bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nicotinamide combined with gemcitabine is an immunomodulatory therapy that restrains pancreatic cancer in mice
Authors: Selvanesan Benson Chellakkan , Meena Kiran , Beck Amanda , Meheus Lydie , Lara Olaya , Rooman Ilse , Gravekamp Claudia 
Published: June 2020

ABSTRACTTreatments for pancreatic ductal adenocarcinoma (PDAC) are poorly effective, at least partly due to the tumor’s immune-suppressive stromal compartment. New evidence of positive effects on immune responses in the tumor microenvironment, compelled us to test the combination of gemcitabine (GEM), a standard chemotherapeutic for pancreatic cancer, with nicotinamide (NAM), the amide form of niacin (vitamin B3), in various mouse tumor models of pancreatic cancer, i.e. peritoneal or orthotopic of Panc-02 (KrasG12D) and orthotopic KPC (KrasG12D, p53R172H, Pdx1-Cre) grafts. A significant reduction in tumor weight and number of metastases was found, as well as a significant improved survival of the NAM+GEM group compared to all control groups. Immunohistochemistry and flow cytometry of pancreatic tumors showed a significant decrease in tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC), an increase in the number of CD4 and CD8 T cells and the production of granzyme B in the NAM+GEM group. Moreover, T cell responses to tumor-associated antigen survivin were observed in spleens of the mice that received NAM+GEM but not in those that received single agents or saline. In addition, remodeling of the tumor stroma was observed with decreased collagen I and expression of hyaluronic acid binding protein, reorganization of the immune cells into lymph node like structures, and CD31 positive vessels. Expression profiling for a panel of immuno-oncology genes revealed significant changes in genes involved in migration and activation of T cells, attraction of dendritic cells, and epitope spreading. This study highlights the potential of NAM+GEM as immunotherapy for advanced pancreatic cancer.
An Hourglass Circuit Motif Transforms a Motor Program via Subcellularly Localized Muscle Calcium Signaling and Contraction
Authors: Sando Steven R. , Bhatla Nikhil , Lee Eugene L. Q. , Horvitz H. Robert 
Published: June 2020

AbstractNeural control of muscle function is fundamental to animal behavior. Many muscles can generate multiple distinct behaviors. Nonetheless, individual muscle cells are generally regarded as the smallest units of motor control. We report that muscle cells can alter behavior by contracting subcellularly. We previously discovered that noxious tastes reverse the net flow of particles through theC. eleganspharynx, a neuromuscular pump, resulting in spitting. We now show that spitting results from the subcellular contraction of the anterior region of the pm3 muscle cell. Subcellularly localized calcium increases accompany this contraction. Spitting is controlled by an “hourglass” circuit motif: parallel neural pathways converge onto a single motor neuron that differentially controls multiple muscles and the critical subcellular muscle compartment. We conclude that subcellular muscle units enable modulatory motor control and propose that subcellular muscle contraction is a fundamental mechanism by which neurons can reshape behavior.
Structural basis for polarized elongation of actin filaments
Authors: Zsolnay Vilmos , Katkar Harshwardhan H. , Chou Steven Z. , Pollard Thomas D. , Voth Gregory A. 
Published: June 2020

AbstractActin filaments elongate and shorten much faster at their barbed end than their pointed end, but the molecular basis of this difference has not been understood. We use all-atom molecular dynamics simulations to investigate the properties of subunits at both ends of the filament. The terminal subunits tend towards conformations that resemble actin monomers in solution, while contacts with neighboring subunits progressively flatten the conformation of internal subunits. At the barbed end the terminal subunit is loosely tethered by its DNase-1 loop to the third subunit, because its monomer-like conformation precludes stabilizing contacts with the penultimate subunit. The motions of the terminal subunit make the partially flattened penultimate subunit accessible for binding monomers. At the pointed end, unique contacts between the penultimate and terminal subunits are consistent with existing cryo-EM maps, limit binding to incoming monomers, and flatten the terminal subunit, which likely promotes ATP hydrolysis and rapid phosphate release. These structures explain the distinct polymerization kinetics of the two ends.Significance StatementEukaryotic cells utilize actin filaments to move, change shape, divide, and transport cargo. Decades of experiments have established that actin filaments elongate and shorten significantly faster from one end than the other, but the underlying mechanism for this asymmetry has not been explained. We used molecular dynamics simulations to investigate the structures of the actin filament ends in the ATP, ADP plusγ-phosphate, and ADP nucleotide states. We characterize the structures of actin subunits at both ends of the filament, explain the mechanisms leading to these differences, and connect the divergent structural properties of the two ends to their distinct polymerization rate constants.
Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance
Authors: Duque-Wilckens Natalia , Torres Lisette Y. , Yokoyama Sae , Minie Vanessa A. , Tran Amy M. , Petkova Stela P. , Hao Rebecca , Ramos-Maciel Stephanie , Rios Roberto A. , Jackson Kenneth , Flores-Ramires Francisco J. , Garcia-Carachure Israel , Pesavento Patricia A. , Iñiguez Sergio D. , Grinevich Valery , Trainor Brian C. 
Published: June 2020

AbstractOxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different populations of oxytocin neurons mediate different effects on behavior. Here we inhibited oxytocin synthesis in a social stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv). Oxytocin knock-down prevented stress-induced increases in social vigilance and decreases in social approach. Viral tracing of BNSTmv oxytocin neurons revealed fibers in regions controlling defensive behaviors including lateral hypothalamus, anterior hypothalamus, and anteromedial BNST (BNSTam). Oxytocin infusion into BNSTam in stress naïve mice increased social vigilance and reduced social approach. These results show that a population of extra-hypothalamic oxytocin neurons play a key role in controlling stress-induced social anxiety behaviors.
Increasing flow rate reduces biofouling and colonization by filamentous bacteria in drippers fed with reclaimed wastewater
Authors: Lequette Kévin , Ait-Mouheb Nassim , Wéry Nathalie 
Published: June 2020

AbstractThe clogging of drippers due to the development of biofilms reduces the benefits and is an obstacle to the implementation of drip irrigation technology. The geometry of the dripper channel has an impact on the flow behaviours and head loss. The objective of this study was to analyse the influence of hydrodynamic parameters of three types of drippers (flow rates of 1, 2 and 4 l.h-1) fed by reclaimed wastewater on biofilm development kinetics and on the bacterial community. Using optical coherence tomography, we demonstrated that the inlet of the drippers (mainly the first baffle) and vortex zones are the most sensitive area for biofouling. Drippers with the lowest flow rate (1 l.h-1) and the smallest channel section were the favourable areas to biofouling. The low inlet velocity (0.34 m.s-1) in this type of dripper compared to 2 l.h-1(0.61 m.s-1) and 4 l.h-1(0.78 m.s-1) drippers can favour the deposition and development of biofilms. In addition, the water velocity influenced the structure of the bacterial communities in the biofilm. Low velocity (0.34 m.s-1) favoured the presence ofHydrogenophagaandPseudoxanthomonasgenera at the early stage of biofilm formation and filamentous bacteria belonging to Chloroflexi phylum at the end. So, maintaining a high flow rate and using drippers with a large flow cross-section is an effective way to control the development of biofilms by limiting the presence of filamentous bacteria.
Control of filament length by a depolymerizing gradient
Authors: Datta Arnab , Harbage David , Kondev Jane 
Published: June 2020

AbstractCells assemble microns-long filamentous structures from protein monomers that are nanometers in size. These structures are often highly dynamic, yet in order for them to function properly, cells maintain precise filament lengths. In this paper, we investigate length dependent depolymerization as a mechanism of length control. This mechanism has been recently proposed for flagellar length control in the single cell organisms Chlamydomonas and Giardia. Length dependent depolymerization can arise from a concentration gradient of a depolymerizing protein, such as kinesin-13 in Giardia, along the length of the flagellum. Two possible scenarios are considered, that of a linear and an exponential gradient of depolymerizing proteins. We compute analytically the probability distributions of filament lengths for both scenarios and show how these distributions are controlled by key biochemical parameters through a dimensionless number that we identify. In Chlamydomonas cells it has been well documented that the assembly dynamics of its two flagella are coupled via a shared pool of molecular components, and so we investigate the effect of a limiting monomer pool on the length distributions. Finally, we compare our calculations to experiments. While the computed mean lengths are consistent with observations, the noise is two orders of magnitude smaller than the observed length fluctuations.
The plasticity of the pyruvate dehydrogenase complex confers a labile structure that is associated with its catalytic activity
Authors: Lee Jaehyoun , Oh Seunghee , Bhattacharya Saikat , Zhang Ying , Florens Laurence , Washburn Michael P. , Workman Jerry L. 
Published: June 2020

ABSTRACTThe pyruvate dehydrogenase complex (PDC) is a multienzyme complex that plays a key role in energy metabolism by converting pyruvate to acetyl-CoA. An increase of nuclear PDC has been shown to be correlated with an increase of histone acetylation that requires acetyl-CoA. PDC has been reported to form a ~ 10 MDa macromolecular machine that is proficient in performing sequential catalytic reactions via its three components. In this study, we show that the PDC displays size versatility in an ionic strength-dependent manner using size exclusion chromatography of yeast cell extracts. Biochemical analysis in combination with mass spectrometry indicates that yeast PDC (yPDC) is a salt-labile complex that dissociates into sub-megadalton individual components even under physiological ionic strength. Interestingly, we find that each oligomeric component of yPDC displays a larger size than previously believed. In addition, we show that the mammalian PDC also displays this uncommon characteristic of salt-lability, although it has a somewhat different profile compared to yeast. We show that the activity of yPDC is reduced in higher ionic strength. Our results indicate that the structure of PDC may not always maintain its ~ 10 MDa organization, but is rather variable. We propose that the flexible nature of PDC may allow modulation of its activity.
DNA binding reorganizes the intrinsically disordered C-terminal region of PSC inDrosophilaPRC1
Authors: Kang Jin Joo , Faubert Denis , Boulais Jonathan , Francis Nicole J. 
Published: June 2020

AbstractPolycomb Group (PcG) proteins regulate gene expression by modifying chromatin. A key PcG complex, Polycomb Repressive Complex 1 (PRC1), has two activities: a ubiquitin ligase activity for histone H2A, and a chromatin compacting activity. InDrosophila, the Posterior Sex Combs (PSC) subunit of PRC1 is central to both activities. The N-terminal homology region (HR) of PSC assembles into PRC1, including partnering with dRING to form the ubiquitin ligase for H2A. The intrinsically disordered C-terminal region of PSC (PSC-CTR) compacts chromatin, and inhibits chromatin remodeling and transcriptionin vitro. Both the PSC-HR and the PSC-CTR are essentialin vivo. To understand how these two activities may be coordinated in PRC1, we used cross-linking mass spectrometry (XL-MS) to analyze the conformations of the PSC-CTR in PRC1 and how they change on binding DNA. XL-MS identifies interactions between the PSC-CTR and the core of PRC1, including between the PSC-CTR and PSC-HR. New contacts and overall more compacted PSC-CTR conformations are induced by DNA binding. Protein footprinting of accessible lysine residues in the PSC-CTR reveals an extended, bipartite candidate DNA/chromatin binding surface. Our data suggest a model in which DNA (or chromatin) follows a long path on the flexible PSC-CTR. Intramolecular interactions of the PSC-CTR detected by XL-MS can bring the high affinity DNA/chromatin binding region close to the core of PRC1 without disrupting the interface between the ubiquitin ligase and the nucleosome. Our approach may be applicable to understanding the global organization of other large IDRs that bind nucleic acids.HighlightsAn intrinsically disordered region (IDR) in Polycomb protein PSC compacts chromatinCross-linking mass spectrometry (XL-MS) was used to analyze topology of the PSC IDRProtein footprinting suggests a bipartite DNA binding surface in the PSC IDRA model for the DNA-driven organization of the PSC IDRCombining XL-MS and protein footprinting is a strategy to understand nucleic acid binding IDRsAbstract Figure
Proteomics reveals commitment to germination in barley seeds is marked by loss of stress response proteins and mobilisation of nutrient reservoirs
Authors: Osama Sarah K. , Kerr Edward D. , Yousif Adel M. , Phung Toan K. , Kelly Alison M. , Fox Glen P. , Schulz Benjamin L. 
Published: June 2020

AbstractGermination is a critical process in the reproduction and propagation of flowering plants, and is also the key stage of industrial grain malting. Germination commences when seeds are steeped in water, followed by degradation of the endosperm cell walls, enzymatic digestion of starch and proteins to provide nutrients for the growing plant, and emergence of the radicle from the seed. Dormancy is a state where seeds fail to germinate upon steeping, but which prevents inappropriate premature germination of the seeds before harvest from the field. This can result in inefficiencies in industrial malting. We used Sequential Window Acquisition of all THeoretical ions Mass Spectrometry (SWATH-MS) proteomics to measure changes in the barley seed proteome throughout germination. We found a large number of proteins involved in desiccation tolerance and germination inhibition rapidly decreased in abundance after imbibition. This was followed by a decrease in proteins involved in lipid, protein and nutrient reservoir storage, consistent with induction and activation of systems for nutrient mobilisation to provide nutrients to the growing embryo. Dormant seeds that failed to germinate showed substantial biochemical activity distinct from that of seeds undergoing germination, with differences in sulfur metabolic enzymes, endogenous alpha-amylase/trypsin inhibitors, and histone proteins. We verified our findings with analysis of germinating barley seeds from two commercial malting facilities, demonstrating that key features of the dynamic proteome of germinating barley seeds were conserved between laboratory and industrial scales. The results provide a more detailed understanding of the changes in the barley proteome during germination and give possible target proteins for testing or to inform selective breeding to enhance germination or control dormancy.
China’s trade policy towards Latin America: an analysis of free trade agreements policy
Authors: Lopez Dorotea , Munoz Felipe 
Published: June 2020

PurposeThe emergence of China in the international trading system has shifted its gravity center, as the country has become one of the mayor actors in international economic relations. Through the subscription of preferential agreements, China is building a network of strategic partnerships worldwide, including Latin America. The purpose of this paper is to answer the questions: Do free trade agreements (FTAs) between China and Latin American countries contribute to expand trade flows and enhance products diversification?Design/methodology/approachThree countries have an FTA with China, Chile (2005), Peru (2009) and Costa Rica (2010). Through an econometric estimation based on a gravity model, the authors expect to determine the impact of these agreements over both trade flows and products.FindingsThe study shows that FTAs have a positive impact on both bilateral trade flows and on the number of exchanged products. Nevertheless, this impact is positive but diminishes in time. The authors confirm that these agreements allowed for a substantive expansion of trade between Latin American economies and China, becoming relevant for policymakers regarding the bi-regional relation.Originality/valueThe study contributes to the understanding of the bilateral trade relations between China and Latin American countries, giving evidence of the magnitude of the impact of FTAs. Through new data, at a six-digit level of detail, this study improves current knowledge regarding bilateral economic relations.
Satisfaction and purchase intention of imported fresh fruits based on familiarity: a case of Korean pears in Taiwan
Authors: Seo Sunhee (Sunny) , Kim Kawon , Nurhidayati Vieta Annisa 
Published: June 2020

PurposeThis study aims to investigate the influence of image and reputation of imported fresh fruits on consumer satisfaction and purchase intentions. The moderating role of familiarity with imported fruits was also assessed.Design/methodology/approachA total of 332 Taiwanese consumers who had purchased imported Korean pears participated using an online survey and were grouped based on their familiarity to Korean pears. Multi-group analysis with structural equation modeling was used to test the hypotheses.FindingsImage and reputation of imported Korean pears were identified as predictors of the satisfaction and purchase intention. Multi-group analysis results found the moderating effect of familiarity between image and satisfaction. Images were identified as predictors of the satisfaction and purchase intention of imported Korean pears for consumers with low familiarity, whereas image did not show any influence on satisfaction for consumers with high familiarity.Originality/valueThis study can contribute to the limited understanding of imported fresh fruit markets and provides insights into familiarity for consuming imported fresh fruits.
UK consumers' willingness to pay for laying hen welfare
Authors: Dunne Chloe , Siettou Christie 
Published: June 2020

PurposeThis study investigates UK consumers’ perception and willingness to pay (WTP) for egg attributes associated with laying hen welfare, namely with beak-trimming practices and injurious feather pecking (IP). The aim is to examine any change in WTP after improved consumer awareness.Design/methodology/approachBuilding upon existing literature, the authors designed an online survey in which the method of discrete choice experiment (DCE) was employed. The study includes two identical DCEs with the second being introduced after respondents were presented with an educational excerpt about beak-trimming practices, on farm IP occurrence and the docile nature of white egg laying hens – reducing IP.FindingsThe mixed logit regression model demonstrated that consumers' WTP for egg attributes associated with beak trimming and IP decreased in the second DCE (12.6% for organic and 2.55% for free-range). For eggshell colour, the analysis revealed a shift from a preference to brown eggs to indifference between eggshell colours.Originality/valueOverall, UK consumers have a preference in higher hen welfare resulting in a decrease in WTP once they are aware of welfare losses in current systems; however, more insights are required in terms of the promotion of white shelled eggs as a means of reducing IP on UK farms.
Conceptions of digital libraries: an African perspective
Authors: Owusu-Ansah Christopher M. 
Published: June 2020

Purpose
The purpose of this paper was to explore African conceptions of digital libraries from the perspective of the historical literature. This paper argues that the concept of digital libraries is a western creation and that there was a need for developing societies to develop their own conceptions to guide their own digital library development agenda.

Design/methodology/approach
The paper is based on a literature review. The paper makes use of publicly-available literature on the theme of digital libraries from both the Western and African perspectives. The search terms used were “digital libraries”, “Africa digital libraries”, “electronic libraries”, “information communication technologies/libraries” and “institutional repositories”. A total of 89 publications were examined for this purpose.

Findings
The analysis revealed that most of the initial digital library initiatives in Africa emanated from the west with African countries benefiting from international initiatives to expand access to information resources to bridge the global digital divide. However, due to a number of contextual challenges such as lack of sustainable funding and inadequate capacity and strategy, the development of digital libraries was hampered. Thus, even though digital libraries enjoy considerable goodwill, there remain negative conceptions of digital libraries in Africa.

Practical implications
Information institutions in African countries must evolve a unified conception of digital libraries as this would largely drive the direction of digital library development towards achieving the developmental goals of the continent.

Originality/value
The study applies the attributes of innovation to explain contextual factors shaping African conceptions of digital libraries.
A neglected issue: informal settlements, urban development, and disaster risk reduction in Latin America and the Caribbean
Authors: Sandoval Vicente , Sarmiento Juan Pablo 
Published: June 2020

PurposeThis paper introduces the state of informal settlements in Latin America and the Caribbean, and it explores potential relationships between informal settlements and national policies on urban development and disaster risk reduction, especially on how risk governance and disaster resilience are conceived and practiced by governments.Design/methodology/approach17 Habitat III National Reports issued during the preparatory process toward the New Urban Agenda in 2016 are analyzed using statistics and qualitative methods. Some quantitative variables, such as access to drinking water and sewerage in the region, are combined with qualitative data from references to the Sendai Framework and national urban policies in the mentioned reports. Countries in the study include Argentina, Barbados, Bolivia, Brazil, Chile, Colombia, Costa Rica, Cuba, Dominican Republic, Ecuador, Guatemala, Honduras, Jamaica, Mexico, Paraguay, Peru, and Uruguay.FindingsResults show that the situation of informal settlements in the region is complex and presents two different realities that coexist: one group of countries in which provision of basic urban services poses great challenges for a significant proportion of the urban population, while the other group in which urban informality and precariousness persists despite better statistics. Risk governance and disaster resilience principles are scarcely articulated in existing urban development discourses in the region.Originality/valueThe preparatory process toward the New Urban Agenda allowed to conduct an original updated cross-country analysis and to identify cross-cutting issues on informality, risk reduction, and urban development in the region.