bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computationally Efficient Modelling of Stochastic Spatio-Temporal Dynamics in Biomolecular Networks
Authors: Kim Jongrae , Foo Mathias , Bates Declan G. 
Published: February 2018

AbstractMeasurement techniques in biology are now able to provide data on the trajectories of multiple individual molecules simultaneously, motivating the development of techniques for the stochastic spatio-temporal modelling of biomolecular networks. However, standard approaches based on solving stochastic reaction-diffusion equations are computationally intractable for large-scale networks. We present a novel method for modeling stochastic and spatial dynamics in biomolecular networks using a simple form of the Langevin equation with noisy kinetic constants. Spatial heterogeneity in molecular interactions is decoupled into a set of compartments, where the distribution of molecules in each compartment is idealised as being uniform. The reactions in the network are then modelled by Langevin equations with correcting terms, that account for differences between spatially uniform and spatially non-uniform distributions, and that can be readily estimated from available experimental data. The accuracy and extreme computational efficiency of the approach is demonstrated on a model of the epidermal growth factor receptor network in the human mammary epithelial cell.
Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ
Authors: Khanal Prem , Jia Zongchao , Yang Xiaolong 
Published: February 2018

AbstractHippo signalling pathway is an emerging signalling pathway that plays important roles in organ size control, tumorigenesis, metastasis, stress response, apoptosis, stem cell differentiation and renewal during development and tissue homeostasis. Recent studies reported that human serine/threonine protein kinase, Mst1, a core component of the Hippo pathway can be activated through formation of homodimer. However, it is still unclear whether or not other components of the Hippo pathway are also regulated through dimerization. Here we provide the first evidence that Hippo components and oncoprotein YAP2L and TAZ can form homodimer in vitro and in vivo by forming disulphide bond through cysteine residue(s). We have also shown that the homodimers of YAP2L/TAZ are more stable and showed more oncogenic behaviour than their corresponding monomers as revealed by colony formation and cell transformation assay. Since cysteine post-translational regulation plays important roles in redox signalling, tumorigenesis and drug resistance, further studies on the functional effect of this dimerization through post-translational modulation of cysteine residues in YAP2L/TAZ will provide a significant contribution to our understanding of the roles of YAP2L/TAZ in cancer development and therapy.
Onset and Evolution of Southern Annular Mode-Like Changes at Centennial Timescale
Authors: Moreno P. I. , Vilanova I. , Villa-Martínez R. , Dunbar R. B. , Mucciarone D. A. , Kaplan M. R. , Garreaud R. D. , Rojas M. , Moy C. M. , De Pol-Holz R. , Lambert F. 
Published: February 2018

AbstractThe Southern Westerly Winds (SWW) are the surface expression of geostrophic winds that encircle the southern mid-latitudes. In conjunction with the Southern Ocean, they establish a coupled system that not only controls climate in the southern third of the world, but is also closely connected to the position of the Intertropical Convergence Zone and CO2 degassing from the deep ocean. Paradoxically, little is known about their behavior since the last ice age and relationships with mid-latitude glacier history and tropical climate variability. Here we present a lake sediment record from Chilean Patagonia (51°S) that reveals fluctuations of the low-level SWW at mid-latitudes, including strong westerlies during the Antarctic Cold Reversal, anomalously low intensity during the early Holocene, which was unfavorable for glacier growth, and strong SWW since ~7.5 ka. We detect nine positive Southern Annular Mode-like events at centennial timescale since ~5.8 ka that alternate with cold/wet intervals favorable for glacier expansions (Neoglaciations) in southern Patagonia. The correspondence of key features of mid-latitude atmospheric circulation with shifts in tropical climate since ~10 ka suggests that coherent climatic shifts in these regions have driven climate change in vast sectors of the Southern Hemisphere at centennial and millennial timescales.
Cisplatin Enhances Hepatitis B Virus Replication and PGC-1α Expression through Endoplasmic Reticulum Stress
Authors: Li Xiaosong , Pan E. , Zhu Junke , Xu Lei , Chen Xuemei , Li Jingjing , Liang Li , Hu Yuan , Xia Jie , Chen Juan , Chen Wannan , Hu Jieli , Wang Kai , Tang Ni , Huang Ailong 
Published: February 2018

AbstractChronic hepatitis B infection remains a serious public health issue worldwide. Hepatitis B virus (HBV) reactivation is commonly reported in patients receiving anticancer therapy, immunosuppressive therapy, or organ and tissue transplantation. However, the precise mechanisms underlying chemotherapeutic agent-related HBV reactivation remain unclear. Here, we report that peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) plays a central role in cisplatin-induced HBV transcription and replication. First, cisplatin treatment upregulated the expression levels of PGC-1α and hepatocyte nuclear factor 4 alpha (HNF-4α) in both HBV-replicating cells and an HBV-transgenic mouse model. PGC-1α coactivates with HNF-4α, which interacts with a core promoter and enhancer II region of HBV genome, thereby promoting HBV production. In contrast, knockdown of PGC-1α and HNF-4α by RNA interference in hepatoma cells reversed HBV activation in response to cisplatin. Additionally, PGC-1α upregulation depended on cisplatin-mediated endoplasmic reticulum (ER) stress. We further observed that the recruitment of cyclic AMP-responsive element-binding protein plays a crucial role for PGC-1α transcriptional activation in cisplatin-treated cells. Finally, pharmacologic inhibition of ER stress impaired PGC-1α upregulation and HBV production induced by cisplatin treatment. These findings demonstrate novel molecular mechanisms indicating that ER stress-PGC1α signaling pathway plays a critical role in cisplatin-evoked HBV reactivation.
Climate-Driven Crop Yield and Yield Variability and Climate Change Impacts on the U.S. Great Plains Agricultural Production
Authors: Kukal Meetpal S. , Irmak Suat 
Published: February 2018

AbstractClimate variability and trends affect global crop yields and are characterized as highly dependent on location, crop type, and irrigation. U.S. Great Plains, due to its significance in national food production, evident climate variability, and extensive irrigation is an ideal region of investigation for climate impacts on food production. This paper evaluates climate impacts on maize, sorghum, and soybean yields and effect of irrigation for individual counties in this region by employing extensive crop yield and climate datasets from 1968–2013. Variability in crop yields was a quarter of the regional average yields, with a quarter of this variability explained by climate variability, and temperature and precipitation explained these in singularity or combination at different locations. Observed temperature trend was beneficial for maize yields, but detrimental for sorghum and soybean yields, whereas observed precipitation trend was beneficial for all three crops. Irrigated yields demonstrated increased robustness and an effective mitigation strategy against climate impacts than their non-irrigated counterparts by a considerable fraction. The information, data, and maps provided can serve as an assessment guide for planners, managers, and policy- and decision makers to prioritize agricultural resilience efforts and resource allocation or re-allocation in the regions that exhibit risk from climate variability.
PANDA: Protein function prediction using domain architecture and affinity propagation
Authors: Wang Zheng , Zhao Chenguang , Wang Yiheng , Sun Zheng , Wang Nan 
Published: February 2018

AbstractWe developed PANDA (Propagation of Affinity and Domain Architecture) to predict protein functions in the format of Gene Ontology (GO) terms. PANDA at first executes profile-profile alignment algorithm to search against PfamA, KOG, COG, and SwissProt databases, and then launches PSI-BLAST against UniProt for homologue search. PANDA integrates a domain architecture inference algorithm based on the Bayesian statistics that calculates the probability of having a GO term. All the candidate GO terms are pooled and filtered based on Z-score. After that, the remaining GO terms are clustered using an affinity propagation algorithm based on the GO directed acyclic graph, followed by a second round of filtering on the clusters of GO terms. We benchmarked the performance of all the baseline predictors PANDA integrates and also for every pooling and filtering step of PANDA. It can be found that PANDA achieves better performances in terms of area under the curve for precision and recall compared to the baseline predictors. PANDA can be accessed from http://dna.cs.miami.edu/PANDA/.
Inhibitory modulation of cytochrome c oxidase activity with specific near-infrared light wavelengths attenuates brain ischemia/reperfusion injury
Authors: Sanderson Thomas H. , Wider Joseph M. , Lee Icksoo , Reynolds Christian A. , Liu Jenney , Lepore Bradley , Tousignant Reneé , Bukowski Melissa J. , Johnston Hollie , Fite Alemu , Raghunayakula Sarita , Kamholz John , Grossman Lawrence I. , Przyklenk Karin , Hüttemann Maik 
Published: February 2018

AbstractThe interaction of light with biological tissue has been successfully utilized for multiple therapeutic purposes. Previous studies have suggested that near infrared light (NIR) enhances the activity of mitochondria by increasing cytochrome c oxidase (COX) activity, which we confirmed for 810 nm NIR. In contrast, scanning the NIR spectrum between 700 nm and 1000 nm revealed two NIR wavelengths (750 nm and 950 nm) that reduced the activity of isolated COX. COX-inhibitory wavelengths reduced mitochondrial respiration, reduced the mitochondrial membrane potential (ΔΨm), attenuated mitochondrial superoxide production, and attenuated neuronal death following oxygen glucose deprivation, whereas NIR that activates COX provided no benefit. We evaluated COX-inhibitory NIR as a potential therapy for cerebral reperfusion injury using a rat model of global brain ischemia. Untreated animals demonstrated an 86% loss of neurons in the CA1 hippocampus post-reperfusion whereas inhibitory NIR groups were robustly protected, with neuronal loss ranging from 11% to 35%. Moreover, neurologic function, assessed by radial arm maze performance, was preserved at control levels in rats treated with a combination of both COX-inhibitory NIR wavelengths. Taken together, our data suggest that COX-inhibitory NIR may be a viable non-pharmacologic and noninvasive therapy for the treatment of cerebral reperfusion injury.
African swine fever virus encodes for an E2-ubiquitin conjugating enzyme that is mono- and di-ubiquitinated and required for viral replication cycle
Authors: Freitas Ferdinando B. , Frouco Gonçalo , Martins Carlos , Ferreira Fernando 
Published: February 2018

AbstractAfrican swine fever virus is the etiological agent of a contagious and fatal acute haemorrhagic viral disease for which there are no vaccines or therapeutic options. The ASFV encodes for a putative E2 ubiquitin conjugating enzyme (ORF I215L) that shows sequence homology with eukaryotic counterparts. In the present study, we showed that pI215L acts as an E2-ubiquitin like enzyme in a large range of pH values and temperatures, after short incubation times. Further experiments revealed that pI215L is polyubiquitinated instead of multi-mono-ubiquitinated and Cys85 residue plays an essential role in the transthioesterification reaction. In infected cells, I215L gene is transcribed from 2 hours post infection and immunoblot analysis confirmed that pI215L is expressed from 4 hpi. Immunofluorescence studies revealed that pI215L is recruited to viral factories from 8 hpi and a diffuse distribution pattern throughout the nucleus and cytoplasm. siRNA studies suggested that pI215L plays a critical role in the transcription of late viral genes and viral DNA replication. Altogether, our results emphasize the potential use of this enzyme as target for drug and vaccine development against ASF.
Effectiveness and Safety of Different Rivaroxaban Dosage Regimens in Patients with Non-Valvular Atrial Fibrillation: A Nationwide, Population-Based Cohort Study
Authors: Huang Hsin-Yi , Lin Shin-Yi , Cheng Shou-Hsia , Wang Chi-Chuan 
Published: February 2018

AbstractThe objective of this study is to evaluate the effectiveness of different rivaroxaban dosage regimens in preventing ischemic stroke and systemic thromboembolism among Asians. A retrospective cohort study was conducted on data from nationwide insurance claims in Taiwan. Patients with non-valvular atrial fibrillation under warfarin or rivaroxaban therapy were included. Propensity score matching was used to balance the covariates, and Cox-proportional hazard models were applied to compare the effectiveness and safety of each treatment group. Rivaroxaban was associated with a significantly lower risk of venous thromboembolism (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.29–0.92, P = 0.02) and intracranial hemorrhage (HR: 0.48; 95% CI: 0.32–0.72, P < 0.001) than warfarin. Rivaroxaban 20 mg and 15 mg were associated with a significantly lower risk of ischemic stroke (20 mg, HR: 0.48; CI: 0.29–0.80, P = 0.005; 15 mg, HR: 0.69; CI: 0.53–0.90, P = 0.005), but rivaroxaban 10 mg was not. In the subgroup analysis of patients older than 65 years, the results were generally the same, except that rivaroxaban had a significantly lower risk of ischemic stroke than warfarin.
Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model
Authors: Courbon Guillaume , Lamarque Raphaëlle , Gerbaix Maude , Caire Robin , Linossier Marie-Thérèse , Laroche Norbert , Thomas Mireille , Thomas Thierry , Vico Laurence , Marotte Hubert 
Published: February 2018

AbstractPeriarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly related to synovial inflammation. However, strong bone loss has also described at the time of arthritis onset. Recently, a paradoxical exacerbation of joint damage was described when blocking sclerostin in various arthritis models. Thus, we aimed to determine kinetics of bone loss and its mechanisms in the adjuvant induced arthritis (AIA) rat model of RA. AIA was induced (n = 35) or not (n = 35) at day 0. In addition to well-known arthritis at day 12, we showed with 3D-imaging and histomorphometry that bone microstructural alterations occurred early from day 8 post-induction, characterized by cortical porosity and trabecular bone loss. Active osteoclastic surfaces were increased from day 8 with RANKL upregulation. More surprisingly SOST and DKK1 were overexpressed from day 6 and followed by a dramatic decrease in bone formation from day 8. At the time of arthritis onset, SOST and DKK1 returned to control values, but frizzled related protein 1 (SFRP1), proinflammatory cytokines, and MMPs started to increase. Bone alterations before arthritis onset reinforce the hypothesis of an early bone involvement in arthritis. Kinetics of osteocyte markers expression should be considered to refine Wnt inhibitor treatment strategies.
Association between autonomic control indexes and mortality in subjects admitted to intensive care unit
Authors: Porta Alberto , Colombo Riccardo , Marchi Andrea , Bari Vlasta , De Maria Beatrice , Ranuzzi Giovanni , Guzzetti Stefano , Fossali Tommaso , Raimondi Ferdinando 
Published: February 2018

AbstractThis study checks whether autonomic markers derived from spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP) and from their interactions with spontaneous or mechanical respiration (R) are associated with mortality in patients admitted to intensive care unit (ICU). Three-hundred consecutive HP, SAP and R values were recorded during the first day in ICU in 123 patients. Population was divided into survivors (SURVs, n = 83) and non-survivors (NonSURVs, n = 40) according to the outcome. SURVs and NonSURVs were aged- and gender-matched. All subjects underwent modified head-up tilt (MHUT) by tilting the bed back rest segment to 60°. Autonomic control indexes were computed using time-domain, spectral, cross-spectral, complexity, symbolic and causality techniques via univariate, bivariate and conditional approaches. SAP indexes derived from time-domain, model-free complexity and symbolic approaches were associated with the endpoint, while none of HP variability markers was. The association was more powerful during MHUT. Linear cross-spectral and causality indexes were useless to separate SURVs from NonSURVs, while nonlinear bivariate symbolic markers were successful. When indexes were combined with clinical scores, only SAP variance provided complementary information. Cardiovascular control variability indexes, especially when derived after an autonomic challenge such as MHUT, can improve mortality risk stratification in ICU.
The relationship between self-enhancing humor and precuneus volume in young healthy individuals with high and low cognitive empathy
Authors: Li Bingbing , Li Xu , Pan Yangu , Qiu Jiang , Zhang Dajun 
Published: February 2018

AbstractA self-enhancing humor style (SEHS) plays an important role in the regulation of negative emotion through humorous perspective-taking. Following the mind-reading theories of humor, we investigated the relationship between gray-matter volume (GMV) of brain areas related to theory of mind and SEHS in young college students, using voxel-based morphometry analysis. We then performed a voxel-wise analysis of covariance to assess any moderation effect of cognitive empathy on the relationship. Results demonstrated that higher SEHS scores were associated with larger GMV of the precuneus in the group with high cognitive empathy, but there was no association in the group with low cognitive empathy. These results suggest that high cognitive empathy and increased precuneus volume can predict greater use of self-enhancing humor in young healthy individuals.
HIF-1α hampers dendritic cell function and Th1 generation during chronic visceral leishmaniasis
Authors: Hammami Akil , Abidin Belma Melda , Heinonen Krista M. , Stäger Simona 
Published: February 2018

AbstractInflammation, although responsible for controlling infection, is often associated with the pathogenesis of chronic diseases. Leishmania donovani, the causative agent of visceral leishmaniasis, induces a strong inflammatory response that leads to splenomegaly and ultimately immune suppression. Inflamed tissues are typically characterized by low levels of oxygen, a microenvironment that triggers the hypoxia-inducible transcription factor 1α (HIF-1α). Although HIF-1α plays an integral role in dendritic cell function, its involvement in the generation of protective Th1 responses against Leishmania has not yet been studied. Here we demonstrate that HIF-1α inhibits IL-12 production in dendritic cells, limiting therefore Th1 cell development. Indeed, depletion of HIF-1α in CD11c+ cells resulted in higher and sustained expression of IL-12 and complete abrogation of IL-10. Moreover, CD11c-specific HIF-1α-deficient mice showed higher frequencies of IFN-γ-producing CD4 T cells in the spleen and bone marrow and, consequently, a significantly reduced parasite burden in both organs. Taken together, our results suggest that HIF-1α expression in dendritic cells largely contributes to the establishment of persistent Leishmania infection and may therefore represent a possible therapeutic target.
Reactive Oxygen Species Mediate the Suppression of Arterial Smooth Muscle T-type Ca2+ Channels by Angiotensin II
Authors: Hashad Ahmed M. , Sancho Maria , Brett Suzanne E. , Welsh Donald G. 
Published: February 2018

AbstractVascular T-type Ca2+ channels (CaV3.1 and CaV3.2) play a key role in arterial tone development. This study investigated whether this conductance is a regulatory target of angiotensin II (Ang II), a vasoactive peptide that circulates and which is locally produced within the arterial wall. Patch clamp electrophysiology performed on rat cerebral arterial smooth muscle cells reveals that Ang II (100 nM) inhibited T-type currents through AT1 receptor activation. Blocking protein kinase C failed to eliminate channel suppression, a finding consistent with unique signaling proteins enabling this response. In this regard, inhibiting NADPH oxidase (Nox) with apocynin or ML171 (Nox1 selective) abolished channel suppression highlighting a role for reactive oxygen species (ROS). In the presence of Ni2+ (50 µM), Ang II failed to modulate the residual T-type current, an observation consistent with this peptide targeting CaV3.2. Selective channel suppression by Ang II impaired the ability of CaV3.2 to alter spontaneous transient outward currents or vessel diameter. Proximity ligation assay confirmed Nox1 colocalization with CaV3.2. In closing, Ang II targets CaV3.2 channels via a signaling pathway involving Nox1 and the generation of ROS. This unique regulatory mechanism alters BKCa mediated feedback giving rise to a “constrictive” phenotype often observed with cerebrovascular disease.
A motif within the armadillo repeat of Parkinson’s-linked LRRK2 interacts with FADD to hijack the extrinsic death pathway
Authors: Antoniou Nasia , Vlachakis Dimitrios , Memou Anna , Leandrou Emmanouela , Valkimadi Polytimi-Eleni , Melachroinou Katerina , Re Diane B. , Przedborski Serge , Dauer William T. , Stefanis Leonidas , Rideout Hardy J. 
Published: February 2018

AbstractIn experimental models, both in vivo and cellular, over-expression of Parkinson’s linked mutant leucine-rich repeat kinase 2 (LRRK2) is sufficient to induce neuronal death. While several cell death associated proteins have been linked to LRRK2, either as protein interactors or as putative substrates, characterization of the neuronal death cascade remains elusive. In this study, we have mapped for the first time the domain within LRRK2 that mediates the interaction with FADD, thereby activating the molecular machinery of the extrinsic death pathway. Using homology modeling and molecular docking approaches, we have identified a critical motif within the N-terminal armadillo repeat region of LRRK2. Moreover, we show that co-expression of fragments of LRRK2 that contain the FADD binding motif, or deletion of this motif itself, blocks the interaction with FADD, and is neuroprotective. We further demonstrate that downstream of FADD, the mitochondrial proteins Bid and Bax are recruited to the death cascade and are necessary for neuronal death. Our work identifies multiple novel points within neuronal death signaling pathways that could potentially be targeted by candidate therapeutic strategies and highlight how the extrinsic pathway can be activated intracellularly in a pathogenic context.