bluuebunny/crossref_metadata_2025_split huggingface dataset:
Policy should change to improve invited speaker diversity and reflect trainee diversity
Authors: Hagan Ada K. , Pollet Rebecca M. , Libertucci Josie 
Published: October 2019

AbstractThe biomedical sciences have a problem retaining white women and underrepresented minorities in academia. Despite increases in the representation of these groups in faculty candidate pools, they are still underrepresented at the faculty level, particularly at the Full Professor level. The lack of diverse individuals at the Full Professor level contributes to the attrition of women and under-represented minorities, as it confirms unconscious biases. The presence of unconscious biases contribute to feelings of not belonging by trainees and are amplified by visual representation of who is presented as the “top scientist in their field”. Top scientists are not only defined by the attainment of Full Professorships, but also through invited seminar series. Invitations for faculty to present their research at other university departments is highly valued offer that provides an opportunity for collaborations and networking. However, if invited speakers do not represent the demographics of current trainees, these visual representations of successful scientists may contribute to decreased attitudes of self-identification as a scientist, ultimately resulting in trainees leaving the field or the academy. In this study, we compare invited-speaker demographics to the current trainee demographics in one microbiology and immunology department and find that trainees are not proportionally represented by speakers invited to the department. Our investigation prompted changes in policy for how invited speakers are selected in the future to invite a more diverse group of scientists. To facilitate this process, we developed a set of tips and a web-based resource that allows scientists, committees, and moderators to identify members of under-served groups. These resources can be easily adapted by other fields or sub-fields to promote inclusion and diversity at seminar series’, conferences, and colloquia.
Salt Inducible Kinases as Novel Notch Interactors in the DevelopingDrosophilaRetina
Authors: Şahin H. Bahar , Sayın Sercan , Buğra Kuyaş , Çelik Arzu 
Published: October 2019

AbstractDevelopmental processes require strict regulation of proliferation, differentiation and patterning for the generation of final organ size. Aberrations in these fundamental events are critically important in understanding tumorigenesis and cancer progression. Salt inducible kinases (Siks) are evolutionarily conserved genes involved in diverse biological processes, including salt sensing, metabolism, muscle and skeletal development. Recent findings implicate SIKs in tumor suppression or progression. However, their role in development remains largely unknown.Using a sensitized tumor model in theDrosophilaeye, we show that perturbations of Sik function exacerbates tumor-like tissue overgrowth and metastasis. Furthermore, we show that bothDrosophila Sikgenes,Sik2andSik3, are required for proper eye development. We propose that an important target of Siks may be the Notch pathway, as we demonstrate epistasis between Siks and Notch pathway members and identify putative phosphorylation motifs on Notch, Delta and Fringe. Finally, we investigate Sik expression in the developing retina and show that Sik2 is expressed in all photoreceptors in close proximity to cell junctions, while Sik3 appears to be expressed specifically in R3/R4 cells in the developing eye. Combined, our data suggest thatSikgenes are important in tissue specification, growth, and that their dysregulation may contribute to tumor formation.
Antiviral signalling in human IPSC-derived neurons recapitulates neurodevelopmental disorder phenotypes
Authors: Warre-Cornish Katherine , Perfect Leo , Nagy Roland , Reid Matthew J. , Mueller Annett , Evans Amanda L. , Ghevaert Cédric , McAlonan Grainne , Loth Eva , Murphy Declan , Srivastava Deepak P. , Price Jack 
Published: October 2019

AbstractMaternal immune activation increases the risk of neurodevelopmental disorders. Elevated cytokines, such as interferon-gamma (IFNγ), in offspring’s brains play a central role. IFNγ activates an antiviral cellular state, limiting viral entry and replication. In addition, IFNγ has been implicated in brain development. Here, we hypothesise that IFNγ-induced antiviral signalling contributes to molecular and cellular phenotypes associated with neurodevelopmental disorders. We find that transient IFNγ treatment of neural progenitors derived from human induced pluripotent stem cells (hIPSCs) persistently increases neurite outgrowth, phenocopying hIPSC-neurons from autistic individuals. IFNγ upregulates antiviral PML bodies and MHC class I (MHCI) genes, which persists through neuronal differentiation. Critically, IFNγ-induced neurite outgrowth requires both PML and MHCI. We also find that IFNγ disproportionately alters expression of autism and schizophrenia risk genes, suggesting convergence between these genetic and environmental risk factors. Together, these data indicate that IFNγ-induced antiviral signalling may contribute to neurodevelopmental disorder aetiology.
Woody plants constructing tundra soils
Authors: Kemppinen Julia , Niittynen Pekka , Virkkala Anna-Maria , Happonen Konsta , Riihimäki Henri , Aalto Juha , Luoto Miska 
Published: October 2019

AbstractIn tundra, woody plants are expanding towards higher latitudes and altitudes due to increasingly favourable climatic conditions. Their expansion may also occur through increases in the coverage and height of the plants. These shifts may cascade further across the ecosystem, such as in the foundations of tundra: that is, in the soils. Yet, little is known about the effects woody plants have on local soil conditions. Here, we examined if the coverage and height of woody plants affect the growing-season soil moisture and temperature as well as soil organic carbon stocks. We carried out a field observation study in a dwarf shrub–dominated tundra and built a hierarchical model. We found that, after controlling for other possible factors influencing woody plants and soil conditions (namely, topography, snow, and the overall plant coverage), the coverage of woody plants inversely correlated with all three soil conditions. Yet, we found no link between the woody plant height to the soil variables. This indicates that woody plants affect local soil conditions in various ways, depending upon whether their expansion occurs though the growth of coverage or their height. Nevertheless, woody plants likely alter the very ground of the entire tundra system and feedback into the global climate system through the water, energy, and carbon cycles of tundra.
Circuit mechanisms underlying chromatic encoding in Drosophila photoreceptors
Authors: Heath Sarah L. , Christenson Matthias P. , Oriol Elie , Saavedra-Weisenhaus Maia , Kohn Jessica R. , Behnia Rudy 
Published: October 2019

AbstractSpectral information is commonly processed in the brain through generation of antagonistic responses to different wavelengths. In many species, these color opponent signals arise as early as photoreceptor terminals. Here, we measure the spectral tuning of photoreceptors in Drosophila. In addition to a previously described pathway comparing wavelengths at each point in space, we find a horizontal-cell-mediated pathway similar to that found in mammals. This pathway enables additional spectral comparisons through lateral inhibition, expanding the range of chromatic encoding in the fly. Together, these two pathways enable optimal decorrelation of photoreceptor signals. A biologically constrained model accounts for our findings and predicts a spatio-chromatic receptive field for fly photoreceptor outputs, with a color opponent center and broadband surround. This dual mechanism combines motifs of both an insect-specific visual circuit and an evolutionarily convergent circuit architecture, endowing flies with the unique ability to extract chromatic information at distinct spatial resolutions.
Precise hyperacuity estimation of spike timing from calcium imaging
Authors: Hoang Huu , Sato Masa-aki , Shinomoto Shigeru , Tsutsumi Shinichiro , Hashizume Miki , Ishikawa Tomoe , Kano Masanobu , Ikegaya Yuji , Kitamura Kazuo , Kawato Mitsuo , Toyama Keisuke 
Published: October 2019

SummaryTwo-photon imaging is a major recording technique in neuroscience, but it suffers from several limitations, including a low sampling rate, the nonlinearity of calcium responses, the slow dynamics of calcium dyes and a low signal-to-noise ratio, all of which impose a severe limitation on the application of two-photon imaging in elucidating neuronal dynamics with high temporal resolution. Here, we developed a hyperacuity algorithm (HA_time) based on an approach combining a generative model and machine learning to improve spike detection and the precision of spike time inference. First, Bayesian inference estimates the calcium spike model by assuming the constancy of the spike shape and size. A support vector machine employs this information and detects spikes with higher temporal precision than the sampling rate. Compared with conventional thresholding, HA_time improved the precision of spike time estimation up to 20-fold for simulated calcium data. Furthermore, the benchmark analysis of experimental data from different brain regions and simulation of a broader range of experimental conditions showed that our algorithm was among the best in a class of hyperacuity algorithms. We encourage experimenters to use the proposed algorithm to precisely estimate hyperacuity spike times from two-photon imaging.
Pal stabilises the bacterial outer membrane during constriction by a mobilisation-and-capture mechanism
Authors: Szczepaniak Joanna , Holmes Peter , Rajasekar Karthik , Kaminska Renata , Samsudin Firdaus , Inns Patrick George , Rassam Patrice , Khalid Syma , Murray Seán M. , Redfield Christina , Kleanthous Colin 
Published: October 2019

SummaryCoordination of outer membrane constriction with septation is critical to faithful division in Gram-negative bacteria and vital to the barrier function of the membrane. Recent studies suggest this coordination is through the active accumulation of the peptidoglycan-binding outer membrane lipoprotein Pal at division sites by the Tol system, but the mechanism is unknown. Here, we show that Pal accumulation atEscherichia colidivision sites is a consequence of three key functions of the Tol system. First, Tol mobilises Pal molecules in dividing cells, which otherwise diffuse very slowly due to their binding of the cell wall. Second, Tol actively captures mobilised Pal molecules and deposits them at the division septum. Third, the active capture mechanism is analogous to that used by the inner membrane protein TonB to dislodge the plug domains of outer membrane TonB-dependent nutrient transporters. We conclude that outer membrane constriction is coordinated with cell division by active mobilisation-and-capture of Pal at division septa by the Tol system.
Construction of habitat-specific training sets to achieve species-level assignment in 16S rRNA gene datasets
Authors: Escapa Isabel F. , Huang Yanmei , Chen Tsute , Lin Maoxuan , Kokaras Alexis , Dewhirst Floyd E. , Lemon Katherine P. 
Published: October 2019

ABSTRACTBackgroundThe low cost of 16S rRNA gene sequencing facilitates population-scale molecular epidemiological studies. Existing computational algorithms can parse 16S rRNA gene sequences to high-resolution Amplicon Sequence Variants (ASVs), which represent consistent labels comparable across studies. Assigning these ASVs to species-level taxonomy strengthens the ecological and/or clinical relevance of 16S rRNA gene-based microbiota studies and further facilitates data comparison across studies.ResultsTo achieve this, we developed a broadly applicable method for constructing high-resolution training sets based on the phylogenic relationships among microbes found in a habitat of interested. When used with the naïve Bayesian Ribosomal Database Project (RDP) Classifier, this training set achieved species/supraspecies-level taxonomic assignment of 16S rRNA gene-derived ASVs. The key steps for generating such a training set are: 1) constructing an accurate and comprehensive phylogenetic-based, habitat-specific database; 2) compiling multiple 16S rRNA gene sequences to represent the natural sequence variability of each taxon in the database; 3) trimming the training set to match the sequenced regions, if necessary; and 4) placing species sharing closely related sequences into a supraspecies taxonomic level to preserve subgenus-level resolution. As proof of principle, we developed a V1-V3 region training set for the bacterial microbiota of the human aerodigestive tract using the full-length 16S rRNA gene reference sequences compiled in our expanded Human Oral Microbiome Database (eHOMD). We also overcame technical limitations to successfully use Illumina sequences for the 16S rRNA gene V1-V3 region, the most informative segment for classifying bacteria native to the human aerodigestive tract. Finally, we generated a full-length eHOMD 16S rRNA gene training set, which we used in conjunction with an independent PacBio Single Molecule, Real-Time (SMRT)-sequenced sinonasal dataset to validate the representation of species in our training set. This also established the effectiveness of a full-length training set for assigning taxonomy of long-read 16S rRNA gene datasets.ConclusionHere, we present a systematic approach for constructing a phylogeny-based, high-resolution, habitat-specific training set that permits species/supraspecies-level taxonomic assignment to short- and long-read 16S rRNA gene-derived ASVs. This advancement enhances the ecological and/or clinical relevance of 16S rRNA gene-based microbiota studies.
Interferon-responsive genes are targeted during the establishment of human cytomegalovirus latency
Authors: Elder Elizabeth G. , Krishna Benjamin A. , Williamson James , Lim Eleanor Y. , Poole Emma , Sedikides George X. , Wills Mark , O’Connor Christine M. , Lehner Paul J. , Sinclair John 
Published: October 2019

AbstractHuman cytomegalovirus (HCMV) latency is an active process which remodels the latently infected cell to optimise latent carriage and reactivation. This is achieved, in part, through the expression of viral genes, including the G-protein coupled receptor US28. Here, we use an unbiased proteomic screen to assess changes in host proteins induced by US28, revealing that interferon-inducible genes are downregulated by US28. We validate that MHC Class II and two PYHIN proteins, MNDA and IFI16, are downregulated during experimental latency in primary human CD14+monocytes. We find that IFI16 is targeted rapidly during the establishment of latency in a US28-dependent manner, but only in undifferentiated myeloid cells, a natural site of latent carriage. Finally, by overexpressing IFI16, we show that IFI16 can activate the viral major immediate early promoter and immediate early gene expression during latency via NF-κB, a function which explains why downregulation of IFI16 during latency is advantageous for the virus.ImportanceHuman cytomegalovirus (HCMV) is a ubiquitous herpesvirus which infects 50-100% of humans worldwide. HCMV causes a lifelong subclinical infection in immunocompetent individuals, but is a serious cause of mortality and morbidity in the immunocompromised and in neonates. In particular, reactivation of HCMV in the transplant setting is a major cause of transplant failure and related disease. Therefore, a molecular understanding of HCMV latency and reactivation could provide insights into potential ways to target the latent viral reservoir in at-risk patient populations.
Leveraging genetic data to investigate molecular targets and drug repurposing candidates for treating alcohol use disorder and hepatotoxicity
Authors: Gray Joshua C. , Murphy Mikela , Leggio Lorenzo 
Published: October 2019

AbstractBackgroundNovel treatments for alcohol use disorder (AUD) and alcohol-related liver disease (ALD) are greatly needed. Genetic information can improve drug discovery rates by facilitating the identification of novel biological targets and potential drugs for repurposing.MethodsThe present study utilized a recently developed Bayesian approach, Integrative Risk Gene Selector (iRIGS), to identify additional risk genes for alcohol consumption using SNPs from the largest alcohol consumption GWAS to date (N = 941,280). iRIGS incorporates several genomic features and closeness of these genes in network space to compute a posterior probability for protein coding genes near each SNP. We subsequently used the Target Central Resource Database to search for drug-protein interactions for these newly identified genes and previously identified risk genes for alcohol consumption.ResultsWe identified several genes that are novel contributions to the previously published alcohol consumption GWAS. Namely, ACVR2A, which is critical for liver function and linked to anxiety and cocaine self-administration, and PRKCE, which has been linked to alcohol self-administration. Notably, only a minority of the SNPs (18.4%) were linked to genes with confidence (≥.75), underscoring the need to apply multiple methods to assign function to loci. Finally, several previously identified risk genes for alcohol consumption code for proteins that are implicated in liver function and are targeted by drugs that are promising candidates for managing hepatotoxicity (e.g., metformin).ConclusionsThis study demonstrates the value of incorporating regulatory information and drug-protein interaction data to highlight additional molecular targets and drug repurposing candidates for treating AUD and ALD.
Ancient genomes reveal early Andean farmers selected common beans while preserving diversity
Authors: Emiliano Trucchi , Andrea Benazzo , Martina Lari , Alice Iob , Stefania Vai , Laura Nanni , Elisa Bellucci , Elena Bitocchi , Chunming Xu , Scott Jackson A , Verónica Lema , Pilar Babot , Nurit Oliszewski , Adolfo Gil , Gustavo Neme , Teresa Michieli Catalina , Monica De Lorenzi , Lucio Calcagnile , David Caramelli , Bastiaan Star , Hugo de Boer , Sanne Boessenkool , Roberto Papa , Giorgio Bertorelle 
Published: October 2019

AbstractAll crops are the product of a domestication process that started less than 12,000 years ago from one or more wild populations [1, 2]. Farmers selected desirable phenotypic traits, such as improved energy accumulation, palatability of seeds or reduced natural shattering [3], while leading domesticated populations through several more or less gradual demographic contractions [2, 4]. As a consequence, erosion of wild genetic variation [5] is typical of modern cultivars making them highly susceptible to pathogens, pests and environmental change [6,7]. The loss of genetic diversity hampers further crop improvement programs to increase food production in a changing world, posing serious threats to food security [8,9]. Using both ancient and modern seeds, we analyzed the temporal dynamic of genetic variation and selection during the domestication process of the common bean (Phaseolus vulgaris) that occurred in the Southern Andes. Here we show that most domestic traits were selected for prior to 2,500 years ago, with no or only minor loss of whole-genome variation. In fact, i) all ancient domestic genomes dated between 600 and 2,500 years ago are highly variable - at least as variable as a modern genome from the wild; the genetic erosion that we observe in modern cultivars is therefore a recent process that occurred in the last centuries; ii) the majority of changes at coding genes that differentiate wild and domestic genomes are already present in the ancient genomes analyzed here. Considering that most desirable phenotypic traits are likely controlled by multiple polymorphic genes [10], a likely explanation of this decoupling of selection and genomic erosion is that early farmers applied a relatively weak selection pressure [2] by using many phenotypically similar but genomically diverse individuals as breeders. Selection strategies during the last few centuries were probably less sustainable and produced further improvements focusing on few plants carrying the traits of interest, at the cost of marked genetic erosion.
Chemogenetic modulation and single-photon calcium imaging in anterior cingulate cortex reveal a mechanism for effort-based decisions
Authors: Hart Evan E. , Blair Garrett J. , O’Dell Thomas J. , Blair Hugh T. , Izquierdo Alicia 
Published: October 2019

ABSTRACTThe anterior cingulate cortex (ACC) is implicated in effort exertion and choices based on effort cost, but it is still unclear how it mediates this cost-benefit evaluation. Here, male rats were trained to exert effort for a high-value reward (sucrose pellets) in a progressive ratio lever pressing task. Trained rats were then tested in two conditions: a no-choice condition where lever pressing for sucrose was the only available food option, and a choice condition where a low-value reward (lab chow) was freely available as an alternative to pressing for sucrose. Disruption of ACC—via either chemogenetic inhibition or excitation—reduced lever pressing in the choice, but not in the no-choice, condition. We next looked for value coding cells in ACC during effortful behavior and reward consumption phases during choice and no-choice conditions. For this, we utilized in vivo miniaturized fluorescence microscopy to reliably track responses of the same cells and compare how ACC neurons respond during the same effortful behavior where there was a choice versus when there was no-choice. We found that lever-press and sucrose-evoked responses were significantly weaker during choice compared to no-choice sessions, which may have rendered them more susceptible to chemogenetic disruption. Taken together, findings from our interference experiments and neural recordings suggest that a mechanism by which ACC mediates effortful decisions is in the discrimination of the utility of available options. ACC regulates these choices by providing a stable population code for the relative value of different options.Significance StatementThe anterior cingulate cortex (ACC) is implicated in effort-based decision making. Here, we used chemogenetics and in vivo calcium imaging to explore its mechanism. Rats were trained to lever press for a high-value reward and tested in two conditions: a no-choice condition where lever pressing for the high-value reward was the only option, and a choice condition where a low-value reward was also available. Inhibition or excitation of ACC reduced effort toward the high value option, but only in the choice condition. Neural responses in ACC were weaker in the choice compared to the no-choice condition. A mechanism by which ACC regulates effortful decisions is in providing a stable population code for the discrimination of the utility of available options.