bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution, not transgenerational plasticity, explains the divergence of acorn ant thermal tolerance across an urban-rural temperature cline
Authors: Martin Ryan A. , Chick Lacy D. , Yilmaz Aaron R. , Diamond Sarah E. 
Published: March 2019

AbstractDisentangling the mechanisms of phenotypic shifts in response to environmental change is critical, and although studies increasingly disentangle phenotypic plasticity from evolutionary change, few explore the potential role for transgenerational plasticity in this context. Here, we evaluate the potential role that transgenerational plasticity plays in phenotypic divergence of acorn ants in response to urbanization. F2 generation worker ants (offspring of lab-born queens) exhibited similar divergence among urban and rural populations as F1 generation worker ants (offspring of field-born queens) indicating that evolutionary differentiation rather than transgenerational plasticity was responsible for shifts towards higher heat tolerance and diminished cold tolerance in urban acorn ants. Hybrid matings between urban and rural populations provided further insight into the genetic architecture of thermal adaptation. Heat tolerance of hybrids more resembled the urban-urban pure type, whereas cold tolerance of hybrids more resembled the rural-rural pure type. As a consequence, thermal tolerance traits in this system appear to be influenced by dominance rather than being purely additive traits, and heat and cold tolerance might be determined by separate genes. Though transgenerational plasticity does not explain divergence of acorn ant thermal tolerance, its role in divergence of other traits and across other urbanization gradients merits further study.
Histological validation of per-bundle water diffusion metrics within a region of fiber crossing following axonal degeneration
Authors: Rojas-Vite Gilberto , Coronado-Leija Ricardo , Narvaez-Delgado Omar , Ramírez-Manzanares Alonso , Marroquín José Luis , Noguez-Imm Ramsés , Aranda Marcos L. , Scherrer Benoit , Larriva-Sahd Jorge , Concha Luis 
Published: March 2019

AbstractMicro-architectural characteristics of white matter can be inferred through analysis of diffusion-weighted magnetic resonance imaging (dMRI). The diffusion-dependent signal can be analyzed through several methods, with the tensor model being the most frequently used due to its straightforward interpretation and relaxed acquisition parameters. While valuable information can be gained from the tensor-derived metrics in regions of homogeneous tissue organization, this model does not provide reliable microstructural information at crossing fiber regions, which are pervasive throughout human white matter. Several multiple fiber models have been proposed that seem to overcome the limitations of the tensor, with few providing per-bundle dMRI-derived metrics. However, biological interpretations of such metrics are limited by the lack of histological confirmation. To this end, we developed a straightforward biological validation framework. Unilateral retinal ischemia was induced in ten rats, which resulted in axonal (Wallerian) degeneration of the corresponding optic nerve, while the contralateral was left intact; the intact and injured axonal populations meet at the optic chiasm as they cross the midline, generating a fiber crossing region in which each population has different diffusion properties. Five rats served as controls. High-resolutionex vivodMRI was acquired five weeks after experimental procedures. We correlated and compared histology to per-bundle descriptors derived from three novel methodologies for dMRI analysis (constrained spherical deconvolution and two multi-tensor representations). We found a tight correlation between axonal density (as evaluated through automatic segmentation of histological sections) with per-bundle apparent fiber density and fractional anisotropy (derived from dMRI). The multi-fiber methods explored were able to correctly identify the damaged fiber populations in a region of fiber crossings (chiasm). Our results provide validation of metrics that bring substantial and clinically useful information about white-matter tissue at crossing fiber regions. Our proposed validation framework is useful to validate other current and future dMRI methods.
A novel network controllability algorithm to target personalized driver genes for discovering combinational drugs of individual cancer patient
Authors: Guo Wei-Feng , Zhang Shao-Wu , Zeng Tao , Chen Luonan 
Published: March 2019

AbstractTreating cancer in precision medicine, it is important to identify the personalized combinational drugs under consideration of the individual heterogeneity. Many bioinformatics tools for the personalized driver genes identification have presented promising clues in determining candidate personalized drug targets for the personalized drugs discovery. However, it has not been studied how to fill the gap between personalized driver genes identification and personalized combinational drugs discovery. In this work, we developed a novel algorithm of structure network Controllability-based Personalized driver Genes and combinational Drug identification (CPGD), aiming to mine the personalized driver genes and identify the combinational drugs of an individual cancer patient. On two benchmark cancer datasets, the performance of CPGD for predicting the clinical efficacious combinational drugs is superior to that of other state-of-the-art driver gene-focus algorithms in terms of precision accuracy. In particular, by quantifying and referring the relationships between target genes of pairwise combinatorial drugs and disease module genes on breast cancer data set, CPGD can significantly divide patients into the discriminative high-risk and low-risk groups for risk asessment in combination therapy. In addition, CPGD can further enhance cancer subtyping by providing computationally personalized side effect signatures for individual patients. Collectively, CPGD provided a new and effecient bioinformatics tool from structure network controllability perspective for discovering personalized combinational drugs with personalized side effect consideration, so as to effectively support personalized risk assessement and disease subtyping.SignificanceIt is quite challenging to predict personalized combinational drugs rather than patient-cohort‘s drugs based on cancer omics data. In this work, a novel structure network Controllability-based algorithm (CPGD) from feedback vertex sets control perspective was developed, for discovering efficacious combinational drugs of an individual cancer patient by targeting the personalized driver genes. The CPGD contains three methodological advances by exploring more precise mathematical models on high-throughput personalized multi-omics data. The first is that a proper network structure is constructed to characterize the gene regulatory mechanism of an individual patient. The second is that considering the weight information of network edges/relations improves the performance for predicting clinical efficacious combinational drugs compared with other drivers-focus methods. And the third is that proper evaluation metrics for personalized combinational drugs prioritization, personalized risk assessment and disease subtyping are designed when evaluating the performance of CPGD.
Nicotinamide Deficiency in Primary Open-Angle Glaucoma
Authors: Nzoughet Judith Kouassi , de la Barca Juan Manuel Chao , Guehlouz Khadidja , Leruez Stéphanie , Coulbault Laurent , Allouche Stéphane , Bocca Cinzia , Muller Jeanne , Amati-Bonneau Patrizia , Gohier Philippe , Bonneau Dominique , Simard Gilles , Milea Dan , Lenaers Guy , Procaccio Vincent , Reynier Pascal 
Published: March 2019

ABSTRACTPurposeTo investigate the plasma concentration of nicotinamide in primary open-angle glaucoma (POAG).MethodsPlasma of 34 POAG individuals were compared to that of 30 age-and sex-matched controls using a semi-quantitative method based on liquid chromatography coupled to high-resolution mass spectrometry. Subsequently, an independent quantitative method, based on liquid chromatography coupled to mass spectrometry, was used to assess nicotinamide concentration in the plasma from the same initial cohort and from a replicative cohort of 20 POAG individuals and 15 controls.ResultsUsing the semi-quantitative method, the plasma nicotinamide concentration was significantly lower in the initial cohort of POAG individuals compared to and further confirmed in the same cohort, using the targeted quantitative method, with mean concentrations of 0.14 µM (median: 0.12 µM; range: 0.06-0.28 µM) in the POAG group (−30 %;p= 0.022), and 0.19 µM (median: 0.18 µM; range: 0.08-0.47 µM) in the control group. The quantitative dosage also disclosed a significantly lower plasma nicotinamide concentration (−33 %;p= 0.011) in the replicative cohort with mean concentrations of 0.14 µM (median: 0.14 µM; range: 0.09-0.25 µM) in the POAG group, and 0.19 µM (median: 0.21 µM; range: 0.09-0.26 µM) in the control group.ConclusionsGlaucoma is associated with lower plasmatic nicotinamide levels, compared to controls, suggesting that nicotinamide supplementation might become a future therapeutic strategy. Further studies are needed, in larger cohorts, to confirm these preliminary findings.
A Bayesian framework for inferring the influence of sequence context on single base modifications
Authors: Ling Guy , Miller Danielle , Nielsen Rasmus , Stern Adi 
Published: March 2019

AbstractThe probability of single base modifications (mutations and DNA/RNA modifications) is expected to be highly influenced by the flanking nucleotides that surround them, known as the sequence context. This phenomenon may be mainly attributed to the enzyme that modifies or mutates the genetic material, since most enzymes tend to have specific sequence contexts that dictate their activity. Thus, identification of context effects may lead to the discovery of additional editing sites or unknown enzymatic factors. Here, we develop a statistical model that allows for the detection and evaluation of the effects of different sequence contexts on mutation rates from deep population sequencing data. This task is computationally challenging, as the complexity of the model increases exponentially as the context size increases. We established our novel Bayesian method based on sparse model selection methods, with the leading assumption that the number of actual sequence contexts that directly influence mutation rates is minuscule compared to the number of possible sequence contexts. We show that our method is highly accurate on simulated data using pentanucleotide contexts, even when accounting for noisy data. We next analyze empirical population sequencing data from polioviruses and detect a significant enrichment in sequence contexts associated with deamination by the cellular deaminases ADAR 1/2. In the current era, where next generation sequencing data is highly abundant, our approach can be used on any population sequencing data to reveal context-dependent base alterations, and may assist in the discovery of novel mutable sites or editing sites.
Lactate potentiates differentiation and expansion of cytotoxic T cells
Authors: Rundqvist Helene , Veliça Pedro , Barbieri Laura , Gameiro Paulo A. , Cunha Pedro P. , Gojkovic Milos , Mijwel Sara , Ahlstedt Emil , Foskolou Iosifina P. , Ruiz-Pérez María Victoria , Arsenian-Henriksson Marie , Ule Jernej , Östman Arne , Johnson Randall S. 
Published: March 2019

AbstractExercise has a range of effects on metabolism. In animal models, repeated exertion reduces malignant tumour progression, and clinically, exercise can improve outcome for cancer patients. The etiology of the effect of exercise on tumour progression is unclear, as are the cellular actors involved. We show here that exercise-induced reduction in tumour growth is dependent on CD8+ T cells and that lactate, which is produced at high levels during exertion, increases proliferative capacity and cytotoxicity of CD8+ T cells. We found that at elevated levels lactate is used as a fuel during T cell activation. We further found that injection of lactate into animals can reduce malignant tumour growth in a dose-and CD8+ T cell-dependent manner. These data demonstrate that lactate can act to increase the anti-tumour activity of cytotoxic T cells, and in so doing, reduce cancer progression.
Soil protist diversity in the Swiss western Alps is better predicted by topo-climatic than by edaphic variables
Authors: Seppey Christophe V.W. , Broennimann Olivier , Buri Aline , Yashiro Erika , Pinto-Figueroa Eric , Singer David , Blandenier Quentin , Mitchell Edward A.D. , Hirzel Hélène Niculita , Guisan Antoine , Lara Enrique 
Published: March 2019

AbstractAimGeneral trends in spatial patterns of macroscopic organisms diversity can be reasonably well predicted from correlative models, using for instance topo-climatic variables for plants and animals allowing inference over large scales. By contrast, soil microorganisms diversity is generally considered as mostly driven by edaphic variables and, therefore, difficult to extrapolate on a large spatial scale based on predictive models. Here, we compared the power of topo-climatic vs. edaphic variables for predicting the diversity of various soil protist groups at the regional scale.LocationSwiss western Alps.TaxaFull protist community and nine clades belonging to three functional groups: parasites (Apicomplexa, Oomycota, Phytomyxea), phagotrophs (Sarcomonadea, Tubulinea, Spirotrichea) and phototrophs (Chlorophyta, Trebouxiophyceae, Bacillariophyta).MethodsWe extracted soil environmental DNA from 178 sites along a wide range of elevations with a random-stratified sampling design. We defined protist Operational Taxonomic Units assemblages by metabarcoding of the V4 region of the ribosomal RNA small sub-unit gene. We assessed and modelled the diversity (Shannon index) patterns of all selected groups as a function of topo-climatic and edaphic variables using Generalized Additive Models.ResultsThe respective significance of topo-climatic and edaphic variables varied among taxonomic and – to a certain extent – functional groups: while many variables explained significantly the diversity of phototrophs this was less the case for parasites. Generally, topo-climatic variables had a better predictive power than edaphic variables, yet predictive power varied among taxonomic and functional groups.Main conclusionsTopo-climatic variables are, on average, better predictors of protist diversity at the landscape scale than edaphic variables, which opens the way to wide-scale sampling designs avoiding costly and time-consuming laboratory protocols. However, predictors of diversity differ considerably among taxonomic and functional groups; such relationships may be due to direct and/or indirect, e.g. biotic influences. Future prospects include using such spatial models to predict hotspots of diversity or pathogens outbreaks.
Targeting MOG to skin macrophages prevents EAE in macaques through TGFβ-induced peripheral tolerance
Authors: Fovet Claire-Maëlle , Stimmer Lev , Contreras Vanessa , Horellou Philippe , Hubert Audrey , Sediki Nabila , Chapon Catherine , Tricot Sabine , Leroy Carole , Flament Julien , Massonneau Julie , Tchitchek Nicolas , ’t Hart Bert A. , Zurawski Sandra , Klucar Peter , Deiva Kumaran , Zurawski Gerard , Oh SangKon , Le Grand Roger , Serguera Ché 
Published: March 2019

AbstractTo study the effect of vaccination on tolerization to the myelin antigen MOG we used a macaque model of experimental autoimmune encephalitis (EAE) in which immunization with recombinant human myelin oligodendrocyte glycoprotein (rhMOG) elicits brain inflammation and demyelination mediated by MOG-specific autoreactive CD4+ T lymphocytes and anti-MOG IgG. For antigen targeting to tolerizing antigen presenting cells, we used a recombinant antibody directed to the Dendritic Cells (DC)-Asialoglycoprotein receptor (DC-ASGPR). The intradermal administration of an anti-DC-ASGPR-MOG fusion protein, but not a control anti-DC-ASGPR-PSA (prostate specific antigen) protein, protected monkeys committed to develop EAE. Although effective treatment did not modify anti-MOG IgG production, it prevented the CD4+ T lymphocyte activation and pro-inflammatory cytokine production. Moreover, animals treated with anti-DC-ASGPR-MOG experienced a rise of MOG-specific CD4+CD25+FOXP3+CD39+ regulatory T cells as well as a TGFβ1, TGFβ2 and IL-8 upsurge after rhMOG re-immunization. Our results indicate that the pathogenicity of autoantibodies directed to MOG is mitigated in the presence of MOG-specific regulatory lymphocytes. This vaccination scheme appears suitable to treat relapsing autoimmune diseases with identified autoantigens such as that harboring anti-MOG or anti-AQP4 autoantibodies.
SPiQE: an automated analytical tool for detecting and characterising fasciculations in amyotrophic lateral sclerosis
Authors: Bashford J , Wickham A , Iniesta R , Drakakis E , Boutelle M , Mills K , Shaw C 
Published: March 2019

AbstractOBJECTIVESFasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). Compared to concentric needle EMG, high-density surface EMG (HDSEMG) is non-invasive and records fasciculation potentials (FPs) from greater muscle volumes over longer durations. To detect and characterise FPs from vast data sets generated by serial HDSEMG, we developed an automated analytical tool.METHODSSix ALS patients and two control patients (one with benign fasciculation syndrome and one with multifocal motor neuropathy) underwent 30-minute HDSEMG from biceps and gastrocnemius monthly. In MATLAB we developed a novel, innovative method to identify FPs amidst fluctuating noise levels. One hundred repeats of 5-fold cross validation estimated the model’s predictive ability.RESULTSBy applying this method, we identified 5,318 FPs from 80 minutes of recordings with a sensitivity of 83.6% (+/-0.2 SEM), specificity of 91.6% (+/-0.1 SEM) and classification accuracy of 87.9% (+/-0.1 SEM). An amplitude exclusion threshold (100μV) removed excessively noisy data without compromising sensitivity. The resulting automated FP counts were not significantly different to the manual counts (p=0.394).CONCLUSIONWe have devised and internally validated an automated method to accurately identify FPs from HDSEMG, a technique we have named Surface Potential Quantification Engine (SPiQE).SIGNIFICANCELongitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.HighlightsSPiQE combines serial high-density surface EMG with an innovative signal-processing methodologySPiQE identifies fasciculations in ALS patients with high sensitivity and specificityThe optimal noise-responsive model achieves an average classification accuracy of 88%
Direct control of shell regeneration by the mantle tissue in the pearl oysterPinctada fucatavia accelerating CaCO3 nucleation
Authors: Huang Jingliang , Liu Yangjia , Jiang Taifeng , Dong Wentao , Zheng Guilian , Xie Liping , Zhang Rongqing 
Published: March 2019

AbstractMolluscan bivalves rapidly repair the damaged shells to prevent further injury. However, it remains unclear how this process is precisely controlled. In this study, we applied scanning electronic microscopy, transmission electronic microscopy and histochemical analysis to examine the detailed shell regeneration process of the pearl oysterPinctada fucata. It was found that the shell damage caused the mantle tissue to retract, which resulted in dislocation of the mantle zones to their correspondingly secreted shell layers. However, the secretory repertoires of the different mantle zones remained unchanged. As a result, the dislocation of the mantle tissue dramatically affected the shell morphology, and the unusual presence of the submarginal zone on the nacreous layers caused de novo precipitation of prismatic layers on the nacreous layers. Real-time PCR revealed that the expression of the shell matrix proteins (SMPs) were significantly upregulated, which was confirmed by the thermal gravimetric analysis (TGA) of the newly formed shell. The increased matrix secretion accelerated CaCO3nucleation thus promoting shell deposition. Taken together, our study revealed the close relationship between the physiological activities of the mantle tissue and the morphological change of the regenerated shells.
Temporal variation of fatty acid composition and pesticides in honeybeesApis melliferaand beebread
Authors: Gooley Zuyi C. , Gooley Aaron C. 
Published: March 2019

AbstractA twelve-month study was conducted on changes in fatty acid composition and pesticide residues in honeybees and beebread. In honeybees, saturated fatty acid and monounsaturated fatty acid gradually increased as summer began then decreased when spring started, and polyunsaturated fatty acid had an opposite seasonal trend. Similar fluctuation was observed in the beebread collected from the same hive as those honeybees through summer to fall, especially in the essential fatty acids omega-6 and omega-3. Honeybees’ lipid metabolism can be disrupted after being exposed to a sub-lethal level of pesticide. Although three out of sixteen analyzed pesticides were detected in beebread samples summer through fall in our study, we were not able to find any negative affect of those pesticides on the honeybees’ fatty acid composition. Temporary field-realistic pesticide exposure may weaken honeybees but are unlikely to show any reflection in their fat bodies if the colony was otherwise healthy.
A distinct pool of Nav1.5 channels at the lateral membrane of murine ventricular cardiomyocytes
Authors: Rougier Jean-Sébastien , Essers Maria C. , Gillet Ludovic , Guichard Sabrina , Sonntag Stephan , Shmerling Doron , Abriel Hugues 
Published: March 2019

AbstractBackgroundIn cardiac ventricular muscle cells, the presence of voltage-gated sodium channels Nav1.5 at the lateral membrane depends in part on the interaction between the dystrophin-syntrophin complex and the Nav1.5 C-terminal PDZ-domain-binding sequence Ser-Ile-Val (SIV motif). α1-Syntrophin, a PDZ-domain adaptor protein, mediates the interaction between Nav1.5 and dystrophin at the lateral membrane of cardiac cells. Using the cell-attached patch-clamp approach on cardiomyocytes expressing Nav1.5 in which the SIV motif is deleted (ΔSIV), sodium current (INa) recordings from the lateral membrane revealed an SIV-motif-independent INa. Since immunostainings have suggested that Nav1.5 is expressed in transverse (T-) tubules, this remaining INa might be conducted by channels in the T-tubules. Of note, a recent study using heterologous expression systems showed that α1-syntrophin also interacts with the Nav1.5 N-terminus, which may explain the SIV-motif independent INa at the lateral membrane of cardiomyocytes.AimTo address the role of α1-syntrophin in regulating the INa at the lateral membrane of cardiac cells.Methods and resultsPatch-clamp experiments in cell-attached configuration were performed on the lateral membranes of wild-type, α1-syntrophin knock-down, and ΔSIV ventricular mouse cardiomyocytes. Compared to wild-type, a reduction of the lateral INa was observed in myocytes from α1-syntrophin knockdown hearts. However, similar to ΔSIV myocytes, a remaining INa was still recorded. In addition, cell-attached INa recordings from lateral membrane did not differ significantly between non-detubulated and detubulated ΔSIV cardiomyocytes. Lastly, we obtained evidence suggesting that cell-attached patch-clamp experiments on the lateral membrane cannot record currents conducted by channels in T-tubules such as calcium channels.ConclusionAltogether, these results suggest the presence of a sub-pool of sodium channels at the lateral membrane of cardiomyocytes that is independent of α1-syntrophin and the PDZ-binding motif of Na 1.5, located in membrane domains outside of T-tubules. The question of a T-tubular pool of Nav1.5 channels however remains open.