bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of Illinois’ comprehensive handheld phone ban on talking on handheld and handsfree cellphones while driving
Authors: Benedetti Marco H. , Lu Bo , Kinnear Neale , Li Li , Delgado M. Kit , Zhu Motao 
Published: April 2022

ABSTRACTIntroductionDistracted driving has been linked to multiple driving decrements and is responsible for thousands of motor vehicle fatalities annually. Most US states have enacted restrictions on cellphone use while driving, the strictest of which prohibit any manual operation of a cellphone while driving. Illinois enacted such a law in 2014. To better understand how this law affected cellphone behaviors while driving, we estimated associations between Illinois’ handheld phone ban and self-reported talking on handheld, handsfree, and any cellphone (handheld or handsfree) while driving.MethodsWe leveraged data from annual administrations of the Traffic Safety Culture Index from 2012-2017 in Illinois and a set of control states. We cast the data into a difference-in-differences (DID) modeling framework, which compared Illinois to control states in terms of pre-to post-intervention changes in the proportion of drivers who self-reported the three outcomes. We fit separate models for each outcome, and fit additional models to the subset of drivers who talk on cellphones while driving.ResultsIn Illinois, the pre-to post-intervention decrease in the drivers’ probability of self-reporting talking on a handheld phone was significantly more extreme than that of drivers in control states (DID estimate −0.22; 95% CI −0.31, −0.13). Among drivers who talk on cellphones while driving, those in Illinois exhibited a more extreme increase in the probability of talking on a handsfree phone while driving than those control states (DID estimate 0.13; 95% CI 0.03, 0.23).ConclusionsOur results suggest that Illinois’ handheld phone ban reduced talking on handheld phones while driving and corroborated the hypothesis that the ban promoted harm-reduction via substitution from handheld to handsfree phones among drivers who talk on the phone while driving.Practical ApplicationsOur findings should encourage other states to enact comprehensive handheld phone bans to improve traffic safety.
Debugging and consolidating multiple synthetic chromosomes reveals combinatorial genetic interactions
Authors: Zhao Yu , Coelho Camila , Hughes Amanda L. , Lazar-Stefanita Luciana , Yang Sandy , Brooks Aaron N. , Walker Roy S. K. , Zhang Weimin , Lauer Stephanie , Hernandez Cindy , Mitchell Leslie A. , Agmon Neta , Shen Yue , Sall Joseph , Fanfani Viola , Jalan Anavi , Rivera Jordan , Liang Feng-Xia , Stracquadanio Giovanni , Steinmetz Lars M. , Cai Yizhi Patrick , Boeke Jef D. 
Published: April 2022

AbstractThe Sc2.0 project is building a eukaryotic synthetic genome from scratch, incorporating thousands of designer features. A major milestone has been achieved with the assembly of all individual Sc2.0 chromosomes. Here, we describe the consolidation of multiple synthetic chromosomes using endoreduplication intercross to generate a strain with 6.5 synthetic chromosomes. Genome-wide chromosome conformation capture and long-read direct RNA sequencing were performed on this strain to evaluate the effects of designer modifications, such as loxPsym site insertion, tRNA relocation, and intron deletion, on 3D chromosome organization and transcript isoform profiles. To precisely map “bugs”, we developed a method, CRISPR Directed Biallelic URA3-assisted Genome Scan, or “CRISPR D-BUGS”, exploiting directed mitotic recombination in heterozygous diploids. Using this method, we first fine-mapped a synII defect resulting from two loxPsym sites in the 3’ UTR of SHM1. This approach was also used to map a combinatorial bug associated with synIII and synX, revealing a highly unexpected genetic interaction that links transcriptional regulation, inositol metabolism and tRNASerCGA abundance. “Starvation” for tRNASerCGA leads to insufficient levels of the key positive inositol biosynthesis regulator, Swi3, which contains tandem UCG codons. Finally, to expedite consolidation, we employed a new method, chromosome swapping, to incorporate the largest chromosome (synIV), thereby consolidating more than half of the Sc2.0 genome in a single strain.
Reduced affinity of calcium sensing-receptor heterodimers and reduced mutant homodimer trafficking combine to impair function in a mouse model of Familial Hypocalciuric Hypercalcemia Type 1
Authors: Wang Xiaohua , Lundblad James , Smith Stephen M. 
Published: April 2022

AbstractHeterozygous loss-of-function mutation of the calcium sensing-receptor (CaSR), causes familial hypocalciuric hypercalcemia type 1 (FHH1), a typically benign condition characterized by mild hypercalcemia. In contrast, homozygous mutation of this dimer-forming G-protein coupled receptor manifests as the lethal neonatal severe hyperparathyroidism (NSHPT). To investigate the mechanisms by which CaSR mutations lead to these distinct disease states, we engineered wild-type (WT) and an exon 5-deficient disease-causing mutation, and transfected expression constructs into human embryonic kidney (HEK) cells. WT protein was mainly membrane-expressed whereas the mutant CaSR protein (mCaSR) was confined to the cytoplasm. Co-expression of WT CaSR directed mCaSR to the cell membrane. In assays of CaSR function, increases in extracellular [Ca2+] ([Ca2+]o) increased intracellular [Ca2+] ([Ca2+]i) in cells expressing WT CaSR while the response was reduced in cells coexpressingmutant and WT receptor. Untransfected cells or those expressing mCaSR alone, showed minimal, equivalent responses to increased [Ca2+]o. Immunoprecipitation experiments confirmed an association between mutant and wild-type CaSR. The affinity of the WT CaSR for calcium was three times greater than that of the heterodimer. The maximal functional response to [Ca]o was dependent on localization of CaSR to the membrane level and independent of homo- or heterodimerizations. In summary, these results suggest that heterodimerization of WT and mCaSR receptors, rescues the trafficking defect of the mutant receptors and also reduces the affinity of the WT-mutant heterodimer for [Ca]o. In contrast, the homozygous mutants do not produce functional receptors on cell membrane. These data indicate how substantial differences between signaling of hetero- and homodimeric mutants lead to profound differences in the severity of disease in heterozygous and homozygous carriers of these mutations.
Intradiscal Inflammatory Stimulation Induces Spinal Pain Behavior and Intervertebral Disc DegenerationIn Vivo
Authors: Lisiewski Lauren E. , Jacobsen Hayley E. , Viola Dan C. M. , Kenawy Hagar M. , Kiridly Daniel N. , Chahine Nadeen O. 
Published: April 2022

AbstractDegeneration of the intervertebral disc (IVD) is known to occur naturally over time, with the severity of pain varying widely. Other components of the degenerative environment, including structural disruption and inflammatory cytokine levels, and their correlation with pain severity have been studied. However, the role of the inflammatory environment in activating degenerative changes that manifest as a pain phenotype has not been elucidated. Previous studies have aimed to recreate the sustained inflammatory environment exhibited during human disc degeneration in a rat model. Most commonly, a puncture injury has been used causing structural damage and only initiating an acute inflammatory response. This study utilized injection of lipopolysaccharide (LPS), a pro-inflammatory stimulus, into the rat discin vivoto create the desired sustained inflammatory environment independent of physical disruption. LPS injections resulted in upregulation of pro-inflammatory cytokines and an immunogenic response. The structural integrity of the IVD was also altered demonstrated by changes in histological score, disc height, and mechanical properties. Ultimately, a sustained inflammatory environment led to both local and radiating mechanical sensitivity, demonstrating that the pain phenotype experienced during disc degeneration can be initiated solely by a sustained inflammatory profile. Markers indicative of nerve ingrowth into the IVD were also expressed suggesting a potential mechanism for the pain exhibited by animals. This rat injury model will allow for future study of the direct relationship between inflammation and pain in the degenerative environment.
Sex-specific differences in rotarod performance and type 1 cannabinoid receptor levels in a rat model of traumatic brain injury treated with Δ9-tetrahydrocannabinol
Authors: Black Tallan , Zagoog Ayat , Roebuck Andrew J , Greba Quentin , Neary J. Patrick , Howland John G. , Laprairie Robert B. 
Published: April 2022

AbstractTraumatic brain injuries (TBI) remain one of the leading causes of death and disability world-wide. One emerging area of TBI research is the involvement of the endocannabinoid system (ECS) in response to TBI. Endogenous cannabinoids modulate inflammation, pain, anxiety, and neurotransmitter release through the activation of the cannabinoid receptors CB1R and CB2R. CB1R and CB2R are activated by exogenous cannabinoids such as Δ9-tetrahydrocannabinol (THC) found inCannabis sativa. As public perceptions change in the wake ofCannabislegalization, research into the potential harmful and therapeutic effects of THC following TBI deserve exploration. In this preliminary study, we investigated sex differences in behavioral effects, CB1R abundance, and cytokine profiles in a rat model of moderate TBI treated with 1 mg·kg-1THC (i.p.). Neither TBI nor THC treatment altered catalepsy, body temperature, nociception, or spontaneous alternation as measured in the y-maze. TBI reduced male rotarod performance in both vehicle and THC-treated groups, and THC treatment decreased performance in Sham-TBI rats when compared to vehicle controls. Female rats that received a TBI and THC exhibited lower relative CB1R density when compared to the Sham-TBI+THC group. TBI was associated with reduced interleukin-4 in males; THC increased interleukin-6 in TBI males compared to Sham-TBI. These preliminary results highlight fundamental sex differences in the response of the ECS following TBI. Our results indicate the need for further investigation of the ECS and phytocannabinoids post-TBI in both acute and chronic phases.Significance StatementThe endogenous cannabinoid system is a potential target in the pathophysiology and treatment of traumatic brain injury (TBI). In this study we observed TBI reduced rotarod performance in male rats only and performance was not affected by THC. Female rats the received THC and TBI displayed lower cortical cannabinoid receptor 1 levels. These early results showcase sex differences in rodent models of TBI and the endogenous cannabinoid system.
Genotypic and phenotypic diversity of the multidrug-resistant Mycobacterium tuberculosis strains from eastern India
Authors: Ghosh Arup , Bal Himadri , Biswas Viplov Kumar , Das Dasarathi , Pati Sanghmitra , Raghav Sunil 
Published: April 2022

AbstractMycobacterium tuberculosis (Mtb) poses a great challenge to human health and wellbeing and hinders economic growth of a region. India along with other south east Asian countries are known as high Tuberculosis burden countries. Adoption of whole genome sequencing in studying genetic diversity, evolution, transmission pattern and drug resistance development provided a great opportunity for developing and improving diagnostic and therapeutic approaches. In our study we have sequenced 118 Mtb whole genome from North East(NE) and Odisha as a representative of the diversity in eastern region of India for the first time. We observed high prevalence of multi-drug resistant(MDR) lineage-2(n=52) strains in NE whereas presence of mostly lineage-1(n=30) & 3 (n=11) strains in Odisha. The MDR strains from Sikkim demonstrated similar resistance profile of fluroquinolones and pair-wise SNP distances showed presence of local transmission clusters. We also detected significant enrichment of short INDELs in MDR samples in contrast to drug susceptible samples. This study provides molecular level insight into Mtb strains of eastern region in comparison with Indian and global perspective.
SARS-ANI: A Global Open Access Dataset of Reported SARS-CoV-2 Events in Animals
Authors: Nerpel Afra , Yang Liuhuaying , Sorger Johannes , Käsbohrer Annemarie , Walzer Chris , Desvars-Larrive Amélie 
Published: April 2022

AbstractThe zoonotic origin of SARS-CoV-2, the etiological agent of COVID-19, is not yet fully resolved. Although natural infections in animals are reported in a wide range of species, large knowledge and data gaps remain regarding SARS-CoV-2 animal hosts. We used two major health databases to extract unstructured data and generated a comprehensive global dataset of thoroughly documented SARS-CoV-2 events in animals. The dataset integrates relevant epidemiological and clinical data on each event and is readily usable for analytical purposes. We also share the code for technical and visual validation of the data and created a user-friendly dashboard for data exploration. Data on SARS-CoV-2 occurrence in animals is critical to adapt monitoring strategy, prevent the formation of animal reservoirs, and tailor future human and animal vaccination programs. The FAIRness and analytical flexibility of the data will support research efforts on SARS-CoV-2 at the human-animal-environment interface. We intend to update this dataset weekly for at least one year and, through collaborative processes, to develop the dataset further and expand its use.
Crosstalk between glucose metabolism and morphogen signalling specifies tonotopic identity in developing hair cells
Authors: O’Sullivan James DB , Blacker Thomas S , Scott Claire , Chang Weise , Ahmed Mohi , Yianni Val , Mann Zoe F 
Published: April 2022

AbstractIn vertebrates with elongated auditory organs, mechanosensory hair cells (HCs) are organised such that complex sounds are broken down into their component frequencies along the proximal-to-distal long (tonotopic) axis. Acquisition of frequency-specific morphologies at the appropriate positions along the chick cochlea, the basilar papilla (BP), requires that nascent HCs determine their tonotopic positions during development. The complex signalling within the auditory organ between the developing HC and its local niche along the axis is currently poorly understood. Here we apply NAD(P)H fluorescence lifetime imaging (FLIM) to reveal metabolic gradients along the tonotopic axis of the developing BP. Re-shaping these gradients during development, by inhibiting different branch points of cytosolic glucose catabolism, alters normal morphogen signalling and abolishes tonotopic patterning, normalising the graded differences in hair cell morphology along the BP. These findings highlight a causal link between morphogen signalling and metabolic reprogramming in specifying tonotopic identity in developing auditory HCs.
Quantitation of FGFR3 signaling via GRB2 recruitment on micropatterned surfaces
Authors: Hartl Ingrid , Brumovska Veronika , Striedner Yasmin , Yasari Atena , Schütz Gerhard J. , Sevcsik Eva , Tiemann-Boege Irene 
Published: April 2022

AbstractFibroblast growth factor receptors (FGFRs) initiate signal transduction via the RAS/MAPK pathway by their tyrosine-kinase activation known to determine cell-growth, tissue differentiation and apoptosis. Recently, many missense mutations have been reported for FGFR3, but we only know the functional effect for a handful of them. Some of these mutations result in aberrant FGFR3 signaling and are associated with various genetic disorders and oncogenic conditions. Here we employed micropatterned surfaces to specifically enrich fluorophore-tagged FGFR3 (mGFP-FGFR3) in certain areas of the plasma membrane of living cells. Receptor activation was then quantified via the recruitment of the downstream signal transducer GRB2 tagged with mScarlet (GRB2-mScarlet) to FGFR3 patterns. With this system, we tested the activation of FGFR3 upon ligand addition (fgf1 and fgf2) in the wildtype (WT), as well as in different FGFR3 mutants associated with congenital disorders (G380R, Y373C, K650Q, K650E). Our data showed that the addition of ligands increased GRB2 recruitment to WT FGFR3, with fgf1 having a stronger effect than fgf2. For all mutants, we found an increased basal receptor activity, and only for two of the four mutants (G380R and K650Q), activity was further increased upon ligand addition. Compared to previous reports, two mutant receptors (K650Q and K650E) had either an unexpectedly high or low activation state, respectively. This may be explained by the different receptor populations probed, since the micropatterning method specifically reports on signaling events at the plasma membrane.Graphical AbstractSpecifications: The maximum size of the image should be 200 × 500 pixels with a minimum resolution of 300 dpi, using Arial font with a size of 10-16 points; Preferred file types: TIFF, EPS, PDF or MS Office filesResearch HighlightsQuantification of FGFR3 signaling in live cells on micropatterned surfacesAnalysis of GRB2 recruitment to the mature receptor at the plasma membraneLigand-independent kinase activation of FGFR3 mutantsActivation of FGFR3 at the cell surface can be different than in bulk cell extracts
Broadly neutralizing antibodies target the coronavirus fusion peptide
Authors: Dacon Cherrelle , Tucker Courtney , Peng Linghang , Lee Chang-Chun D. , Lin Ting-Hui , Yuan Meng , Cong Yu , Wang Lingshu , Purser Lauren , Williams Jazmean K. , Pyo Chul-Woo , Kosik Ivan , Hu Zhe , Zhao Ming , Mohan Divya , Cooper Andrew , Peterson Mary , Skinner Jeff , Dixit Saurabh , Kollins Erin , Huzella Louis , Perry Donna , Byrum Russell , Lembirik Sanae , Zhang Yi , Yang Eun Sung , Chen Man , Leung Kwanyee , Weinberg Rona S. , Pegu Amarendra , Geraghty Daniel E. , Davidson Edgar , Douagi Iyadh , Moir Susan , Yewdell Jonathan W. , Schmaljohn Connie , Crompton Peter D. , Holbrook Michael R. , Nemazee David , Mascola John R. , Wilson Ian A. , Tan Joshua 
Published: April 2022

AbstractThe potential for future coronavirus outbreaks highlights the need to develop strategies and tools to broadly target this group of pathogens. Here, using an epitope-agnostic approach, we identified six monoclonal antibodies that bound to spike proteins from all seven human-infecting coronaviruses. Epitope mapping revealed that all six antibodies target the conserved fusion peptide region adjacent to the S2’ cleavage site. Two antibodies, COV44-62 and COV44-79, broadly neutralize a range of alpha and beta coronaviruses, including SARS-CoV-2 Omicron subvariants BA.1 and BA.2, albeit with lower potency than RBD-specific antibodies. In crystal structures of Fabs COV44-62 and COV44-79 with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine at the S2’ cleavage site. Importantly, COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings identify the fusion peptide as the target of the broadest neutralizing antibodies in an epitope-agnostic screen, highlighting this site as a candidate for next-generation coronavirus vaccine development.One-Sentence SummaryRare monoclonal antibodies from COVID-19 convalescent individuals broadly neutralize coronaviruses by targeting the fusion peptide.
Short-course but not prolonged treatment with ATR inhibitor AZD6738 integrates with radiotherapy to generate a tumor antigen-specific CD8+ T cell expansion in the periphery
Authors: Vendetti Frank P. , Clump David A. , Schamus-Haynes Sandra , DiMayorca Maria , Islam Naveed , Chang Jina , Beumer Jan H. , Bakkenist Christopher J. 
Published: April 2022

AbstractATR kinase is a central regulator of the DNA damage response. While ATR kinase inhibitors (ATRi’s) are known to sensitize cancer cells to DNA damage, their effect on immune cells is not known. Here we show in mice that short-course AZD6738 (ATRi) on days 1-3 decreases proliferating T cells in the tumor and periphery and that cessation of ATRi causes a proliferative rebound. Integrating radiation on days 1-2 (RT) with ATRi on days 1-3 increases IFN-β in the tumor and activates tumor antigen-specific CD8+ T cells in the tumor-draining lymph node (DLN). RT with short-course ATRi induces an expansion of tumor antigen-specific CD8+ T cells in the DLN. In contrast, RT with prolonged daily ATRi blocks expansion of antigen-specific CD8+ T cells, despite increased IFN-β and activation of CD8+ T cells. Our data identifies critical schedule considerations for ATRi with RT, immunotherapy and genotoxic therapies.
Electrophysiological normative responses to emotional, neutral, and cigarette-related images
Authors: Versace Francesco , Sambuco Nicola , Deweese Menton M. , Cinciripini Paul M. 
Published: April 2022

AbstractTo create reproducible emotional probes, affective scientists rely on sets of standardized pictures that are normed using subjective ratings of valence and emotional arousal. Yet, to investigate psychophysiological emotional responses, it might be more appropriate to select pictures using normative neurophysiological responses rather than normative subjective ratings. Here, we provide electrophysiological normative responses for 323 emotional pictures (215 from the IAPS) covering a wide range of categories (erotica, romantic, appetizing foods, landscapes, people engaged in mundane activities, household objects, disgusting objects, accidents, sad people, violence, mutilations, and cigarette-related contents). Event-related potentials (ERPs) and subjective ratings of pleasure and emotional arousal were collected from 763 individuals (52% females, 41% white) aged between 18 and 65 (mean = 43). For each image, the mean amplitude of the late positive potential (LPP, an electrophysiological index of motivational relevance) and the mean subjective ratings of valence and arousal were calculated. We validated our procedure by showing that the subjective ratings of valence and arousal from this sample were highly correlated to the IAPS’ published norms (Pearson r=.97 for pleasure and r=.82 for emotional arousal). LPP responses and subjective ratings of emotional arousal also were correlated (Pearson r = .61), but some categories that participants reported being significantly more arousing than neutral (i.e., food, landscapes, and unpleasant objects) did not evoke LPPs significantly different from those evoked by neutral pictures. Researchers interested in probing the brain’s affective systems can use these electrophysiological normative responses to create emotional probes that evoke reliable neuroaffective responses.
Between-area communication through the lens of within-area neuronal dynamics
Authors: Gozel Olivia , Doiron Brent 
Published: April 2022

AbstractA core problem in systems and circuits neuroscience is deciphering the origin of shared dynamics in neuronal activity: do they emerge through local network interactions, or are they inherited from external sources? We explore this question with large-scale networks of spatially ordered spiking neuron models where a downstream network receives input from an upstream sender network. We show that linear measures of the communication between the sender and receiver networks can discriminate between emergent or inherited population dynamics. Faithful communication requires a match in the dimensionality of the sender and receiver population activities, along with an alignment of their shared fluctuations. However, a nonlinear mapping between the sender – receiver activity or downstream emergent population-wide fluctuations can impair linear communication. Our work exposes the benefits and limitations of linear measures when analyzing between-area communication in circuits with rich population-wide neuronal dynamics.