bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism
Authors: Du Weinan , Zhang Luchang , Brett-Morris Adina , Aguila Brittany , Kerner Janos , Hoppel Charles L. , Puchowicz Michelle , Serra Dolors , Herrero Laura , Rini Brian I. , Campbell Steven , Welford Scott M. 
Published: November 2017

AbstractClear cell renal cell carcinoma (ccRCC) is histologically defined by its lipid and glycogen-rich cytoplasmic deposits. Alterations in the VHL tumor suppressor stabilizing the hypoxia-inducible factors (HIFs) are the most prevalent molecular features of clear cell tumors. The significance of lipid deposition remains undefined. We describe the mechanism of lipid deposition in ccRCC by identifying the rate-limiting component of mitochondrial fatty acid transport, carnitine palmitoyltransferase 1A (CPT1A), as a direct HIF target gene. CPT1A is repressed by HIF1 and HIF2, reducing fatty acid transport into the mitochondria, and forcing fatty acids to lipid droplets for storage. Droplet formation occurs independent of lipid source, but only when CPT1A is repressed. Functionally, repression of CPT1A is critical for tumor formation, as elevated CPT1A expression limits tumor growth. In human tumors, CPT1A expression and activity are decreased versus normal kidney; and poor patient outcome associates with lower expression of CPT1A in tumors in TCGA. Together, our studies identify HIF control of fatty acid metabolism as essential for ccRCC tumorigenesis.
Elevated moisture stimulates carbon loss from mineral soils by releasing protected organic matter
Authors: Huang Wenjuan , Hall Steven J. 
Published: November 2017

AbstractMoisture response functions for soil microbial carbon (C) mineralization remain a critical uncertainty for predicting ecosystem-climate feedbacks. Theory and models posit that C mineralization declines under elevated moisture and associated anaerobic conditions, leading to soil C accumulation. Yet, iron (Fe) reduction potentially releases protected C, providing an under-appreciated mechanism for C destabilization under elevated moisture. Here we incubate Mollisols from ecosystems under C3/C4plant rotations at moisture levels at and above field capacity over 5 months. Increased moisture and anaerobiosis initially suppress soil C mineralization, consistent with theory. However, after 25 days, elevated moisture stimulates cumulative gaseous C-loss as CO2and CH4to >150% of the control. Stable C isotopes show that mineralization of older C3-derived C released following Fe reduction dominates C losses. Counter to theory, elevated moisture may significantly accelerate C losses from mineral soils over weeks to months—a critical mechanistic deficiency of current Earth system models.
Oncogenic PIK3CA induces centrosome amplification and tolerance to genome doubling
Authors: Berenjeno Inma M. , Piñeiro Roberto , Castillo Sandra D. , Pearce Wayne , McGranahan Nicholas , Dewhurst Sally M. , Meniel Valerie , Birkbak Nicolai J. , Lau Evelyn , Sansregret Laurent , Morelli Daniele , Kanu Nnennaya , Srinivas Shankar , Graupera Mariona , Parker Victoria E. R. , Montgomery Karen G. , Moniz Larissa S. , Scudamore Cheryl L. , Phillips Wayne A. , Semple Robert K. , Clarke Alan , Swanton Charles , Vanhaesebroeck Bart 
Published: November 2017

AbstractMutations in PIK3CA are very frequent in cancer and lead to sustained PI3K pathway activation. The impact of acute expression of mutant PIK3CA during early stages of malignancy is unknown. Using a mouse model to activate the Pik3caH1047R hotspot mutation in the heterozygous state from its endogenous locus, we here report that mutant Pik3ca induces centrosome amplification in cultured cells (through a pathway involving AKT, ROCK and CDK2/Cyclin E-nucleophosmin) and in mouse tissues, and increased in vitro cellular tolerance to spontaneous genome doubling. We also present evidence that the majority of PIK3CAH1047R mutations in the TCGA breast cancer cohort precede genome doubling. These previously unappreciated roles of PIK3CA mutation show that PI3K signalling can contribute to the generation of irreversible genomic changes in cancer. While this can limit the impact of PI3K-targeted therapies, these findings also open the opportunity for therapeutic approaches aimed at limiting tumour heterogeneity and evolution.
International roadmap for artificial gravity research
Authors: Clément Gilles 
Published: November 2017

AbstractIn this paper, we summarize the current and future research activities that will determine the requirements for implementing artificial gravity (AG) to mitigate the effects of long duration exposure to microgravity on board exploration class space vehicles. NASA and its international partners have developed an AG roadmap that contains a common set of goals, objectives, and milestones. This roadmap includes both ground-based and space-based projects, and involves human subjects as well as animal and cell models. It provides a framework that facilitates opportunities for collaboration using the full range of AG facilities that are available worldwide, and a forum for space physiologists, crew surgeons, astronauts, vehicle designers, and mission planners to review, evaluate, and discuss the issues of incorporating AG technologies into the vehicle design.
Vertebrate food products as a potential source of prion-like α-synuclein
Authors: Killinger Bryan Andrew , Labrie Viviane 
Published: November 2017

AbstractThe aberrant aggregation of the protein α-synuclein is thought to be involved in Parkinson’s disease (PD). However, the factors that lead to initiation and propagation of α-synuclein aggregation are not clearly understood. Recently, the hypothesis that α-synuclein aggregation spreads via a prion-like mechanism originating in the gut has gained much scientific attention. If α-synuclein spreads via a prion-like mechanism, then an important question becomes, what are the origins of this prion-like species? Here we review the possibility that α-synuclein aggregation could be seeded via the ingestion of a prion-like α-synuclein species contained within food products originating from vertebrates. To do this, we highlight current evidence for the gut-to-brain hypothesis of PD, and put this in context of available routes of α-synuclein prion infectivity via the gastrointestinal (GI) tract. We then discuss meat as a ready exogenous source of α-synuclein and how certain risk factors, including inflammation, may allow for dietary α-synuclein to pass from the GI lumen into the host to induce pathology. Lastly, we review epidemiological evidence that dietary factors may be involved in PD. Overall, research to date has yet to directly test the contribution of dietary α-synuclein to the mechanism of initiation and progression of the disease. However, numerous experimental findings, including the potent seeding and spreading behavior of α-synuclein fibrils, seem to support, at least in part, the feasibility of an infection with a prion α-synuclein particle via the GI tract. Further studies are required to determine whether dietary α-synuclein contributes to seeding pathology in the gut.
Disulfide loop cleavage of Legionella pneumophila PlaA boosts lysophospholipase A activity
Authors: Lang Christina , Hiller Miriam , Flieger Antje 
Published: November 2017

AbstractL. pneumophila, an important facultative intracellular bacterium, infects the human lung and environmental protozoa. At least fifteen phospholipases A (PLA) are encoded in its genome. Three of which, namely PlaA, PlaC, and PlaD, belong to the GDSL lipase family abundant in bacteria and higher plants. PlaA is a lysophospholipase A (LPLA) that destabilizes the phagosomal membrane in absence of a protective factor. PlaC shows PLA and glycerophospholipid: cholesterol acyltransferase (GCAT) activities which are activated by zinc metalloproteinase ProA via cleavage of a disulphide loop. In this work, we compared GDSL enzyme activities, their secretion, and activation of PlaA. We found that PlaA majorly contributed to LPLA, PlaC to PLA, and both substrate-dependently to GCAT activity. Western blotting revealed that PlaA and PlaC are type II-secreted and both processed by ProA. Interestingly, ProA steeply increased LPLA but diminished GCAT activity of PlaA. Deletion of 20 amino acids within a predicted disulfide loop of PlaA had the same effect. In summary, we propose a model by which ProA processes PlaA via disulfide loop cleavage leading to a steep increase in LPLA activity. Our results help to further characterize the L. pneumophila GDSL hydrolases, particularly PlaA, an enzyme acting in the Legionella-containing phagosome.
Phosphoproteomics of cAMP signaling of Bordetella adenylate cyclase toxin in mouse dendritic cells
Authors: Novák Jakub , Fabrik Ivo , Linhartová Irena , Link Marek , Černý Ondřej , Stulík Jiří , Šebo Peter 
Published: November 2017

AbstractThe adenylate cyclase toxin (CyaA) of the whooping cough agent Bordetella pertussis subverts immune functions of host myeloid cells expressing the αMβ2 integrin (CD11b/CD18, CR3 or Mac-1). CyaA delivers into cytosol of cells an extremely catalytically active adenylyl cyclase enzyme, which disrupts the innate and adaptive immune functions of phagocytes through unregulated production of the key signaling molecule cAMP. We have used phosphoproteomics to analyze cAMP signaling of CyaA in murine bone marrow-derived dendritic cells. CyaA action resulted in alterations of phosphorylation state of a number of proteins that regulate actin cytoskeleton homeostasis, including Mena, Talin-1 and VASP. CyaA action repressed mTOR signaling through activation of mTORC1 inhibitors TSC2 and PRAS40 and altered phosphorylation of multiple chromatin remodelers, including the class II histone deacetylase HDAC5. CyaA toxin action further elicited inhibitory phosphorylation of SIK family kinases involved in modulation of immune response and provoked dephosphorylation of the transcriptional coactivator CRTC3, indicating that CyaA-promoted nuclear translocation of CRTC3 may account for CyaA-induced IL-10 production. These findings document the complexity of subversive physiological manipulation of myeloid phagocytes by the CyaA toxin, serving in immune evasion of the pertussis agent.
Understanding heat patterns produced by vehicular flows in urban areas
Authors: Zhu Rui , Wong Man Sing , Guilbert Éric , Chan Pak-Wai 
Published: November 2017

AbstractVehicular traffic has strong implication in the severity and degree of Urban Heat Island (UHI) effect in a city. It is crucial to map and monitor the spatio-temporal heat patterns from vehicular traffic in a city. Data observed from traffic counting stations are readily available for mapping the traffic-related heat across the stations. However, macroscopic models utilizing traffic counting data to estimate dynamic directional vehicular flows are rarely established. Our work proposes a simple and robust cell-transmission-model to simulate all the possible cell-based origin-destination trajectories of vehicular flows over time, based on the traffic counting stations. Result shows that the heat patterns have notable daily and weekly periodical circulation/pattern, and volumes of heat vary significantly in different grid cells. The findings suggest that vehicular flows in some places are the dominating influential factor that make the UHI phenomenon more remarkable.
In vivo evidence that RBM5 is a tumour suppressor in the lung
Authors: Jamsai Duangporn , Watkins D. Neil , O’Connor Anne E. , Merriner D. Jo , Gursoy Selen , Bird Anthony D. , Kumar Beena , Miller Alistair , Cole Timothy J. , Jenkins Brendan J. , O’Bryan Moira K. 
Published: November 2017

AbstractCigarette smoking is undoubtedly a risk factor for lung cancer. Moreover, smokers with genetic mutations on chromosome 3p21.3, a region frequently deleted in cancer and notably in lung cancer, have a dramatically higher risk of aggressive lung cancer. The RNA binding motif 5 (RBM5) is one of the component genes in the 3p21.3 tumour suppressor region. Studies using human cancer specimens and cell lines suggest a role for RBM5 as a tumour suppressor. Here we demonstrate, for the first time, an in vivo role for RBM5 as a tumour suppressor in the mouse lung. We generated Rbm5 loss-of-function mice and exposed them to a tobacco carcinogen NNK. Upon exposure to NNK, Rbm5 loss-of-function mice developed lung cancer at similar rates to wild type mice. As tumourigenesis progressed, however, reduced Rbm5 expression lead to significantly more aggressive lung cancer i.e. increased adenocarcinoma nodule numbers and tumour size. Our data provide in vivo evidence that reduced RBM5 function, as occurs in a large number of patients, coupled with exposure to tobacco carcinogens is a risk factor for an aggressive lung cancer phenotype. These data suggest that RBM5 loss-of-function likely underpins at least part of the pro-tumourigenic consequences of 3p21.3 deletion in humans.
Population-scale organization of cerebellar granule neuron signaling during a visuomotor behavior
Authors: Sylvester Sherika J. G. , Lee Melanie M. , Ramirez Alexandro D. , Lim Sukbin , Goldman Mark S. , Aksay Emre R. F. 
Published: November 2017

AbstractGranule cells at the input layer of the cerebellum comprise over half the neurons in the human brain and are thought to be critical for learning. However, little is known about granule neuron signaling at the population scale during behavior. We used calcium imaging in awake zebrafish during optokinetic behavior to record transgenically identified granule neurons throughout a cerebellar population. A significant fraction of the population was responsive at any given time. In contrast to core precerebellar populations, granule neuron responses were relatively heterogeneous, with variation in the degree of rectification and the balance of positive versus negative changes in activity. Functional correlations were strongest for nearby cells, with weak spatial gradients in the degree of rectification and the average sign of response. These data open a new window upon cerebellar function and suggest granule layer signals represent elementary building blocks under-represented in core sensorimotor pathways, thereby enabling the construction of novel patterns of activity for learning.
MRI Simulation Study Investigating Effects of Vessel Topology, Diffusion, and Susceptibility on Transverse Relaxation Rates Using a Cylinder Fork Model
Authors: Shazeeb Mohammed Salman , Kalpathy-Cramer Jayashree , Issa Bashar 
Published: November 2017

AbstractBrain vasculature is conventionally represented as straight cylinders when simulating blood oxygenation level dependent (BOLD) contrast effects in functional magnetic resonance imaging (fMRI). In reality, the vasculature is more complicated with branching and coiling especially in tumors. Diffusion and susceptibility changes can also introduce variations in the relaxation mechanisms within tumors. This study introduces a simple cylinder fork model (CFM) and investigates the effects of vessel topology, diffusion, and susceptibility on the transverse relaxation rates R2* and R2. Simulations using Monte Carlo methods were performed to quantify R2* and R2 by manipulating the CFM at different orientations, bifurcation angles, and rotation angles. Other parameters of the CFM were chosen based on physiologically relevant values: vessel diameters (~2‒10 µm), diffusion rates (1 × 10−11‒1 × 10−9 m2/s), and susceptibility values (3 × 10−8–4 × 10−7 cgs units). R2* and R2 measurements showed a significant dependence on the bifurcation and rotation angles in several scenarios using different vessel diameters, orientations, diffusion rates, and susceptibility values. The angular dependence of R2* and R2 using the CFM could potentially be exploited as a tool to differentiate between normal and tumor vessels. The CFM can also serve as the elementary building block to simulate a capillary network reflecting realistic topological features.
Modulation of individual auditory-motor coordination dynamics through interpersonal visual coupling
Authors: Miyata Kohei , Varlet Manuel , Miura Akito , Kudo Kazutoshi , Keller Peter E. 
Published: November 2017

AbstractThe current study investigated whether visual coupling between two people producing dance-related movements (requiring whole-body auditory-motor coordination) results in interpersonal entrainment and modulates individual auditory-motor coordination dynamics. Paired participants performed two kinds of coordination tasks – either knee flexion or extension repeatedly with metronome beats (Flexion-on-the-beat and Extension-on-the-beat conditions) while standing face-to-face or back-to-back to manipulate visual interaction. The results indicated that the relative phases between paired participants’ movements were closer to 0° and less variable when participants could see each other. In addition, visibility of the partner reduced individual differences in the dynamics of auditory-motor coordination by modulating coordination variability and the frequency of phase transitions from Extension-on-the-beat to Flexion-on-the-beat. Together, these results indicate that visual coupling takes place when paired participants can see each other and leads to interpersonal entrainment during rhythmic auditory-motor coordination, which compensates for individual differences via behavioural assimilation and thus enables individuals to achieve unified and cohesive performances.
PsiQuaSP–A library for efficient computation of symmetric open quantum systems
Authors: Gegg Michael , Richter Marten 
Published: November 2017

AbstractIn a recent publication we showed that permutation symmetry reduces the numerical complexity of Lindblad quantum master equations for identical multi-level systems from exponential to polynomial scaling. This is important for open system dynamics including realistic system bath interactions and dephasing in, for instance, the Dicke model, multi-Λ system setups etc. Here we present an object-oriented C++ library that allows to setup and solve arbitrary quantum optical Lindblad master equations, especially those that are permutationally symmetric in the multi-level systems. PsiQuaSP (Permutation symmetry for identical Quantum Systems Package) uses the PETSc package for sparse linear algebra methods and differential equations as basis. The aim of PsiQuaSP is to provide flexible, storage efficient and scalable code while being as user friendly as possible. It is easily applied to many quantum optical or quantum information systems with more than one multi-level system. We first review the basics of the permutation symmetry for multi-level systems in quantum master equations. The application of PsiQuaSP to quantum dynamical problems is illustrated with several typical, simple examples of open quantum optical systems.
Development of a quantitative NS1-capture enzyme-linked immunosorbent assay for early detection of yellow fever virus infection
Authors: Ricciardi-Jorge Taissa , Bordignon Juliano , Koishi Andrea , Zanluca Camila , Mosimann Ana Luiza , Duarte dos Santos Claudia Nunes 
Published: November 2017

AbstractYellow fever is an arboviral disease that causes thousands of deaths every year in Africa and the Americas. However, few commercial diagnostic kits are available. Non-structural protein 1 (NS1) is an early marker of several flavivirus infections and is widely used to diagnose dengue virus (DENV) infection. Nonetheless, little is known about the dynamics of Yellow fever virus (YFV) NS1 expression and secretion, to encourage its use in diagnosis. To tackle this issue, we developed a quantitative NS1-capture ELISA specific for YFV using a monoclonal antibody and recombinant NS1 protein. This test was used to quantify NS1 in mosquito and human cell line cultures infected with vaccine and wild YFV strains. Our results showed that NS1 was detectable in the culture supernatants of both cell lines; however, a higher concentration was maintained as cell-associated rather than secreted into the extracellular milieu. A panel of 73 human samples was used to demonstrate the suitability of YFV NS1 as a diagnostic tool, resulting in 80% sensitivity, 100% specificity, a 100% positive predictive value and a 95.5% negative predictive value compared with RT-PCR. Overall, the developed NS1-capture ELISA showed potential as a promising assay for the detection of early YF infection.
Regulation of mating type switching by the mating type genes and RME1 in Ogataea polymorpha
Authors: Yamamoto Katsuyoshi , Tran Thi N. M. , Takegawa Kaoru , Kaneko Yoshinobu , Maekawa Hiromi 
Published: November 2017

AbstractSaccharomyces cerevisiae and its closely related yeasts undergo mating type switching by replacing DNA sequences at the active mating type locus (MAT) with one of two silent mating type cassettes. Recently, a novel mode of mating type switching was reported in methylotrophic yeast, including Ogataea polymorpha, which utilizes chromosomal recombination between inverted-repeat sequences flanking two MAT loci. The inversion is highly regulated and occurs only when two requirements are met: haploidy and nutritional starvation. However, links between this information and the mechanism associated with mating type switching are not understood. Here we investigated the roles of transcription factors involved in yeast sexual development, such as mating type genes and the conserved zinc finger protein Rme1. We found that co-presence of mating type a1 and α2 genes was sufficient to prevent mating type switching, suggesting that ploidy information resides solely in the mating type locus. Additionally, RME1 deletion resulted in a reduced rate of switching, and ectopic expression of O. polymorpha RME1 overrode the requirement for starvation to induce MAT inversion. These results suggested that mating type switching in O. polymorpha is likely regulated by two distinct transcriptional programs that are linked to the ploidy and transmission of the starvation signal.
Strategic inhibition of distractors with visual working memory contents after involuntary attention capture
Authors: Lu Jiachen , Tian Lili , Zhang Jiafeng , Wang Jing , Ye Chaoxiong , Liu Qiang 
Published: November 2017

AbstractPrevious research has suggested that visual working memory (VWM) contents had a guiding effect on selective attention, and once participants realized that the distractors shared the same information with VWM contents in the search task, they would strategically inhibit the potential distractors with VWM contents. However, previous behavioral studies could not reveal the way how distractors with VWM contents are inhibited strategically. By employing the eye-tracking technique and a dual-task paradigm, we manipulated the probability of memory items occurring as distractors to explore this issue. Consistent with previous behavioral studies, the results showed that the inhibitory effect occurred only in the high-probability condition, while the guiding effect emerged in the low-probability condition. More importantly, the eye-movement results indicated that in the high-probability condition, once few (even one) distractors with VWM contents were captured at first, all the remaining distractors with VWM contents would be rejected as a whole. However, in the low-probability condition, attention could be captured by the majority of distractors with VWM contents. These results suggested that the guiding effect of VWM contents on attention is involuntary in the early stage of visual search. After the completion of this involuntary stage, the guiding effect of task-irrelevant VWM contents on attention could be strategically controlled.