bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Structured Professional Development Curriculum for Postdoctoral Fellows Leads to Recognized Knowledge Growth
Authors: Steen Kaylee , Vornhagen Jay , Weinberg Zara Y. , Boulanger-Bertolus Julie , Rao Arvind , Gardner Margery Evans , Subramanian Shoba 
Published: October 2020

AbstractPostdoctoral training enables research independence and professional readiness. National reports have emphasized professional development as a critical component of this training period. In response, many institutions are establishing transferable skills training workshops for postdocs; however, the lack of structured programs and an absence of methods to assess outcomes beyond participant satisfaction surveys are critical gaps in postdoctoral training. To address these shortcomings, we took the approach of structured programming and developed a method for controlled assessment of outcomes. Our program You3(You, Your Team, Your Project), co-designed by postdoctoral fellows, focused on a structured array of management and leadership skills agnostic of ultimate career path(s). We then measured outcomes in a controlled manner, by systematically comparing perceived knowledge and growth of participants with non-participants as the control group. You3participants discern greater growth, independent of number of years in training, in competencies overall compared to the control group. This growth was shown by multiple criteria including self-reporting and associative analysis. Correspondingly, You3participants reported greater knowledge in 75% of the modules when compared to controls. These data indicate that structured learning, where postdocs commit to a curriculum via a cohort-structure, leads to positive outcomes and provides a framework for programs to assess outcomes in a rigorous manner.
Arachidonic acid metabolism controls macrophage alternative activation through regulating oxidative phosphorylation in PPARG dependent manner
Authors: Xu Miao , Wang Xiaohong , Jia Xudong , Li Yongning , Geng Xue , Zhang Lishi , Yang Hui 
Published: October 2020

AbstractMacrophages polarization is mainly controlled by metabolic reprogramming in microenvironment, thus leading to distinct outcomes of various diseases. However, the role of lipid metabolism in the regulation of macrophage alternative activation is incompletely understood. Using human THP-1 and mouse bone marrow derived macrophages polarization models, we revealed a pivotal role for arachidonic acid metabolism in controlling the polarization of M1 and M2 macrophages. We demonstrated that M2 macrophage polarization was inhibited by arachidonic acid, but inversely facilitated by its derived metabolite prostaglandin E2 (PGE2). Furthermore, PPARG bridges these two unconnected processes via modulating oxidative phosphorylation. These results highlight the critical role of arachidonic acid metabolism as an immune regulator in modulating metabolic homeostasis and pathological process.
Transcriptome profiling of the Olig2-expressing astrocyte subtype reveals their unique molecular signature
Authors: Ohayon David , Aguirrebengoa Marion , Escalas Nathalie , Soula Cathy 
Published: October 2020

SummaryAstrocytes are recognized to be a heterogeneous population of cells that differ morphologically, functionally and molecularly. Whether this heterogeneity results from generation of distinct astrocyte cell lineages, each functionally specialized to perform specific tasks, remains an open question. In this study, we used RNA-seq analysis to determine the global transcriptome profile of the Olig2-expressing astrocyte subtype (Olig2-AS), a specific spinal astrocyte subtype which segregates early during development from Olig2 progenitors and differs from other spinal astrocytes by the expression of Olig2. We identified 245 differentially expressed genes. Among them, 135 exhibit higher levels of expression when compared to other populations of spinal astrocytes, indicating that these genes can serve as a ‘unique’functional signature of Olig2-AS. Further analysis highlighted, in particular, enrichment in Olig2-AS of a set of genes specialized in regulating synaptic activity. Our work thus reveals that Olig2 progenitors produce a unique astrocyte subtype specialized to perform certain specific functions.
Behavioral phenotyping of mice lacking the deubiquitinase USP2
Authors: Srikanta Shashank Bangalore , Stojkovic Katarina , Cermakian Nicolas 
Published: October 2020

AbstractUbiquitin specific peptidase 2 (USP2) is a deubiquitinating enzyme expressed almost ubiquitously in the body, including in multiple brain regions. We previously showed that mice lacking USP2 present altered locomotor activity rhythms and response of the clock to light. However, the possible implication of USP2 in regulating other behaviors has yet to be tested. To address this, we ran a battery of behavioral tests onUsp2KO mice. Firstly, we confirmed our prior findings of increased daily activity and reduced activity fragmentation inUsp2KO mice. Further, mice lacking USP2 showed impaired motor coordination and equilibrium, a decrease in anxiety-like behavior, a deficit in short-term recognition memory and in sensorimotor gating. On the other hand, no effects ofUsp2gene deletion were found on spatial memory. Hence, our data uncover the implication of USP2 in different behaviors and expands the range of the known functions of this deubiquitinase.
Chitosan nanoparticle vaccine loaded with crude extracellular proteins ofC. perfringensandSalmonellaflagella is partially protective against necrotic enteritis in broiler chickens
Authors: Akerele Gabriel , Ramadan Nour , Mortada Muhammed , Shanmugasundaram Revathi , Renu Sankar , Renukaradhya Gourapura J. , Selvaraj Ramesh K 
Published: October 2020

AbstractNecrotic enteritis (NE) causes significant economic losses and food shortages world-wide. There are currently no licensed commercial vaccines against NE in broilers. Chitosan nanoparticles were formulated with extracellular proteins ofC. perfringenssurface-tagged withSalmonellaflagellar proteins. One-day-old male broiler chicks were completely randomized to 3 treatments: Non-vaccinated non-challenged as negative control, Vaccinated-challenged, and non-vaccinated challenge as positive control. On day of hatch, d7, and d14 post-hatch, vaccinated-challenged birds were orally gavage with 50μg vaccine in 0.5ml PBS while positive control birds were gavage with 0.5ml PBS only. Birds in the vaccinated-challenged and positive control groups were orally infected on d14 post-hatch, with 5,000 oocysts/bird ofE. maxima, followed by log 8 CFU of a virulent strain of C. perfringens on d19, d20, and d21 post-hatch. From d14 to 21 and d14 to 28 post-hatches, mortality in the vaccinated-challenged group was higher than that in the positive control group, approaching statistical significance (p=0.07). On d21 post-hatch, the mean lesion score of 3 birds/cage in the vaccinated-challenged group was higher than the positive control group, approaching statistical significance (p = 0.05). From d 14 to 28 post-hatch, the feed intake was higher and feed conversion ratio lower in the vaccinated-challenged group compared to the positive control group (p<0.05). On d21 post-hatch, antigen specific recall proliferation in the vaccinated-challenged group was higher than that in the negative and positive control groups (p<0.05). On d21 post-hatch, cecal tonsils CD8+ T lymphocytes expression in the vaccinated-challenged group was similar to the negative control group (p>0.05) but higher than that in the positive control group (p<0.05). Finally, vaccination resulted in an increase in ileal mRNA levels of zonula occluding on d21 post-hatch. In conclusion, there were numerical but not statistically significant decrease in NE lesions and mortality in vaccinated and challenged broilers. Further studies are needed to improve the efficacy of the vaccine and understand the mechanism underlying protection in vaccinated birds.
Metaproteogenomic profiling of chemosynthetic microbial biofilms reveals metabolic flexibility during colonization of a shallow-water gas vent
Authors: Patwardhan Sushmita , Smedile Francesco , Giovannelli Donato , Vetriani Costantino 
Published: October 2020

AbstractTor Caldara is a shallow-water gas vent located in the Mediterranean Sea, with active venting of CO2, H2S. At Tor Caldara, filamentous microbial biofilms, mainly composed ofEpsilon- andGammaproteobacteria, grow on substrates exposed to the gas venting. In this study, we took a metaproteogenomic approach to identify the metabolic potential andin situexpression of central metabolic pathways at two stages of biofilm maturation. Our findings indicate that inorganic reduced sulfur species are the main electron donors and CO2the main carbon source for the filamentous biofilms, which conserve energy by oxygen and nitrate respiration, fix dinitrogen gas and detoxify heavy metals. Three metagenome-assembled genomes (MAGs), representative of key members in the biofilm community, were also recovered. Metaproteomic data show that metabolically active chemoautotrophic sulfide-oxidizing members of theEpsilonproteobacteriadominated the young microbial biofilms, whileGammaproteobacteriabecome prevalent in the established community. The co-expression of different pathways for sulfide oxidation by these two classes of bacteria suggests exposure to different sulfide concentrations within the biofilms, as well as fine-tuned adaptations of the enzymatic complexes. Taken together, our findings demonstrate a shift in the taxonomic composition and associated metabolic activity of these biofilms in the course of the colonization process.
Mechanisms of allosteric and mixed mode aromatase inhibitors
Authors: Souza Samson A. , Held Abby , Lu Wenjie , Drouhard Brendan , Avila Bryant , Leyva-Montes Raul , Hu Michelle , Miller Bill R. , Ng Ho Leung 
Published: October 2020

AbstractAromatase (Cyp19) catalyzes the last biosynthetic step of estrogens in mammals and is a primary drug target for hormone-related breast cancer. However, treatment with aromatase inhibitors is often associated with adverse effects and drug resistance. In this study, we used virtual screening targeting a predicted cytochrome P450 reductase binding site on aromatase to discover four novel non-steroidal aromatase inhibitors. The inhibitors have potencies comparable to the noncompetitive tamoxifen metabolite, endoxifen. Our two most potent inhibitors, AR11 and AR13, exhibit both mixed-type and competitive-type inhibition. The cytochrome P450 reductase-Cyp19 coupling interface likely acts as a transient binding site. Our modeling shows that our inhibitors bind better at different sites near the catalytic site. Our results predict the location of multiple ligand binding sites on aromatase. The combination of modeling and experimental results supports the important role of the reductase binding interface as a low affinity, promiscuous ligand binding site. Our new inhibitors may be useful as alternative chemical scaffolds that may show different adverse effects profiles than current clinically used aromatase inhibitors.
Exploring the pH-dependent structure-dynamics-function relationship of human renin
Authors: Ma Shuhua , Henderson Jack A. , Shen Jana 
Published: October 2020

AbstractRenin is a pepsin-like aspartyl protease and an important drug target for the treatment of hypertension; despite three decades’ research, its pH-dependent structure-function relationship remains poorly understood. Here we employed the continuous constant pH molecular dynamics (CpHMD) simulations to decipher the acid/base roles of renin’s catalytic dyad and the conformational dynamics of the flap, which is a common structural feature among aspartyl proteases. The calculated pKa’s suggest that the catalytic Asp38 and Asp226 serve as the general base and acid, respectively, in agreement with experiment and supporting the hypothesis that renin’s neutral optimum pH is due to the substrate-induced pKashifts of the aspartic dyad. The CpHMD data confirmed our previous hypothesis that hydrogen bond formation is the major determinant of the dyad pKaorder. Additionally, our simulations showed that renin’s flap remains open regardless of pH, although a Tyr-inhibited state is occasionally formed above pH 5. These findings are discussed in comparison to the related aspartyl proteases, includingβ-secretases 1 and 2, capthepsin D, and plasmepsin II. Our work represents a first step towards a systematic understanding of the pH-dependent structure-dynamics-function relationships of pepsin-like aspartyl proteases that play important roles in biology and human disease states.
Sequential Measurements of Catalytic Activities of Multi-Drug-Resistance Transporters and Cytochrome P450 Enzymes by Cytometry of Reaction Rate Constant
Authors: Koshkin Vasilij , Oliveira Mariana Bleker de , Kochmann Sven , Peng Chun , Krylov Sergey N. 
Published: October 2020

ABSTRACTCytometry of reaction rate constant (CRRC) is an accurate and robust approach to characterize cell-population heterogeneity using rate constants of cellular processes for which kinetic mechanisms are known. We work on a CRRC-based method to develop predictors of tumor chemoresistance driven by two processes: drug extrusion by multi-drug-resistance (MDR) transporters and drug inactivation by cytochrome-P450 enzymes (CYP). Each of the two possess is studied with its specific substrate and the process activity is characterized by a corresponding unimolecular rate constant. Due to the incompatibility of MDR and CYP assays, MDR and CYP activities may be difficult to measure simultaneously suggesting that they may need to be measured sequentially. The sequential measurements may also impose a problem: the results of the second assay may be affected by artifacts exerted by the first assay. The goal of this work was to understand whether the cells have a memory of the first assay that significantly affects the results of the second assay. To achieve this goal, we compared CRRC results for two orders of sequential measurements: the MDR→CYP order in which MDR activity is measured before CYP activity and the CYP→MDR order in which CYP activity is measured before MDR activity. It was found that the results of the CYP assay were similar in both orders; on the contrary, the results of the MDR assay were significantly different. Our findings suggest that MDR and CYP activity can be studied sequentially provided that MDR activity is measured first and CYP activity second.
Predicting Cell-Penetrating Peptides: Building and Interpreting Random Forest based prediction Models
Authors: Yadahalli Shilpa , Verma Chandra S. 
Published: October 2020

AbstractTargeting intracellular pathways with peptide drugs is becoming increasingly desirable but often limited in application due to their poor cell permeability. Understanding cellular permeability of peptides remains a major challenge with very little structure-activity relationship known. Fortunately, there exist a class of peptides called Cell-Penetrating Peptides (CPPs), which have the ability to cross cell membranes and are also capable of delivering biologically active cargo into cells. Discovering patterns that make peptides cell-permeable have a variety of applications in drug delivery. In the current study, we build prediction models for CPPs exploring features covering a range of properties based on amino acid sequences, using Random forest classifiers which are often more interpretable than other ensemble machine learning algorithms. While obtaining prediction accuracies of ~96%, we also interpret our prediction models using TreeInterpreter, LIME and SHAP to decipher the contributions of important features and optimal feature space for CPP class. We propose that our work might offer an intuitive guide for incorporating features that impart cell-penetrability into the design of novel CPPs.
Double-layer flexible neuronal probe with closely spaced electrodes for high-densityin-vivobrain recordings
Authors: Pimenta Sara , Rodrigues José A. , Machado Francisca , Ribeiro João F. , Maciel Marino J. , Bondarchuk Oleksandr , Monteiro Patrícia , Gaspar João , Correia José H. , Jacinto Luis 
Published: October 2020

AbstractFlexible probes for brain activity recordings are an attractive emerging approach that reduces mechanical mismatch between probe and neuronal tissue, thus minimizing the risk of brain damage or glial scaring. Although promising, flexible probes still present some technical challenges namely: i) how to overcome probe buckling during brain insertion given its intrinsically low mechanical rigidity; ii) how to fabricate closely spaced electrode configurations for high density recordings by standard lithography techniques in the flexible substrate. Here, we present a new flexible probe based solely on standard and low-cost lithography processes, which has closely spaced 10 μm diameter gold electrode sites on a polyimide substrate with inter-site distances of only 5 μm. By using a double-layer design and fabrication approach we were able to accommodate closely spaced electrode sites at two different depths from probe surface while also providing additional stiffening, just sufficient to prevent probe buckling during brain insertion. Detailed probe characterization through metrology of structural and electrical properties and chemical composition analysis, as well as functional assessment throughin vivohigh-density recordings of neuronal activity in the mouse cortex, confirmed the viability of this new fabrication approach and that this probe can be used for obtaining high quality brain recordings with excellent signal-to-noise ratio (SNR).
Temporal changes in metabolism late in seed development affect biomass composition in soybean
Authors: Kambhampati Shrikaar , Aznar-Moreno Jose A. , Bailey Sally R. , Arp Jennifer J. , Chu Kevin L. , Bilyeu Kristin D. , Durrett Timothy P. , Allen Doug K 
Published: October 2020

ABSTRACTThe inverse correlation between protein and oil production in soybeans is well-documented; however, it has been based primarily on the composition of mature seeds. Though this is the cumulative result of events over the course of soybean seed development, it does not convey information specific to metabolic fluctuations during developmental growth regimes. Maternal nutrient supply via seed coat exudate measurements and metabolite levels within the cotyledon were assessed across development to identify trends in the accumulation of central carbon and nitrogen metabolic intermediates. Active metabolic operation during late seed development was probed through transient labeling with13C substrates. The results indicated: i) a drop in lipid during seed maturation with a concomitant increase in carbohydrates, ii) a transition from seed filling to maturation phase characterized by quantitatively balanced changes in the carbon use and CO2release, iii) changes in measured carbon and nitrogen resources supplied maternally over development, iv)13C metabolites processed through gluconeogenesis towards sustained carbohydrate accumulation as the maternal nutrient supply diminishes, and v) oligosaccharide biosynthetic metabolism during seed coat senescence at maturation. These results highlight temporal engineering targets for altering final biomass composition to increase the value of soybeans and a path to breaking the inverse seed protein and oil correlation.One-sentence summaryAssessment of temporal changes in metabolism during soybean seed development indicated that lipid turnover during maturation contributes carbon for gluconeogenic production of carbohydrates.
The moderating roles of technological self-efficacy and time management in the technostress and employee performance relationship through burnout
Authors: Yener Serdar , Arslan Aykut , Kilinç Sebahattin 
Published: October 2020

PurposeThe ongoing dispute as to whether using technology extensively at work may cause harm continues to gain momentum. Thus, the need for more research on the harmful effect of using technology at work and on the indirect effects on work performance is needed. The call for additional moderators in technostress research is still ongoing. The research contributes to the abovementioned gaps in the literature by analyzing a model with two moderators.Design/methodology/approachThe sample population was chosen randomly from the lists provided by civil-servant unions and the chamber of commerce subsidiaries in the northwest region of Turkey. The employees received letters that explained the purpose of the study; the questionnaires sent to them. Out of 500 forms, 328 were returned. PLS-SEM technique was selected for hypothesis testing.FindingsThe results revealed support for all the hypotheses, and proposed moderators can be used to mitigate the harms of technostress and burnout. The findings have implications for both theory and practice.Research limitations/implicationsThe limitation of this research is its sample characteristics. Due to the cross-sectional nature of the data set, it is difficult to claim causality. Therefore, readers should use caution when extending generalizations to a broader population. As for the theoretical implications, the interest in the challenges posed by various technologies in the workplace on human psychology and health over the long term is quite new. And there is still room for other mediating and moderating mechanism for the interplay between technostress and related outcomes.Practical implicationsOne of the practical implications is that technology at work might have the potential to create stress, sometimes greater than its benefits. The effects that might be created by other sources of stress when combined with stress related to technology in the workplace should also be taken seriously. There are tools to reduce the harm caused by technostress that practitioners could make use of such as time-management interventions.Originality/valueThe dispute whether using technology extensively at work may cause harm rather than advantage continues to confuse people, and with time it is gaining momentum. Thus, there is necessity for more research on the harms of technology, and especially on the indirect effects on work performance. Second, the vast technostress literature seems to neglect to discern task performance from contextual one as the dependent variable. Lastly, the call for additional moderators in technostress research is still prevailing. The research contributes to the abovementioned gaps in the literature by analyzing a model with two moderators.