bluuebunny/crossref_metadata_2025_split huggingface dataset:
TMS Over Dorsolateral Prefrontal Cortex Affects the Timing of Motor Imagery but not Overt Action: Further Support for the Motor-Cognitive Model
Authors: Martel Marie , Glover Scott 
Published: February 2022

AbstractThe Motor-Cognitive model suggests a functional dissociation between motor imagery and overt action, in contrast to the Functional Equivalence view of common processes between the two behaviours. According to the Motor-Cognitive model, motor imagery differs from overt action primarily through the use of executive resources to monitor and elaborate a motor image during execution, which can result in a lack of correspondence between motor imagery and its overt action counterpart. The present study examined the importance of executive resources in motor imagery by using TMS to impair the function of the dorsolateral prefrontal cortex while measuring the time to complete imagined versus overt actions. In two experiments, TMS over the dorsolateral prefrontal cortex slowed motor imagery but did not affect overt actions. TMS over the same region also interfered with performance of a mental calculation task, though it did not reliably affect less demanding cognitive tasks also thought to rely on executive functions. Taken together, these results were consistent with the Motor-Cognitive model but not with the idea of functional equivalence. The implications of these results for the theoretical understanding of motor imagery, and potential applications of the Motor-Cognitive model to the use of motor imagery in training and rehabilitation, are discussed.
Activation of the neonatal immune system in healthy neonates within hours of birth
Authors: Ariyakumar Gaayathri , Gee Sarah , Das Abhishek , Kamdar Shraddha , Tribe Rachel M , Gibbons Deena L 
Published: February 2022

AbstractIt is now established that immune maturation occurs along a defined trajectory in the weeks and months after birth, but the immediate changes that occur within immune cells following birth is less clear. In this study, we monitored the immune profile of neonates via analysis of paired samples (n= 28) of cord blood and heel prick blood taken at varying times post term delivery by caesarean section. This paired approach accounted for the between-subject variability often observed over the first week of life. We identified rapid changes in immune cell populations within hours of birth. Specifically, we observed increased proliferation in effector T cells (but not regulatory T cells) that exhibited an increase in cytokine producing ability and also an increase in the percentage of CD3 T cells over this short time frame. This indicates that the mobilisation of the immune system is immediate post birth, presumably as a response to sudden exposure to the external environment, antigen or stress. Hence, immune development may start to occur more rapidly than previously proposed and as such, to study this trajectory, blood sampling should begin as soon after birth as possible.
Widening the landscape of transcriptional regulation of green algal photoprotection
Authors: Arend Marius , Yuan Yizhong , Ruiz-Sola M. Águila , Omranian Nooshin , Nikoloski Zoran , Petroutsos Dimitris 
Published: February 2022

AbstractAvailability of light and CO2, substrates of microalgae photosynthesis, is frequently far from optimal. Microalgae activate photoprotection under strong light, to prevent oxidative damage, and the CO2 Concentrating Mechanism (CCM) under low CO2, to raise intracellular CO2 levels. The two processes are interconnected; yet, the underlying transcriptional regulators remain largely unknown. Employing a large transcriptomics data compendium ofChlamydomonas reinhardtii’sresponses to different light and carbon supply, we reconstructed a consensus genome-scale gene regulatory network from complementary inference approaches and used it to elucidate transcriptional regulators of photoprotection. We showed that the CCM regulator LCR1 also controls photoprotection, and that QER7, a Squamosa Binding Protein, suppresses photoprotection- and CCM-gene expression under the control of the blue light photoreceptor Phototropin. By demonstrating the existence of regulatory hubs that channel light- and CO2-mediated signals into a common response, our study provides an accessible resource to dissect gene expression regulation in this microalga.
Factors associated with the decay of anti-SARS-CoV-2 neutralizing antibodies among recipients of an adenoviral vector-based AZD1222 and a whole-virion inactivated (BBV152) vaccine in Chennai, India: a prospective, longitudinal, cohort study
Authors: Selvavinayagam Sivaprakasam T , Yong Yean Kong , Tan Hong Yien , Zhang Zhong-Ying , Subramanian Gurunathan , Rajeshkumar Manivannan , Vasudevan Kalaivani , Jayapal Priyanka , Narayanasamy Krishnasamy , Ramesh Dinesh , Palani Sampath , Larsson Marie , Esaki M Shankar , Raju Sivadoss 
Published: February 2022

ABSTRACTBackgroundThe magnitude of protection conferred after recovery from COVID-19 or by vaccine administration, and the duration of protective immunity developed, remains ambiguous.MethodsWe investigated the factors associated with antibody decay in 519 individuals who received treatment for COVID-19-related illness or received COVID-19 vaccination with two commercial vaccines, viz., an adenoviral vector-based (AZD1222) and a whole-virion-based inactivated (BBV152) vaccine in Chennai, India from March 2021. Blood samples collected during regular follow-up post-infection/vaccination andwere examined for anti-SARS-CoV-2 IgG by a commercial automated chemiluminescent immunoassay (CLIA).ResultsAge and underlying comorbidities were the two variables that were independently associated with the development of breakthrough infection. Individuals who were >60 years of age with underlying comorbid conditions had a ∼15 times and ∼10 times greater risk for developing a breakthrough infection and hospitalization, respectively. The time elapsed since the first booster dose was associated with attrition in anti-SARS-CoV-2 IgG, where each month passed was associated with an ebb in the neutralizing antibody levels by a coefficient of -6 units.ConclusionsOur findings advocate that the elderly with underlying comorbidities require a second booster dose with AZD1222 and BBV152.
A Clinically Translatable Immune-based Classification of HPV-associated Head and Neck Cancer with Implications for Biomarker-Driven Treatment Deintensification and Immunotherapy
Authors: Zeng Peter YF. , Cecchini Matthew J. , Barrett John W. , Shammas-Toma Matthew , De Cecco Loris , Serafini Mara S. , Cavalieri Stefano , Licitra Lisa , Hoebers Frank , Brakenhoff Ruud H. , Leemans C René , Scheckenbach Kathrin , Poli Tito , Wang Xiaowei , Liu Xinyi , Laxague Francisco , Prisman Eitan , Poh Catherine , Bose Pinaki , Dort Joseph C. , Shaikh Mushfiq H. , Ryan Sarah EB. , Dawson Allie , Khan Mohammed I. , Howlett Christopher J. , Stecho William , Plantinga Paul , da Silva Sabrina Daniela , Hier Michael , Khan Halema , MacNeil Danielle , Mendez Adrian , Yoo John , Fung Kevin , Lang Pencilla , Winquist Eric , Palma David A. , Ziai Hedyeh , Amelio Antonio L. , Li Shawn S-C. , Boutros Paul C. , Mymryk Joe S. , Nichols Anthony C. 
Published: February 2022

AbstractPurposeHuman papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the fastest rising cancer in North America. There is significant interest in treatment de-escalation for these patients given the generally favourable prognosis. However, 15-30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to predict the survival of patients with newly diagnosed HPV+ HNSCC.MethodsWe created a prognostic score (UWO3) that was successfully validated in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Transcriptomic data from two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes.ResultsA three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival at 5 years to the immune desert (HR= 9.0, 95% CI 3.2–25.5, P=3.6×10−5) and mixed (HR=6.4, 95%CI 2.2–18.7, P=0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation.ConclusionsThe UWO3 immune score could enable biomarker-driven clinical decision-making for patients with HPV+ HNSCC based on robust outcome prediction across six independent cohorts. The superior survival of immune rich patients supports de-intensification strategies, while the inferior outcomes of the immune desert patients suggest the potential for intensification and/or immunotherapy. Prospective de-escalation and intensification clinical trials are currently being planned.
Tracing the trajectories of SARS-CoV-2 variants of concern between December 2020 and September 2021 in the Canary Islands (Spain)
Authors: Ciuffreda Laura , González-Montelongo Rafaela , Alcoba-Florez Julia , García-Martínez de Artola Diego , Gil-Campesino Helena , Rodríguez-Pérez Héctor , Íñigo-Campos Antonio , Miguel-Martínez Isabel De , Tosco-Nuñez Tomás , Díez-Gil Oscar , Valenzuela-Fernández Agustín , Lorenzo-Salazar José M. , Flores Carlos 
Published: February 2022

AbstractSeveral variants of concern (VOCs) explain most of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) epidemic waves in Europe. We aimed to dissect the spread of the SARS-CoV-2 VOCs in the Canary Islands (Spain) between December 2020 and September 2021 at a micro-geographical level. We sequenced the viral genome of 8,224 respiratory samples collected in the archipelago. We observed that Alpha (B.1.1.7) and Delta (B.1.617.2 and sub-lineages) were ubiquitously present in the islands, while Beta (B.1.351) and Gamma (P.1/P.1.1) had a heterogeneous distribution and were responsible for fewer and more controlled outbreaks. This work represents the largest effort for viral genomic surveillance in the Canary Islands so far, helping the public health bodies in decision-making throughout the pandemic.
Effect of physical activity calorie equivalent (PACE) labels on energy purchased in cafeterias: a stepped-wedge randomised controlled trial
Authors: Reynolds James P. , Ventsel Minna , Hobson Alice , Pilling Mark A. , Pechey Rachel , Jebb Susan A. , Hollands Gareth J. , Marteau Theresa M. 
Published: February 2022

AbstractBackgroundA recent meta-analysis suggested that using physical activity calorie equivalent (PACE) labels results in people selecting and consuming less energy. Only one included study was conducted in a naturalistic setting, in four convenience stores. The current study aimed to estimate the effect of PACE labels on energy purchased in worksite cafeterias.Methods and findingsA stepped-wedge randomised controlled trial to test the effect of PACE labels (which include kcal content and minutes of walking required to expend the energy content of the labelled food) on energy purchased. The setting was ten worksite cafeterias in England, which were randomised to the order in which they introduced PACE labels on selected food and drinks following a baseline period. The study ran for 12 weeks with over 250,000 transactions recorded on electronic tills. The primary outcome was total energy (kcal) purchased from intervention items per day. The secondary outcomes were: energy purchased from non-intervention items per day, total energy purchased per day, and revenue. Regression models showed no evidence of an overall effect on energy purchased from intervention items, -1.3% (95% CI -3.5% to 0.9%) during the intervention. Of the 10 cafeterias, there were null results in five, significant reductions in four, and a significant increase in one. There was also no evidence for an effect on energy purchased from non-intervention items, -0.0% (95% CI -1.8% to 1.8%), and no clear evidence for total items -1.6% (95% CI -3.3% to 0.0%). Revenue increased during the intervention, 1.1% (95% CI 0.4% to 1.9%). Study limitations include using energy purchased and not energy consumed, and access only to transaction-level sales, rather than individual-level data.ConclusionOverall, the evidence was consistent with PACE labels not changing energy purchased in worksite cafeterias. There was considerable variation in effects between cafeterias, suggesting potentially important unmeasured moderators.Trial registrationThe study was prospectively registered on ISRCTN (date: 30.03.21; ISRCTN31315776).
Activation of the actin/MRTF-A/SRF signalling pathway in pre-malignant mammary epithelial cells by P-cadherin is essential for transformation
Authors: Faria Lídia , Canato Sara , Jesus Tito T. , Gonçalves Margarida , Guerreiro Patrícia S. , Lopes Carla S. , Meireles Isabel , Morais de Sá Eurico , Paredes Joana , Janody Florence 
Published: February 2022

AbstractAlterations in the expression or function of cell adhesion molecules have been implicated in all steps of tumour progression. Among those, P-cadherin expression is highly enriched in basal-like breast cancer, a molecular subset of triple-negative breast carcinomas, playing a central role in inducing cancer cell self-renewal, as well as collective cell migration and invasion capacity. To decipher the P-cadherin-dependent signalling network, we generated a humanised P-cadherin fly model, establishing a clinically relevant platform for functional exploration of P-cadherin effectors in vivo. We report that actin nucleators, MRTF and SRF are main effectors of P-cadherin functional effects. In addition, we validated these findings in a human mammary epithelial cell line with conditional activation of the Src oncogene, which recapitulates molecular events taking place during cellular transformation. We show that prior to triggering the gain of malignant phenotypes, Src induces a transient increase in P-cadherin expression levels, which correlates with MRTF-A accumulation, its nuclear translocation and the upregulation of SRF target genes. Moreover, knocking down P-cadherin, or preventing Factin polymerization with Latrunculin A, impairs SRF transcriptional activity. Furthermore, blocking MRTF-A nuclear translocation with CCG-203971 hampers proliferation, selfrenewal and invasion. Thus, in addition to sustaining malignant phenotypes, P-cadherin can also play a major role in the very early stages of breast carcinogenesis by promoting a transient boost of MRTF-A/SRF signalling through actin regulation.
Siderophore production and utilization by microbes in the North Pacific Ocean
Authors: Park Jiwoon , Durham Bryndan P. , Key Rebecca S. , Groussman Ryan D. , Pinedo-Gonzalez Paulina , Hawco Nicholas J. , John Seth G. , Carlson Michael C.G. , Lindell Debbie , Juranek Laurie , Ferrón Sara , Ribalet Francois , Armbrust E. Virginia , Ingalls Anitra E. , Bundy Randelle M. 
Published: February 2022

AbstractSiderophores are strong iron-binding molecules produced and utilized by microbes to acquire the limiting nutrient iron (Fe) from their surroundings. Despite their importance as a component of the iron-binding ligand pool in seawater, data on the distribution of siderophores and the microbes that use them are limited. Here we measured the concentrations and types of dissolved siderophores during two cruises in April 2016 and June 2017 that transited from the iron-replete, low-macronutrient North Pacific Subtropical Gyre (NPSG) through the North Pacific Transition Zone (NPTZ) to the iron-deplete, high-macronutrient North Pacific Subarctic Frontal Zone (SAFZ). Surface siderophore concentrations in 2017 were higher in the NPTZ (4.0 – 13.9 pM) than the SAFZ (1.2 – 5.1 pM), which may be partly attributed to stimulated siderophore production by environmental factors such as dust-derived iron concentrations (up to 0.51 nM). Multiple types of siderophores were identified on both cruises, including ferrioxamines, amphibactins and iron-free forms of photoreactive siderophores, which suggest active production and use of diverse siderophores across latitude and depth. Additionally, the widespread genetic potential for siderophore biosynthesis and uptake across latitude and the variability in the taxonomic composition of bacterial communities that transcribe putative ferrioxamine, amphibactin and salmochelin transporter genes at different latitudes suggest that particular microbes actively produce and use siderophores, altering siderophore distributions and the bioavailability of iron across the North Pacific.
The SPOC domain is a phosphoserine binding module that bridges transcription machinery with co- and post-transcriptional regulators
Authors: Appel Lisa-Marie , Grishkovskaya Irina , Benedum Johannes , Franke Vedran , Polyansky Anton , Neudolt Andrea , Wunder Anna , Zagrovic Bojan , Akalin Altuna , Djinovic-Carugo Kristina , Slade Dea 
Published: February 2022

AbstractThe heptarepeats of the C-terminal domain (CTD) of RNA polymerase II (Pol II) are extensively modified throughout the transcription cycle. The CTD coordinates RNA synthesis and processing by recruiting transcription regulation factors as well as RNA capping, splicing and 3’end processing factors. The SPOC domain of PHF3 was recently identified as a new CTD reader domain specifically binding to phosphorylated serine-2 residues in adjacent CTD repeats. Here, we establish the SPOC domains of the human proteins DIDO, SHARP and RBM15 as phosphoserine binding modules that can act as CTD readers but also recognize other phosphorylated binding partners. We report the crystal structure of SHARP (SPEN) SPOC-CTD and identify the molecular determinants for its specific binding to phosphorylated serine-5. PHF3 and DIDO SPOC domains preferentially interact with the Pol II elongation complex, while RBM15 and SHARP SPOC domains engage with the m6A writer and reader proteins. Our findings establish the SPOC domain as a major interface between the transcription machinery and regulators of transcription and co-transcriptional processes.
Multitrait Genome-Wide Analysis in the UK Biobank Reveals Novel and Distinct Variants Influencing Cardiovascular Traits in Africans and Europeans
Authors: Sinkala Musalula , Elsheikh Samar , Mbiyavanga Mamana , Cullinan Joshua , Mulder Nicola 
Published: February 2022

AbstractIn exploring the trans-ancestral genetic nuances of cardiovascular traits, we conducted a multi-trait genome-wide association study focusing on African (AFR) and European (EUR) populations in the UK Biobank. Here, we identify 50 genomic risk loci in the AFR population, among which 43 are novel discoveries associated with four cardiovascular traits. Similarly, we identify 829 loci in the EUR population, with 47 being novel. Also, at these loci, we identify 52 SNPs (45 novel) in the AFR population and 1,856 SNPs (957 novel) in the EUR population, among which 83 are shared, highlighting both the shared and rich diversity of the genetic underpinnings of cardiovascular disease across populations. Furthermore, functional mapping of these SNPs reveals distinct distribution patterns, with the EUR population showing a higher proportion in intronic and untranslated regions. Further, our study unravels population-specific genetic associations, identifying 3,011 genes exclusive to the EUR group and 36 distinct to the AFR group. Additionally, gene enrichment analyses show unique enriched pathways for each population, highlighting the potential influence of genetic ancestry on cardiovascular trait mechanisms and manifestation. Collectively, our results underscore the importance of population-specific approaches in studying the genetic underpinnings of cardiovascular health and further indicate potential avenues for personalised medicine and targeted interventions.
What are the reference strains of Acinetobacter baumannii referring to?
Authors: Philippe Chantal , Valcek Adam , Whiteway Clémence , Robino Etienne , Nesporova Kristina , Bové Mona , Coenye Tom , De Pooter Tim , De Coster Wouter , Strazisar Mojca , Kenyon Johanna , Van der Henst Charles 
Published: February 2022

AbstractWe assembled the whole genome sequence (WGS) of a collection of 43 non-redundant modern clinical isolates and four broadly used reference strains of Acinetobacter baumannii. Comparison of these isolates and their WGS confirmed the high heterogeneity in capsule loci, sequence types, the presence of virulence and antibiotic resistance genes. However, a significant portion of clinical isolates strongly differ when compared to several reference strains in the light of colony morphology, cellular density, capsule production, natural transformability and in vivo virulence. These genetic and phenotypic differences between current circulating strains of A. baumannii and established reference strains could hamper the study of A. baumannii as an entity. The broadly used reference strains led to the current state of the art of the A. baumannii field, however, we propose that established reference strains in the A. baumannii field should be carefully used, because of the high genetic and phenotypic heterogeneities. In this study, we generated a collection of high-quality nucleotide sequences of 43 modern clinical isolates with the corresponding multi-level phenotypic characterizations. Beside the contribution of novel fundamental observations generated in this study, the phenotypic and genetic data, along with the bacterial strains themselves, will be further accessible using the first open access online platform called “Acinetobase”. Therefore, a rational choice of modern strains will be possible to select the ones that suit the needs of specific biological questions.
Transient DNA binding to gapped DNA substrates links DNA sequence to the single-molecule kinetics of protein-DNA interactions
Authors: Andrews Rebecca , Steuer Horst , El-Sagheer Afaf H. , Mazumder Abhishek , el Sayyed Hafez , Shivalingam Arun , Brown Tom , Kapanidis Achillefs N. 
Published: February 2022

ABSTRACTProtein interactions with nucleic acids are central to all genetic processes and many biotechnological applications. While many sequence-dependent protein-DNA interactions have been studied in detail using single-molecule methods, there is no standard high-throughput way to link the complex single-molecule kinetics of protein-DNA interactions with the DNA sequence of a single molecule. Here we provide the missing link by introducing a single-molecule imaging method (Gap-Seq) that interrogates DNA sequences via transient binding of short fluorescent DNA to a single DNA molecule previously used to characterise a protein-DNA interaction. In Gap-Seq, we identify a base by the degree of binding of 6-9 nt-long DNAs to surface-immobilised DNA substrates featuring a short single-stranded gap. To facilitate detection, we also developed a fluorescence quenching strategy that allows single-molecule detection at up to 500 nM of unbound fluorescent DNA. We link single-base differences on single DNA molecules to the kinetics of protein-DNA interactions by studying the interaction of a transcription activator with its cognate site. Finally, we show that our assay can address mixed sequences by distinguishing between two different sequences immobilised on the same field of view, paving the way for interrogation of sequence libraries for both mechanistic work and biotechnological applications.