory signatures, and pathogenic hallmarks.

Results

A metagenomic gut microbiota analysis revealed the overgrowth of sulfatase-secreting bacteria and sulfate-reducing bacteria in the gastrointestinal tracts of mice upon daily CS feeding. Sulfatase-secreting bacteria compromise gut integrity through prompting mucin degradation and mucus lesions, which were evident from the upregulation of secretary leukocyte protease inhibitor (SLPI) and mucin 1/4 (MUC-1/4). A synchronous elevation of lipopolysaccharide (LPS) and tumor necrosis factor α (TNF-α) levels in the serum as well as cerebral, hepatic, cardiac and muscular tissues suggests bacterial endotoxinemia, chronic low-grade inflammation and mitochondrial dysfunction, eventually leading to the onset of global inflammatory pathogenesis towards arthritis, dementia, tumor, and fatty liver.

Conclusions

CS triggers the early-phase and multi-systemic pathogenesis like arthritis, dementia, tumor, and fatty liver by enhancing gut opportunistic infection and evoking low-grade inflammation in mice. A plausible reason for the inconsistency of CS in treatment of osteoarthritis (OA) was also discussed.
Tandem histone-binding domains enhance the activity of a synthetic chromatin effector
Authors: Tekel Stefan J. , Vargas Daniel , Song Lusheng , LaBaer Joshua , Haynes Karmella A.
Published: June 2017

Fusion proteins that specifically interact with biochemical marks on chromosomes represent a new class of synthetic transcriptional regulators that decode cell state information rather than DNA sequences. In multicellular organisms, information relevant to cell state, tissue identity, and oncogenesis is often encoded as biochemical modifications of histones, which are bound to DNA in eukaryotic nuclei and regulate gene expression states. We have previously reported the development and validation of the “Polycomb-based transcription factor” (PcTF), a fusion protein that recognizes histone modifications through a protein-protein interaction between its polycomb chromodomain (PCD) motif and trimethylated lysine 27 of histone H3 (H3K27me3) at genomic sites. We demonstrated that PcTF activates genes at methyl-histone-enriched loci in cancer-derived cell lines. However, PcTF induces modest activation of a methyl-histone associated reporter compared to a DNA-binding activator. Therefore, we modified PcTF to enhance its target affinity. Here, we demonstrate the activity of a modified regulator called Pc2TF, which has two tandem copies of the H3K27me3-binding PCD at the N-terminus. Pc2TF shows higher affinity for H3K27me3in vitroand shows enhanced gene activation in HEK293 cells compared to PcTF. These results provide compelling evidence that the intrinsic histone-binding activity of the PCD motif can be used to tune the activity of synthetic histone-binding transcriptional regulators.
Widespread signatures of negative selection in the genetic architecture of human complex traits
Authors: Zeng Jian , de Vlaming Ronald , Wu Yang , Robinson Matthew R , Lloyd-Jones Luke , Yengo Loic , Yap Chloe , Xue Angli , Sidorenko Julia , McRae Allan F , Powell Joseph E , Montgomery Grant W , Metspalu Andres , Esko Tonu , Gibson Greg , Wray Naomi R , Visscher Peter M , Yang Jian
Published: June 2017

Estimation of the joint distribution of effect size and minor allele frequency (MAF) for genetic variants is important for understanding the genetic basis of complex trait variation and can be used to detect signature of natural selection. We develop a Bayesian mixed linear model that simultaneously estimates SNP-based heritability, polygenicity (i.e. the proportion of SNPs with nonzero effects) and the relationship between effect size and MAF for complex traits in conventionally unrelated individuals using genome-wide SNP data. We apply the method to 28 complex traits in the UK Biobank data (N= 126,752), and show that on average across 28 traits, 6% of SNPs have nonzero effects, which in total explain 22% of phenotypic variance. We detect significant (p < 0.05/28 =1.8×10−3) signatures of natural selection for 23 out of 28 traits including reproductive, cardiovascular, and anthropometric traits, as well as educational attainment. We further apply the method to 27,869 gene expression traits (N= 1,748), and identify 30 genes that show significant (p < 2.3×10−6) evidence of natural selection. All the significant estimates of the relationship between effect size and MAF in either complex traits or gene expression traits are consistent with a model of negative selection, as confirmed by forward simulation. We conclude that natural selection acts pervasively on human complex traits shaping genetic variation in the form of negative selection.
GOLabeler: Improving Sequence-based Large-scale Protein Function Prediction by Learning to Rank
Authors: You Ronghui , Zhang Zihan , Xiong Yi , Sun Fengzhu , Mamitsuka Hiroshi , Zhu Shangfeng
Published: June 2017

Motivation: Gene Ontology (GO) has been widely used to annotate functions of proteins and understand their biological roles. Currently only ¡1% of more than 70 million proteins in UniProtKB have experimental GO annotations, implying the strong necessity of automated function prediction (AFP) of proteins, where AFP is a hard multi-label classification problem due to one protein with a diverse number of GO terms. Most of these proteins have only sequences as input information, indicating the importance of sequence-based AFP (SAFP: sequences are the only input). Furthermore, homology-based SAFP tools are competitive in AFP competitions, while they do not necessarily work well for so-calleddifficultproteins, which have ¡60% sequence identity to proteins with annotations already. Thus, the vital and challenging problem now is to develop a method for SAFP, particularly for difficult proteins.

Methods: The key of this method is to extract not only homology information but also diverse, deep-rooted information/evidence from sequence inputs and integrate them into a predictor in an efficient and also effective manner. We propose GOLabeler, which integrates five component classifiers, trained from different features, including GO term frequency, sequence alignment, amino acid trigram, domains and motifs, and biophysical properties, etc., in the framework of learning to rank (LTR), a new paradigm of machine learning, especially powerful for multi-label classification.

Results: The empirical results obtained by examining GOLabeler extensively and thoroughly by using large-scale datasets revealed numerous favorable aspects of GOLabeler, including significant performance advantage over state-of-the-art AFP methods.

Contact:zhusf@fudan.edu.cn
Gene Regulatory Divergence Between Locally Adapted Ecotypes in Their Native Habitats
Authors: Gould Billie A. , Chen Yani , Lowry David B.
Published: June 2017

Local adaptation is a key driver of ecological specialization and the formation of new species. Despite its importance, the evolution of gene regulatory divergence among locally-adapted populations is poorly understood, especially how that divergence manifests in nature. Here, we evaluate gene expression divergence and allele-specific gene expression responses for locally-adapted coastal perennial and inland annual accessions of the yellow monkeyflower,Mimulus guttatus, in a field reciprocal transplant experiment. Overall, 6765 (73%) of surveyed genes were differentially expressed between coastal and inland habitats, while 7213 (77%) were differentially expressed between the coastal perennial and inland annual accessions. Further, 18% of transcripts had significant genotype x site (GxE) effects. Habitat-specific differential expression was found for 62% of the GxE transcripts (differential expression in one habitat, but not the other), while only 94 (∼5%) GxE transcripts had crossing reaction norms.Cis-regulatory variation was pervasive, affecting 79% (5532) of differentially expressed genes. We detectedtranseffects for 52% (3611) of differentially expressed genes. Consistent with the supergene hypothesis of chromosome inversion evolution, a locally adaptive inversion was enriched forcis-regulatory divergence. These results provide multiple new insights into the evolution of transcriptome-wide gene regulatory divergence and plasticity among locally adapted populations.