bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Potential of Two Common Pacific Coast Macroalgae for Mitigating Methane Emissions from Ruminants
Authors: Brooke Charles G. , Roque Breanna M. , Najafi Negeen , Gonzalez Maria , Pfefferlen Abigail , DeAnda Vannesa , Ginsburg David W. , Harden Maddelyn C. , Nuzhdin Sergey V. , Salwen Joan King , Kebreab Ermias , Hess Matthias 
Published: October 2018

AbstractWith increasing interest in feed based methane mitigation strategies, fueled by local legal directives aimed at methane production from the agricultural sector in California, identifying local sources of biological feed additives will be critical in keeping the implementation of these strategies affordable. In a recent study, the red alga Asparagopsis taxiformis stood out as the most effective species of seaweed to reduce methane production from enteric fermentation. Due to the potential differences in effectiveness based on the location from where A. taxiformis is collected and the financial burden of collection and transport, we tested the potential of A. taxiformis, as well as the brown seaweed Zonaria farlowii collected in the nearshore waters off Santa Catalina Island, CA, USA, for their ability to mitigate methane production during in-vitro rumen fermentation. At a dose rate of 5% dry matter (DM), A. taxiformis reduced methane production by 74% (p ≤ 0.01) and Z. farlowii reduced methane production by 11% (p ≤ 0.04) after 48 hours and 24 hours of in-vitro rumen fermentation respectively. The methane reducing effect of A. taxiformis and Z. farlowii described here make these local macroalgae promising candidates for biotic methane mitigation strategies in the largest milk producing state in the US. To determine their real potential as methane mitigating feed supplements in the dairy industry, their effect in-vivo requires investigation.
Phylogeny, ancestors and anagenesis in the hominin fossil record
Authors: Parins-Fukuchi Caroline , Greiner Elliot , MacLatchy Laura M. , Fisher Daniel C. 
Published: October 2018

AbstractProbabilistic approaches to phylogenetic inference have recently gained traction in paleontological studies. Because they directly model processes of evolutionary change, probabilistic methods facilitate a deeper assessment of variability in evolutionary pattern by weighing evidence for competing models. Although phylogenetic methods used in paleontological studies have generally assumed that evolution proceeds by splitting cladogenesis, extensions to previous models help explore the potential for morphological and temporal data to provide differential support for contrasting modes of evolutionary divergence. Recent methodological developments have integrated ancestral relationships into probabilistic phylogenetic methods. These new approaches rely on parameter-rich models and sophisticated inferential methods, potentially obscuring the respective contributions of data and models. In this study, we describe a simple likelihoodist approach that combines probabilistic models of morphological evolution and fossil preservation to reconstruct both cladogenetic and anagenetic relationships. By applying this approach to a dataset of fossil hominins, we demonstrate the capability of existing models to unveil evidence for anagenesis presented by morphological and temporal data. This evidence was previously recognized by qualitative assessments, but largely ignored by quantitative phylogenetic analyses. For example, we find support for directly ancestral relationships in multiple lineages:Sahelanthropusis ancestral to later hominins;Australopithecus anamensisis ancestral toAu. afarensis;Au. garhiis ancestral toHomo;H. antecessoris ancestral toH. heidelbergensis, which in turn is ancestral to bothH. sapiensandH. neanderthalensis. These results show a benefit of accommodating direct ancestry in phylogenetics. By so doing, quantitative results align more closely with previous qualitative expectations.
Alzheimer’s Amyloid-Beta Intermediates Generated by Polymer-Nanodiscs
Authors: Sahoo Bikash R. , Genjo Takuya , Bekier Michael , Cox Sarah J. , Stoddard Andrea K. , Ivanova Magdalena , Yasuhara Kazuma , Fierke Carol A. , Wang Yanzhuang , Ramamoorthy Ayyalusamy 
Published: October 2018

AbstractPolymethacrylate-copolymer (PMA) encased lipid-nanodiscs (~10 nm) and macro-nanodiscs (>15 nm) are used to study Aβ1-40 aggregation. We demonstrate that PMA-nanodiscs form a ternary association with Aβ and regulate its aggregation kinetics by trapping intermediates. Results demonstrating reduced neurotoxicity of nanodisc-bound Aβ oligomers are also reported.
Sacubitril/valsartan (LCZ696) Significantly Reduces Aldosterone and Increases cGMP Circulating Levels in a Canine Model of RAAS Activation
Authors: Mochel Jonathan P , Teng Chi Hse , Peyrou Mathieu , Giraudel Jerome , Danhof Meindert , Rigel Dean F 
Published: October 2018

AbstractSimultaneous blockade of angiotensin receptors and enhancement of natriuretic peptides (NP) by the first-in-class angiotensin receptor neprilysin (NEP) inhibitor sacubitril/valsartan constitutes an effective approach to treating heart failure. This study examined the effects of sacubitril/valsartan (225 and 675mg/day) vs. placebo, sacubitril (360mg/day), valsartan (900mg/day), and benazepril (5mg/day) on the dynamics of the renin-angiotensin-aldosterone system (RAAS) and the NP system in dogs. Beagle dogs (n=18) were fed a low-salt diet (0.05% Na) for 15 days to model RAAS activation observed in clinical heart failure. Drugs were administered once daily during the last 10 days, while the effects on the RAAS and NPs were assessed on days 1, 5, and 10. Steady-state pharmacokinetics of the test agents were evaluated on day 5. Compared with placebo, sacubitril/valsartan (675mg) substantially increased cGMP circulating levels, while benazepril and valsartan showed no effect. Additionally, sacubitril/valsartan (675mg) and valsartan significantly increased plasma renin activity, angiotensin I and angiotensin II concentrations. Finally, sacubitril/valsartan (both doses), and valsartan significantly decreased plasma aldosterone vs. placebo. Systemic exposure to valsartan following sacubitril/valsartan 675mg administration was similar to that observed with valsartan 900mg administration alone. Sacubitril/valsartan favorably modulates the dynamics of the renin and NP cascades through complementary NEP and RAAS inhibition.
Rate of photosynthetic acclimation to fluctuating light varies widely among genotypes of wheat
Authors: Salter William T. , Merchant Andrew M. , Richards Richard A. , Trethowan Richard , Buckley Thomas N. 
Published: October 2018

HighlightSignificant variation exists in the acclimation time of photosynthesis following dark-to-light transitions across wheat genotypes, under field and controlled conditions. Slow acclimation reduced daily carbon assimilation by up to 16%.AbstractCrop photosynthesis and yield are limited by slow photosynthetic induction in sunflecks. We quantified variation in induction kinetics across diverse genotypes of wheat for the first time. In a preliminary study using penultimate leaves of 58 genotypes grown in the field, we measured induction kinetics for maximum assimilation rate (Amax) after a shift from full darkness to saturating light (1700 μmol m−2 s−1) with 1-4 replicates per genotype. We then grew 10 of these genotypes with contrasting responses in a controlled environment and quantified induction kinetics of carboxylation capacity (Vcmax) from dynamic A vs ci curves after a shift from low to high light (50 to 1500 μmol m−2 s−1), with 5 replicates per genotype. Within-genotype median time for 95% induction (t95) varied from 8.4 to 23.7 min across genotypes for Amax in field-grown penultimate leaves, and from 6.7 to 10.4 min for Vcmaxin chamber-grown flag leaves. Our simulations suggested that non-instantaneous acclimation reduces daily net carbon gain by up to 16%, and that breeding to speed up Vcmax induction in the slowest genotype to match that in the fastest genotype could increase daily net carbon gain by more than 4%, particularly for leaves that experience predominantly short-duration sunflecks.
Targeting RyR2 with a phosphorylation site-specific nanobody Reverses Dysfunction of Failing Cardiomyocytes in Rat
Authors: Li Tian , Shen Yafeng , Lin Fangxing , Fu Wenyan , Liu Shuowu , Fan Xiaoyan , Ye Xuting , Tang Ying , Ding Min , Yang Yongji , Lei Changhai , Hu Shi 
Published: October 2018

AbstractChronic PKA phosphorylation of RyR2 has been shown to increased diastolic SR Ca2+ leak and lead to cardiac dysfunction. Since the change of phosphorylation level of RyR2 is a biomarker of failing heart, we attempted to verify the hypothesis that intracellular gene delivery of a RyR2 targeting phosphorylation site-specific nanobody could preserve contractility of failing myocardium. In present study, we acquired the RyR2-specific nanobodies from a phage display library which are variable domains of camellidae heavy chain-only antibodies (VHH). One of the monoclonal nanobodies, AR185, inhibiting RyR2 phosphorylation in an in vitro assay was then chosen for further investigation. We investigated the potential of adeno-associated virus (AAV)-9-mediated cardiac expression of AR185 against post-ischemic heart failure. Adeno-associated virus gene delivery elevated the intracellular expression AR185 protein in the ischemic heart failure model of rats, and this treatment normalized the systolic and diastolic dysfunction of the failing myocardium in vivo and in vitro by reversing myocardial Ca2+ handling. Furthermore, AR185 gene transfer to failing cardiomyocytes reduced the frequency of sarcoplasmic reticulum (SR) calcium leak, thereby restoring the attenuated intracellular calcium transients and SR calcium load. Moreover, AR185 gene transfer inhibited PKA phosphorylation of RyR2 in failing cardiomyocytes. Our results provided strong pre-clinical experimental evidence of the cardiac expression of RyR2 nanobody with AAV9 vectors as a promising therapeutic strategy for ischemic heart failure.
A perturbed gene network containing PI3K/AKT, RAS/ERK, WNT/β-catenin pathways in leukocytes is linked to ASD genetics and symptom severity
Authors: Gazestani Vahid H. , Pramparo Tiziano , Nalabolu Srinivasa , Kellman Benjamin P. , Murray Sarah , Lopez Linda , Pierce Karen , Courchesne Eric , Lewis Nathan E. 
Published: October 2018

ABSTRACTHundreds of genes are implicated in autism spectrum disorder (ASD) but the mechanisms through which they contribute to ASD pathophysiology remain elusive. Here, we analyzed leukocyte transcriptomics from 1-4 year-old male toddlers with ASD or typical development from the general population. We discovered a perturbed gene network that includes genes that are highly expressed during fetal brain development and which is dysregulated in hiPSC-derived neuron models of ASD. High-confidence ASD risk genes emerge as upstream regulators of the network, and many risk genes may impact the network by modulating RAS/ERK, PI3K/AKT, and WNT/β-catenin signaling pathways. We found that the degree of dysregulation in this network correlated with the severity of ASD symptoms in the toddlers. These results demonstrate how the heterogeneous genetics of ASD may dysregulate a core network to influence brain development at prenatal and very early postnatal ages and, thereby, the severity of later ASD symptoms.
PEPOP: new approaches to mimic non-continous epitopes
Authors: Demolombe Vincent , de Brevern Alexandre , Felicori Liza , NGuyen Christophe , de Avila Ricardo Andrez Machado , Valera Lionel , Jardin-Watelet Bénédicte , Lavigne Géraldine , Lebreton Aurélien , Molina Franck , Moreau Violaine 
Published: October 2018

AbstractBioinformatics methods are helpful to identify new molecules for diagnostic or therapeutic applications. For example, the use of peptides capable of mimicking binding sites has several benefits as replacing a protein difficult to produce, or toxic. Using peptides is less expensive. Peptides are easier to manipulate, and can be used as drugs. Continuous epitope predicted by bioinformatics tools are commonly used and these sequential epitopes are used as such in further experiments. Numerous discontinuous epitope predictors have been developed but only two bioinformatics tools proposed so far to predict peptide sequences: Superficial and PEPOP. PEPOP can generate series of peptide sequences that can replace continuous or discontinuous epitopes in their interaction with their cognate antibody. We have developed an improved version of PEPOP dedicated to answer to the experimentalists’ need for a tool able to handle proteins and to turn them into peptides. The PEPOP web site has been reorganized by peptide prediction category and is therefore better formulated to experimental designs. Since the first version of PEPOP, 32 new methods of peptide design were developed. In total, PEPOP proposes 35 methods in which 34 deal specifically with discontinuous epitopes, the most represented epitope type in nature.We present the user-friendly, well-structured web-site of PEPOP and its validation through the use of predicted immunogenic or antigenic peptides mimicking discontinuous epitopes in different experimental ways. PEPOP proposes 35 methods of peptide design to guide experimentalists in using peptides potentially capable of replacing the cognate protein in its interaction with an Ab.
Benchmarking the PEPOP methods for mimicking discontinuous epitopes
Authors: Demolombe Vincent , de Brevern Alexandre G. , Molina Franck , Lavigne Géraldine , Granier Claude , Moreau Violaine 
Published: October 2018

AbstractComputational methods provide approaches to identify epitopes in protein antigens to help characterizing potential biomarkers identified by high-throughput genomic or proteomic experiments. PEPOP version 1.0 was developed as an antigenic or immunogenic peptide prediction tool. We have now improved this tool by implementing 32 new methods (PEPOP version 2.0) to guide the choice of peptides that mimic discontinuous epitopes and thus potentially able to replace the cognate protein antigen in its interaction with an antibody. In the present work, we describe these new methods and the benchmarking of their performances.Benchmarking was carried out by comparing the peptides predicted by the different methods and the corresponding epitopes determined by X-ray crystallography in a dataset of 75 antigen-antibody complexes. The Sensitivity (Se) and Positive Predictive Value (PPV) parameters were used to assess the performance of these methods. The results were compared to that of peptides obtained either by chance or by using the SUPERFICIAL tool, the only available comparable method.The PEPOP methods were more efficient than, or as much as chance, and 33 of the 34 PEPOP methods performed better than SUPERFICIAL. Overall, “optimized” methods (tools that use the traveling salesman problem approach to design peptides) can predict peptides that best match true epitopes in most cases.
Gibberellin response in the embryo epidermis regulates germination uniformity in response to seed priming
Authors: Mitchell Jack , Mukhtar Nur K. , Skinner Isobel , Bassel George W. 
Published: October 2018

ABSTRACTUniformity in seed germination remains a primary objective in plant-based food production systems, ensuring predictable and synchronized harvest dates, while suppressing weeds. Treatments including priming can be used to increase germination uniformity and increase the value of commercial seeds. Despite the economic and agronomic importance of seed enhancement treatments, little is known as to how they work at a mechanistic level. Using a combination of molecular genetics and microscopy, we established that hydropriming limits embryo growth genetic programs at an early stage of germination. Conversely, gibberellin (GA) and abscisic acid (ABA)-associated molecular processes progress to later stages of this developmental chronology. The response to GA was specifically affected in the epidermis of germinating embryos in response to hydropriming based on reporter gene expression. The reduction of GA response specifically in the embryo epidermis resulted in increased uniformity of seed germination following hydropriming relative to control seeds. This represents the identification of both a molecular signalling pathway and cell type that are acting to enhance the agronomic germination properties of seed populations. This provides molecular and cellular targets which may be genetically manipulated to enhance seed germination and food production in agronomic species.
Pre-operarative Multivariate Connectome Analysis for Glioma Patients
Authors: Crimi Alessandro , Wiestler Benedikt , Kirschke Jan S. , Krieg Sandro M. 
Published: October 2018

AbstractRecent advances in neuroimaging have allowed the use of network analysis to study the brain in a system-based approach. A system-based analysis of gliomas can shed light on mechanisms underlying neuronal connectivity and plasticity and the recovery process, and it could support surgical decision-making. Surgery has been shifting from image-guided surgery to a functional mapping-guided resection where several structural and functional modalities are used. However, reliable identification of eloquent areas during planning of surgical resection is still a challenge. Pre-operative language mapping performed by navigated transcranial magnetic stimulation (nTMS) is of great value as it elucidates functional cortical organization, which might be different from patient to patient due to the heterogeneity of the lesions and individual plasticity. In this paper we propose the construction of an “effective” speech network used for surgical decision making. This is achieved by mapping functionally relevant areas identified by nTMS on tractography-based connectomics. Subsequently we compute graph metrics on the identified speech networks of patients who show preoperative aphasia aiming to identify relevant differences between graph metrics in patients with and without preoperative aphasia. Lastly, the validity of the speech networks is examined by checking the involved graph communities.
Defining the RNA Interactome by Total RNA-Associated Protein Purification
Authors: Shchepachev Vadim , Bresson Stefan , Spanos Christos , Petfalski Elisabeth , Fischer Lutz , Rappsilber Juri , Tollervey David 
Published: October 2018

ABSTRACTUV crosslinking can be used to identify precise RNA targets for individual proteins, transcriptome-wide. We sought to develop a technique to generate reciprocal data, identifying precise sites of RNA-binding proteome-wide. The resulting technique, total RNA-associated protein purification (TRAPP), was applied to yeast (S. cerevisiae) and bacteria (E. coli). In all analyses, SILAC labelling was used to quantify protein recovery in the presence and absence of irradiation. For S. cerevisiae, we also compared crosslinking using 254 nm (UVC) irradiation (TRAPP) with 4-thiouracil (4tU) labelling combined with ~350 nm (UVA) irradiation (PAR-TRAPP). Recovery of proteins not anticipated to show RNA-binding activity was substantially higher in TRAPP compared to PAR-TRAPP. As an example of preferential TRAPP-crosslinking, we tested enolase (Eno1) and demonstrated its binding to tRNA loops in vivo. We speculate that many protein-RNA interactions have biophysical effects on localization and/or accessibility, by opposing or promoting phase separation for highly abundant protein. Homologous metabolic enzymes showed RNA crosslinking in S. cerevisiae and E. coli, indicating conservation of this property. TRAPP allows alterations in RNA interactions to be followed and we initially analyzed the effects of weak acid stress. This revealed specific alterations in RNA-protein interactions; for example, during late 60S ribosome subunit maturation. Precise sites of crosslinking at the level of individual amino acids (iTRAPP) were identified in 395 peptides from 155 unique proteins, following phospho-peptide enrichment combined with a bioinformatics pipeline (Xi). TRAPP is quick, simple and scalable, allowing rapid characterization of the RNA-bound proteome in many systems.
Pore-scale hydrodynamics influence the spatial evolution of bacterial biofilms in a microfluidic porous network
Authors: Aufrecht Jayde A. , Fowlkes Jason , Bible Amber N. , Morrell-Falvey Jennifer , Doktycz Mitchel J. , Retterer Scott T. 
Published: October 2018

AbstractBacteria occupy heterogeneous environments, attaching and growing within pores in materials, living hosts, and matrices like soil. Systems that permit high-resolution visualization of dynamic bacterial processes within the physical confines of a realistic and tractable porous media environment are rare. Here we use microfluidics to replicate the particle shape and packing density of natural sands in a 2D platform to study the flow-induced spatial evolution of bacterial biofilms underground. We discover that initial bacterial dispersal and particle attachment is a stochastic process driven by bacterial rheotactic transport across pore space velocity gradients. Over time, we find that gravity-driven flow conditions activate different cell-clustering phentoypes in EPS producing and EPS defective bacteria strains, which subsequently changes the overall spatial distribution of cells across the porous media network as colonies grow and alter the fluid dynamics of their microenvironment.
Length regulation of multiple flagella that self-assemble from a shared pool of components
Authors: Fai Thomas G. , Mohapatra Lishibanya , Kondev Jane , Amir Ariel 
Published: October 2018

AbstractControl of organelle size is a problem that has intrigued cell biologists for at least a century. The single-celled green algaeChlamydomonas reinhardtiiwith its two 2agella has proved to be a very useful model organism for studies of size control. Numerous experiments have identi1ed motor-driven transport of tubulin to the growing ends of microtubules at the tip of the 2agella as the key component of the machinery responsible for controlling their length. Here we consider a model of 2agellar length control whose key assumption is that proteins responsible for the intra2agellar transport (IFT) of tubulin are present in limiting amounts. We show that this limiting-pool assumption and simple reasoning based on the law of mass action leads to an inverse relationship between the rate at which a 2agellum grows and its length, which has been observed experimentally, and has been shown theoretically to provide a mechanism for length control. Experiments in which one of the two 2agella are severed have revealed the coupled nature of the growth dynamics of the two 2agella, and we extend our length-control model to two 2agella by considering different mechanisms of their coupling. We describe which coupling mechanisms are capable of reproducing the observed dynamics in severing experiments, and why some that have been proposed previously are not. Within our theoretical framework we conclude that if tubulin and IFT proteins are freely exchanged between 2agella simultaneous length control is not possible if the disassembly rate is constant. However, if disassembly depends on the concentration of IFT proteins at the tip of the 2agellum, simultaneous length control can be achieved. Finally, we make quantitative predictions for experiments that could test this model.