bluuebunny/crossref_metadata_2025_split huggingface dataset:
DDX24, a D-E-A-D box RNA helicase, is required for muscle fiber organization and anterior pole specification essential for head regeneration in planarians
Authors: Sarkar Souradeep R. , Dubey Vinay Kumar , Jahagirdar Anusha , Lakshmanan Vairavan , Haroon Mohamed Mohamed , Sowndarya Sai , Sowdhamini Ramanathan , Palakodeti Dasaradhi 
Published: January 2021

ABSTRACTPlanarians have a remarkable ability to undergo whole-body regeneration. The timely establishment of polarity at the wound site followed by the specification of the organizing centers- the anterior pole and the posterior pole, are indispensable for successful regeneration. In planarians, polarity, pole, and positional-information determinants are predominantly expressed by muscles. The molecular toolkit that enables this functionality of planarian muscles however remains poorly understood. Here we report that SMED_DDX24, a D-E-A-D Box RNA helicase and the homolog of human DDX24, is critical for planarian head regeneration. DDX24 is enriched in muscles and its knockdown leads to defective muscle-fiber organization and failure to re-specify anterior pole/organizer. Overall, loss of DDX24 manifests into gross misregulation of many well-characterized positional-control genes and patterning-control genes, necessary for organogenesis and tissue positioning and tissue patterning. In addition, wound-induced Wnt signalling was also upregulated inddx24RNAi animals. Canonical WNT-βCATENIN signalling is known to suppress head identity throughout bilateria, including planarians. Modulating this Wnt activity byβ-catenin-1RNAi, the effector molecule of this pathway, partially rescues theddx24RNAi phenotype, implying that a high Wnt environment inddx24knockdown animals likely impedes their normal head regeneration. Furthermore, at a sub-cellular level, RNA helicases are known to regulate muscle mass and function by regulating their translational landscape.ddx24knockdown leads to the downregulation of large subunit ribosomal RNA and the 80S ribosome peak, implying its role in ribosome biogenesis and thereby influencing the translational output. This aspect seems to be an evolutionarily conserved role of DDX24. In summary, our work demonstrates the role of a D-E-A-D box RNA helicase in whole-body regeneration through muscle fiber organization, and pole and positional-information re-specification, likely mediated through translation regulation.
Survey of peridomestic mammal susceptibility to SARS-CoV-2 infection
Authors: Bosco-Lauth Angela M. , Root J. Jeffrey , Porter Stephanie M. , Walker Audrey E. , Guilbert Lauren , Hawvermale Daphne , Pepper Aimee , Maison Rachel M. , Hartwig Airn E. , Gordy Paul , Bielefeldt-Ohmann Helle , Bowen Richard A. 
Published: January 2021

AbstractWild animals have been implicated as the origin of SARS-CoV-2, but it is largely unknown how the virus affects most wildlife species and if wildlife could ultimately serve as a reservoir for maintaining the virus outside the human population. Here we show that several common peridomestic species, including deer mice, bushy-tailed woodrats, and striped skunks, are susceptible to infection and can shed the virus in respiratory secretions. In contrast, we demonstrate that cottontail rabbits, fox squirrels, Wyoming ground squirrels, black-tailed prairie dogs, house mice, and racoons are not susceptible to SARS-CoV-2 infection. Our work expands upon the existing knowledge base of susceptible species and provides evidence that human-wildlife interactions could result in continued transmission of SARS-CoV-2.
Experimental evidence for the benefits of higher X-ray energies for macromolecular crystallography
Authors: Storm S. L. S. , Axford D. , Owen R. L. 
Published: January 2021

AbstractX-ray induced radiation damage is a limiting factor for the macromolecular crystallographer and data must often be merged from many crystals to yield complete datasets for structure solution of challenging samples. Increasing the X-ray energy beyond the typical 10-15 keV range promises to provide an extension of crystal lifetime via an increase in diffraction efficiency. To date however hardware limitations have negated any possible gains. Through the first use of a Cadmium Telluride Eiger2 detector and a beamline optimised for high energy data collection, we show that at higher energies fewer crystals will be required to obtain complete data, as the diffracted intensity per unit dose increases by a factor of more than 3 between 12.4 and 25 keV. Additionally, those higher energy data provide more information, evidenced by an increase in high-resolution limit of up to 0.3 Å, pointing to a high energy future for synchrotron-based macromolecular crystallography.
High-throughput screening of the ReFRAME, Pandemic Box, and COVID Box drug repurposing libraries against SARS-CoV2 nsp15 endoribonuclease to identify small-molecule inhibitors of viral activity
Authors: Choi Ryan , Zhou Mowei , Shek Roger , Wilson Jesse W. , Tillery Logan , Craig Justin K. , Salukhe Indraneel A. , Hickson Sarah E. , Kumar Neeraj , James Rhema M. , Buchko Garry W , Wu Ruilian , Huff Sydney , Nguyen Tu-Trinh , Hurst Brett L. , Cherry Sara , Barrett Lynn K. , Hyde Jennifer L. , Van Voorhis Wesley C. 
Published: January 2021

AbstractSARS-CoV-2 has caused a global pandemic, and has taken over 1.7 million lives as of mid-December, 2020. Although great progress has been made in the development of effective countermeasures, with several pharmaceutical companies approved or poised to deliver vaccines to market, there is still an unmet need of essential antiviral drugs with therapeutic impact for the treatment of moderate-to-severe COVID-19. Towards this goal, a high-throughput assay was used to screen SARS-CoV-2 nsp15 uracil-dependent endonuclease (endoU) function against 13 thousand compounds from drug and lead repurposing compound libraries. While over 80% of initial hit compounds were pan-assay inhibitory compounds, three hits were confirmed as nsp15 endoU inhibitors in the 1-20 μM range in vitro. Furthermore, Exebryl-1, a β-amyloid anti-aggregation molecule for Alzheimer’s therapy, was shown to have antiviral activity between 10 to 66 μM, in VERO, Caco-2, and Calu-3 cells. Although the inhibitory concentrations determined for Exebryl-1 exceed those recommended for therapeutic intervention, our findings show great promise for further optimization of Exebryl-1 as an nsp15 endoU inhibitor and as a SARS-CoV-2 antiviral.Author summaryDrugs to treat COVID-19 are urgently needed. To address this, we searched libraries of drugs and drug-like molecules for inhibitors of an essential enzyme of the virus that causes COVID-19, SARS-CoV-2 nonstructural protein (nsp)15. We found several molecules that inhibited the nsp15 enzyme function and one was shown to be active in inhibiting the SARS-CoV-2 virus. This demonstrates that searching for SARS-CoV-2 nsp15 inhibitors can lead inhibitors of SARS-CoV-2, and thus therapeutics for COVID-19. We are currently working to see if these inhibitors could be turned into a drug to treat COVID-19.
A brief report of sleep and circadian rhythm quotas in a population of dog owners in North Carolina, USA
Authors: Patel Ujas A. , Gruen Margaret E. , Samson David R. 
Published: January 2021

ABSTRACTObjectivesTo characterize sleep and circadian rhythms of a sample population of healthy, dog-owning adults from North Carolina, USA.MethodsActigraphy was used to analyze sleep-wake patterns in forty-two dog owners from the Raleigh area in North Carolina. Sleep quotas, including sleep duration, efficiency, and fragmentation were measured alongside a Non-parametric Circadian Rhythms Analysis (NPCRA) to quantify strength, consistency, and fragmentation of rhythms.ResultsCompared to females, males demonstrated later sleep onset and sleep end (p<0.01), greater wake after sleep onset and sleep fragmentation (P<0.001), and lower sleep efficiency (p<0.001). The NPCRA revealed comparable relative amplitude (strength) and interdaily stability (consistency), yet less intra-daily variability (fragmentation), than previously reported post-industrial samples.ConclusionsThis study adds to the current data available on sleep and circadian rhythms in discrete human populations and highlights the need for more research characterizing cross-cultural sleep and circadian rhythmicity.
Molecular determinants underlying DS2 activity at δ-containing GABAAreceptors
Authors: Falk-Petersen Christina B. , Rostrup Frederik , Löffler Rebekka , Buchleithner Stine , Harpsøe Kasper , Gloriam David E. , Frølund Bente , Wellendorph Petrine 
Published: January 2021

AbstractDelta selective compound 2 (DS2) is one of the most widely used tools to study selective actions mediated by δ subunit-containing GABAAreceptors. DS2 was discovered over 10 years ago, but despite great efforts, the precise molecular site of action has remained elusive.Using a combination of computational modeling, site-directed mutagenesis and cell-based pharmacological assays, we probed three potential binding sites for DS2 and analogs at α4β1δ receptors: an α4(+)δ(-)interface site in the extracellular domain (ECD), equivalent to the diazepam binding site in αβγ2receptors, and two sites in the transmembrane domain (TMD); one in the α4(+)β1(-)and one in the α4(-)β1(+)interface, with the α4(-)β1(+)site corresponding to the binding site for etomidate and a recently disclosed low-affinity binding site for diazepam. We show that mutations in the ECD site did not abrogate DS2 modulation. However, mutations in the TMD α4(+)β1(-)interface, either α4(S303L) of the α4(+)-side or β1(I289Q) of the β1(-)-side, convincingly disrupted the positive allosteric modulation by DS2. This was consistently demonstrated both in an assay measuring membrane potential changes and by whole-cell patchclamp electrophysiology and rationalized by docking studies. Importantly, general sensitivity to modulators was not compromised in the mutated receptors. This study sheds important light on the long-sought molecular recognition site for DS2, refutes the misconception that the selectivity of DS2 for δ-containing receptors is caused by a direct interaction with the δ-subunit, and instead points towards a functional selectivity of DS2 and its analogs via a surprisingly well-conserved binding pocket in the TMD.Significance statementδ-Containing GABAAreceptors represent potential drug targets for the treatment of several neurological conditions with aberrant tonic inhibition. Yet, no drugs are currently in clinical use. With the identification of the molecular determinants responsible for positive modulation by the know compound DS2, the ground is laid for design of ligands that selectively target δ-containing GABAAreceptor subtypes, for better understanding of tonic inhibition, and, ultimately, for rational development of novel drugs.
RGS14 modulates locomotor behavior and ERK signaling induced by environmental novelty and cocaine within discrete limbic structures
Authors: Foster Stephanie L. , Lustberg Daniel J. , Harbin Nicholas H. , Bramlett Sara N. , Hepler John R. , Weinshenker David 
Published: January 2021

AbstractRationaleIn rodents, exposure to novel environments or psychostimulants promotes locomotor activity. Indeed, locomotor reactivity to novelty strongly predicts behavioral responses to psychostimulants in animal models of addiction. RGS14 is a plasticity restricting protein with unique functional domains that enable it to suppress ERK-dependent signaling as well as regulate G protein activity. Although recent studies show that RGS14 is expressed in multiple limbic regions implicated in psychostimulant- and novelty-induced hyperlocomotion, its function has been studied almost entirely in the context of hippocampal physiology and hippocampusdependent behaviors.ObjectiveWe sought to determine whether RGS14 modulates novelty- and psychostimulant-induced locomotion and neuronal activity.MethodsWe assessedRgs14knockout (RGS14 KO) mice and wild-type (WT) littermate controls using novelty-induced locomotion (NIL) and cocaine-induced locomotion (CIL) behavioral tests with subsequent quantification of c-fos and phosphorylated ERK (pERK) induction in limbic regions that express RGS14.ResultsCompared to WT controls, RGS14 KO mice exhibited attenuated locomotor responses in the NIL test, driven by avoidance of the center of the novel environment. By contrast, RGS14 KO mice demonstrated augmented peripheral locomotion in the CIL test conducted in either a familiar or novel environment. The absence of RGS14 enhanced induction of c-fos and pERK in the central amygdala and hippocampus (areas CA1 and CA2) when cocaine was administered in a novel environment.ConclusionsRGS14 regulates novelty- and psychostimulant-induced hyperlocomotion, particularly with respect to thigmotaxis. Further, our findings suggest RGS14 may reduce neuronal activity in discrete limbic subregions by inhibiting ERK-dependent signaling and transcription.
Plasma biomarkers of Alzheimer’s disease predict cognitive decline and could improve clinical trials in the cognitively unimpaired elderly
Authors: Cullen Nicholas C. , Leuzy Antoine , Janelidze Shorena , Palmqvist Sebastian , Svenningsson Anna L. , Stomrud Erik , Dage Jeffrey L. , Mattsson-Carlgren Niklas , Hansson Oskar 
Published: January 2021

AbstractPlasma biomarkers of amyloid, tau, and neurodegeneration (ATN) need to be characterized in cognitively unimpaired (CU) elderly indviduals. We therefore tested if plasma measurements of amyloid-β (Aβ)42/40, phospho-tau217 (P-tau217), and neurofilament light (NfL) together predict clinical deterioration in 435 CU individuals followed for an average of 4.8 ±1.7 years in the BioFINDER study. A combination of all three plasma biomarkers and basic demographics best predicted change in the cognition (Pre-Alzheimer’s Clinical Composite; R2=0.14, 95% CI [0.12-0.17]; P<0.0001) and subsequent AD dementia (AUC=0.82, 95% CI [0.77-0.91], P<0.0001). In a simulated clinical trial, a screening algorithm combining all three plasma biomarkers would reduce the required sample size by 70% (95% CI [54-81]; P<0.001) with cognition as trial endpoint, and by 63% (95% CI [53-70], P<0.001) with subsequent AD dementia as trial endpoint. Plasma ATN biomarkers show usefulness in cognitively unimpaired populations and could make large clinical trials more feasible and cost-effective.
A discursive analysis of compliance, resistance and escalation to threats in sexually exploitative interactions between offenders and male children
Authors: Seymour‐Smith Sarah , Kloess Juliane A. 
Published: January 2021

There is a notable scarcity of empirical studies focusing on online sexual grooming using real world, naturally occurring data. Limited research with real victims (as opposed to decoys) has indicated that more overt forceful threats are employed by offenders in such interaction; however, they tell us little about how these threats are built up and managed by both parties. Furthermore, the majority of research focuses on female victims, with limited attention paid to male victims. The current study presents a discursive psychology analysis of chat logs between one offender (posing as a teenage girl) and five male victims under the age of 16 years, in order to explore how victims attempt to resist such manoeuvres in situ, and how offenders manage such resistance. The sexualized nature evidenced in our data contrasts with other findings which suggest that boys are not sexually solicited and that interactions with boys are less aggressive and forceful. Our findings demonstrate for the first time how an offender escalated his issuing of threats following victims’ resistance and non‐compliance to requests. Turning points that appeared odd in the online interactions suggest that they may be used to encourage children to be more reflective about any further engagement.
Theory, research and practice in child welfare: The current state of the art in social work
Authors: Frost Nick , Dolan Pat 
Published: January 2021

AbstractThis paper aims to utilize social theory to inform relationship‐based social work practice with children, young people and families. We see ‘direct relationship‐based working’ drawing on theory and evidence as best placed to take forward high quality, humanistic social work practice. We outline the problems with policy and practice development led by the latest high profile ‘scandal’ or by the overemphasis on experimental design and systematic reviews. This issue was highlighted during a recent debate about appropriate methodologies for exploring Family Group Conferences: the debate is explored as illustrative of our concerns. A flexible model is proposed, which draws on eclectic sources of evidence, social theory and professional knowledge. We propose some principles for a reflective, humanistic and responsive form of social work professionalism.
President Biden's international trade agenda: Implications for the Canadian agrifood sector
Authors: Cardwell Ryan , Kerr William A. 
Published: January 2021

AbstractThe 4 years of the Trump administration was marked by a number of events and policies that affected the Canadian agrifood sector. Changes to preferential trade agreements, the collapse of the World Trade Organization's dispute settlement framework, increased domestic support for US farmers, and diplomatic tensions between the United States and China all shaped international trade flows and created an environment of policy uncertainty. The Biden administration will change course on several important trade policy issues. We discuss how these changes could affect the Canadian agrifood sector along a number of dimensions, including a return to multilateralism, (re)engagement in preferential trade agreements, and movements toward a less combative and more predictable trade policy agenda. We expect Canadian agrifood trade flows under the Biden administration to exceed what they would have been under a second Trump administration.
Effects of repetitive transcranial magnetic and deep brain stimulation on long‐range synchrony of oscillatory activity in a rat model of developmental schizophrenia
Authors: Lippmann Benjamin , Barmashenko Gleb , Funke Klaus 
Published: January 2021

AbstractAberrant neuronal network activity likely resulting from disturbed interactions of excitatory and inhibitory systems may be a major cause of cognitive deficits in neuropsychiatric diseases, like within the spectrum of schizophrenic phenotypes. In particular, the synchrony and pattern of oscillatory brain activity appears to be disturbed within limbic networks, e.g. between prefrontal cortex and hippocampus. In a rat model of maternal immune activation (MIA), we compared the acute effects of deep brain stimulation within either medial prefrontal cortex or ventral hippocampus with the effects of repetitive transcranial magnetic stimulation (rTMS), using the intermittent theta‐burst protocol (iTBS), on oscillatory activity within limbic structures. Simultaneous local field potential recordings were made from medial prefrontal cortex, ventral hippocampus, nucleus accumbens and rostral part of ventral tegmental area before and after deep brain stimulation in anaesthetized rats previously (~3 h) treated with sham or verum rTMS. We found a waxing and waning pattern of theta and gamma activity in all structures which was less synchronous in particular between medial prefrontal cortex and ventral hippocampus in MIA offspring. Deep brain stimulation in medial prefrontal cortex and pre‐treatment with iTBS‐rTMS partly improved this pattern. Gamma‐theta cross‐frequency coupling was stronger in MIA offspring and could partly be reduced by deep brain stimulation in medial prefrontal cortex. We can confirm aberrant limbic network activity in a rat MIA model, and at least acute normalizing effects of the neuromodulatory methods. It has to be proven whether these procedures can have chronic effects suitable for therapeutic purposes.
Accountability and legitimacy of non‐profit organisations: Challenging the current status quo and identifying avenues for future research
Authors: Yasmin Sofia , Ghafran Chaudhry 
Published: January 2021

AbstractIssues of accountability, legitimacy and trust have remained at the forefront of debate surrounding non‐profit organisations and their activities. The purpose of this study is to review the literature on non‐profit accountability from the lens of organisational legitimacy. Specifically, we ask what we can learn from the literature on non‐profit organisation (NPO) accountability and consider what further work needs to be done to strengthen NPO legitimacy. We attempt to go beyond mere gap‐spotting and seek to challenge the current status quo within this body of literature.
Effects of feeding lambs fresh versus dried Puccinellia tenuiflora (Griesb.) Scribn. & Merr. on water and nutrient intake and apparent digestibility
Authors: Zhong Rongzhen , Cheng Long , Fang Yi , Li Zelin , Lamptey Vida , Zhou Daowei 
Published: January 2021

AbstractThe objective was to investigate effects of feeding lambs fresh versus dried Puccinellia. tenuiflora (Griesb.) Scribn. & Merr. on nutrient and water intake and apparent digestibility. Twenty‐four lambs were offered fresh or dried (48 hr) grass. The dry matter (DM) content of fresh grass was 65% of dried grass and the neutral detergent fiber exclude ash (aNDFom) content of fresh grass was 87% of dried grass, whereas the metabolizable energy concentration of two forages was similar. Lambs eating fresh grass had higher (p < .05) DM intake (944 versus 837 g DM day−1 sheep−1), metabolizable energy intake (9.1 versus 7.9 MJ day‐1sheep−1), and crude protein intake (86 versus 75 g day‐1 sheep−1) than those eating dried grass. However, there was no significant difference between treatments in drinking water intake, fecal nutrient output or nutrient digestibility. In conclusion, feeding lambs fresh P. tenuiflora improved voluntary feed intake without depressing nutrient digestibility.
Impact of polyelectrolyte‐surfactant interactions on the rheology and wet lubrication performance of conditioning shampoo
Authors: Benhur Adeline Maria , Diaz Jangelis , Amin Samiul 
Published: January 2021

AbstractObjectiveThe purpose of this study is to understand the impact of the cationic polymer merquat on the rheological behavior of the mixed surfactant system of sodium lauryl ether sulfate (SLES) and cocamidopropyl betaine (CapB) as well as the impact of varying formulation conditions on the wet lubrication performance of the SLES‐CapB‐Merquat system.MethodsRotation mechanical Rheometry was used to study the rheological response of the SLES‐CapB‐Merquat systems. Frequency sweeps were conducted to analyze the rheological properties of the system at low frequency ranges and bulk viscosity of the system was studied at high shear rates at varying salt and polymer concentrations. Wet combing tests and hair friction tests were run on the Dia‐stron MTT175 flexible miniature tensile tester in order to evaluate the conditioning effects of the different formulations.ResultsThe SLES‐CapB system on its own exhibits very little viscosity. The bulk rheology results show that the addition of Merquat enhances the viscosity and viscoelastic properties of the SLES‐CapB‐Merquat system indicating the presence of electrostatic interactions between the surfactant and polyelectrolyte. Addition of salt had a significant impact on the system’s rheological response due to the charge screening effect of salt. Wet combing force data indicate that the charged polyelectrolyte binds to the hair substrate resulting in reduced combing force values after the product was applied. The addition of silicone oil to the formulation seemed to greatly enhance the conditioning effect of the formulation.ConclusionThe charge interactions between SLES, CapB and Merquat results in the formation of an integrated gel like network, thus building the viscosity of the system. Variation of parameters like polymer and salt concentration has the potential to modify the bulk rheological properties and consequently the wet lubrication properties of the system.