bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flexible control of Pavlovian-instrumental transfer based on expected reward value
Authors: Marshall Andrew T. , Halbout Briac , Munson Christy N. , Hutson Collin , Ostlund Sean B. 
Published: April 2021

AbstractThe Pavlovian-instrumental transfer (PIT) paradigm is widely used to assay the motivational influence of reward-predictive cues, reflected by their ability to invigorate instrumental behavior. Leading theories assume that a cue’s motivational properties are tied to predicted reward value. We outline an alternative view which recognizes that reward-predictive cues may suppress rather than motivate instrumental behavior under certain conditions, an effect termed positive conditioned suppression. We posit that cues signaling imminent reward delivery tend to inhibit instrumental behavior, which is exploratory by nature, in order to facilitate efficient retrieval of the expected reward. According to this view, the motivation to engage in instrumental behavior during a cue should beinverselyrelated to the value of the predicted reward, since there is more to lose by failing to secure a high-value reward than a low-value reward. We tested this hypothesis in rats using a PIT protocol known to induce positive conditioned suppression. In Experiment 1, cues signaling different reward magnitudes elicited distinct response patterns. Whereas the 1-pellet cue increased instrumental behavior, cues signaling 3 or 9 pellets suppressed instrumental behavior and elicited high levels of food-port activity. Experiment 2 found that reward-predictive cues suppressed instrumental behavior and increased food-port activity in a flexible manner that was disrupted by post-training reward devaluation. Further analyses suggest that these findings were not driven by overt competition between the instrumental and food-port responses. We discuss how the PIT task may provide a useful tool for studying cognitive control over cue-motivated behavior in rodents.
Exploring the metastatic role of the inhibitor of apoptosis BIRC6 in Breast Cancer
Authors: Gómez Bergna Santiago M. , Marchesini Abril , Morales Leslie C. Amorós , Arrías Paula N. , Farina Hernán G. , Romanowski Víctor , Gottardo M. Florencia , Pidre Matias L. 
Published: April 2021

AbstractBreast cancer is the most common cancer as well as the first cause of death by cancer in women worldwide. BIRC6 (baculoviral IAP repeat-containing protein 6) is a member of the inhibitors of apoptosis protein family thought to play an important role in the progression or chemoresistance of many cancers. The aim of the present work was to investigate the role of apoptosis inhibitor BIRC6 in breast cancer, focusing particularly on its involvement in the metastatic cascade.We analyzed BIRC6 mRNA expression levels and Copy Number Variations (CNV) in three breast cancer databases from The Cancer Genome Atlas (TCGA) comparing clinical and molecular attributes. Genomic analysis was performed using CBioportal platform while transcriptomic studies (mRNA expression levels, correlation heatmaps, survival plots and Gene Ontology) were performed with USC Xena and R. Statistical significance was set at p-values less than 0.05.Our analyses showed that there was a differential expression of BIRC6 in cancer samples when compared to normal samples. CNV that involve amplification and gain of BIRC6 gene were correlated with negative hormone receptor tumors, higher prognostic indexes, younger age at diagnosis and both chemotherapy and radiotherapy administration. Transcriptomic and gene-ontology analyses showed that, in conditions of high BIRC6 mRNA levels, there are differential expression patterns in apoptotic, proliferation, and metastatic pathways.In summary, ourin silicoanalyses suggest that BIRC6 exhibits an antiapoptotic, pro-proliferative and an apparent pro-metastatic role and could be a relevant molecular target for treatment of Breast Cancer tumors.
Using camera traps to determine occupancy and breeding in burrowing seabirds
Authors: Bird Jeremy P. , Fuller Richard A. , Pascoe Penny P. , Shaw Justine D. S. 
Published: April 2021

ABSTRACTBurrowing seabirds are important in commercial, ecological and conservation terms. Many populations are in flux owing to both negative and positive anthropogenic impacts, but their ecology makes measuring changes difficult. Reliably recording key metrics, the proportion of burrows with breeding pairs, and the success of breeding attempts, requires burrow-level information on occupancy. We investigated the use of camera traps positioned at burrow entrances for determining the number of breeding pairs in a sample to inform population estimates, and for recording breeding success. Linear Discriminant Analyses of time series activity patterns from camera traps successfully partitioned breeding and non-breeding burrows at different stages of the breeding season and had reasonable predictive ability to determine breeding status on a small test dataset. Compared with traditional techniques for determining burrow occupancy (e.g. manual burrow inspection and playback of conspecific calls at burrow entrances), camera traps can reduce uncertainty in estimated breeding success and potentially breeding status of burrows. Significant up-front investment is required in terms of equipment and human resources but for long-term studies camera traps can deliver advantages, particularly when unanticipated novel observations and the potential for calibrating traditional methods with cameras are factored in.
Single-cell transcriptomics of peripheral blood in the aging mouse
Authors: Teo Yee Voan , Webb Ashley , Neretti Nicola 
Published: April 2021

AbstractCompositional and transcriptional changes in the hematopoietic system have been used as biomarkers of immunosenescence and aging. Here, we use single-cell RNA-sequencing to study the aging peripheral blood in mice, and characterize the changes in cell-type composition and transcriptional profiles associated with age. We identified 17 clusters from a total of 14,588 single cells. We detected a general upregulation of antigen processing and presentation and chemokine signaling pathways and a downregulation of genes involved in ribosome pathways with age. We also observed increased percentage of cells expressing markers of senescence, Cdkn1a and Cdkn2a, in old peripheral blood. In addition, we detected a cluster of activated T cells that are exclusively found in old blood, with lower expression of Cd28 and higher expression of Bcl2 and Cdkn2a, suggesting that the cells are senescent and resistant to apoptosis.
Expression of cell-adhesion molecules inE. coli: a high-throughput method to identify paracellular modulators
Authors: Rollins Jay , Worthington Tyler , Hooke Emily , Hobson Joseph , Wengler Jacob , Hope Sandra , Mizrachi Dario 
Published: April 2021

AbstractCell-adhesion molecules (CAM) are membrane proteins responsible for cell-cell interactions or cell-extracellular matrix interactions. Among these proteins, claudins (CLDN), occludin (OCLN), and junctional adhesion molecules (JAM) are components of the tight junction (TJ), the single proteic structure tasked with safeguarding the paracellular space. The TJ is responsible for controlled permeability of blood-tissue barriers, regulating the passage of molecule passage by size and charge. Currently there is no translational solution to manipulate the TJ with the exception of Focused Ultra-sound (FUS) and Micro bubbling (MB) techniques, still in clinical trials. Here we describe the expression of TJ proteins in the outer membrane ofE. coliand report its consequences. When expression is induced, the unicellular behavior ofE. coliis replaced with multicellular aggregations that can be quantified using Flow Cytometry (FC). The adhesion properties of the aggregates are representative of the individual membrane proteins expressed. This method, called iCLASP (inspection of cell-adhesion molecules aggregation through FC protocols), allows the high-throughput interrogation of small-molecules influence on paracellular permeability, enabling for the first time the discovery of its modulators for therapeutic strategies.
Septins regulate border cell shape and surface geometry downstream of Rho
Authors: Gabbert Allison M. , Mondo James A. , Campanale Joseph P. , Mitchell Noah P. , Myers Adele , Streichan Sebastian J. , Miolane Nina , Montell Denise J. 
Published: April 2021

AbstractSeptins self-assemble into polymers that bind and deform membranesin vitroand regulate diverse cell behaviorsin vivo. How theirin vitroproperties relate to theirin vivofunctions is under active investigation. Here we uncover requirements for septins in detachment and motility of border cell clusters in theDrosophilaovary. Septins and myosin colocalize dynamically at the cluster periphery and share phenotypes, but surprisingly do not impact each other. Instead, Rho independently regulates myosin activity and septin localization. Active Rho recruits septins to membranes while inactive Rho sequesters septins in the cytoplasm. Mathematical analyses reveal how manipulating septin expression alters cluster shape and surface geometry. This study shows that the level of septin expression regulates surface properties at different scales. This work suggests that downstream of Rho, septins tune surface deformability while myosin controls contractility, the combination of which govern cluster shape and movement.
Differential variation of NSCs in root branch orders ofFraxinus mandshuricaRupr. seedlings across different drought intensities and soil substrates
Authors: Ji Li , Liu Yue , Wang Jun , Lu Zhimin , Yang Yuchun , Zhang Lijie 
Published: April 2021

AbstractNon-structural carbohydrates (NSCs) facilitate plants adapt to drought stress, could characterize trees growth and survival ability and buffer against external disturbances. Previous studies have focused on the distribution and dynamics of NSCs among different plant organs under drought conditions. However, discussion about the NSC levels of fine roots in different root branch order were little, especially the relationship between fine root trait variation and NSCs content. The aim of the study is to shed light into the synergistic variation of fine root traits and NSC content in different root branch order under different drought and soil substrate conditions. 2-year-oldFraxinus mandshuricaRupr. potted seedlings were planted in three different soil substrates (humus, loam and sandy-loam soil) and conducted to four drought intensities (CK, mild drought, moderate drought and severe drought) for two months. With the increase of drought intensity, the biomass of fine roots decreased significantly. Under the same drought intensity, seedlings in sandy-loam soil have higher root biomass, and the coefficient of variation of fifth-order roots (37.4%, 44.5% and 53.0% in humus, loam and sandy loam, respectively) is higher than that of lower-order roots. With the increase of drought intensity, the specific root length (SRL) and average diameter (AD) of all five orders increased and decreased, respectively. The fine roots in humus soil had higher soluble sugar content and lower starch content. Also, the soluble sugar and starch content of fine roots showed decreasing and increasing tendency respectively. Soluble sugar and starch explain the highest degree of total variation of fine root traits, that is 32.0% and 32.1% respectively. With ascending root order, the explanation of the variation of root traits by starch decreased (only 6.8% for fifth-order roots). The response of different root branch order fine root morphological traits ofF. mandshuricaseedlings to resource fluctuations ensures that plants maintain and constructure the root development by an economical way to obtain more resources.
Single-cell analysis of early chick hypothalamic development reveals that hypothalamic cells are induced from prethalamic-like progenitors
Authors: Kim Dong Won , Place Elsie , Chinnaiya Kavitha , Manning Elizabeth , Sun Changyu , Dai Weina , Ohyama Kyoji , Burbridge Sarah , Placzek Marysia , Blackshaw Seth 
Published: April 2021

SummaryThe hypothalamus is an evolutionarily ancient brain region that regulates many innate behaviors, but its development is still poorly understood. To identify molecular mechanisms controlling hypothalamic specification and patterning, we used single-cell RNA-Seq to profile multiple stages of early hypothalamic development in the chick. We observe that hypothalamic neuroepithelial cells are initially induced from prethalamic-like cells. Two distinct hypothalamic progenitor populations emerge later, which give rise to paraventricular/mammillary and tuberal hypothalamus. At later developmental stages, the regional organization of the chick and mouse hypothalamus closely resembles one another. This study identifies selective markers for major subdivisions of the developing chick hypothalamus and many uncharacterized candidate regulators of hypothalamic patterning and neurogenesis. As proof of concept for the power of the dataset, we demonstrate that follistatin, a novel prethalamic progenitor-like marker, inhibits hypothalamic induction. This study both clarifies the organization of the early developing hypothalamus and identifies novel molecular mechanisms controlling hypothalamic induction, regionalization, and neurogenesis.HighlightsEarly hypothalamic development was profiled in chick using scRNA-Seq and multiplexed HCR.Hypothalamic cells are induced from prethalamic-like neuroepithelial cells.Distinct paraventricular/mammillary and tuberal progenitor populations emerge later, and hypothalamic organization is evolutionarily conserved.Prethalamic progenitor-derived follistatin inhibits hypothalamic specification.Graphical Abstract
Candelabrum cells are molecularly distinct, ubiquitous interneurons of the cerebellar cortex with specialized circuit properties
Authors: Osorno Tomas , Rudolph Stephanie , Nguyen Tri , Kozareva Velina , Nadaf Naeem , Macosko Evan Z. , Lee Wei-Chung Allen , Regehr Wade G. 
Published: April 2021

AbstractTo understand how the cerebellar cortex transforms mossy fiber (MF) inputs into Purkinje cell (PC) outputs, it is vital to delineate the elements of this circuit. Candelabrum cells (CCs) are enigmatic interneurons of the cerebellar cortex that have been identified based on their morphology, but their electrophysiological properties, synaptic connections, and function remain unknown. Here we clarify these properties using electrophysiology, snRNA sequencing,in situhybridization, and serial electron microscopy. We find that CCs are the most abundant PC layer interneuron. They are GABAergic, molecularly distinct, and present in all cerebellar lobules. Their high resistance renders CC firing highly sensitive to synaptic inputs. CCs are excited by MFs and granule cells, and strongly inhibited by PCs. CCs in turn inhibit molecular layer interneurons, which leads to PC disinhibition. Thus, inputs, outputs and local signals all converge onto CCs to allow them to assume a unique role in controlling cerebellar output.
Multiple 9-1-1 complexes promote homolog synapsis, DSB repair, and ATR signaling during mammalian meiosis
Authors: Pereira Catalina , Arroyo-Martinez Gerardo A. , Guo Matthew Z. , Downey Michael S. , Kelly Emma R. , Grive Kathryn J. , Mahadevaiah Shantha K. , Sims Jennie , Faça Vitor Marcel , Tsai Charlton , Schiltz Carl J. , Wit Niek , Jacobs Heinz , Clark Nathan L. , Freire Raimundo , Turner James M. A. , Lyndaker Amy M. , Brieño-Enríquez Miguel A. , Cohen Paula E. , Smolka Marcus B. , Weiss Robert S. 
Published: April 2021

ABSTRACTDNA damage response mechanisms have meiotic roles that ensure successful gamete formation. While completion of meiotic double-strand break (DSB) repair requires the canonical RAD9A-RAD1-HUS1 (9A-1-1) complex, mammalian meiocytes also express RAD9A and HUS1 paralogs, RAD9B and HUS1B, predicted to form alternative 9-1-1 complexes. The RAD1 subunit is shared by all predicted 9-1-1 complexes and localizes to meiotic chromosomes even in the absence of HUS1 and RAD9A. Here we report that testis-specific RAD1 disruption resulted in impaired DSB repair, germ cell depletion and infertility. UnlikeHus1orRad9adisruption,Rad1loss also caused defects in homolog synapsis, ATR signaling and meiotic sex chromosome inactivation. Comprehensive testis phosphoproteomics revealed that RAD1 and ATR coordinately regulate numerous proteins involved in DSB repair, meiotic silencing, synaptonemal complex formation, and cohesion. Together, these results establish critical roles for both canonical and alternative 9-1-1 complexes in meiotic ATR activation and successful prophase I completion.
Sub-millisecond conformational transitions of short single-stranded DNA lattices by photon correlation single-molecule FRET
Authors: Israels Brett , Albrecht Claire S. , Dang Anson , Barney Megan , von Hippel Peter H. , Marcus Andrew H. 
Published: April 2021

AbstractThermally-driven conformational fluctuations (or ‘breathing’) of DNA plays important roles in the function and regulation of the ‘macromolecular machinery of genome expression.’ Fluctuations in double-stranded (ds) DNA are involved in the transient exposure of pathways to protein binding sites within the DNA framework, leading to the binding of regulatory proteins to single-stranded (ss) DNA templates. These interactions often require that the ssDNA sequences, as well as the proteins involved, assume transient conformations critical for successful binding. Here we use microsecond-resolved single-molecule Förster Resonance Energy Transfer (smFRET) experiments to investigate the backbone fluctuations of short oligothymidine [oligo(dT)n] templates within DNA constructs that can also serve as models for ss-dsDNA junctions. Such junctions, as well as the attached ssDNA sequences, are involved in the binding of ssDNA binding (ssb) proteins that control and integrate the mechanisms of DNA replication complexes. We have used these data to determine multi-order time-correlation functions (TCFs) and probability distribution functions (PDFs) that characterize the kinetic and thermodynamic behavior of the system. We find that the oligo(dT)ntails of ss-dsDNA constructs inter-convert, on sub-millisecond time-scales, between three macrostates with distinctly different end-to-end distances. These are: (i) a ‘compact’ macrostate that represents the dominant species at equilibrium; (ii) a ‘partially extended’ macrostate that exists as a minority species; and (iii) a ‘highly extended’ macrostate that is present in trace amounts. We propose a model for ssDNA secondary structure that advances our understanding of how spontaneously formed nucleic acid conformations may facilitate the activities of ssDNA associating proteins.Significance StatementThe genetic information of living organisms is encoded as sequences of nucleic acid bases in DNA, and is protected by the thermodynamically stable secondary structure of the Watson-Crick double helix. The processing and manipulation of gene sequences by ‘macromolecular machines’ requires that stable segments of duplex DNA be disrupted, and that single-stranded (ss) DNA templates be transiently exposed to the binding sites of DNA associating proteins within the cellular environment. Here we elucidate some of the defining features that control the stability and dynamics of ssDNA secondary structure, using time-resolved methods to detect the presence of transient unstable conformations. Understanding the nature of these instabilities is central to elucidating the mechanisms by which ssDNA templates facilitate protein binding and function.
Fulfilment of technical and hygienic requirements among street food vendors in Slovenia
Authors: Prevolšek Vanja , Ovca Andrej , Jevšnik Mojca 
Published: April 2021

PurposeThis cross-sectional study aimed to evaluate the compliance of hygienic and technical standards of street food vendors in Slovenia with the requirements of the general hygienic food principals set in the Codex Alimentarius and Regulation (EC) No. 852/2004 on the hygiene of foodstuffs.Design/methodology/approachFood vendors were observed directly and discretely using a semi-structured observation sheet that allowed fast evaluation. The employee's behaviour was not affected during the observations because they were not aware of being observed. Each observation lasted approximately 30 min. Food vendors were divided into groups according to their location, type of facility, number of employees and type of food sold.FindingsDepending on the type of street vendor, more inconsistencies were found amongst food stands compared to food trucks and kiosks. Most food trucks and kiosks scored very high in both personal and hygienic-technical standards. Some of the major inconsistencies were lack of suitably located washbasins, improper hand-washing technique, improper waste management, working surfaces that were inadequately separated from consumers, and inconsistent maintenance of the cold chain. Food handlers have been confirmed as a critical risk factor.Research limitations/implicationsDespite methodology validation, the data was collected by a single observer, limiting the ability to obtain a more reliable estimate of the observations. The sample was disproportionate according to the type of street food facilities.Practical implicationsThe results provide a basis for (1) national professional guidelines of good hygiene practices for food business operators, which should cover street food vendors more extensively in future updates, and (2) the development of food safety training programmes tailored for street vendors.Originality/valueThe study provides valuable insights into current hygienic-technical conditions of the street food vending sector.
Eastern European immigrants in the UK
Authors: Rosso Anna 
Published: April 2021

PurposeThe paper aims at examining wage developments among Eastern European immigrants vs UK natives before and after the 2004 enlargement by measuring the extent to which inter-group wage differentials are explainable by these groups' changing attributes or by differences in returns to these characteristics. The enlargement has been a defining moment in British recent history and may have contributed to the unfolding of the events that have culminated in Brexit.Design/methodology/approachThe paper uses a quantitative analysis of the immigrant–native wage gap across the entire distribution by applying the methodology known as the unconditional quantile regression. The analysis is performed before and after the 2004 European Union enlargement to Eastern countries. The data used is the British Labour Force Survey (UK LFS) from 1998 to 2008.FindingsAt all distribution points, a major role is played by occupational downgrading, which increases over time. The results further suggest that the decreased wage levels at the top of the distribution stem mainly from low transferability of skills acquired in the source country.Research limitations/implicationsThe UK LFS does not allow to follow individuals for a long period of time. For this reason, the main limitation of the study is the impossibility to measure for individual-level trajectories in their labour market integration and to account for return migration.Originality/valueThe analysis provides a detailed picture of the wage differences between Eastern European immigrants and natives along the whole wage distribution. The paper also identifies possible causes of the wage gap decrease for EU8 immigrant workers after 2008.