bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feeling Out of Place: Internalized Age Stereotypes Are Associated With Older Employees’ Sense of Belonging and Social Motivation
Authors: Rahn Georg , Martiny Sarah E , Nikitin Jana 
Published: January 2020

Abstract
Older employees are not only confronted with subtle negative stereotypes about cognitive decline, but they also tend to internalize these negative stereotypes (i.e., they agree with the idea that intellectual performance declines in old age and they feel affected by this decline). Previous research has shown that internalizing negative age stereotypes has detrimental effects on work-related outcomes. Little is known about how internalized negative stereotypes shape older employees’ social emotions and social motivation. In the present research, we argue that older adults who internalize negative age stereotypes feel insecure about their belongingness in the workplace and this has negative motivational consequences. Four out of five studies and an aggregate analysis with a total of N = 1,306 older employees (age 50–76 years) supported this hypothesis. Internalized age stereotypes were negatively related to social approach motivation toward coworkers through reduced sense of belonging in the workplace and low positive affect. In addition, internalized age stereotypes were positively related to social avoidance motivation. Investigations of the causality of these relationships revealed mixed results. We discuss these findings from the perspective of socioemotional aging and the need to belong. In sum, the present research adds to knowledge on the role of internalized negative stereotypes for older employees’ social lives and, potentially, their success in the work domain.
State Preemption: Impacts on Advances in Tobacco Control
Authors: Kang Joann Yoon , Kenemer Brandon , Mahoney Margaret , Tynan Michael A. 
Published: January 2020

Context:
Policy is an effective tool for reducing the health harms caused by tobacco use. State laws can establish baseline public health protections. Preemptive legislation at the state level, however, can prohibit localities from enacting laws that further protect their citizens from public health threats.

Approach:
Preemptive state tobacco control laws were assessed using the Centers for Disease Control and Prevention's State Tobacco Activities Tracking and Evaluation System. Based on the assessments, the Centers for Disease Control and Prevention quantified the number of states with certain types of preemptive tobacco control laws in place. In addition, 4 different case examples were presented to highlight the experiences of 4 states with respect to preemption.

Discussion:
Tracking and reporting on preemptive state tobacco control laws through the Centers for Disease Control and Prevention's State Tobacco Activities Tracking and Evaluation System provide an understanding of the number and scope of preemptive laws. Case examples from Hawaii, North Carolina, South Carolina, and Washington provide a detailed account of how preemption affects tobacco control governance at state and local levels within these 4 states.
The antibiofilm effects of docosahexaenoic acid
Authors: Brady Jonathan 
Published: January 2020

The ability of bacteria to form biofilms allows for recalcitrance against conventional antibiotic therapies (Potera, 1999). Therefore, this has contributed to the prevalence of biofilm acquired infections (BAI) clinically (Percival and Kite, 2018) which has resulted in increased morbidity and mortality amongst patients, with immunocompromised patients at risk in particular (Donlan, 2002). Biofilm formation on abiotic and biotic surfaces has enabled bacteria to colonise major organs and medical devices, such as within the lungs, on implant surfaces, contact lenses, and urinary catheters (Vinh and Embil, 2005; Percival et al., 2012; Seth et al., 2012). Docosahexaenoic acid (DHA) is a poly-unsaturated fatty acid known to exhibit antibiofilm and antimicrobial effects (Sun et al., 2017; Kim et al., 2018). Our research has found that DHA possesses strong anti-biofilm effects against Klebsiella pneumoniae and Enterococcus faecalis at low mM concentrations. DHA was capable of reducing biofilm formation by both K. pneumoniae and E. faecalis by approximately 60%. It is believed that this is the first time these effects have been reported. We have also have evidence that DHA in conjunction with an antibiotic is better at reducing biofilm formation by these strains better then either alone.
To date, there is much debate into how DHA exerts these anti-biofilm effects. DHA has been reported to distort bacterial membrane’s therefore, impacting biofilm formation (Sun et al., 2017). We aim to elucidate the precise mechanism of action by utilising a number of genetic approaches alongside the dynamic flow cell system and confocal microscopy.
Sox2 and canonical Wnt signaling interact to activate a developmental checkpoint coordinating morphogenesis with mesodermal fate acquisition
Authors: Kinney Brian A. , Row Richard H. , Tseng Yu-Jung , Weidmann Maxwell D. , Knaut Holger , Martin Benjamin L. 
Published: January 2020

AbstractAnimal embryogenesis requires a precise coordination between morphogenesis and cell fate specification. It is unclear if there are mechanisms that prevent uncoupling of these processes to ensure robust development. During mesoderm induction, mesodermal fate acquisition is tightly coordinated with the morphogenetic process of epithelial to mesenchymal transition (EMT). In zebrafish, cells exist transiently in a partial EMT state during mesoderm induction. Here we show that cells expressing the neural inducing transcription factor Sox2 are held in the partial EMT state, stopping them from completing the EMT and joining the mesodermal territory. This is critical for preventing ectopic neural tissue from forming. The mechanism involves specific interactions between Sox2 and the mesoderm inducing canonical Wnt signaling pathway. When Wnt signaling is inhibited in Sox2 expressing cells trapped in the partial EMT, cells are now able to exit into the mesodermal territory, but form an ectopic spinal cord instead of mesoderm. Our work identifies a critical developmental checkpoint that ensures that morphogenetic movements establishing the mesodermal germ layer are accompanied by robust mesodermal cell fate acquisition.
Immunophenotyping of HER4/YAP axis in breast cancer brain metastasis
Authors: Kalita-de Croft Priyakshi , Lim Malcolm , de Luca Xavier M , Day Bryan W , Saunus Jodi M , Lakhani Sunil R 
Published: January 2020

AbstractBrain metastasis (BrM) is a devastating diagnosis for patients with breast cancer. Identification of immunophenotypical features specific to BrM is crucial for developing effective new therapeutic interventions. Yes-associated protein (YAP) mediates downstream effects of the neuregulin receptor, HER4, on breast cancer cell proliferationin vitro. HER4 is frequently over-expressed in BrM, but the relationship with YAP has not been investigated. This study examined the HER4/YAP axis in patient samples (n=41) from matched primary breast and metastatic brain tumours. Immunohistochemistry analysis revealed HER4 was highly phosphorylated in BrM compared to matched primary tumours (p=0.0022), and this was strongly associated with expression and phosphorylation of dimerization partners HER2 and HER3 (p<0.0001). When compared to a general breast cancer cohort (n=373), we found HER4 activation to be brain metastasis specific (p<0.0001). However, YAP was frequently phosphorylated in both HER4-activated primary breast tumours and brain metastases, suggesting that pro-proliferative YAP signaling is not a major consequence of HER4 activation in these tumours. These results display the complexity of expression of the HER family receptors and the downstream pathways in BrM and suggest simultaneous targeting of multiple receptors might be more advantageous.
MinION-based DNA barcoding of preserved and non-invasively collected wildlife samples
Authors: Seah Adeline , Lim Marisa C.W. , McAloose Denise , Prost Stefan , Seimon Tracie 
Published: January 2020

AbstractThe ability to sequence a variety of wildlife samples with portable, field-friendly equipment will have significant impacts on wildlife conservation and health applications. However, the only currently available field-friendly DNA sequencer, the MinION by Oxford Nanopore Technologies, has a high error rate compared to standard laboratory-based sequencing platforms and has not been systematically validated for DNA barcoding accuracy for preserved and non-invasively collected tissue samples.We tested whether various wildlife sample types, field-friendly methods, and our clustering-based bioinformatics pipeline, SAIGA, can be used to generate consistent and accurate consensus sequences for species identification. Here, we systematically evaluate variation in cytochrome b sequences amplified from scat, hair, feather, fresh frozen liver, and formalin-fixed paraffin-embedded (FFPE) liver. Each sample was processed by three DNA extraction protocols.For all sample types tested, the MinION consensus sequences matched the Sanger references with 99.29-100% sequence similarity, even for samples that were difficult to amplify, such as scat and FFPE tissue extracted with Chelex resin. Sequencing errors occurred primarily in homopolymer regions, as identified in previous MinION studies.We demonstrate that it is possible to generate accurate DNA barcode sequences from preserved and non-invasively collected wildlife samples using portable MinION sequencing, creating more opportunities to apply portable sequencing technology for species identification.
Growth of theFucusembryo: insights into wall-mediated cell expansion through mechanics and transcriptomics
Authors: Linardić Marina , Cokus Shawn J. , Pellegrini Matteo , Braybrook Siobhan A. 
Published: January 2020

AbstractMorphogenesis in walled organisms represents a highly controlled process that involves cell proliferation and expansion; cell growth is regulated through changes in the structure and mechanics of the cells’ walls. Despite taking different evolutionary paths, land plants and some brown algae exhibit developmental and morphological similarities; however, the role of the algal cell wall in morphogenesis remains heavily underexplored. Cell expansion in plants is hypothesized to involve modifications of hemicellulose linkages and pectin gelation in the cell wall. Little is known about the wall-based control of cell expansion in brown algae; however, the algal analog to pectin, alginate, exhibits different gelation depending on its biochemistry. Here we show that cell wall mechanics and alginate biochemistry are correlated with cell expansion versus proliferation in the developingFucus serratusembryo. In the elongating cells of the embryo rhizoid, we found a reduced cell wall stiffness and lower amounts of ‘stiffer’ alginate epitopes. In comparison, the early embryo thallus was shown to undergo cleavage-type cell proliferation, without expansion, and this was correlated with higher amounts of ‘stiff’ alginate epitopes and increased wall stiffness. An embryo development RNAseq dataset was generated to characterize differential gene expression during development. This data set allowed for identification of many enriched GO functions through developmental time. In addition, the transcriptome allowed for the identification of cell-wall related genes whose differential expression may underlie our observed growth phenotypes. We propose that differential gene expression of genes involved in alginate stiffness are strong candidates underlying differential wall stiffness and cell elongation in the developingFucusembryo. Our results show that wall-driven cellular expansion mechanisms in brown algae are similar to those observed in plants. In addition, our data show that cleavage-type cell proliferation exists in brown algae similar to that seen in plant and animal systems indicating a possible conserved developmental phenomenon across the branches of multicellular life.
Loss and recovery of transcriptional plasticity after long-term adaptation to global change conditions in a marine copepod
Authors: Brennan Reid S. , deMayo James A. , Dam Hans G. , Finiguerra Michael , Baumann Hannes , Pespeni Melissa H. 
Published: January 2020

AbstractAdaptive evolution from standing genetic variation and physiological plasticity will fuel resilience in the geologically unprecedented warming and acidification of the earth’s oceans. For marine animals, however, we have much to learn about the mechanisms, interactions, and costs of adaptation. Here, using 20 generations of experimental evolution followed by three generations of reciprocal transplantation, we investigate the relationship between adaptation and plasticity in the marine copepod,Acartia tonsa, in future greenhouse conditions (high temperature, high CO2). We find highly parallel genetic adaptation to greenhouse conditions in genes related to stress response, gene expression regulation, actin regulation, developmental processes, and energy production. However, reciprocal transplantation showed that genetic adaptation resulted in a loss of transcriptional plasticity, reduced fecundity, and reduced population growth when greenhouse animals were returned to ambient conditions or reared in low food conditions, suggestive of genetic assimilation after 20 generations of adaptation. Despite the loss of plasticity at F21, after three successive transplant generations, greenhouse-adapted animals were able to match the ambient-adaptive transcriptional profile. Concurrent changes in allele frequencies and erosion of nucleotide diversity suggest that this recovery occurred via adaptation back to ancestral conditions. These results demonstrate the power of experimental evolution from natural populations to reveal the mechanisms, timescales of responses, consequences, and reversibility of complex, physiological adaptation. While plasticity facilitated initial survival in global change conditions, it eroded after 20 generations as populations genetically adapted, limiting resilience to new stressors and previously benign environments.
Germinal center B cells separate signals for selection and division like compact discs
Authors: Meyer-Hermann Michael 
Published: January 2020

SummarySelection of B cells in germinal center (GC) reactions is pivotal to the generation of high affinity antibodies and memory B cells. Knowledge about B cell selection is limited to individual interactions and lacks global understanding. Here, seemingly contradictory experiments are unified in a common concept by separation of signals for the frequency of fate decision from the strength of cell division, which can then be controlled independently, similar to the separation of frequency and amplitude in digital audio signals. Based on this concept of information processing, three theories of B cell selection are developed that can be distinguish by predicted experiments drawn from computer simulations. Understanding encoding of information in molecular states is critical for targeted immune interventions.
Two-photon voltage imaging of spontaneous activity from multiple neurons reveals network activity in brain tissue
Authors: Li Binglun , Chavarha Mariya , Kobayashi Yuho , Yoshinaga Satoshi , Nakajima Kazunori , Lin Michael Z. , Inoue Takafumi 
Published: January 2020

AbstractRecording the electrical activity of multiple neurons simultaneously would greatly facilitate studies on the structure and function of neuronal circuits. Using fluorescent genetically encoded voltage indicators (GEVI) would be especially desirable, as it would allow cell type-selectivity, longitudinal recordings, and further optical manipulations. By expressing the GEVI ASAP3 viain uteroelectroporation and rapidly imaging neurons in densely labelled tissues via random-access multi-photon microscopy, we achieve voltage recording of multiple neurons in brain slice with single-trial single-voxel resolution. This approach enables monitoring of subthreshold membrane potential changes and action potentials from multiple locations in soma and dendrites for tens of minutes. By optically recording spontaneous electrical activities in somatosensory cortex neurons, we provide evidence for the development of intralaminar horizontal connections in layer 2/3 with greater sensitivity than calcium imaging. Single-trial optical voltage recordings using ASAP3 thus enables the investigation of network connectivity at cellular resolution.
Inducible epithelial resistance improves survival of Sendai virus pneumonia in mice by both inactivating virus and preventing CD8+T cell-mediated immunopathology
Authors: Wali S. , Flores J. R. , Jaramillo A.M. , Goldblatt D. L. , Pantaleón García J. , Tuvim M. J. , Dickey B. F. , Evans S. E. 
Published: January 2020

AbstractViral pneumonias remain a global health threat necessitating novel strategies to prevent and treat these lower respiratory tract infections. We have reported that mice treated with a combination of inhaled Toll-like receptor (TLR) 2/6 and TLR 9 agonists (Pam2-ODN) are broadly protected against respiratory pathogens. Although a single inhalation of Pam-ODN prevents acute morbidity and chronic complications associated with viral pneumonias, the mechanisms underlying this protection remain incompletely elucidated. Here, we show in a lethal paramyxovirus model that Pam2-ODN-enhanced survival is associated with robust virus inactivation that occurs prior to internalization by lung epithelial cells. However, it was also noted that viral mortality in sham-treated mice temporally corresponded with CD8+T cell-enriched lung inflammation that peaks after the viral burden wanes. Pam2-ODN treatment also blocked this injurious inflammation, but the attenuation of lymphocytic inflammation and the reduction in virus burden were both lost when inducible reactive oxygen species generation was inhibited. Depleting CD8+T cells before or after viral challenge underscored the balanced roles of CD8+T cells in antiviral immunity and fatal immunopathology, but did not obviate the Pam2-ODN antiviral protection. These findings identify multifunctional inducible antiviral mechanisms and may reveal means to protect susceptible individuals against respiratory infections.
Intrinsically disordered domain of kinesin-3 Kif14 enables unique functional diversity
Authors: Zhernov Ilia , Diez Stefan , Braun Marcus , Lansky Zdenek 
Published: January 2020

ABSTRACTIn addition to their force-generating motor domains, kinesin motor proteins feature various accessory domains enabling them to fulfil a variety of functions in the cell. Human kinesin-3, Kif14, localizes to the midbody of the mitotic spindle and is involved in the progression of cytokinesis. The specific motor properties enabling Kif14’s cellular functions, however, remain unknown. Here, we show in vitro that it is the intrinsically disordered N-terminal domain of Kif14 that enables unique functional diversity of the motor. Using single molecule TIRF microscopy we observed that the presence of the disordered domain i) increased the Kif14 run-length by an order of magnitude, rendering the motor super-processive and enabling the motor to pass through highly crowded microtubule areas shielded by cohesive layers of microtubule-associated protein tau, which blocks less processive motors ii) enabled robust, autonomous Kif14 tracking of growing microtubule tips, independent of microtubule end-binding (EB) proteins and iii) enabled Kif14 to crosslink parallel microtubules and to drive the relative sliding of antiparallel ones. We explain these features of Kif14 by the observed increased affinity of the disordered domain for GTP-like tubulin and the observed diffusible interaction of the disordered domain with the microtubule lattice. We hypothesize that the disordered domain tethers the motor domain to the microtubule forming a diffusible foothold. We suggest that the intrinsically disordered N-terminal anchoring domain of Kif14 is a regulatory hub supporting the various cellular functions of Kif14 by tuning the motor’s interaction with microtubules.
Germline genetic contribution to the immune landscape of cancer
Authors: Sayaman Rosalyn W. , Saad Mohamad , Thorsson Vésteinn , Hendrickx Wouter , Roelands Jessica , Mokrab Younes , Farshidfar Farshad , Kirchhoff Tomas , Sweis Randy F. , Bathe Oliver F. , Porta-Pardo Eduard , Campbell Michael J. , Stretch Cynthia , Hu Donglei , Huntsman Scott , Graff Rebecca E. , Syed Najeeb , Radvanyi Laszlo , Shelley Simon , Wolf Denise , Marincola Francesco M. , Ceccarelli Michele , Galon Jérôme , Ziv Elad , Bedognetti Davide 
Published: January 2020

SummaryThe role of germline genetics in shaping the tumor immune landscape is largely unknown. Using genotypes from >9,000 individuals in The Cancer Genome Atlas, we investigated the association of common and rare variants with 139 well-defined immune traits. Our analysis of common variants identified 10 immune traits with significant heritability estimates, and an additional 23 with suggestive heritability, including estimates of T-cell subset abundance and interferon signaling. We performed genome-wide association on the 33 heritable traits and identified 23 genome-wide significant loci associated with at least one immune trait, including SNPs in theIFIH1locus previously associated with several autoimmune diseases. We also found significant associations between immune traits and pathogenic or likely-pathogenic rare variants inBRCA1and in genes functionally linked to telomere stabilization, and Wnt/Beta-catenin signaling. We conclude that germline genetic variants significantly impact the composition and functional orientation of the tumor immune microenvironment.
CRISPR Mutants of Three Y Chromosome Genes Suggest Gradual Evolution of Fertility Functions inDrosophila melanogaster
Authors: Hafezi Yassi , Sruba Samantha R. , Tarrash Steven R. , Wolfner Mariana F. , Clark Andrew G. 
Published: January 2020

ABSTRACTGene-poor, repeat-rich regions of the genome are poorly understood and have been understudied due to technical challenges and the misconception that they are degenerating “junk”. Yet multiple lines of evidence indicate these regions may be an important source of variation that could drive adaptation and species divergence, particularly through regulation of fertility. The ∼40 Mb Y chromosome ofDrosophila melanogastercontains only 16 known protein-coding genes and is highly repetitive and entirely heterochromatic. Most of the genes originated from duplication of autosomal genes and have reduced nonsynonymous substitution rates, suggesting functional constraint. We devised a genetic strategy for recovering and retaining stocks with sterile Y-linked mutations and combined it with CRISPR to create mutants with deletions that disrupt three Y-linked genes. Two genes,PRYandFDY, had no previously identified functions. We found thatPRYmutant males are sub-fertile, butFDYmutant males had no detectable fertility defects.FDY, the newest known gene on the Y chromosome, may have fertility effects that are conditional or too subtle to detect. The third gene,CCY, had been predicted but never formally shown to be required for male fertility. CRISPR-targeting and RNAi ofCCYcaused male sterility. Surprisingly, however, ourCCYmutants were sterile even in the presence of an extra wild-type Y chromosome, suggesting that perturbation of the Y chromosome can lead to dominant sterility. Our approach provides an important step toward understanding the complex functions of the Y chromosome and parsing which functions are accomplished by genes versus repeat elements.