bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDK inhibitors reduce cell proliferation and reverse hypoxia-induced metastasis of neuroblastoma tumours in a chick embryo model
Authors: Swadi Rasha R. , Sampat Keerthika , Herrmann Anne , Losty Paul D. , See Violaine , Moss Diana J. 
Published: August 2018

AbstractNeuroblastoma is a paediatric cancer with a poor prognosis. This is in part due to the widespread metastasis at time of presentation, which is refractory to current treatment modalities. New therapeutic agents that can control not only tumour growth but also metastasis are urgently needed.One current therapeutic option used in the clinic is differentiation therapy with retinoic acid, where the terminal differentiation of the neuroblastoma cells reduces tumour growth in the primary tumour as well as at metastatic sites. However, retinoic acid only works in a subset of patients.We investigated the potential of CDK inhibitors on neuroblastoma cell differentiation, tumour progression and metastasis by utilising a 3R compliant cost effective preclinical chick embryo model. In both SK-N-AS and BE(2)C cell lines, when engrafted on the chorioallantoic membrane of chick embryos, we observed a reduction of tumour cell proliferation as well as a reduction in hypoxia preconditioning-driven metastasis by 60%. In addition, the expression of a panel of genes with known roles in metastasis, which increased upon hypoxia-preconditioning, was largely reduced by a CDK1 inhibitor. These results provide a promising alternative to currently existing therapies and might aid the development of new treatment protocols for retinoic acid-resistant patients.
ADP heptose, a novel pathogen-associated molecular pattern associated with Helicobacter pylori type 4 secretion
Authors: Pfannkuch Lennart , Hurwitz Robert , Traulsen Jan , Kosma Paul , Schmid Monika , Meyer Thomas F. 
Published: August 2018

AbstractThe gastric pathogen Helicobacter pylori activates the NF-κB pathway in human epithelial cells via the α-kinase 1 (Alpk1)–TIFA axis. We and others have previously shown that heptose 1,7-bisphosphate (HBP) acts as a pathogen-associated molecular pattern (PAMP). HBP is an intermediate of lipopolysaccharide (LPS) synthesis in H. pylori and other gram-negative bacteria. Deletion of the hldE (rfaE) gene encoding the enzyme responsible for HBP synthesis, as well as deletion of further upstream genes, causes loss of NF-κB stimulation by H. pylori, while deletion of the downstream phosphatase encoding gene gmhB does not. This has led to the conclusion that HBP is the PAMP responsible for NF-κB induction. Here, our attempts to identify HBP in lysates of H. pylori revealed surprisingly low amounts that fail to explain NF-κB activation. Instead, we identified ADP heptose, a major downstream metabolite of HdlE, as the predominant PAMP in H. pylori lysates, exhibiting ∼100-fold stronger activity compared to HBP. It therefore appears that synthesis of ADP heptose from HBP in H. pylori occurs independently of GmhB. The data lead us to conclude that ADP heptose constitutes the key PAMP, secreted via the pathogen’s cagPAI encoded type 4 secretion (T4SS).
Is Actin Filament and Microtubule Growth Reaction- or Diffusion-Limited?
Authors: Pausch J. , Pruessner G. 
Published: August 2018

AbstractInside cells of living organisms, actin filaments and microtubules self-assemble and dissemble dynamically by incorporating actin or tubulin from the cell plasma or releasing it into their tips’ surroundings. Such reaction-diffusion systems can show diffusionor reaction-limited behaviour. However, neither limit explains the experimental data: while the offset of the linear relation between growth speed and bulk tubulin density contradicts the diffusion limit, the surprisingly large variance of the growth speed rejects a pure reaction limit. In this Letter, we accommodate both limits and use a Doi-Peliti field-theory model to estimate how diffusive transport is perturbing the chemical reactions at the filament tip. Furthermore, a crossover bulk density is predicted at which the limiting process changes from chemical reactions to diffusive transport. In addition, we explain and estimate larger variances of the growth speed.
Aperture Phase Modulation with Adaptive Optics: A Novel Approach for Speckle Reduction and Structure Extraction in Optical Coherence Tomography
Authors: Zhang Pengfei , Manna Suman K. , Miller Eric B. , Jian Yifan , Meleppat Ratheesh Kumar , Sarunic Marinko V. , Pugh Edward N. , Zawadzki Robert J. 
Published: August 2018

Abstract:Speckle is an inevitable consequence of the use of coherent light in optical coherence tomography (OCT), and often acts as noise that obscures micro-structures of biological tissue. We here present a novel method of suppressing speckle noise intrinsically compatible with adaptive optics (AO) in OCT system: by modulating the phase inside the imaging system pupil aperture with a segmented deformable mirror, thus producing minor perturbations in the point spread function (PSF) to create un-correlated speckle pattern between B-scans, and further averaging to wash out the speckle but maintain the structures. It is a well-controlled and universal method which can efficiently determine the optimal range of phase modulation that minimizing speckle noise while maximizing image resolution and signal strength for different systems and/or samples. As an active method, its effectiveness and efficiency were demonstrated by both ex-vivo non-biological and in-vivo biological applications.
Understanding visual attention with RAGNAROC: A Reflexive Attention Gradient through Neural AttRactOr Competition
Authors: Wyble Brad , Callahan-Flintoft Chloe , Chen Hui , Marinov Toma , Sarkar Aakash , Bowman Howard 
Published: August 2018

AbstractA quintessential challenge for any perceptual system is the need to focus on task-relevant information without being blindsided by unexpected, yet important information. The human visual system incorporates several solutions to this challenge, one of which is a reflexive covert attention system that is rapidly responsive to both the physical salience and the task-relevance of new information. This paper presents a model that simulates behavioral and neural correlates of reflexive attention as the product of brief neural attractor states that are formed across the visual hierarchy when attention is engaged. Such attractors emerge from an attentional gradient distributed over a population of topographically organized neurons and serve to focus processing at one or more locations in the visual field, while inhibiting the processing of lower priority information. The model moves towards a resolution of key debates about the nature of reflexive attention, such as whether it is parallel or serial, and whether suppression effects are distributed in a spatial surround, or selectively at the location of distractors. Most importantly, the model develops a framework for understanding the neural mechanisms of visual attention as a spatiotopic decision process within a hierarchy and links them to observable correlates such as accuracy, reaction time, and the N2pc and PDcomponents of the EEG. This last contribution is the most crucial for repairing the disconnect that exists between our understanding of behavioral and neural correlates of attention.
Diatoms diversify and turn over faster in freshwater than marine environments
Authors: Nakov Teofil , Beaulieu Jeremy Michael , Alverson Andrew James 
Published: August 2018

AbstractMany clades that span the marine-freshwater boundary are disproportionately more diverse in the younger, shorter-lived, and scarcer freshwater environments than they are in the marine realm. This disparity is thought to be related to differences in diversification rates between marine and freshwater lineages. However, marine and freshwaters are not ecologically homogeneous, so the study of diversification across the salinity divide should also account for other potentially interacting variables. In diatoms, freshwater and substrate-associated (benthic) lineages are several-fold more diverse than their marine and suspended (planktonic) counterparts. These imbalances provide an excellent system to understand whether these variables interact with diversification. Using multistate hidden-state speciation and extinction models we found that freshwater lineages diversify faster than marine lineages regardless of whether they inhabit the plankton or the benthos. Freshwater lineages also had higher turnover rates (speciation + extinction), suggesting that habitat transitions impact speciation and extinction rates jointly. The plankton-benthos contrast was also consistent with state-dependent diversification, but with modest differences in diversification and turnover rates. Asymmetric, and bidirectional transitions rejected hypotheses about the plankton and freshwaters as absorbing, inescapable habitats. Our results further suggest that the high turnover rate of freshwater diatoms is related to high turnover of freshwater systems themselves.
Plasticity of the electrical connectome ofC. elegans
Authors: Bhattacharya Abhishek , Aghayeva Ulkar , Berghoff Emily , Hobert Oliver 
Published: August 2018

AbstractThe patterns of electrical synapses of an animal nervous system (“electrical connectome”), as well as the functional properties and plasticity of electrical synapses, are defined by the neuron type-specific complement of electrical synapse constituents. We systematically examine here properties of the electrical connectome of the nematodeC. elegansthrough a genome- and nervous system-wide analysis of the expression pattern of the central components of invertebrate electrical synapses, the innexins, revealing highly complex combinatorial patterns of innexin expression throughout the nervous system. We find that the complex expression patterns of 12 out of 14 neuronally expressed innexins change in a strikingly neuron type-specific manner throughout most of the nervous system, if animals encounter harsh environmental conditions and enter the dauer arrest stage. We systematically describe the plasticity of locomotory patterns of dauer stage animals and, by analyzing several individual electrical synapses, we demonstrate that dauer stage-specific electrical synapse remodeling is responsible for specific aspects of the altered locomotory patterns as well as altered chemosensory behavior of dauer stage animals. We describe an intersectional gene regulatory mechanism, involving terminal selector and FoxO transcription factors that are responsible for inducing innexin expression changes in a neuron type- and environment-specific manner. Taken together, our studies illustrate the remarkably dynamic nature of electrical synapses on a nervous system-wide level and describe regulatory strategies for how these alterations are achieved.
Yes-associated protein (YAP) is required in maintaining normal ovarian follicle development and function
Authors: Plewes Michele R. , Hou Xiaoying , Zhang Pan , Wood Jennifer , Cupp Andrea , Davis John S. 
Published: August 2018

ABSTRACTYes-associated protein (YAP) is one of the major components of the Hippo signaling pathway, also known as the Salvador/Warts/Hippo (SWH) pathway. Although the exact extracellular signal that controls the Hippo pathway is currently unknown, increasing evidence supports a critical role of the Hippo pathway in embryonic development, regulation of organ size, and carcinogenesis. The ovary is one of few adult tissues that exhibit cyclical changes. Ovarian follicles, the basic units of ovary, are composed of a single oocyte surrounded by expanding layers of granulosa and theca cells. Granulosa cells (GCs) produce sex steroids and growth factors, which facilitate the development of the follicle and maturation of the oocyte. It has been reported that YAP is highly expressed in human GC tumors, but the role of YAP in normal ovarian follicle development is largely unknown. In current study, we examined YAP expression in bovine ovaries. We demonstrate that downstream hippo signaling effector protein, YAP and transcription co-activator, TAZ, are present and localization of both YAP and TAZ are density-dependent. Likewise, YAP and TAZ are critically involved in granulosa cell proliferation. Furthermore, reducing YAP in granulosa cells inhibits FSH-induced aromatase expression and estradiol biosynthesis. The data suggest that YAP plays an important role in the development of ovarian follicles and estradiol synthesis, which are necessary for maintaining normal ovarian function.
Stepping up to Teaching in Business: Understanding Teaching Effectiveness for Small Classes
Authors: Paladino Angela 
Published: August 2018

AbstractThis article provides those teaching in small classes in an Australian tertiary environment with some recommendations on how to get started and tips for effective teaching. The focus of the advice is on small class teaching, which is generally comprised of fewer than 30 students. The tips presented are centred on being organised, understanding your content and your students, generating engagement and norms for participation, as well as investing in adaptable skill development. A seven step process to teaching effectiveness is reviewed. These tips provide teachers with foundational knowledge that can be transferred to teaching large classes.
The Longitudinal Surveys of Australian Youth: 20 Years and Beyond
Authors: Parvazian Somayeh , Semo Ronnie 
Published: August 2018

AbstractThe Longitudinal Surveys of Australian Youth (LSAY) follow several cohorts of young Australians as they move through secondary school, into further study, work and other destinations. The LSAY datasets provide an evidence‐based capacity for sophisticated exploration of policy and research questions through insights into individual changes, transitions and trajectories across the life‐course of young Australians. This article aims to provide an update on the progress of LSAY, including its history, evolution of the sample, sample maintenance activities, updates to the information collected, developments to the survey, the many uses that have been made of the data and possible enhancements.
The Economic Consequences of Mr Trump
Authors: Corden Max , Garnaut Ross 
Published: August 2018

AbstractThe Trump administration has embarked upon two large economic policy initiatives at a time of full employment: increasing the budget deficit by cutting personal and corporate tax rates; and increasing protection, especially against countries with which the United States has bilateral trade deficits. These initiatives are meant to reduce trade deficits and increase employment and incomes in the US manufacturing sector. Economic analysis tells us that the result will be larger trade deficits, and weaker total tradeables, including manufacturing employment. There may or may not be a net gain for employment and incomes in those industries which have been the greatest beneficiaries of protection. Trump's protection policies will damage incomes in the United States and the rest of the world; the damage will be greater if other countries retaliate or emulate. Alternative policies that compensate losers from free trade would give better results.
Insane Arsonists: An Early 21st Century Sample
Authors: Leong Gregory B. , Mueller Crystal , Feldsher Mendel 
Published: August 2018

AbstractWe studied all individuals (n = 41) who had been found not guilty by reason of insanity for arson and who were committed to a California state psychiatric hospital on October 1, 2016 in a cross‐sectional analysis. This group of insane arsonists contained 33 (80.5%) males and eight (19.5%) females with a mean age at the time of the index arson of 35.9 years. At least 87.8% (n = 36) were considered to not have been participating in psychiatric treatment at the time of the index arson. Five (12.2%) of the insane arsonists had previously been found not guilty by reason of insanity for arson or had been convicted of having committed arson. Our findings suggest that lack of participation in psychiatric treatment was the most important factor in contributing to the index arson and the most important problem to be addressed in subsequent psychiatric treatment plans.
Impact of PD‐L1, transforming growth factor‐β expression and tumor‐infiltrating CD8+ T cells on clinical outcome of patients with advanced thymic epithelial tumors
Authors: Duan Jianchun , Liu Xidong , Chen Han , Sun Yu , Liu Yiqiang , Bai Hua , Wang Jie 
Published: August 2018

BackgroundAdvanced thymic epithelial tumors (TETs) are indolent and poorly responsive to chemotherapy. PD‐1/PD‐L1 inhibitors have shown remarkable clinical benefit in several cancers; however, many immunomodulatory molecules have been identified that affect the immune response. This study examined the progonostic roles of PD‐L1, transforming growth factor‐β (TGF‐β), and CD8+ tumor‐infiltrating lymphocytes (CD8+ TILs) in patients with TETs.MethodsRetrospective analysis was performed on the data of 20 patients with stage IV thymic carcinoma and 13 with stage III/IV invasive thymoma. Tissue biopsies were obtained before first‐line chemotherapy was administered. Protein levels were assessed by immunohistochemistry. Objective response rate, overall survival (OS), and progression‐free survival (PFS) were analyzed.ResultsPatients with advanced thymic carcinoma exhibited higher levels of PD‐L1 and TGF‐β than patients with advanced invasive thymic carcinoma (PD‐L1: 65.0% vs. 46.2%, P = 0.472; TGF‐β: 65.0% vs. 15.4%, P = 0.011). Five advanced thymic carcinoma patients with low levels of PD‐L1 and TGF‐β exhibited high levels of CD8 staining. The median OS was 29.5 months patients with high TGF‐β expression versus 62.9 in patients with low TGF‐β (P = 0.052). In patients with advanced thymic carcinoma, the median PFS in the high PD‐L1 expression group was 13.3 months versus 23.5 (P = 0.043) in the low PD‐L1, and the median OS was 50.7 months in the high CD8 expression versus 15.1 in the CD8 low group (P = 0.154).ConclusionsOur results showed the prognostic roles of PD‐L1, TGF‐β, and CD8+ TILs in patients with advanced TETs, and the potential for development of anti‐PD‐1/PD‐L1 therapies.
Assessing adequacy of models of phyletic evolution in the fossil record
Authors: Voje Kjetil Lysne 
Published: August 2018

Abstract

Comparing relative fit of different models of evolutionary dynamics to time series of phyletic change is a common tool when interpreting the fossil record. However, a measure of relative fit is no guarantee the preferred model describes the data well. Selecting a good model is essential for robust inferences, but we are currently lacking tools to investigate if a model of phyletic evolution represents an adequate description of trait dynamics in fossil data.

This study develops a general statistical framework implemented in R for assessing the adequacy of the three most commonly used models of evolution in the fossil record; stasis, directional change and random walk. The statistical framework is applied to 300 fossil time series in order to assess how often the three models represent adequate descriptions of evolutionary dynamics in the fossil record.

The model that showed the best relative fit to a particular fossil time series (using AICc) passed all adequacy tests in 219 out of 300 cases (73%, directional trend = 76%, stasis = 64%, random walk = 81%). It is therefore not uncommon that the best model according to AICc does not adequately describe the trait dynamics in a fossil time series.

Statistical tests of model adequacy ease evaluation of whether a particular model is a good descriptor of phyletic evolution and can assist in making meaningful inferences of model parameters (e.g., as rates of evolution) and interpretations of evolution in the fossil record.
Not all data are equal: Influence of data type and amount in spatial conservation prioritisation
Authors: Kujala Heini , Lahoz‐Monfort José Joaquín , Elith Jane , Moilanen Atte 
Published: August 2018

AbstractDecisions about land use significantly influence biodiversity globally. The field of spatial conservation prioritisation explores allocation of conservation effort, including for reserve network expansion, targeting habitat restoration, or minimising ecological impacts of development. Inevitably, the utility of such planning depends on the quantity and quality input data, including spatial information on biodiversity, threats, and cost of action. In this work we systematically develop understanding about the significance of these different data types in spatial conservation prioritisation.We clarify the common ways different data types enter an analysis, develop mathematical models to understand the effects of data in spatial prioritisation, and survey literature to establish typical quantities of different types of data used. We use Jackknife analysis to derive the expected change in site values, when a single new data layer is added to a prioritisation. We validate mathematical formulae for expected impacts using simulations.A survey of scientific literature reveals that typical spatial prioritisation analyses include hundreds of biodiversity feature layers (species, habitat types, ecosystem services), but the count of cost, threat or habitat condition layers is typically 0–5. Due to these differences, and the mathematical formulations commonly used to combine data types, the influence of a single cost, threat, or habitat condition data layer can be an order or two higher than the influence of a single biodiversity feature layer. In a classical cost‐effectiveness formulation (benefits divided by costs, B/C) the influence of a single cost layer can even be as large as the joint influence of thousands of species distributions. We also clarify how changes in data impact site values and spatial priority rankings differently, with the latter being further influenced by data correlations, the spread of numeric values inside data layers and other data characteristics. For example, costs influence priorities significantly if cost is positively correlated with biodiversity, but the correlation is the other way around for biodiversity and habitat condition.This work helps conservation practitioners to direct efforts when collating data for spatial conservation planning. It also helps decision makers understand where to focus attention when interpreting conservation plans and their uncertainties.
Inflammaging impairs peripheral nerve maintenance and regeneration
Authors: Büttner Robert , Schulz Alexander , Reuter Michael , Akula Asha K. , Mindos Thomas , Carlstedt Annemarie , Riecken Lars B. , Baader Stephan L. , Bauer Reinhard , Morrison Helen 
Published: August 2018

AbstractThe regenerative capacity of peripheral nerves declines during aging, contributing to the development of neuropathies, limiting organism function. Changes in Schwann cells prompt failures in instructing maintenance and regeneration of aging nerves; molecular mechanisms of which have yet to be delineated. Here, we identified an altered inflammatory environment leading to a defective Schwann cell response, as an underlying mechanism of impaired nerve regeneration during aging. Chronic inflammation was detected in intact uninjured old nerves, characterized by increased macrophage infiltration and raised levels of monocyte chemoattractant protein 1 (MCP1) and CC chemokine ligand 11 (CCL11). Schwann cells in the old nerves appeared partially dedifferentiated, accompanied by an activated repair program independent of injury. Upon sciatic nerve injury, an initial delayed immune response was followed by a persistent hyperinflammatory state accompanied by a diminished repair process. As a contributing factor to nerve aging, we showed that CCL11 interfered with Schwann cell differentiation in vitro and in vivo. Our results indicate that increased infiltration of macrophages and inflammatory signals diminish regenerative capacity of aging nerves by altering Schwann cell behavior. The study identifies CCL11 as a promising target for anti‐inflammatory therapies aiming to improve nerve regeneration in old age.