bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Orbitofrontal Cortex in Temporal Cognition
Authors: Romero Sosa Juan Luis , Buonomano Dean , Izquierdo Alicia 
Published: October 2020

AbstractOne of the most important factors in decision making is estimating the value of available options. Subregions of the prefrontal cortex, including the orbitofrontal cortex (OFC), have been deemed essential for this process. Value computations require a complex integration across numerous dimensions, including, reward magnitude, effort, internal state, and time. The importance of the temporal dimension is well-illustrated by temporal discounting tasks, in which subjects select between smaller-sooner versus larger-later rewards. The specific role of OFC in telling time and integrating temporal information into decision making remains unclear. Based on the current literature, in this review we reevaluate current theories of OFC function, accounting for the influence of time. Incorporating temporal information into value estimation and decision making requires distinct, yet interrelated, forms of temporal information including the ability to tell time, represent time, create temporal expectations, and the ability to use this information for optimal decision making in a wide range of tasks, including temporal discounting and wagering. We use the term ‘temporal cognition’ to refer to the integrated use of these different aspects of temporal information. We suggest that the OFC may be a critical site for the integration of reward magnitude and delay, and thus important for temporal cognition.
Genomic analysis ofCryaa-R49C andCryab-R120G knockin mutant mice: 10-year follow-up
Authors: Kolling Fred , Ringelberg Carol , Wallace Mia , Andley Usha 
Published: October 2020

AbstractObjectiveTwo experimental samples from a mouse line containing Cryaa or Cryab modifications on a predominantly C57Bl/6 background using 129Sv mouse strain embryonic stem cells were investigated. The objective was to reexamine the precise genetic background of the mice 10 years after they were converted to the C57Bl/6 background.ResultsThe genetic backgrounds of the mice were assessed at the DartMouse™ Speed Congenic Core Facility at the Geisel School of Medicine at Dartmouth. DartMouse used the Illumina, Inc. Infinium Genotyping Assay to interrogate a custom panel of 5307 SNPs that were spread throughout the genome. The raw SNP data were analyzed using the DartMouse SNaP-Map™ and Map-Synth™ software, which allowed for genetic background identification at each SNP location for every mouse. As part of the analysis, 323 SNPs were eliminated from the data prior to generating chromosome maps due to internal quality control protocols. Of the remaining 4984 SNPs, 44.56% were uninformative (not polymorphic between the two relevant genetic backgrounds) and approximately 0.91% gave uninterpretable data. The remaining 54.53% of the returned SNPs were well distributed throughout the genome. The genetic backgrounds were determined to be 98-99% C57Bl/6J, which was the desired background.
Non-phylogenetic identification of co-evolving genes for reconstructing the archaeal Tree of Life
Authors: Rangel L. Thibério , Soucy Shannon M. , Setubal João C. , Gogarten Johann Peter , Fournier Gregory P. 
Published: October 2020

AbstractAssessing the phylogenetic compatibility between individual gene families is a crucial and often computationally demanding step in many phylogenomics analyses. Here we describe the Evolutionary Similarity Index (IES) to assess shared evolution between gene families using a weighted Orthogonal Distance Regression applied to sequence distances. This approach allows for straightforward pairing of paralogs between co-evolving gene families without resorting to multiple tests, ora prioriassumptions of molecular interactions between protein products from assessed genes. The utilization of pairwise distance matrices, while less informative than phylogenetic trees, circumvents error-prone comparisons between trees whose topologies are inherently uncertain. Analyses of simulated gene family evolution datasets showed thatIESwas more accurate and less susceptible to noise than popular tree-based methods (Robinson-Foulds and geodesic distance) for assessing evolutionary signal compatibility, since it bypasses phylogenetic reconstruction and its inherent uncertainty. ApplyingIESto a real dataset of 1,322 genes from 42 archaeal genomes identified eight major clusters of gene families with compatible evolutionary trends. Four of these clusters included genes with a taxonomic distribution across all archaeal phyla, while other clusters included a subset of taxa that do not map to generally accepted archaeal clades, indicating possible shared horizontal transfers by clustered gene families. We identify one strongly connected set of 62 genes from the same cluster, occurring as both single-copy and multiple homologs per genome, with compatible phylogenetic reconstructions closely matching previously published species trees for Archaea. AnIESimplementation is available athttps://github.com/lthiberiol/evolSimIndex.
Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex
Authors: Kim Mean-Hwan , Radaelli Cristina , Thomsen Elliot R. , Machen Deja , Chartrand Tom , Jorstad Nikolas L. , Mahoney Joseph T. , Taormina Michael J. , Long Brian , Baker Katherine , Campagnola Luke , Casper Tamara , Clark Michael , Dee Nick , D’Orazi Florence , Gamlin Clare , Kalmbach Brian , Kebede Sara , Lee Brian R. , Ng Lindsay , Trinh Jessica , Cobbs Charles , Gwinn Ryder P. , Keene C. Dirk , Ko Andrew L. , Ojemann Jeffrey G. , Silbergeld Daniel L. , Sorensen Staci A. , Berg Jim , Smith Kimberly , Nicovich Philip R. , Jarsky Tim , Murphy Gabe , Zeng Hongkui , Ting Jonathan T. , Levi Boaz P. , Lein Ed S. 
Published: October 2020

ABSTRACTRodent studies have demonstrated that synaptic dynamics from excitatory to inhibitory neuron types are often dependent on the target cell type. However, these target cell-specific properties have not been well investigated in human cortex, where there are major technical challenges in reliably identifying cell types. Here, we take advantage of newly developed methods for human neurosurgical tissue analysis with multiple patch-clamp recordings,post-hocfluorescentin situhybridization (FISH), and prospective GABAergic AAV-based labeling to investigate synaptic properties between pyramidal neurons and PVALB- vs. SST- positive interneurons. We find that there are robust molecular differences in synapse-associated genes between these neuron types, and that individual presynaptic pyramidal neurons evoke postsynaptic responses with heterogeneous synaptic dynamics in different postsynaptic cell types. Using molecular identification with FISH and classifiers based on transcriptomically identified PVALB neurons analyzed with Patch-seq methods, we find that PVALB neurons typically show depressing synaptic characteristics, whereas other interneuron types including SST-positive neurons show facilitating characteristics. Together, these data support the existence of target cell-specific synaptic properties in human cortex that are similar to rodent, thereby indicating evolutionary conservation of local circuit connectivity motifs from excitatory to inhibitory neurons and their synaptic dynamics.
Multiple neuronal networks coordinate Hydra mechanosensory behavior
Authors: Badhiwala Krishna N. , Primack Abby S. , Juliano Celina E. , Robinson Jacob T. 
Published: October 2020

AbstractHydra vulgaris is an emerging model organism for neuroscience due to its small size, transparency, genetic tractability, and regenerative nervous system; however, fundamental properties of its sensorimotor behaviors remain unknown. Here, we use microfluidic devices combined with fluorescent calcium imaging and surgical resectioning to study how the diffuse nervous system coordinates Hydra’s mechanosensory response. Mechanical stimuli cause animals to contract, and we find this response relies on at least two distinct networks of neurons in the oral and aboral regions of the animal. Different activity patterns arise in these networks depending on whether the animal is contracting spontaneously or contracting in response to mechanical stimulation. Together, these findings improve our understanding of how Hydra’s diffuse nervous system coordinates sensorimotor behaviors. These insights help reveal how sensory information is processed in an animal with a diffuse, radially symmetric neural architecture unlike the dense, bilaterally symmetric nervous systems found in most model organisms.
EfgA is a conserved formaldehyde sensor that halts bacterial translation in response to elevated formaldehyde
Authors: Bazurto Jannell V. , Nayak Dipti D. , Ticak Tomislav , Davlieva Milya , Lee Jessica A. , Lambert Leah B. , Benski Olivia J. , Quates Caleb J. , Johnson Jill L. , Patel Jagdish Suresh , Ytreberg F. Marty , Shamoo Yousif , Marx Christopher J. 
Published: October 2020

AbstractNormal cellular processes give rise to toxic metabolites that cells must mitigate. Formaldehyde is a universal stressor and potent metabolic toxin that is generated in organisms from bacteria to humans. Methylotrophic bacteria such asMethylorubrum extorquensface an acute challenge due to their production of formaldehyde as an obligate central intermediate of single-carbon metabolism. Mechanisms to sense and respond to formaldehyde were speculated to exist in methylotrophs for decades but had never been discovered. Here we identify a member of the DUF336 domain family, namedefgAfor enhanced formaldehyde growth, that plays an important role in endogenous formaldehyde stress response inM. extorquensPA1 and is found almost exclusively in methylotrophic taxa. Our experimental analyses reveal that EfgA is a formaldehyde sensor that inhibits translation in response to elevated levels of formaldehyde. Heterologous expression of EfgA inEscherichia coliincreases formaldehyde resistance, indicating that its interaction partners are widespread and conserved and may include translational machinery. EfgA represents the first example of a formaldehyde stress response system that does not involve enzymatic detoxification. Thus, EfgA comprises a unique stress response mechanism in bacteria, whereby a single protein directly senses elevated levels of a toxic intracellular metabolite and modulates translational activity.
Diverse viral proteases activate the NLRP1 inflammasome
Authors: Tsu Brian V. , Beierschmitt Christopher , Ryan Andrew P. , Agarwal Rimjhim , Mitchell Patrick S. , Daugherty Matthew D. 
Published: October 2020

ABSTRACTThe NLRP1 inflammasome is a multiprotein complex that is a potent activator of inflammation. Mouse NLRP1B can be activated through proteolytic cleavage by the bacterial Lethal Toxin (LeTx) protease, resulting in degradation of the N-terminal domains of NLRP1B and liberation of the bioactive C-terminal domain, which includes the caspase activation and recruitment domain (CARD). However, a natural pathogen-derived effector that can activate human NLRP1 remains unknown. Here, we use an evolutionary model to identify several proteases from diverse picornaviruses that cleave human NLRP1 within a rapidly evolving region of the protein, leading to host-specific and virus-specific activation of the NLRP1 inflammasome. Our work demonstrates that NLRP1 acts as a “tripwire” to recognize the enzymatic function of a wide range of viral proteases, and suggests that host mimicry of viral polyprotein cleavage sites can be an evolutionary strategy to activate a robust inflammatory immune response.
Proximity Biotin Labeling Reveals KSHV Interferon Regulatory Factor Networks
Authors: Kumar Ashish , Salemi Michelle , Bhullar Resham , Guevara-Plunkett Sara , Lyu Yuanzhi , Wang Kang-Hsin , Izumiya Chie , Campbell Mel , Nakajima Ken-ichi , Izumiya Yoshihiro 
Published: October 2020

AbstractStudies on “HIT&RUN” effects by viral protein are difficult when using traditional affinity precipitation-based techniques under dynamic conditions, because only proteins interacting at a specific instance in time can be precipitated by affinity purification. Recent advances in proximity labeling (PL) have enabled study of both static and dynamic protein-protein interactions. Here we applied PL method with recombinant Kaposi’s sarcoma-associated herpesvirus (KSHV). KSHV, a gamma-herpesvirus, uniquely encodes four interferon regulatory factors (IRFs 1-4) in the genome, and we identified KSHV vIRF-1 and vIRF-4 interacting proteins during reactivation. Fusion of mini-TurboID with vIRF-1 or vIRF-4 did not interfere with KSHV gene expression, DNA replication, orde novoinfections. PL identified 213 and 70 proteins for vIRF-1 and vIRF-4 respectively, which possibly interact during KSHV reactivation, and 47 of those were shared between the two vIRFs; the list also includes three viral proteins, ORF17, thymidine kinase, and vIRF-4. Functional annotation of respective interacting proteins showed highly overlapping biological functions such as mRNA processing and transcriptional regulation by TP53. Involvement of commonly interacting 44 cellular proteins in innate immune regulation were examined by siRNAs, and we identified that splicing factor 3B (SF3B) family proteins were clearly involved in interferons transcription and suppressed KSHV reactivation. We propose that recombinant TurboID-KSHV is a powerful tool to probe key cellular proteins that play a role in KSHV replication, and selective splicing factors may have a function beyond connecting two exon sequences to regulate innate immune responses.ImportanceViral protein interaction with a host protein shows at least two sides: (i) taking host protein functions for its own benefit and (ii) disruption of existing host protein complex formation to inhibit undesirable host responses. Due to use of affinity-precipitation approaches, the majority of our studies focused on how the virus takes advantage of the newly-formed protein interactions for its own replication. Proximity labeling (PL) however, can also highlight the transient and negative effects – those interactions which lead to dissociation from the existing protein complex. Here we highlight the power of PL in combination with recombinant KSHV to study viral host interactions.
Dissecting Mammalian Spermatogenesis Using Spatial Transcriptomics
Authors: Chen Haiqi , Murray Evan , Laumas Anisha , Li Jilong , Nie Xichen , Hotaling Jim , Guo Jingtao , Cairns Bradley R. , Macosko Evan Z. , Cheng C. Yan , Chen Fei 
Published: October 2020

SummarySingle-cell RNA sequencing has revealed extensive molecular diversity in gene programs governing mammalian spermatogenesis but fails to delineate their dynamics in the native context of seminiferous tubules — the spatially-confined functional units of spermatogenesis. Here, we use Slide-seq, a novel spatial transcriptomics technology, to generate a comprehensive spatial atlas that captures the spatial gene expression patterns at near single-cell resolution in the mouse and human testis. By using Slide-seq data, we devise a computational framework that accurately localizes testicular cell types in individual seminiferous tubules. Unbiased spatial transcriptome analysis systematically identifies spatially patterned genes and gene programs, nominating genes with previously underappreciated but important functions in spermatogenesis. Using the human testicular spatial atlas, we identify two spatially segregated spermatogonial populations composed of stem cells at distinct transcriptional states. Finally, a comparison of the spatial atlas generated from the wild type and diabetic mouse testis reveals a disruption in the spatial cellular organization in diabetic seminiferous tubules.
Performance of three freely available methods for extracting white matter hyperintensities: FreeSurfer, UBO Detector and BIANCA
Authors: Hotz Isabel , Deschwanden Pascal Frédéric , Liem Franziskus , Mérillat Susan , Kollias Spyridon , Jäncke Lutz 
Published: October 2020

AbstractWhite matter hyperintensities (WMH) of presumed vascular origin are frequently found in MRIs of healthy older adults. WMH are also associated with aging and cognitive decline. Here, we compared and validated three freely available algorithms for WMH extraction: FreeSurfer, UBO Detector, and BIANCA (Brain Intensity AbNormality Classification Algorithm) using a longitudinal dataset comprising MRI data of cognitively healthy older adults (baselineN= 231, age range 64–87 years). As reference we manually segmented WMH in T1w, 3D FLAIR, 2D FLAIR images. These manual segmentations were then used to assess the segmentation accuracy of the different automated algorithms. Further, we assessed the relationships of WMH volume estimates provided by the algorithms with Fazekas scores and age. FreeSurfer underestimated the WMH volumes and scored worst in Dice Similarity Coefficient (DSC = 0.434) but its WMH volumes strongly correlated with the Fazekas scores (rs= 0.73). BIANCA accomplished the highest DCS (0.602) with 3D FLAIR images. However, the relations with the Fazekas scores were only moderate, especially in the 2D FLAIR images (rs= 0.41), and many outlier WMH volumes were detected when exploring within-person trajectories (2D FLAIR: ~30%). UBO Detector performed similarly to BIANCA in DSC with both modalities and reached the best DSC in 2D FLAIR (0.531) without requiring a tailored training dataset. In addition, it achieved very high associations with the Fazekas scores (2D FLAIR:rs= 0.80).In summary, our results emphasize the importance of carefully contemplating the choice of the WMH segmentation algorithm and MR-modality.
Diluvial nation: building imperial Japan through floods
Authors: Yoshikawa Lisa 
Published: October 2020

PurposeThis article assesses the development of flood relief and recovery, and their narratives, as political sites for the central and local governments to negotiate each other's standing and role in imperial Japan.Design/methodology/approachThe article examines local flood narratives, most prominently from Okayama, to assess how imperial Japan's central government intruded into the periphery through disaster relief, and how the localities negotiated and challenged Tokyo's political agenda on the ground and through these narratives.FindingsThe above sources reveal that the national government attempted to use flood experiences to unite the pluralizing society by three main means: building meteorological stations, relief laws, and through the imperial being. The process was systematized gradually, and local prefectures aided and challenged Tokyo's attempts. The prefectures also used disasters to try to bring unity within their community.Originality/valueHistorical flood narratives are often used to mine data from which future preventative and management measures are constructed. The article suggests the narratives' political nature, and hence the nuances that must be considered in these efforts.
A critical analysis of safety performance indicators in construction
Authors: Shaikh Aziz Yousif , Osei‐Kyei Robert , Hardie Mary 
Published: October 2020

PurposeSafety performance indicators are a major research concern globally in the construction sector, so this study aims to systematically analyse construction safety performance indicators from some top research publications from 2000 to 2019.Design/methodology/approachSystematic review was performed using Scopus search engine and relevant publications were compiled. Visual and far reaching search in all publications were performed. Final analysis was done to evaluate selected attributes.FindingsThe outcome of the analysis showed growing interest in research on construction safety performance indicators since 2000. From the review, 48 safety performance indicators are identified from 41 selected publications. The most reported safety performance indicators were safety climate, safety orientation, management commitment to safety, near-miss and job site audits. It was noted further that USA, Australia, Canada and China have been international locations of attention for most research on construction safety performance indicators. The 48 safety indicators are classified into six categories, namely people indicators, culture indicators, processes indicators, infrastructure indicators, metrics indicators and technology indicatorsPractical implicationsThe findings identified provide researchers and practitioners a summary of the safety indicators in the construction sector through a vision to streamline future applications and increase the safety performance in the construction sector.Originality/valueA safety performance indicators' list has been established for the adoption of future empirical research. The findings will make a significant contribution to current but limited knowledge on safety performance indicators in construction industry.
Design principles for creating digital badges to support learning
Authors: Horstman Theresa , Tierney Gavin , Tzou Carrie 
Published: October 2020

Purpose
This paper aims to focus on two areas of digital badge design that impact learner experience: the value and meaning of badges outside of their original context and badge function and platform functionality that impact learner experience.

Design/methodology/approach
This research uses a design-based research approach. For this paper, components of badge systems were analyzed to identify the characteristics of learning experiences in each program.

Findings
Findings in this paper are from a National Science Foundation-funded project where digital badge systems were co-designed to connect informal science learning with college credit. The badge design principles presented to address the value of badges and badge function and platform functionality, as well as making program design more systematic and using badge design as a conceptual, organizing design framework for improved educational programs.

Research limitations/implications
Though this research is limited in the number of programs examined, the findings provide a framework for the language and standards to discuss and implement digitals badges.

Practical implications
This paper will be of use to programing developers seeking to integrate badges into their educational programs or simply reexamine their educational goals and opportunities for learners.

Originality/value
This paper challenges the conventional use of badges for simply increasing learner engagement by illustrating that the badge design and development process can improve program design and subsequent learner experience rather than serving purely as a learner motivational tool.