bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selecting forChlamydomonas reinhardtiifitness in a liquid algal growth system compatible with the International Space Station Veggie plant growth chamber
Authors: Zhang Junya , Müller Bárbara S.F. , Tyre Kevin N. , Bai Fang , Hu Ying , Resende Marcio F.R. , Rathinasabapathi Bala , Settles A. Mark 
Published: January 2020

AbstractA biological life support system for spaceflight would capture carbon dioxide waste produced by living and working in space to generate useful organic compounds. Photosynthesis is the primary mechanism to fix carbon into organic molecules. Microalgae are highly efficient at converting light, water, and carbon dioxide into biomass, particularly under limiting, artificial light conditions that are a necessity in space photosynthetic production. Although there is great promise in developing algae for chemical or food production in space, most spaceflight algae growth studies have been conducted on solid agar-media to avoid handling liquids in microgravity. Here we report that breathable plastic tissue culture bags can support robust growth ofChlamydomonas reinhardtiiin the Veggie plant growth chamber, which is used on the International Space Station to grow terrestrial plants. Live cultures can be stored for at least one month in the bags at room temperature. The gene set required for growth in these photobioreactors was tested through a short-wave ultraviolet light (UVC) mutagenesis and selection experiment with wild-type (CC-5082) andcw15mutant (CC-1883) strains. Genome sequencing identified UVC-induced mutations, which were enriched for transversions and nonsynonymous mutations relative to natural variants among laboratory strains. Genes with mutations indicating positive selection were enriched for information processing genes related to DNA repair, RNA processing, translation, cytoskeletal motors, kinases, and ABC transporters. These data suggest modification of signal transduction and metabolite transport may be needed to improve growth rates in this spaceflight production system.
Distraction attenuates goal-directed neural responses for food rewards
Authors: Duif Iris , Wegman Joost , de Graaf Kees , Smeets Paul A.M. , Aarts Esther 
Published: January 2020

AbstractDistracted eating can lead to increased food intake, but it is unclear how. We hypothesized that distraction affects the change in motivated responses for food reward after satiation. To investigate this, 38 healthy normal-weight participants (28F, 10M) performed a detection task varying in attentional load (high or low distraction) during fMRI. Simultaneously, they exerted effort for food rewards (sweet or savory) by repeated button presses. Two fMRI runs were separated by outcome devaluation (satiation) of one of the reward outcomes, to assess outcome-sensitive, i.e. goal-directed, responses. Behavioral results showed no effect of distraction on effort for food reward following outcome devaluation. At an uncorrected threshold (p<0.001), distraction decreased goal-directed responses (devalued versus valued) in the right inferior frontal gyrus (rIFG). Importantly, these distraction-sensitive rIFG responses correlated negatively (r= - 0.40,p= 0.014) with the effect of distraction on the number of button presses. Specifically, decreased rIFG responses due to distraction related to increased button presses for food reward after satiation, in line with the rIFG’s established role in response inhibition. Furthermore, distraction decreased functional connectivity between the rIFG (seed) and left putamen for valued versus devalued food rewards (pFWE(cluster)<0.05). Our results suggest that distraction attenuates the ability to inhibit responses for food reward after satiation by affecting the rIFG. Furthermore, distraction attenuated connectivity between two regions involved in response inhibition – rIFG and putamen – after outcome devaluation. These results may explain why distraction can lead to overeating in our current, distracting, environment. The study was preregistered at:https://osf.io/ad2qk.
Solid-Phase Peptide Capture and Release for Bulk and Single-Molecule Proteomics
Authors: Howard Cecil J , Floyd Brendan M. , Bardo Angela M. , Swaminathan Jagannath , Marcotte Edward M. , Anslyn Eric V. 
Published: January 2020

AbstractThe field of proteomics has expanded recently with more sensitive techniques for the bulk measurement of peptides as well as single-molecule techniques. One limiting factor for some of these methods is the need for multiple chemical derivatizations and highly pure proteins free of contaminants. We demonstrate a solid-phase capture strategy suitable for the proteolysis, purification, and subsequent chemical modification of peptides. We use this resin on an HEK293T cell lysate and perform one-pot proteolysis, capture, and derivatization to generate a cellular proteome that identified over 40,000 bead-bound peptides. We also show that this capture can be reversed in a traceless manner, such that it is amenable for single-molecule proteomics techniques. With this technique, we perform a fluorescent labeling and C-terminal derivatization on a peptide and subject it to fluorosequencing, demonstrating that washing the resin is sufficient to remove excess dyes and other reagents prior to single-molecule protein sequencing.
Functionalized Mesoporous Silicas Direct Structural Polymorphism of Amyloid-β Fibrils
Authors: Lucas Michael J. , Pan Henry S. , Verbeke Eric J. , Webb Lauren J. , Taylor David W. , Keitz Benjamin K. 
Published: January 2020

AbstractThe aggregation of Amyloid-β (Aβ) is associated with the onset of Alzheimer’s Disease (AD) and involves a complex kinetic pathway as monomers self-assemble into fibrils. A central feature of amyloid fibrils is the existence of multiple structural polymorphs, which complicates the development of disease-relevant structure-function relationships. Developing these relationships requires new methods to control fibril structure. In this work, we demonstrate that mesoporous silicas (SBA-15) functionalized with hydrophobic (SBA-PFDTS) and hydrophilic groups (SBA-PEG) direct the aggregation kinetics and resulting structure of Aβ1-40fibrils. The hydrophilic SBA-PEG had little effect on amyloid kinetics while as-synthesized and hydrophobic SBA-PFDTS accelerated aggregation kinetics. Subsequently, we quantified the relative population of fibril structures formed in the presence of each material using electron microscopy. Fibrils formed from Aβ1-40exposed to SBA-PEG were structurally similar to control fibrils. In contrast, Aβ1-40incubated with SBA-15 or SBA-PFDTS formed fibrils with shorter cross-over distances that were more structurally representative of fibrils found in AD patient-derived samples. Overall, these results suggest that mesoporous silicas and other exogenous materials are promising scaffolds for thede novoproduction of specific fibril polymorphs of Aβ1-40and other amyloidogenic proteins.Significance StatementA major challenge in understanding the progression of Alzheimer’s Disease lies in the various fibril structures, or polymorphs, adopted by Amyloid-β (Aβ). Heterogenous fibril populations may be responsible for different disease phenotypes and growing evidence suggests that Aβ fibrils formedin vitroare structurally distinct from patient-derived fibrils. To help bridge this gap, we used surface-functionalized mesoporous silicas to influence the formation of Aβ1-40fibrils and evaluated the distribution of resulting fibril polymorphs using electron microscopy (EM). We found that silicas modified with hydrophobic surfaces resulted in fibril populations with shorter cross-over distances that are more representative of Aβ fibrils observedex vivo. Overall, our results indicate that mesoporous silicas may be leveraged for the production of specific Aβ polymorphs.
A novel redox-active switch in Fructosamine-3-kinases expands the regulatory repertoire of the protein kinase superfamily
Authors: Shrestha Safal , Katiyar Samiksha , Sanz-Rodriguez Carlos E. , Kemppinen Nolan R. , Kim Hyun W. , Kadirvelraj Renuka , Panagos Charalampos , Keyhaninejad Neda , Colonna Maxwell , Chopra Pradeep , Byrne Dominic P. , Boons Geert J. , van der Knaap Esther , Eyers Patrick A. , Edison Arthur S. , Wood Zachary A. , Kannan Natarajan 
Published: January 2020

AbstractAberrant regulation of metabolic kinases by altered redox homeostasis is a major contributing factor in aging and disease such as diabetes. However, the biochemical mechanisms by which metabolic kinases are regulated under oxidative stress is poorly understood. In this study, we demonstrate that the catalytic activity of a conserved family of Fructosamine-3-kinases (FN3Ks), which are evolutionarily related to eukaryotic protein kinases (ePKs), are regulated by redox-active cysteines in the kinase domain. By solving the crystal structure of FN3K homolog fromArabidopsis thaliana(AtFN3K), we demonstrate that it forms an unexpected strand-exchange dimer in which the ATP binding P-loop and adjoining beta strands are swapped between two chains in the dimer. This dimeric configuration is characterized by strained inter-chain disulfide bonds that stabilize the P-loop in an extended conformation. Mutational analysis and solution studies confirm that the strained disulfides function as redox “switches” to reversibly regulate FN3K activity and dimerization. Consistently, we find that human FN3K (HsFN3K), which contains an equivalent P-loop Cys, is also redox-sensitive, whereas ancestral bacterial FN3K homologs, which lack a P-loop Cys, are not. Furthermore, CRISPR knockout of FN3K in human HepG2 cells results in significant upregulation of redox metabolites including glutathione. We propose that redox regulation evolved progressively in FN3Ks in response to changing cellular redox conditions. Our studies provide important new insights into the origin and evolution of redox regulation in the protein kinase superfamily and open new avenues for targeting HsFN3K in diabetic complications.
A healthy childhood environment helps to combat inherited susceptibility to obesity
Authors: Hüls Anke , Wright Marvin N , Bogl Leonie H , Kaprio Jaakko , Lissner Lauren , Molnár Denes , Moreno Luis , De Henauw Stefaan , Siani Alfonso , Veidebaum Toomas , Ahrens Wolfgang , Pigeot Iris , Foraita Ronja ,   on behalf of the IDEFICS/I.Family consortia
Published: January 2020

AbstractObjectivesTo investigate the degree by which the inherited susceptibility to obesity is modified by environmental factors during childhood and adolescence.DesignCohort study with repeated measurements of diet, lifestyle factors and anthropometry.SettingThe pan-European IDEFICS/I.Family cohortParticipants8,609 repeated observations from 3,098 children aged 2 to 16 years, examined between 2007 and 2014.Main outcome measuresBody mass index (BMI) and waist circumference. Genome-wide polygenic risk scores (PRS) to capture the inherited susceptibility of obesity were calculated using summary statistics from independent genome-wide association studies of BMI. Gene-environment interactions of the PRS with sociodemographic (European region, socioeconomic status) and lifestyle factors (diet, screen time, physical activity) were estimated.ResultsThe PRS was strongly associated with BMI (r2= 0.11, p-value = 7.9 × 10−81) and waist circumference (r2= 0.09, p-value = 1.8 × 10−71) in our cohort. The associations with BMI increased from r2=0.03 in 3-year olds to r2=0.18 in 14-year olds and associations with waist circumference from r2=0.03 to r2=0.14. Being in the top decile of the PRS distribution was associated with 3.63 times higher odds for obesity (95% confidence interval (CI): [2.57, 5.14]). We observed significant interactions with demographic and lifestyle factors for BMI as well as waist circumference. The risk of becoming obese among those with higher genetic susceptibility was ~38% higher in children from Southern Europe (BMI: p-interaction = 0.0066, Central vs. Southern Europe) and ~61% higher in children with a low parental education (BMI: p-interaction = 0.0012, low vs. high). Furthermore, the risk was attenuated by a higher intake of dietary fiber (BMI: p-interaction=0.0082) and shorter screen times (BMI: p-interaction=0.018).ConclusionsOur results highlight that a healthy childhood environment might partly offset a genetic predisposition to obesity during childhood and adolescence.
Recessive deleterious variation has a limited impact on signals of adaptive introgression in human populations
Authors: Zhang Xinjun , Kim Bernard , Lohmueller Kirk E. , Huerta-Sánchez Emilia 
Published: January 2020

AbstractAdmixture with archaic hominins has altered the landscape of genomic variation in modern human populations. Several gene regions have been previously identified as candidates of adaptive introgression (AI) that facilitated human adaptation to specific environments. However, simulation-based studies have suggested that population genetics processes other than adaptive mutations, such as heterosis from recessive deleterious variants private to populations before admixture, can also lead to patterns in genomic data that resemble adaptive introgression. The extent to which the presence of deleterious variants affect the false-positive rate and the power of current methods to detect AI has not been fully assessed. Here, we used extensive simulations to show that recessive deleterious mutations can increase the false positive rates of tests for AI compared to models without deleterious variants. We further examined candidates of AI in modern humans identified from previous studies and show that, although deleterious variants may hinder the performance of AI detection in modern humans, most signals remained robust when deleterious variants are included in the null model. While deleterious variants may have a limited impact on detecting signals of adaptive introgression in humans, we found that at least two AI candidate genes,HYAL2andHLA, are particularly susceptible to high false positive rates due to the recessive deleterious mutations. By quantifying parameters that affect heterosis, we show that the high false positives are largely attributed to the high exon densities together with low recombination rates in the genomic regions, which can further be exaggerated by the population growth in recent human evolution. Although the combination of such parameters is rare in the human genome, caution is still warranted in other species with different genomic composition and demographic histories.
Combined Treatment with Dopamine Receptor Antagonists and Radiation Creates a Metabolic Vulnerability in Mouse Models of Glioblastoma
Authors: Saki Mohammad , Bhat Kruttika , Cheng Fei , He Ling , Zhang Le , Ioannidis Angeliki , Nathanson David , Tsang Jonathan , Nghiemphu Phioanh Leia , Cloughesy Timothy F. , Liau Linda M. , Kornblum Harley I. , Pajonk Frank 
Published: January 2020

AbstractBackgroundGlioblastoma is the deadliest brain tumor in adults and the standard-of-care consists of surgery followed by radiation and treatment with temozolomide. Overall survival times for patients suffering from glioblastoma are unacceptably low indicating an unmet need for novel treatment options.MethodsUsing patient-derived glioblastoma lines and mouse models of glioblastoma we test the effect of radiation and the dopamine receptor antagonist on glioblastoma self-renewalin vitroand survivalin vivo.A possible resistance mechanism is investigated using RNA-Sequencing.ResultsTreatment of glioma cells with the dopamine receptor antagonist quetiapine reduced glioma cell self-renewalin vitroand combined treatment of mice with quetiapine and radiation prolonged the survival of glioma-bearing animals. The combined treatment induced the expression of genes involved in cholesterol biosynthesis. This rendered the tumors vulnerable to simultaneous treatment with atorvastatin and further significantly prolonged the survival of the animals.ConclusionsOur results indicate high efficacy of a triple combination of quetiapine, atorvastatin and radiation against glioblastoma without increasing the toxicity of radiation. With both drugs readily available for clinical use our study could be rapidly translated into a clinical trial.
Defoliation-induced compensatory transpiration is compromised inSUT4-RNAiPopulus
Authors: Harding Scott A. , Frost Christopher J. , Tsai Chung-Jui 
Published: January 2020

AbstractLeaf sucrose contents are high in species of the genusPopulusand other temperate tree taxa. Sucrose is subcellularly compartmentalized, but assumptions about the physiological relevance of such partitioning remain largely unexplored. In this study, the effects of partial defoliation treatments on water uptake, leaf gas exchange properties, non-structural carbohydrate abundance in source and sink organs, and growth were compared in poplars with normal or impaired intracellular sucrose trafficking. The tonoplast sucrose transporter PtaSUT4 is well expressed in leaves ofP. tremula×P. alba(INRA 717-IB4), and its inhibition by RNA-interference (RNAi) is known to affect leaf sucrose abundance. After partial defoliation, maximum photosynthesis rates increased while intercellular CO2decreased with trajectories that were similar in wild type andSUT4-RNAi lines. Leaf transpiration increased more robustly in wild-type than RNAi plants, while leaf water content increased more in RNAi lines. Stomatal conductance did not differ between genotypes, nor did it increase with defoliation. Post-defoliation reductions in steady-state levels of sucrose, the major hexoses (glucose and fructose) and starch were similar in wild-type andSUT4-RNAi shoot sinks. Water uptake and stem growth after partial defoliation were not as well sustained in RNAi as in wild-type plants. The data suggest that vacuolar efflux of sucrose by PtaSUT4 more clearly facilitated adjustments in water uptake than sucrose export following leaf removal.
Rotten-skin disease significantly changed giant spiny frog(Paa spinosa) gut microbiota
Authors: He Tuoyu , Jiang Yun , Wang Pengpeng , Xiang Jianguo , Pan Wangcheng 
Published: January 2020

AbstractThe composition and abundance of gut microbiota is essential for host health and immunity. Gut microbiota is symbiotic with the host, so changes in the host diet, development, and health will lead to changes in the gut microbiota. Conversely, changes in the gut microbiota also affect the host conditions. In this experiment, 16S rRNA high-throughput sequencing was used to compare the gut microbiota composition of 5 healthyPaa Spinosaand 6P. spinosawith rotten-skin disease. Results: the gut microbiota composition was significant difference between diseasedP. spinosaand the healthyP. spinosa; LEfSe analysis showed that the relative abundance ofMethanocorpusculum, Parabacteroides, AF12, PW3, Epulopiscium, andOscillospirawere significantly higher in the diseasedP. spinosa, while the relative abundance ofSerratia, Eubacteium, Citrobacter, andMorganellawere significantly lower. Conclusion: Rotten-skin disease changedP. spinosagut microbiota significantly; The relative abundance ofEpulopisciumandOscillospiramight be related to the health conditions of the host skin and gallbladder; The relative abundance ofSerratiaandEubacteiummight be important for maintaining the gut microbiota ecosystem.
SpikeForest: reproducible web-facing ground-truth validation of automated neural spike sorters
Authors: Magland Jeremy F. , Jun James J. , Lovero Elizabeth , Morley Alexander J. , Hurwitz Cole L. , Buccino Alessio P. , Garcia Samuel , Barnett Alex H. 
Published: January 2020

AbstractSpike sorting is a crucial but time-intensive step in electrophysiological studies of neuronal activity. While there are many popular software packages for spike sorting, there is little consensus about which are the most accurate under different experimental conditions. SpikeForest is an open-source and reproducible software suite that benchmarks the performance of automated spike sorting algorithms across an extensive, curated database of electrophysiological recordings with ground truth, displaying results interactively on a continuously-updating website. With contributions from over a dozen participating laboratories, our database currently comprises 650 recordings (1.3 TB total size) with around 35,000 ground-truth units. These data include extracellular recordings paired with intracellular voltages, state-of-the-art simulated recordings, and hybrid synthetic datasets. Ten of the most frequently used modern spike sorting codes are wrapped under a common Python framework and evaluated on a compute cluster using an automated pipeline. SpikeForest validates and documents community progress in automated spike sorting, and guides neuroscientists to an optimal choice of sorter and parameters for a wide range of probes and brain regions.
Impact of phosphorylation on thermal stability of proteins
Authors: Potel Clément M. , Kurzawa Nils , Becher Isabelle , Typas Athanasios , Mateus André , Savitski Mikhail M. 
Published: January 2020

SummaryReversible protein phosphorylation regulates virtually every cellular process and is arguably the most well-studied post-translational modification. Still, less than 3% of the phosphorylation sites identified in humans have annotated functions. Functionally-relevant phosphorylation sites are known to trigger conformational changes to proteins and/or to regulate their interactions with other proteins, nucleic acids and small molecules - all of which can be reflected in the thermal stability of a protein. Thus, combining thermal proteome profiling (TPP) with phosphoproteomics (phospho-TPP) provides a way to assess the functional relevance of identified phosphorylation sites on a proteome-wide scale by comparing the melting behavior of a protein and its phosphorylated form(s). We performed phospho-TPP experiments in HeLa cells with an optimized protocol, and conclude that phosphorylation does affect protein thermal stability, but to a much lesser extent than previously reported.
Identification of phosphosites that alter protein thermal stability
Authors: Smith Ian R. , Hess Kyle N. , Bakhtina Anna A. , Valente Anthony S. , Rodríguez-Mias Ricard A. , Villén Judit 
Published: January 2020

ABSTRACTProteomics has enabled the cataloguing of 100,000s of protein phosphorylation sites1, however we lack methods to systematically annotate their function. Phosphorylation has numerous biological functions, yet biochemically all involve changes in protein structure and interactions. These biochemical changes can be recapitulated by measuring the difference in stability between the protein and the phosphoprotein. Building on recent work, we present a method to infer phosphosite functionality by reliably measuring such differences at the proteomic scale.