bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the role of phase lag in multi-appendage metachronal swimming of euphausiids
Authors: Ford Mitchell P. , Santhanakrishnan Arvind 
Published: July 2020

AbstractMetachronal paddling is a common method of drag-based aquatic propulsion, in which a series of swimming appendages are oscillated, with the motion of each appendage phase-shifted relative to the neighboring appendages. Ecologically and economically important euphausiid species such as Antarctic krill (E. superba) swim constantly by stroking their paddling appendages (pleopods), with locomotion accounting for the bulk of their metabolic expenditure. They tailor their swimming gaits for behavioral and energetic needs by changing pleopod kinematics. The functional importance of inter-pleopod phase lag (ϕ) to metachronal swimming performance and wake structure is unknown. To examine this relation, we developed a geometrically and dynamically scaled robot (‘krillbot’) capable of self-propulsion. Krillbot pleopods were prescribed to mimic published kinematics of fast-forward swimming (FFW) and hovering (HOV) gaits ofE. superba, and the Reynolds number and Strouhal number of the krillbot matched well with those calculated for freely-swimmingE. superba. In addition to examining published kinematics with unevenϕbetween pleopod pairs, we modifiedE. superbakinematics to uniformly varyϕfrom 0% to 50% of the cycle. Swimming speed and thrust were largest for FFW withϕbetween 15%-25%, coincident withϕrange observed in FFW gait of E. superba. In contrast to synchronous rowing (ϕ=0%) where distances between hinged joints of adjacent pleopods were nearly constant throughout the cycle, metachronal rowing (ϕ>0%) brought adjacent pleopods closer together and moved them farther apart. This factor minimized body position fluctuation and augmented metachronal swimming speed. Though swimming speed was lowest for HOV, a ventrally angled downward jet was generated that can assist with weight support during feeding. In summary, our findings show that inter-appendage phase lag can drastically alter both metachronal swimming speed and the large-scale wake structure.
Mechanism and effects of the skeletal muscle Nav1.4 inhibition by cannabidiol
Authors: Ghovanloo Mohammad-Reza , Choudhury Koushik , Bandaru Tagore S. , Fouda Mohamed A. , Rayani Kaveh , Rusinova Radda , Phaterpekar Tejas , Nelkenbrecher Karen , Watkins Abeline R. , Poburko Damon , Thewalt Jenifer , Andersen Olaf S. , Delemotte Lucie , Goodchild Samuel J. , Ruben Peter C. 
Published: July 2020

ABSTRACTCannabis sativacontains active constituents called phytocannabinoids. Some phytocannabinoids are psychotropic and others are not. The primary non-psychotropic phytocannabinoid is cannabidiol (CBD), which is proposed to be therapeutic against many conditions, including muscle spasms. Mechanisms have been proposed for the action of CBD on different systems, involving multiple targets, including the voltage-gated sodium channel (Nav) family, which are heavily implicated in many of the conditions CBD has been reported to relieve. In this study, we investigated the modulatory mechanism of CBD on Nav1.4. Based on previous results, we tested the hypothesis that CBD mechanism of action involves: 1) modulation of membrane elasticity, which indirectly contributes to Nav inhibition; and 2) physical block of the Nav pore. We first performed molecular dynamic (MD) simulations to visualize CBD effects and localization inside the membrane, and then performed NMR to verify the MD results, showing CBD localizes below membrane headgroups. Then, we performed a gramicidin-based fluorescence (GFA) assay that showed CBD alters membrane elasticity. Next, we used site-directed mutagenesis in (F1586A) and around (WWWW) the Nav1.4 pore. Removing the local anesthetic binding site with F1586A reduced CBD block of INa. Occluding the fenestrations with WWWW blocked CBD access from the membrane into the Nav1.4 pore. However, stabilization of inactivation, via CBD-induced changes in membrane elasticity persisted, in WWWW. To investigate the potential therapeutic value of CBD against some Nav1.4 channelopathies, we used a pathogenic variant of Nav1.4, P1158S, known to cause myotonia and periodic paralysis. We found CBD reduces excitability in both wild-type and the mixed myotonia/periodic paralysis variant. Ourin-vitro/in-silicoresults suggest that CBD may have therapeutic value against myotonia. Because Nav1.4 is crucial to skeletal muscle contraction, we used rat diaphragm myography and found the presence of saturating levels of CBD reduces skeletal muscle contraction.SUMMARYWe used multidisciplinary approaches to show the mechanism and pathway by which CBD inhibits the skeletal muscle, Nav1.4. Our results suggest CBD modulates membrane elasticity and directly interacts with Nav1.4 within its pore.
Soft ticks perform evaporative cooling during blood-feeding
Authors: Lazzari Claudio R. , Fauquet Aurélie , Lahondère Chloé , Araújo Ricardo N. , Pereira Marcos H. 
Published: July 2020

AbstractFeeding on the blood of warm-blooded vertebrates is associated to thermal stress in haematophagous arthropods. It has been demonstrated that blood-sucking insects protect their physiological integrity either by synthesising heat-shock proteins or by means of thermoregulatory mechanisms. In this work, we describe the first thermoregulatory mechanism in a tick species,Ornithodoros rostratus. By performing real-time infrared thermography during feeding on mice we found that this acarian eliminates big amounts of fluid (urine) through their coxal glands; this fluid quickly spreads over the cuticular surface and its evaporation cools-down the body of the tick. The spread of the fluid is possible thanks to capillary diffusion through the sculptured exoskeleton ofOrnithodoros. We discuss our findings in the frame of the adaptive strategies to cope with the thermal stress experienced by blood-sucking arthropods at each feeding event warm-blooded hosts.
Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report
Authors: Mulligan Mark J. , Lyke Kirsten E. , Kitchin Nicholas , Absalon Judith , Gurtman Alejandra , Lockhart Stephen , Neuzil Kathleen , Raabe Vanessa , Bailey Ruth , Swanson Kena A. , Li Ping , Koury Kenneth , Kalina Warren , Cooper David , Fontes-Garfias Camila , Shi Pei-Yong , Türeci Ӧzlem , Tompkins Kristin R. , Walsh Edward E. , Frenck Robert , Falsey Ann R. , Dormitzer Philip R. , Gruber William C. , Şahin Uğur , Jansen Kathrin U. 
Published: July 2020

AbstractIn March 2020, the WHO declared a pandemic of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1 With >8.8 million cases and >450,000 deaths reported globally, a vaccine is urgently needed. We report the available safety, tolerability, and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose escalation study among healthy adults, 18-55 years of age, randomized to receive 2 doses, separated by 21 days, of 10 μg, 30 μg, or 100 μg of BNT162b1, a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titers in sera increased with dose level and after a second dose. Geometric mean neutralizing titers reached 1.8-to 2.8-fold that of a panel of COVID-19 convalescent human sera. These results support further evaluation of this mRNA vaccine candidate.
A reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay for the rapid detection of SARS-CoV-2 within nasopharyngeal and oropharyngeal swabs at Hampshire Hospitals NHS Foundation Trust
Authors: Fowler Veronica L. , Armson Bryony , Gonzales Jose L. , Wise Emma L. , Howson Emma L. A. , Vincent-Mistiaen Zoe , Fouch Sarah , Maltby Connor J. , Grippon Seden , Munro Simon , Jones Lisa , Holmes Tom , Tillyer Claire , Elwell Joanne , Sowood Amy , Santos Helio , de Peyer Oliver , Dixon Sophie , Hatcher Thomas , Sivanesan Suvetha , Patrick Helen , Laxman Shailen , Walsh Charlotte , Andreou Michael , Morant Nick , Clark Duncan , Moore Nathan , Houghton Rebecca , Cortes Nicholas , Kidd Stephen P. 
Published: July 2020

AbstractThe COVID-19 pandemic has illustrated the importance of rapid, accurate diagnostic testing for the effective triaging and cohorting of patients and timely tracking and tracing of cases. However, a surge in diagnostic testing quickly resulted in worldwide competition for the same sample preparation and real-time RT-PCR diagnostic reagents (rRT-PCR). Consequently, Hampshire Hospitals NHS Foundation Trust, UK sought to diversify their diagnostic portfolio by exploring alternative amplification chemistries including those that permit direct testing without RNA extraction. This study describes the validation of a SARS-CoV-2 RT-LAMP assay, which is an isothermal, autocycling, strand-displacement nucleic acid amplification technique which can be performed on extracted RNA (RNA RT-LAMP) or directly from swab (Direct RT-LAMP). Analytical specificity (ASp) of this new RT-LAMP assay was 100% and analytical sensitivity (ASe) was between 1⨯101and 1⨯102copies when using a synthetic DNA target. The overall diagnostic sensitivity (DSe) and specificity (DSp) of RNA RT-LAMP was 97% and 99% respectively, relative to the standard of care (SoC) rRT-PCR. When a CTcut-off of 33 was employed, above which increasingly evidence suggests there is a very low risk of patients shedding infectious virus, the diagnostic sensitivity was 100%. The DSe and DSp of Direct-RT-LAMP was 67% and 97%, respectively. When setting CTcut-offs of ≤33 and ≤25, the DSe increased to 75% and 100%, respectively. Time from swab-to-result for a strong positive sample (CT< 25) was < 15 minutes. We propose that RNA RT-LAMP could replace rRT-PCR where there is a need for increase in throughput, whereas Direct RT-LAMP could be used as a screening tool for triaging patients into appropriate hospitals wards, at GP surgeries and in care homes, or for population screening to identify super shedders. Direct RT-LAMP could also be used during times of high prevalence to save critical extraction and rRT-PCR reagents by screening out those strong positives from diagnostic pipelines.
Handyfuge-LAMP: low-cost and electricity-free centrifugation for isothermal SARS-CoV-2 detection in saliva
Authors: Li Ethan , Larson Adam , Kothari Anesta , Prakash Manu 
Published: July 2020

AbstractPoint of care diagnostics for COVID-19 detection are vital to assess infection quickly and at the source so appropriate measures can be taken. The loop-mediated isothermal amplification (LAMP) assay has proven to be a reliable and simple protocol that can detect small amounts of viral RNA in patient samples (<10 genomes per μL) (Nagamine, Hase, and Notomi 2002). Recently, Rabe and Cepko at Harvard published a sensitive and simple protocol for COVID-19 RNA detection in saliva using an optimized LAMP assay (Rabe and Cepko, 2020).This LAMP protocol has the benefits of being simple, requiring no specialized equipment; rapid, requiring less than an hour from sample collection to readout; and cheap, costing around $1 per reaction using commercial reagents. The pH based colorimetric readout also leaves little ambiguity and is intuitive. However, a shortfall in many nucleic acid-based methods for detection in saliva samples has been the variability in output due to the presence of inhibitory substances in saliva. Centrifugation to separate the reaction inhibitors from inactivated sample was shown to be an effective way to ensure reliable LAMP amplification. However, a centrifuge capable of safely achieving the necessary speeds of 2000 RPM for several minutes often costs hundreds of dollars and requires a power supply.We present here an open hardware solution- Handyfuge - that can be assembled with readily available components for the cost of <5 dollars a unit and could be used together with the LAMP assay for point of care detection of COVID-19 RNA from saliva. The device is then validated using the LAMP protocol from Rabe and Cepko. With the use of insulated coolers for reagent supply chain and delivery, the assay presented can be completed without the need for electricity or any laboratory scale infrastructure.
The structure of enteric human adenovirus 41 - a leading cause of diarrhea in children
Authors: Rafie K. , Lenman A. , Fuchs J. , Rajan A. , Arnberg N. , Carlson L.-A. 
Published: July 2020

AbstractHuman adenovirus (HAdV) types F40 and F41 are a prominent cause of diarrhea and diarrhea-associated mortality in young children worldwide. These enteric HAdVs differ strikingly in tissue tropism and pathogenicity from respiratory and ocular adenoviruses, but the structural basis for this divergence has been unknown. Here we present the first structure of an enteric HAdV - HAdV-F41 - determined by cryo-EM to a resolution of 3.8Å. The structure reveals extensive alterations to the virion exterior as compared to non-enteric HAdVs, including a unique arrangement of capsid protein IX. The structure also provides new insights into conserved aspects of HAdV architecture such as a proposed location of protein V, which links the viral DNA to the capsid, and assembly-induced conformational changes in the penton base protein. Our findings provide the structural basis for adaptation to a fundamentally different tissue tropism of enteric HAdVs.
Inhibitory ultrapotent chemogenetics activate dopamine D1 receptor-expressing medium spiny neurons
Authors: Gantz Stephanie C. , Ortiz Maria M. , Belilos Andrew J. , Moussawi Khaled 
Published: July 2020

SUMMARYUltrapotent chemogenetics, including the chloride-permeable inhibitory PSAM4-GlyR receptor, were recently proposed as a powerful strategy to selectively control neuronal activity in awake, behaving animals. We aimed to validate the inhibitory function of PSAM4-GlyR in dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) in the ventral striatum. Activation of PSAM4-GlyR with the uPSEM792ligand enhanced rather than suppressed the activity of D1-MSNsin vivoas indicated by increased c-fos expression in D1-MSNs. Whole-cell recordings in mouse brain slices showed that activation of PSAM4-GlyR did not inhibit firing of action potentials in D1-MSNs. Activation of PSAM4-GlyR depolarized D1-MSNs, attenuated GABAergic inhibition, and shifted the reversal potential of PSAM4-GlyR current to more depolarized potentials, perpetuating the depolarizing effect of receptor activation. The data show that ‘inhibitory’ PSAM4-GlyR chemogenetics may actually activate certain cell types, and highlight the pitfalls of utilizing chloride conductances to inhibit neurons.
The association of Plk1 with the Astrin-Kinastrin complex promotes formation and maintenance of a metaphase plate
Authors: Geraghty Zoë , Barnard Christina , Uluocak Pelin , Gruneberg Ulrike 
Published: July 2020

AbstractErrors in mitotic chromosome segregation can lead to DNA damage and aneuploidy, both hallmarks of cancer. To achieve synchronous error-free segregation, mitotic chromosomes must align at the metaphase plate with stable amphitelic attachments to microtubules emanating from opposing spindle poles. The Astrin-Kinastrin/SKAP complex, also containing DYNLL1 and MYCBP, is a spindle and kinetochore protein complex with important roles in bipolar spindle formation, chromosome alignment and microtubule-kinetochore attachment. However, the molecular mechanisms by which Astrin-Kinastrin fulfils these diverse roles are not fully understood. Here we characterise a direct interaction between Astrin and the mitotic kinase Plk1. We identify the Plk1-binding site on Astrin as well as four Plk1 phosphorylation sites on Astrin. Regulation of Astrin-Kinastrin by Plk1 is dispensable for bipolar spindle formation and bulk chromosome congression but promotes stable microtubule-kinetochore attachments and metaphase plate maintenance. It is known that Plk1 activity is required for effective microtubule-kinetochore attachment formation, and we suggest that Astrin phosphorylation by Plk1 contributes to this process.SummaryWe demonstrate that Plk1 binds to and phosphorylates the N-terminus of Astrin. This interaction promotes recruitment of the Astrin-complex to kinetochores and stabilises microtubule-kinetochore-attachments in situations when mitosis is delayed.
Legal personality in Aotearoa New Zealand: an example of integrated thinking on sustainable development
Authors: Barrett Mereana , Watene Krushil , McNicholas Patty 
Published: July 2020

PurposeThis paper aims to set the scene for an emerging conversation on the Rights of Nature as articulated by a philosophy of law called Earth Jurisprudence, which privileges the whole Earth community over the profit-driven structures of the existing legal and economic systems.Design/methodology/approachThe study used a wide range of thought from literature relating to philosophy, humanities, environmental economics, sustainable development, indigenous rights and legal theory to show how Earth Jurisprudence resonates with two recent treaties of Waitangi settlements in Aotearoa New Zealand that recognise the Rights of Nature.FindingsIndigenous philosophies have become highly relevant to sustainable and equitable development. They have provided an increasingly prominent approach in advancing social, economic, environmental and cultural development around the world. In Aotearoa New Zealand, Maori philosophies ground the naming of the Te Urewera National Park and the Whanganui River as legal entities with rights.Practical implicationsRecognition of the Rights of Nature in Aotearoa New Zealand necessitates a radical re-thinking by accounting researchers, practitioners and educators towards a more ecocentric view of the environment, given the transformation of environmental law and our responsibilities towards sustainable development.Originality/valueThis relates to the application of Earth Jurisprudence legal theory as an alternative approach towards thinking about integrated reporting and sustainable development.
Social and motor skills of children and youth with autism from the perspectives of caregivers
Authors: Redquest Brianne , Bryden Pamela , Fletcher Paula 
Published: July 2020

Purpose
This study aims to explore social and motor impairments of children with autism through the perspectives of their caregivers. Social and motor deficits among people with autism are well documented. There is support to suggest a reciprocal relationship between social and motor deficits among people with autism, in that social deficits can act as a barrier to motor skill development and motor deficits can act as a barrier to social skill development.

Design/methodology/approach
This study explored social and motor impairments of children with autism through the perspectives of eight caregivers of children with autism.

Findings
Many salient findings emerged from the interviews conducted with caregivers, particularly concerning the social and motor development of their children. The relationships between their children’s social and motor deficits were also highlighted.

Research limitations/implications
It is important that health-care professionals educate parents about the consequences of motor impairments or delays and their associations with the development of social skills. As such, routine motor skill monitoring and assessments by caregivers and health-care professionals should be encouraged.

Originality/value
To the best of authors’ knowledge, this is the first paper to investigate motor and social deficits of children with autism from the caregivers’ perspectives.
Optimization algorithms for construction site layout planning: a systematic literature review
Authors: Xu Maozeng , Mei Zhongya , Luo Siyu , Tan Yi 
Published: July 2020

PurposeThis paper aims to analyze and provide insight on the algorithms for the optimization of construction site layout planning (CSLP). It resolves problems, such as the selection of suitable algorithms, considering the optimality, optimization objectives and representation of layout solutions. The approaches for the better utilization of optimization algorithms are also presented.Design/methodology/approachTo achieve the above, existing records (results = 200) were selected from three databases: Web of Science, ScienceDirect and Scopus. By implementing a systematic protocol, the articles related to the optimization algorithms for the CLSP (results = 75) were identified. Moreover, various related themes were collated and analyzed according to a coding structure.FindingsThe results indicate the consistent and increasing interest on the optimization algorithms for the CLSP, revealing that the trend in shifting to smart approaches in the construction industry is significant. Moreover, the interest in metaheuristic algorithms is dominant because 65.3% of the selected articles focus on these algorithms. The optimality, optimization objectives and solution representations are also important in algorithm selection. With the employment of other algorithms, self-developed applications and commercial software, optimization algorithms can be better utilized for solving CSLP problems. The findings also identify the gaps and directions for future research.Research limitations/implicationsThe selection of articles in this review does not consider the industrial perspective and practical applications of commercial software. Further comparative analyses of major algorithms are necessary because this review only focuses on algorithm types.Originality/valueThis paper presents a comprehensive systematic review of articles published in the recent decade. It significantly contributes to the demonstration of the status and selection of CLSP algorithms and the benefit of using these algorithms. It also identifies the research gaps in knowledge and reveals potential improvements for future research.