bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intake of dietary fiber, fruits, and vegetables, and risk of diverticulitis
Authors: Ma Wenjie , Nguyen Long H. , Song Mingyang , Jovani Manol , Liu Po-Hong , Cao Yin , Tam Idy , Wu Kana , Giovannucci Edward L. , Strate Lisa L. , Chan Andrew T. 
Published: December 2018

ABSTRACTBackground & AimsAlthough low fiber intake has been considered a risk factor for diverticulitis, prospective evidence is limited and conflicting, with little known about variation in the protective effects according to food sources. We assessed the associations of intakes of fiber and major food sources of fiber including fruits and vegetables with risk of diverticulitis.MethodsWe followed 50,019 women in the Nurses’ Health Study (1990-2014) and 48,292 men in the Health Professionals Follow-up Study (1986-2014) who were free of diverticulitis, cancer, and inflammatory bowel disease at baseline. Incident diverticulitis was identified through self-report with validity confirmed by review of medical records.ResultsDuring a mean follow-up time of 22 years, we documented 4,343 incident cases of diverticulitis in women and 1,142 cases in men. Compared to participants in the lowest quintile, the multivariable HRs (95% CIs) of diverticulitis in the highest quintile of total fiber intake were 0.86 (0.78-0.95;P-trend=0.002) among women and 0.63 (0.51-0.79;P-trend<0.001) among men. Fiber from different food sources, except for vegetable fiber in women, was associated with a decreased risk of diverticulitis. Furthermore, total whole fruit intake was associated with reduced risk of diverticulitis in both cohorts with a multivariable HR for diverticulitis of 0.95 (0.92-0.98;P-trend<0.001) in women and 0.91 (0.86-0.96;P-trend<0.001) in men for every serving increase of total whole fruit intake per day.ConclusionsHigher intake of dietary fiber and fiber from different food sources are associated with a lower risk of diverticulitis. A greater intake of whole fruit is also associated with reduced risk.
CCN4 shifts melanoma cells from a fragile proliferative state to a resilient metastatic state
Authors: Deng Wentao , Fernandez Audry , McLaughlin Sarah L. , Klinke David J. 
Published: December 2018

ABSTRACTWhile deregulated intracellular signaling initiates melanoma, intercellular crosstalk within the tumor microenvironment, often coordinated by soluble factors, is essential for melanoma progression and metastasis. One such secreted matricellular protein, cellular communication network factor 4 (CCN4), stimulates metastasis in other malignancies. Here, we report that CCN4 expression is associated progressively with reduced overall survival in patients with primary melanomas. To reveal the roles of CCN4 in melanoma progression, we used mouse melanoma models and knocked outCcn4using a homology-directed repair CRISPR/CAS9 system to generate pools ofCcn4-knockout cells.In vitroassays supported previous findings using clones generated using a double nickase-based CRISPR/CAS9 system that CCN4 promoted an epithelial – mesenchymal-like transition in melanoma cells and stimulated invasion and metastasis. We also found that, whileCcn4knockout enhanced cell growth in optimal 2D culture conditions, the knockout suppressed certain cell survival signaling pathways and rendered cells less resistant to stress conditions. Tumor cell growth assays at sub-optimal conditionsin vitro, quantitative analysis of tumor growth assaysin vivo,and transcriptomics analysis of human melanoma cell lines suggested that CCN4 repressed cell growth and simultaneously enhanced cell survival. The collective role of CCN4 suggests a potential therapeutic target for limiting metastatic invasion in melanoma and a biomarker for metastatic potential.
Mutations In PIK3C2A Cause Syndromic Short Stature, Skeletal Abnormalities, and Cataracts Associated With Ciliary Dysfunction
Authors: Tiosano Dov , Feldman Hagit Baris , Chen Anlu , Hitzert Marrit M. , Schueler Markus , Gulluni Federico , Wiesener Antje , Bergua Antonio , Mory Adi , Copeland Brett , Gleeson Joseph G. , Rump Patrick , van Meer Hester , Sival Deborah A. , Haucke Volker , Kriwinsky Josh , Knaup Karl X. , Reis André , Hauer Nadine N. , Hirsch Emilio , Roepman Ronald , Pfundt Rolph , Thiel Christian T. , Wiesener Michael S. , Aslanyan Mariam G. , Buchner David A. 
Published: December 2018

AbstractPIK3C2A is a class II member of the phosphoinositide 3-kinase (PI3K) family that catalyzes the phosphorylation of phosphatidylinositol (PI) into PI(3)P and the phosphorylation of PI(4)P into PI(3,4)P2. We identified homozygous loss-of-function mutations in PIK3C2A in children from three independent consanguineous families with short stature, coarse facial features, cataracts with secondary glaucoma, multiple skeletal abnormalities, neurological manifestations, among other findings. Cellular studies of patient-derived fibroblasts found that they lacked PIK3C2A protein, had impaired cilia formation and function, and demonstrated reduced proliferative capacity. Collectively, the genetic and molecular data implicate mutations in PIK3C2A in a new Mendelian disorder of PI metabolism, thereby shedding light on the critical role of a class II PI3K in growth, vision, skeletal formation and neurological development. This discovery expands what is known about disorders of PI metabolism and helps unravel the role of PIK3C2A and class II PI3Ks in health and disease.
The consensus molecular classification of muscle-invasive bladder cancer
Authors: Kamoun Aurélie , de Reyniès Aurélien , Allory Yves , Sjödahl Gottfrid , Robertson A. Gordon , Seiler Roland , Hoadley Katherine A. , Al-Ahmadie Hikmat , Choi Woonyoung , Groeneveld Clarice S. , Castro Mauro A. A. , Fontugne Jacqueline , Eriksson Pontus , Mo Qianxing , Kardos Jordan , Zlotta Alexandre , Hartmann Arndt , Dinney Colin P. , Bellmunt Joaquim , Powles Thomas , Malats Núria , Chan Keith S. , Kim William Y. , McConkey David J. , Black Peter C. , Dyrskjøt Lars , Höglund Mattias , Lerner Seth P. , Real Francisco X. , Radvanyi François ,   The Bladder Cancer Molecular Taxonomy Group
Published: December 2018

AbstractMuscle-Invasive Bladder Cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, yielding diverse sets of subtypes, which hampers the clinical implications of such knowledge. Here, we report the results of a large international effort to reach a consensus on MIBC molecular subtypes. Using 1750 MIBC transcriptomes and a network-based analysis of six independent MIBC classification systems, we identified a consensus set of six molecular classes: Luminal Papillary (24%), Luminal Non-Specified (8%), Luminal Unstable (15%), Stroma-rich (15%), Basal/Squamous (35%), and Neuroendocrine-like (3%). These consensus classes differ regarding underlying oncogenic mechanisms, infiltration by immune and stromal cells, and histological and clinical characteristics. This consensus system offers a robust framework that will enable testing and validating predictive biomarkers in future clinical trials.
Destabilizing evolutionary and eco-evolutionary feedbacks drive empirical eco-evolutionary cycles
Authors: Cortez Michael H. , Patel Swati , Schreiber Sebastian J. 
Published: December 2018

ABSTRACTWe develop a method to identify how ecological, evolutionary, and eco-evolutionary feedbacks influence system stability. We apply our method to nine empirically-parameterized eco-evolutionary models of exploiter-victim systems from the literature and identify which particular feedbacks cause some systems to converge to a steady state or to exhibit sustained oscillations. We find that ecological feedbacks involving the interactions between all species and evolutionary and eco-evolutionary feedbacks involving only the interactions between exploiter species (predators or pathogens) are typically stabilizing. In contrast, evolutionary and eco-evolutionary feedbacks involving the interactions between victim species (prey or hosts) are destabilizing more often than not. We also find that while eco-evolutionary feedbacks rarely altered system stability from what would be predicted from just ecological and evolutionary feedbacks, eco-evolutionary feedbacks have the potential to alter system stability at faster or slower speeds of evolution. As the number of empirical studies demonstrating eco-evolutionary feedbacks increases, we can continue to apply these methods to determine whether the patterns we observe are common in other empirical communities.
Engineering of chimeric polyketide synthases using SYNZIP docking domains
Authors: Klaus Maja , D’Souza Alicia D. , Nivina Aleksandra , Khosla Chaitan , Grininger Martin 
Published: December 2018

AbstractEngineering of assembly line polyketide synthases (PKSs) to produce novel bioactive compounds has been a goal for over twenty years. The apparent modularity of PKSs has inspired many engineering attempts in which entire modules or single domains were exchanged. In recent years, it has become evident that certain domain-domain interactions are evolutionarily optimized, and if disrupted, cause a decrease of the overall turnover rate of the chimeric PKS. In this study, we compared different types of chimeric PKSs in order to define the least invasive interface and to expand the toolbox for PKS engineering. We generated bimodular chimeric PKSs in which entire modules were exchanged, while either retaining a covalent linker between heterologous modules or introducing a non-covalent docking domain- or SYNZIP domain-mediated interface. These chimeric systems exhibited non-native domain-domain interactions during intermodular polyketide chain translocation. They were compared to otherwise equivalent bimodular PKSs in which a non-covalent interface was introduced between the condensing and processing parts of a module, resulting in non-native domain interactions during the extender unit acylation and polyketide chain elongation steps of their catalytic cycles. We show that the natural PKS docking domains can be efficiently substituted with SYNZIP domains and that the newly introduced non-covalent interface between the condensing and processing parts of a module can be harnessed for PKS engineering. Additionally, we established SYNZIP domains as a new tool for engineering PKSs by efficiently bridging non-native interfaces without perturbing PKS activity.
Computational exploration of molecular receptive fields in the olfactory bulb reveals a glomerulus-centric chemical map
Authors: Soelter Jan , Schumacher Jan , Spors Hartwig , Schmuker Michael 
Published: December 2018

AbstractProgress in olfactory research is currently hampered by incomplete knowledge about chemical receptive ranges of primary receptors. Moreover, the chemical logic underlying the arrangement of computational units in the olfactory bulb has still not been resolved. We undertook a large-scale approach at characterising molecular receptive ranges (MRRs) of glomeruli innervated by the MOR18-2 olfactory receptor in the dorsal olfactory bulb (dOB). Guided by an iterative approach that combined biological screening and machine learning, we selected 214 odorants to characterise the response of MOR18-2 and its neighbouring glomeruli. We discovered several previously unknown odorants activating MOR18-2 glomeruli, and we obtained detailed MRRs of MOR18-2 glomeruli and their neighbours. Physico-chemical MRR descriptions revealed that the spatial layout of glomeruli followed a chemical logic. Our results confirm earlier findings that demonstrate a partial chemical map underlying glomerular arrangement in the dOB. Moreover, our novel methodology that combines machine learning and physiological measurements lights the way towards future high-throughput studies to deorphanise and characterise structure-activity relationships in olfaction.
Fission Yeast Cells Grow Approximately Exponentially
Authors: Pickering Mary , Hollis Lauren Nicole , D’Souza Edridge , Rhind Nicholas 
Published: December 2018

ABSTRACTHow the rate of cell growth is influenced by cell size is a fundamental question of cell biology. The simple model that cell growth is proportional to cell size, based on the proposition that larger cells have proportionally greater synthetic capacity than smaller cells, leads to the predication that the rate of cell growth increases exponentially with cell size. However, other modes of cell growth, including bilinear growth, have been reported. The distinction between exponential and bilinear growth has been explored in particular detail in the fission yeastSchizosaccharomyces pombe. We have revisited the mode of fission yeast cell growth using high-resolution time-lapse microscopy and find, as previously reported, that these two growth models are difficult to distinguish both because of the similarity in shapes between exponential and bilinear curves over the two-fold change in length of a normal cell cycle and because of the substantial biological and experimental noise inherent to these experiments. Therefore, we contrived to have cells grow more than two fold, by holding them in G2 for up to eight hours. Over this extended growth period, in which cells grow up to 5.5-fold, the two growth models diverge to the point that we can confidently exclude bilinear growth as a general model for fission yeast growth. Although the growth we observe is clearly more complicated than predicted by simple exponential growth, we find that exponential growth is a robust approximation of fission yeast growth, both during an unperturbed cell cycle and during extended periods of growth.
Targeted genomic integration of EGFP under tubulin beta 3 class III promoter and mEos2 under tryptophan hydroxylase 2 promoter does not produce sufficient levels of reporter gene expression
Authors: Menzorov Aleksei G. , Orishchenko Konstantin E. , Fishman Veniamin S. , Shevtsova Anastasia A. , Mungalov Roman V. , Pristyazhnyuk Inna E. , Kizilova Elena A. , Matveeva Natalia M. , Alenina Natalia , Bader Michael , Rubtsov Nikolai B. , Serov Oleg L. 
Published: December 2018

AbstractNeuronal tracing is a modern technology that is based on the expression of fluorescent proteins under the control of cell type-specific promoters. However, random genomic integration of the reporter construct often leads to incorrect spatial and temporal expression of the marker protein. Targeted integration (or knock-in) of the reporter coding sequence is supposed to provide better expression control by exploiting endogenous regulatory elements. Here we describe the generation of two fluorescent reporter systems: EGFP under pan-neural marker class III β-tubulin (Tubb3) promoter and mEos2 under serotonergic neuron specific tryptophan hydroxylase 2 (Tph2) promoter. Differentiation of Tubb3-EGFP ES cells into neurons revealed that though Tubb3-positive cells express EGFP, its expression level is not sufficient for the neuronal tracing by routine fluorescent microscopy. Similarly, the expression levels of mEos2-TPH2 in differentiated ES cells was very low and could be detected only on mRNA level using PCR-based methods. Our data shows that the use of endogenous regulatory elements to control transgene expression is not always beneficial compared to random genomic integration.
Roles and responsibilities in integrated care for dementia
Authors: Robertshaw David , Cross Ainslea 
Published: December 2018

Purpose
Effective integrated healthcare systems require capable, trained workforces with leadership, shared governance and co-ordination. The purpose of this paper is to characterise roles and responsibilities in relation to integrated care from the perspective of massive open online course (MOOC) participants.

Design/methodology/approach
MOOC discussion board posts were analysed using framework analysis consisting of transcription, familiarisation, coding, developing an analytical framework and application of the framework.

Findings
Boundaries and key issues surrounding roles and responsibilities were highlighted and participants suggested a number of enablers which could enhance integrated care in addition to barriers to consider and overcome.

Originality/value
Enablers included introduction of shared communication and IT systems to support continuity of care. Awareness and understanding of dementia was seen as crucial to promote person-centred care and care planning. The roles of education and experience were highlighted. Barriers preventing effective roles and suitable responsibility include funding, role conflicts, time constraints and time-consuming paperwork.
Arguing about Indigenous administrative participation in the Whitlam era: A representation theory analysis
Authors: Ganter Elizabeth 
Published: December 2018

AbstractIn 1974 Prime Minister Gough Whitlam established the Royal Commission on Australian Government Administration (‘the Commission’), appointing HC Coombs as chair. The Commission's brief was ‘to inquire into and report on the administrative organization and services of the Australian Government’ giving particular attention to, among other issues, public servants’ ‘participation in forming policy and making decisions’. From the outset the Commission aligned itself with the view that Aboriginal people were ‘less than proportionately represented in the administration’. The Commission asked CD Rowley to prepare a report on Aboriginal issues. Barrie Dexter, Secretary of the newly established Department of Aboriginal Affairs and Charles Perkins, Assistant Secretary and Arrernte man from Central Australia, both gave evidence to the Commission. The competing ideas on Indigenous administrative participation expressed by Coombs, Rowley, Dexter and Perkins in the course of the Commission will be considered through the lens of representation theory. While all four doubted the capacity of the bureaucracy to provide a meaningful channel for Indigenous representation internally, each argued from a different view of representation. Understanding their positions on how Indigenous people should be represented in public administration, including their assumption that there would also be external Indigenous representation, could shed light on tensions that are still present today.
Recalibrating the machinery of government for Indigenous affairs: Towards a new policy design for self‐determination
Authors: Perche Diana 
Published: December 2018

AbstractRelations between First Nations and the Commonwealth government are in a parlous state in Australia, and the Commonwealth government's response to the Uluru Statement from the Heart has prompted much criticism from First Nations leaders. This paper examines the impact of one of the significant changes made by the Abbott government, the machinery of government change placing Indigenous Affairs into the Department of Prime Minister and Cabinet, with a Minister for Indigenous Affairs sitting in Cabinet. It considers the rationale for the move and explores the implications of the loss of a ‘shadow team’ function and the placement of a sensitive portfolio in the highly politicised environment of a central agency. Given that the current governance arrangements are not ‘fit for purpose’, the paper notes the call by First Nations organisations in the Redfern Statement for the establishment of a stand‐alone Department of Aboriginal and Torres Strait Islander Affairs, and recommends adoption of this as a partial government response to demands for First Nations self‐determination.
Orofacial neuralgia associated with a middle cerebral artery aneurysm
Authors: Mascarenhas RJ , Hapangama ND , Mews PJ , Burlakoti A , Ranjitkar S 
Published: December 2018

AbstractChronic orofacial pain of neuropathic origin can present diagnostic and management dilemmas to dental practitioners and also affects the patient's quality of life. Intracranial aneurysms are a potential cause of stroke (e.g. sub‐arachnoid haemorrhage) that is usually associated with, high rates of mortality and morbidity. A patient who had been previously managed for symptoms of temporomandibular joint disorder (TMD) presented with sharp, shooting pain of moderate intensity. It was precipitated by swallowing, and radiated to the right throat, posterior border of the mandible, ear and temporomandibular joint. Clinical and radiological investigations ruled out odontogenic pain, TMD and other more common types of facial pain. Magnetic resonance imaging revealed a 7 × 6 mm aneurysm in the right middle cerebral artery (MCA) which was subsequently surgically clipped. Interestingly, the facial pain resolved after this procedure. Compression of the insular region of the brain innervated by the trigeminal, glossopharyngeal and vagus nerves provides a plausible explanation for the pain reported. To our knowledge, this is the first case of facial neuralgia associated with an aneurysm in the MCA which emphasizes the importance of a multidisciplinary approach in the diagnosis and management of unusual cases of chronic orofacial pain.
Parasite in peril? A new species of mite in the genus Ophiomegistus Banks (Parasitiformes: Paramegistidae) on an endangered host, the pygmy bluetongue lizard Tiliqua adelaidensis (Peters) (Squamata: Scincidae)
Authors: Derne Bonnie T. , Hutchinson Mark N. , Weinstein Philip , Gardner Michael G. , Halliday Bruce 
Published: December 2018

AbstractHost‐parasite relationships are generally understudied in wild populations but have a potential to influence host population dynamics and the broader ecosystem, which becomes particularly important when the host is endangered. Herein we describe a new species of parasitic mite from the genus Ophiomegistus (Parasitiformes: Mesostigmata: Paramegistidae) of an endangered South Australian skink; the pygmy bluetongue lizard (Tiliqua adelaidensis). Adult mites were observed on lizard hosts in three different host populations, among which prevalence varied. No temporal trend in prevalence was evident over two spring‐summer seasons of monitoring. We hypothesise that the reliance on burrows as refuges by T. adelaidensis may be essential for the completion of the mite life cycle and also for horizontal transmission. The conservation implications of not only its effect on the host, but also its potential status as an endangered species itself, are considered.