bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer’s disease
Authors: Ho Kim Jae , Franck Julien , Kang Taewook , Heinsen Helmut , Ravid Rivka , Ferrer Isidro , Hee Cheon Mi , Lee Joo-Yong , Shin Yoo Jong , Steinbusch Harry W , Salzet Michel , Fournier Isabelle , Mok Park Young 
Published: June 2015

AbstractAlzheimer’s disease (AD) is the most common form of dementia; however, mechanisms and biomarkers remain unclear. Here, we examined hippocampal CA4 and dentate gyrus subfields, which are less studied in the context of AD pathology, in post-mortem AD and control tissue to identify possible biomarkers. We performed mass spectrometry-based proteomic analysis combined with label-free quantification for identification of differentially expressed proteins. We identified 4,328 proteins, of which 113 showed more than 2-fold higher or lower expression in AD hippocampi than in control tissues. Five proteins were identified as putative AD biomarkers (MDH2, PCLO, TRRAP, YWHAZ and MUC19 isoform 5) and were cross-validated by immunoblotting, selected reaction monitoring and MALDI imaging. We also used a bioinformatics approach to examine upstream signalling interactions of the 113 regulated proteins. Five upstream signalling (IGF1, BDNF, ZAP70, MYC and cyclosporin A) factors showed novel interactions in AD hippocampi. Taken together, these results demonstrate a novel platform that may provide new strategies for the early detection of AD and thus its diagnosis.
Investigation of the subcellular architecture of L7 neurons of Aplysia californica using magnetic resonance microscopy (MRM) at 7.8 microns
Authors: Lee Choong H. , Flint Jeremy J. , Hansen Brian , Blackband Stephen J. 
Published: June 2015

AbstractMagnetic resonance microscopy (MRM) is a non-invasive diagnostic tool which is well-suited to directly resolve cellular structures in ex vivo and in vitro tissues without use of exogenous contrast agents. Recent advances in its capability to visualize mammalian cellular structure in intact tissues have reinvigorated analytical interest in aquatic cell models whose previous findings warrant up-to-date validation of subcellular components. Even if the sensitivity of MRM is less than other microscopic technologies, its strength lies in that it relies on the same image contrast mechanisms as clinical MRI which make it a unique tool for improving our ability to interpret human diagnostic imaging through high resolution studies of well-controlled biological model systems. Here, we investigate the subcellular MR signal characteristics of isolated cells of Aplysia californica at an in-plane resolution of 7.8 μm. In addition, direct correlation and positive identification of subcellular architecture in the cells is achieved through well-established histology. We hope this methodology will serve as the groundwork for studying pathophysiological changes through perturbation studies and allow for development of disease-specific cellular modeling tools. Such an approach promises to reveal the MR contrast changes underlying cellular mechanisms in various human diseases, for example in ischemic stroke.
TERT Promoter Mutations Are Predictive of Aggressive Clinical Behavior in Patients with Spitzoid Melanocytic Neoplasms
Authors: Lee Seungjae , Barnhill Raymond L. , Dummer Reinhard , Dalton James , Wu Jianrong , Pappo Alberto , Bahrami Armita 
Published: June 2015

AbstractSpitzoid neoplasms constitute a morphologically distinct category of melanocytic tumors, encompassing Spitz nevus (benign), atypical Spitz tumor (intermediate malignant potential) and spitzoid melanoma (fully malignant). Currently, no reliable histopathological criteria or molecular marker is known to distinguish borderline from overtly malignant neoplasms. Because TERT promoter (TERT-p) mutations are common in inherently aggressive cutaneous conventional melanoma, we sought to evaluate their prognostic significance in spitzoid neoplasms. We analyzed tumors labeled as atypical Spitz tumor or spitzoid melanoma from 56 patients with available follow-up data for the association of TERT-p mutations, biallelic CDKN2A deletion, biallelic PTEN deletion, kinase fusions, BRAF/NRAS mutations, nodal status and histopathological parameters with risk of hematogenous metastasis. Four patients died of disseminated disease and 52 patients were alive and disease free without extranodal metastasis (median follow-up, 32.5 months). We found TERT-p mutations in samples from the 4 patients who developed hematogenous metastasis but in none of tumors from patients who had favorable outcomes. Presence of TERT-p mutations was the most significant predictor of haematogenous dissemination (P < 0.0001) among variables analyzed. We conclude that TERT-p mutations identify a clinically high-risk subset of patients with spitzoid tumors. Application of TERT-p mutational assays for risk stratification in the clinic requires large-scale validation.
Retina specific GCAPs in zebrafish acquire functional selectivity in Ca2+-sensing by myristoylation and Mg2+-binding
Authors: Sulmann Stefan , Vocke Farina , Scholten Alexander , Koch Karl-Wilhelm 
Published: June 2015

AbstractZebrafish photoreceptor cells express six guanylate cyclase-activating proteins (zGCAPs) that share a high degree of amino acid sequence homology, but differ in Ca2+-binding properties, Ca2+-sensitive target regulation and spatial-temporal expression profiles. We here study a general problem in cellular Ca2+-sensing, namely how similar Ca2+-binding proteins achieve functional selectivity to control finely adjusted cellular responses. We investigated two parameters of critical importance for the trigger and switch function of guanylate cyclase-activating proteins: the myristoylation status and the occupation of Ca2+-binding sites with Mg2+. All zGCAPs can be myristoylated in living cells using click chemistry. Myristoylation does not facilitate membrane binding of zGCAPs, but it significantly modified the regulatory properties of zGCAP2 and zGCAP5. We further determined for all zGCAPs at least two binding sites exhibiting high affinities for Ca2+ with KD values in the submicromolar range, whereas for other zGCAPs (except zGCAP3) the affinity of the third binding site was in the micromolar range. Mg2+ either occupied the low affinity Ca2+-binding site or it shifted the affinities for Ca2+-binding. Hydrodynamic properties of zGCAPs are more influenced by Ca2+ than by Mg2+, although to a different extent for each zGCAP. Posttranslational modification and competing ion-binding can tailor the properties of similar Ca2+-sensors.
Population genetic structure of Oryza sativa in East and Southeast Asia and the discovery of elite alleles for grain traits
Authors: Dang Xiaojing , Giang Tran Thi Thu , Mawuli Edzesi Wisdom , Liang Lijun , Liu Qiangming , Liu Erbao , Wang Yang , Qiang Sheng , Liu Linglong , Hong Delin 
Published: June 2015

AbstractWe investigated the nuclear simple sequence repeat (SSR) genotypes of 532 rice (Oryza sativaL.) accessions collected from East and Southeast Asia and detected abundant genetic diversity within the population. We identified 6 subpopulations and found a tendency towards directional evolution inO. sativafrom low to high latitudes, with levels of linkage disequilibrium (LD) in the 6 subpopulations ranging from 10 to 30 cM. We then investigated the phenotypic data for grain length, grain width, grain thickness and 1,000-grain weight over 4 years. Using a genome-wide association analysis, we identified 17 marker-trait associations involving 14 SSR markers on 12 chromosome arms and 8 of the 17 associations were novel. The elite alleles were mined based on the phenotypic effects of the detected quantitative trait loci (QTLs). These elite alleles could be used to improve target traits through optimal cross designs, with the expected results obtained by pyramiding or substituting the elite alleles per QTL (independent of possible epistatic effects). Together, these results provide an in-depth understanding of the genetic diversity pattern among rice-grain traits across a broad geographic scale, which has potential use in future research work, including studies related to germplasm conservation and molecular breeding by design.
Constructing lncRNA functional similarity network based on lncRNA-disease associations and disease semantic similarity
Authors: Chen Xing , Clarence Yan Chenggang , Luo Cai , Ji Wen , Zhang Yongdong , Dai Qionghai 
Published: June 2015

AbstractIncreasing evidence has indicated that plenty of lncRNAs play important roles in many critical biological processes. Developing powerful computational models to construct lncRNA functional similarity network based on heterogeneous biological datasets is one of the most important and popular topics in the fields of both lncRNAs and complex diseases. Functional similarity network consturction could benefit the model development for both lncRNA function inference and lncRNA-disease association identification. However, little effort has been attempted to analysis and calculate lncRNA functional similarity on a large scale. In this study, based on the assumption that functionally similar lncRNAs tend to be associated with similar diseases, we developed two novel lncRNA functional similarity calculation models (LNCSIM). LNCSIM was evaluated by introducing similarity scores into the model of Laplacian Regularized Least Squares for LncRNA–Disease Association (LRLSLDA) for lncRNA-disease association prediction. As a result, new predictive models improved the performance of LRLSLDA in the leave-one-out cross validation of various known lncRNA-disease associations datasets. Furthermore, some of the predictive results for colorectal cancer and lung cancer were verified by independent biological experimental studies. It is anticipated that LNCSIM could be a useful and important biological tool for human disease diagnosis, treatment and prevention.
0.5–50 GHz dielectric characterisation of breast cancer tissues
Authors: Martellosio A. , Pasian M. , Bozzi M. , Perregrini L. , Mazzanti A. , Svelto F. , Summers P.E. , Renne G. , Bellomi M. 
Published: June 2015

Cancer affects a significant percentage of people, and early detection techniques are important for prompt and effective treatment. The use of microwave frequencies to achieve non‐invasive and non‐destructive cancer detections is currently under investigation by several research groups. In this frequency range, the dielectric properties of the biological tissue determine the interactions of the tissue with electromagnetic fields. Knowledge of the dielectric properties of both the normal and the malignant human tissues is therefore a fundamental starting point. A dielectric spectroscopy system, based on the use of a reflectometry setup, was used to perform an extensive experimental campaign on fresh surgical specimens. The measurement system allowed achieving a broadband dielectric characterisation of biological tissues up to 50 GHz, thus including millmetre‐wave (mm‐wave) frequencies. In the case of breast tissues, the results showed that the malignant and normal tissues exhibit significantly different complex dielectric permittivities of up to 50 GHz, due to their respective high and low water content. This permittivity difference is well detectable, and this paves the way to new screening methods based on mm‐wave imaging systems.
Contingency and entrenchment in protein evolution under purifying selection
Authors: Shah Premal , McCandlish David M. , Plotkin Joshua B. 
Published: June 2015

Significance
How large a role does history play in evolution? Do later events depend critically on specific earlier events, or do all events occur more or less independently? If a change occurs early in evolution, does it become easier or harder to revert the change as time proceeds? Here, we explore these ideas in the context of protein evolution, by simulating sequence evolution under purifying selection and then systematically permuting the order of amino acid substitutions. Our results suggest that the amino acid substitutions that occur in evolution are typically contingent on the presence of prior substitutions, and that substitutions that occur early in evolution become entrenched and difficult to modify as subsequent substitutions accrue.
Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions
Authors: Fuchikami Manabu , Thomas Alexandra , Liu Rongjian , Wohleb Eric S. , Land Benjamin B. , DiLeone Ralph J. , Aghajanian George K. , Duman Ronald S. 
Published: June 2015

Significance
Clinical studies report that a single, low dose of ketamine produces a rapid antidepressant response in treatment-resistant depressed patients. Although rodent studies have begun to elucidate the molecular mechanisms underlying the behavioral actions of ketamine, the brain regions and cellular mechanisms have not been defined. Using a combination of pharmacological silencing and optogenetic stimulation approaches, the results of the current study demonstrate that ketamine infusion or optogenetic stimulation of the infalimbic prefrontal cortex produces antidepressant behavioral and synaptic responses similar to the actions of systemic ketamine. These findings further elucidate the mechanisms underlying the therapeutic actions of ketamine and will enhance the development of safer rapid-acting and efficacious agents.
Establishing task- and modality-dependent dissociations between the semantic and default mode networks
Authors: Humphreys Gina F. , Hoffman Paul , Visser Maya , Binney Richard J. , Lambon Ralph Matthew A. 
Published: June 2015

SignificanceFunctional neuroimaging has established that most cognitive functions are supported by distributed neural networks. Hundreds of studies have investigated the semantic network (SN) and the default mode network (DMN) (neural deactivation when undertaking a variety of tasks). These stable networks are increasingly used as biomarkers in neurological and psychiatric investigations. Despite implicating overlapping neural regions and shared cognitive mechanisms, the relationship between the two networks has received minimal attention. Analyses of a large multitask distortion-corrected functional MRI (fMRI) dataset established that both networks fractionate, depending on the semantic nature of the task, stimulus type, modality, and task difficulty. The implications for the SN, variability in the DMN and its cognitive coherence, and interpretation of resting-state fMRI data are discussed.
A simple nutrient-dependence mechanism for predicting the stoichiometry of marine ecosystems
Authors: Galbraith Eric D. , Martiny Adam C. 
Published: June 2015

Significance
The elemental ratios of nitrogen, phosphorus, and carbon in marine phytoplankton can diverge significantly from the “Redfield ratio,” but the underlying reasons have been hard to elucidate. As a result, global biogeochemical models often ignore this stoichiometric variability. Here we show that, hidden within the noise of a large dataset of particulate measurements, a surprisingly consistent relationship exists between community P:C and dissolved phosphate concentrations. The plasticity of ecosystem stoichiometry in the face of nutrient scarcity, with greater plasticity for P relative to N, appears to explain the main divergences from the Redfield ratio. When included in a simple model, the relationship implies a more important role for low latitude nutrient cycling in the biological pump than is commonly assumed.
Disregulated expression of the transcription factor ThPOK during T-cell development leads to high incidence of T-cell lymphomas
Authors: Lee Hyung-Ok , He Xiao , Mookerjee-Basu Jayati , Zhongping Dai , Hua Xiang , Nicolas Emmanuelle , Sulis Maria Luisa , Ferrando Adolfo A. , Testa Joseph R. , Kappes Dietmar J. 
Published: June 2015

Significance
We demonstrate a novel and unexpected role of the transcription factor ThPOK as a potent oncogene in mice. During normal T-cell development, T-helper-inducing POZ/Krueppel-like factor (ThPOK) is selectively expressed in thymocytes developing to the CD4 lineage and is necessary for their differentiation. However, when ThPOK is expressed indiscriminately in all thymocytes, it causes highly penetrant thymic lymphoma. Strong T-cell receptor (TCR) signal rescues thymocytes from ThPOK-dependent lymphoma development, whereas weak signals promote lymphomagenesis. These results demonstrate a novel correlation between ThPOK, TCR signal strength, and lymphomagenesis. We also present evidence that ectopic ThPOK expression gives rise to a preleukemic and self-perpetuating precursor population, akin to a tumor stem cell.
Inference of transcriptional regulation in cancers
Authors: Jiang Peng , Freedman Matthew L. , Liu Jun S. , Liu Xiaole Shirley 
Published: June 2015

Significance
We developed an efficient and accurate computational framework, RABIT (regression analysis with background integration), and comprehensively integrated public transcription factor (TF)-binding profiles with TCGA tumor-profiling datasets in 18 cancer types. To systematically search for cancer-associated TFs, RABIT controls the effect of tumor-confounding factors on transcriptional regulation, such as copy number alteration, DNA methylation, and TF somatic mutation. Our predicted TF regulatory activity in tumors is highly consistent with the knowledge from cancer gene databases and reveals many previously unidentified cancer-associated TFs. We also analyzed RNA-binding protein regulation in cancer and demonstrated that RABIT is a general platform for predicting oncogenic gene expression regulators.
Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops
Authors: Paslawski Wojciech , Lillelund Ove K. , Kristensen Julie Veje , Schafer Nicholas P. , Baker Rosanna P. , Urban Sinisa , Otzen Daniel E. 
Published: June 2015

Significance
How a protein folds in a membrane is a problem of central biological significance. Although extensively investigated for globular proteins, there are very limited data available for membrane proteins due to the difficulties of finding a tractable model system. We present a study of the folding of a six-transmembrane helix protein, the rhomboid protease GlpG, which folds according to a two-state model in a membrane-mimicking mixed micelle surfactant system. By recording the kinetics of folding and unfolding of 69 GlpG mutants and performing an extensive ϕ-value analysis, we propose a folding mechanism and discuss its possible interpretations and implications. These data serve as an excellent starting point for computational studies of membrane protein folding mechanisms and kinetics.
Climate mediates hypoxic stress on fish diversity and nursery function at the land–sea interface
Authors: Hughes Brent B. , Levey Matthew D. , Fountain Monique C. , Carlisle Aaron B. , Chavez Francisco P. , Gleason Mary G. 
Published: June 2015

Significance
Human populations are rapidly expanding along Earth's coastlines, increasing stress to coastal ecosystems and the services they provide. One of these stressors comes from an increase in nutrient inputs from coastal land development that can enter estuaries and coastal seas leading to algal blooms that deplete oxygen from the water, a condition known as hypoxia. In this study, we investigated how coastal hypoxia influences fish diversity, the nursery habitat for juvenile fish, and fisheries production in adjacent offshore waters. We found that severity in hypoxia corresponded with declines to fish diversity, nursery quality, and offshore fisheries. Furthermore, intensification of El Niño mediated hypoxia by improving dissolved oxygen conditions, demonstrating that climate can influence anthropogenic stressors affecting coastal ecosystem services.
Novel pathways for fuels and lubricants from biomass optimized using life-cycle greenhouse gas assessment
Authors: Balakrishnan Madhesan , Sacia Eric R. , Sreekumar Sanil , Gunbas Gorkem , Gokhale Amit A. , Scown Corinne D. , Toste F. Dean , Bell Alexis T. 
Published: June 2015

Significance
The development of renewable liquid fuels and bioproducts is critical to reducing global reliance on petroleum and mitigating climate change, particularly for applications where few low-carbon alternatives exist. We combine chemical catalysis with life-cycle greenhouse gas (GHG) modeling to create a new platform for producing biobased aviation fuel and automotive lubricant base oils. The recyclable catalysts we developed are capable of converting sugar and biomass-derived alkyl methyl ketones into cyclic enones via condensation reactions. These products can subsequently be hydrodeoxygenated to create a new class of aviation fuel and lubricant candidates with superior cold flow properties, density, and viscosity that substantially reduce GHG emissions relative to conventional petroleum.
High-resolution view of the spring bloom initiation and net community production in the Subantarctic Southern Ocean using glider data
Authors: Thomalla Sandy J. , Racault Marie-Fanny , Swart Sebastiaan , Monteiro Pedro M. S. 
Published: June 2015

AbstractIn the Southern Ocean, there is increasing evidence that seasonal to subseasonal temporal scales, and meso- to submesoscales play an important role in understanding the sensitivity of ocean primary productivity to climate change. This drives the need for a high-resolution approach to resolving biogeochemical processes. In this study, 5.5 months of continuous, high-resolution (3 h, 2 km horizontal resolution) glider data from spring to summer in the Atlantic Subantarctic Zone is used to investigate: (i) the mechanisms that drive bloom initiation and high growth rates in the region and (ii) the seasonal evolution of water column production and respiration. Bloom initiation dates were analysed in the context of upper ocean boundary layer physics highlighting sensitivities of different bloom detection methods to different environmental processes. Model results show that in early spring (September to mid-November) increased rates of net community production (NCP) are strongly affected by meso- to submesoscale features. In late spring/early summer (late-November to mid-December) seasonal shoaling of the mixed layer drives a more spatially homogenous bloom with maximum rates of NCP and chlorophyll biomass. A comparison of biomass accumulation rates with a study in the North Atlantic highlights the sensitivity of phytoplankton growth to fine-scale dynamics and emphasizes the need to sample the ocean at high resolution to accurately resolve phytoplankton phenology and improve our ability to estimate the sensitivity of the biological carbon pump to climate change.