bluuebunny/crossref_metadata_2025 huggingface dataset:
When the whole is less than the sum of its parts: maximum object category information and behavioral prediction in multiscale activation patterns
Authors: Karimi-Rouzbahani Hamid , Woolgar Alexandra
Published: February 2022

Neural codes are reflected in complex, temporally and spatially specific patterns of activation. One popular approach to decode neural codes in electroencephalography (EEG) is multivariate decoding. This approach examines the discriminability of activity patterns across experimental conditions to test if EEG contains information about those conditions. However, conventional decoding analyses ignore aspects of neural activity which are informative. Specifically, EEG data can be decomposed into a large number of mathematically distinct features (e.g., entropy, Fourier and Wavelet coefficients) which can reflect different aspects of neural activity. We previously compared 30 such features of EEG data, and found that visual category, and participant behavior, can be more accurately predicted using multiscale spatiotemporally sensitive Wavelet coefficients than mean amplitude (Karimi-Rouzbahani et al., 2021b). Here, we considered that even this larger set of features may only partially capture the underlying neural code, because the brain could use a combination of encoding protocols within a single trial which is not reflected in any one mathematical feature alone. To check, we combined those mathematical features using state-of-the-art supervised and unsupervised feature selection procedures (n = 17). Across 3 datasets, we compared decoding of visual object category between these 17 sets of combined features, and between combined and individual features. Object category could be robustly decoded using the combined features from all of the 17 algorithms. However, the combination of features, which were equalized in dimension to the individual features, were outperformed in most of the time points by the most informative individual feature (Wavelet coefficients). Moreover, the Wavelet coefficients also explained the behavioral performance more accurately than the combined features. These results suggest that a single but multiscale encoding protocol may capture the neural code better than any combination of features. Our findings put new constraints on the models of neural information encoding in EEG.
Identification of novel leaf rust seedling resistance loci in Iranian bread wheat germplasm using genome-wide association mapping
Authors: Delfan Saba , Bihamta Mohammad Reza , Dadrezaei Seyed Taha , Abbasi Alireza , Alipour Hadi , Imani Jafargholi , Kogel Karl-Heinz
Published: February 2022

Leaf or brown rust caused by Puccinia triticina Eriks. (Pt) is a major biotic constraint threatening bread wheat production worldwide. The continued evolution of new races of Pt necessitates a constant search for the identification of new resistance genes, or QTLs, to enhance the resistance durability of bread varieties. On a panel of 320 bread wheat accessions, we used a genome-wide association study (GWAS) technique to map loci associated with Pt resistance using single-nucleotide polymorphism markers (SNPs) generated by genotyping-by-sequencing (GBS). The panel was tested with five Pt races gathered from different regions of IRAN to identify loci associated with seedling resistance. After estimating genetic relatedness and population structure among accessions, GWAS discovered a total of 19 SNPs on chromosomes 1B, 2B, 3A, 3B, 4A, 5B, 5D, 6A, 6B, 6D, 7B, and 7D that were significantly associated with seedling stage resistance. The three SNP markers rs12954, rs34220, and rs42447 on chromosomes 5D, 6A, and 7D, respectively, associated with resistance to Pt race PKTTS expressing potential new loci for leaf rust resistance. Overall, this research gives an integrated perspective of leaf rust resistance resources in Iranian bread wheat and recognizes new resistance loci that will be valuable to expand the set of resistance genes available to control this serious disease.
Rapid estimation of cryptic adult abundance and breeding dynamics in a critically endangered elasmobranch from close-kin mark recapture
Authors: Patterson TA , Hillary R , Feutry P , Gunasakera R , Marthick J , Pillans RD
Published: February 2022

Abstract

Elasmobranchs are one of the most highly-threatened vertebrate taxa. Estimating abundance of spawning adults is often extremely challenging, yet crucial for prioritization of conservation measures. Emblematic of these challenges, the speartooth shark (Glyphis glyphis, Müller and Henle, 1839) was initially known only from rare specimens collected in a few tropical regions river systems of Australia and Papua New Guinea. Listed as critically endangered in Australia (where only six adults have ever been recorded) and endangered by the IUCN, such scarcity and limited distribution prevent direct assessments of abundance or reproductive biology. We used close-kin mark-recapture to estimate the abundance of matureG. glyphisin a genetically isolated population in the Wenlock River, Queensland, Australia. From 224 juvenile/sub-adults and 2 adult samples taken over three years (2013-2016), 46 half-sibling and 33 full-sibling pairs were found. The adult population was estimated at 897 (80% Credible interval 531 – 1684) with a sex ratio (based on mitochondrial DNA) highly skewed to males (females – 0.09: males – 0.91). Based on juveniles sampled in different years that shared a mother, 71% of females were estimated to skip-spawn. In an average year we estimate 44 breeding females occupy the system. Importantly, these methods constitute a viable and relatively rapid approach to obtain robust estimates of absolute abundance and other key population parameters for similar rare species.
Polyelectrolyte brush bilayers at thermal equilibrium: Density functional theory and molecular dynamic simulations
Authors: Edwards Mike J.
Published: February 2022

In this article, the equilibrium properties of Polyelectrolyte brush bilayers is studied. The density functional theory framework as well as the benchmark molecular dynamic simulations are employed to indicate the correct equation of state. Both techniques turn out that the equation of state neutral polymer brush bilayers scales with the wall distance asD−4. Additionally, it turns out that the electrostatic interactions does not change the universal power laws. The only difference is that the charged systems posses larger pressure due to stored electrostatic energy.

SIGNIFICANCE

Studying Polyelectrolyte brush bilayers is important because it exists widely in nature, biology and industry. In biology, they could be found in mammalian synivial joints as well as in the cellular structures.
Basolateral amygdala to insular cortex activity makes sign-tracking behavior insensitive to outcome value
Authors: Keefer Sara E. , Kochli Daniel E. , Calu Donna J.
Published: February 2022

Goal-tracking rats are sensitive to Pavlovian outcome devaluation while sign-tracking rats are devaluation insensitive. During outcome devaluation, goal-tracking (GT) rats flexibly modify responding to cues based on the current value of the associated outcome. However, sign-tracking (ST) rats rigidly respond to cues regardless of the current outcome value. Our prior study demonstrated disconnection of the basolateral amygdala (BLA) and anterior insular cortex (aIC) decreased both goal- and sign-tracking behaviors. Given the role of these regions in appetitive motivation and behavioral flexibility we predicted that disrupting BLA to aIC pathway during outcome devaluation would reduce flexibility in GT rats and reduce rigid appetitive motivation in ST rats. We inhibited the BLA to aIC pathway by infusing inhibitory DREADDs (hM4Di-mcherry) or control (mCherry) virus into the BLA and implanted cannulae into the aIC to inhibit BLA terminals using intracranial injections of clozapine N-oxide (CNO). After training, we used a within subject satiety-induced outcome devaluation procedure in which we sated rats on training pellets (devalued condition) or homecage chow (valued condition). All rats received bilateral CNO infusions into the aIC prior to brief non-reinforced test sessions. Contrary to our hypothesis, BLA-IC inhibition did not interfere with devaluation sensitivity in GT rats but did make ST behaviors sensitive to devaluation. Intermediate rats showed the opposite effect, showing rigid in responding to cues with BLA-aIC pathway inactivation. Together, these results demonstrate BLA-IC projections mediate tracking-specific Pavlovian devaluation sensitivity and highlights the importance of considering individual differences in Pavlovian approach when evaluating circuitry contributions to behavioral flexibility.
The comparison of Post-Operative Complications pre Covid era versus during Covid-Era based on Clavien-Dindo-classification: A Systematic Review and Meta-Analysis
Authors: Farsi Yeganeh , Shojaeian Fatemeh , Ahmad Safavi-Naini Seyed Amir , Honarvar Mohammadjavad , Mohammadzadeh Benyamin , Nasiri Mohammad Javad
Published: February 2022

Introduction

Coronavirus Disease 2019 (COVID -19) pandemic challenged the healthcare system drastically, and it was concomitant with a remarkable decline in surgeries and modified routine care of patients worldwide. This systematic review and meta-analysis aimed to compare the surgical complications before COVID -19 (Pre-COVID) and after COVID -19 (post-COVID) appearance using the Clavien-Dindo classification (CDC).

Methods

between January 1, 2019, to November 3, 2021, we performed a comprehensive search in PubMed/Medline and Scopus for studies reporting the postoperative complications based on/transformable to CDC.

Result

From 909 screened articles, 34 studies were included for systematic review. Among included articles, 11 were eligible for meta-analysis. Nineteen thousand one hundred thirty-seven patients (pre-COVID: 3522, post-COVID: 15615) were included, mostly undergoing elective surgeries (86.32%). According to CDC classification, there were no significant change between pre-COVID and post-COVID for grade 1 (Odds ratio (OR) and 95% confidence interval (95-CI): 0.99, 0.60-1.63, p=0.96), grade 2 (OR and 95-CI: 0.65, 0.42-1.01, p = 0.055), grade 3 (OR and 95-CI: 0.86, 0.48-1.57, p=0.64), grade 4 (OR and 95-CI: 0.85, 0.46-1.57, p =0.60). However, the postoperative mortality was lower before the COVID -19 outbreak (OR and 95-CI: 0.51, 0.27-0.95, p= 0.035). The included studies for systematic review and meta-analysis had a low risk of bias and unsignificant publication bias.

Conclusion

Although delivering routine surgery was challenging, the postoperative complications during the pandemic remained identical to the pre-pandemic era. The stricter patient selection tending to choose more critical states and more advanced clinical stages of the operated patients may explain some extent of higher mortality during the pandemic. Adopting preventive strategies helped deliver surgeries during the outbreak of COVID -19 while limiting the capacity of operations and admissions.
Protein-protein interaction prediction for targeted protein degradation
Authors: Orasch O. , Weber N. , Müller M. , Amanzadi A. , Gasbarri C. , Trummer C.
Published: February 2022

Protein-protein interactions (PPIs) play a fundamental role in various biological functions; thus, detecting PPI sites is essential for understanding diseases and developing new drugs. PPI prediction is of particular relevance for the development of drugs employing targeted protein degradation, as their efficacy relies on the formation of a stable ternary complex involving two proteins. However, experimental methods to detect PPI sites are both costly and time-intensive. In recent years, computer-aided approaches have been developed as screening tools, but these tools are primarily based on sequence information and are therefore limited in their ability to address spatial requirements and have thus far not been applied to targeted protein degradation.

Here, we present a new deep learning architecture based on the concept of graph representation learning that can predict interaction sites and interactions of proteins based on their surface representations. We demonstrate that our model reaches state-of-the-art performance using AUROC scores on the established MaSIF dataset. We furthermore introduce a new dataset with more diverse protein interactions and show that our model generalizes well to this new data. These generalization capabilities allow our model to predict the PPIs relevant for targeted protein degradation, which we show by demonstrating the high accuracy of our model for PPI prediction on the available ternary complex data. Our results suggest that PPI prediction models can be a valuable tool for screening protein pairs while developing new drugs for targeted protein degradation.
Modulation of nuclear and cytoplasmic mRNA fluctuations by time-dependent stimuli: analytical distributions
Authors: Filatova Tatiana , Popović Nikola , Grima Ramon
Published: February 2022

Temporal variation of environmental stimuli leads to changes in gene expression. Since the latter is noisy and since many reaction events occur between the birth and death of an mRNA molecule, it is of interest to understand how a stimulus affects the transcript numbers measured at various sub-cellular locations. Here, we construct a stochastic model describing the dynamics of signal-dependent gene expression and its propagation downstream of transcription. For any time-dependent stimulus and assuming bursty gene expression, we devise a procedure which allows us to obtain time-dependent distributions of mRNA numbers at various stages of its life-cycle, e.g. in its nascent form at the transcription site, post-splicing in the nucleus, and after it is exported to the cytoplasm. We also derive an expression for the error in the approximation whose accuracy is verified via stochastic simulation. We find that, depending on the frequency of oscillation and the time of measurement, a stimulus can lead to cytoplasmic amplification or attenuation of transcriptional noise.
Quantitative contribution of the spacer length in the supercoiling-sensitivity of bacterial promoters
Authors: Forquet Raphaël , Nasser William , Reverchon Sylvie , Meyer Sam
Published: February 2022

DNA supercoiling acts as a global transcriptional regulator in bacteria, but the promoter sequence or structural determinants controlling its effect remain unclear. It was previously proposed to modulate the torsional angle between the -10 and -35 hexamers, and thereby regulate the formation of the closed-complex depending on the length of the “spacer” between them. Here, we develop a ther-modynamic model of this notion based on DNA elasticity, providing quantitative and parameter-free predictions on the relative activation of promoters containing a short vs long spacer when the DNA supercoiling level is varied. The model is tested through an analysis of in vitro and in vivo expression assays of mutant promoters with variable spacer lengths, confirming its accuracy for spacers ranging from 15 to 19 nucleotides, except those of 16 nucleotides where other regulatory mechanisms likely overcome the effect of this specific step. An analysis at the whole-genome scale in E. coli then demonstrates a significant effect of the spacer length on the genomic expression after transient or inheritable superhelical variations, validating the model’s predictions. Altogether, this study shows that the torsional constraints associated to promoter binding by RNA Polymerase underpin a basal and global regulatory mechanism independent of specific transcription factors.
Distinct subpopulations of DN1 thymocytes exhibit preferential γδ T lineage potential
Authors: Oh Seungyoul , Liu Xin , Tomei Sara , Luo Mengxiao , Skinner Jarrod P. , Berzins Stuart P. , Naik Shalin H. , Gray Daniel H.D. , Chong Mark M.W.
Published: February 2022

The αβ and γδ T cell lineages are both are thought to differentiate in the thymus from common uncommitted progenitors. The earliest stage of T cell development is known as known as CD4-CD8-double negative 1 (DN1). These thymocytes have previously been revealed to be a heterogenous mixture of cells, which of only the CD117+fraction have been proposed to be true T cell progenitors that progress to the DN2 and DN3 thymocyte stages, at which point the development of the αβ and γδ T cell lineages diverge. However, recently, it has been shown that at least some γδ T cells are actually derived from a subset of CD117-DN thymocytes. Along with other ambiguities, this suggests that T cell development may not be as straightforward as previously thought. To better understand early T cell development, particularly the heterogeneity of DN1 thymocytes, we performed single cell RNA sequence (scRNAseq) of mouse DN and γδ thymocytes and show that the various DN stages are indeed comprised of transcriptionally diverse subpopulations of cells. We also show that multiple subpopulations of DN1 thymocytes exhibit preferential development towards the γδ lineage. Furthermore, specific γδ-primed DN1 subpopulations preferentially develop into IL-17 or IFNγ-producing γδ T cells. We show that DN1 subpopulations that only give rise to IL-17-producing γδ T cells already express many of the transcription factors associated with type 17 immune cell differentiation, while the DN1 subpopulations that can give rise to IFNγ-producing γδ T cell already express transcription factors associated with type 1 immune cell differentiation.
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

The 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

It 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

Availability 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

Background

The magnitude of protection conferred after recovery from COVID-19 or by vaccine administration, and the duration of protective immunity developed, remains ambiguous.

Methods

We 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).

Results

Age 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.

Conclusions

Our 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

Purpose

Human 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.

Methods

We 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.

Results

A 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.

Conclusions

The 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

Several 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

Background

A 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 findings

A 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.

Conclusion

Overall, 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 registration

The 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

Alterations 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

Siderophores 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

The 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

In 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

We 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

Protein 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.
Loading-Induced Bone Formation is Mediated by Wnt1 Induction in Osteoblast-Lineage Cells
Authors: Lawson Lisa Y. , Migotsky Nicole , Chermside-Scabbo Christopher J. , Shuster John T. , Joeng Kyu Sang , Civitelli Roberto , Lee Brendan , Silva Matthew J.
Published: February 2022

Mechanical loading on the skeleton stimulates bone formation. Although the exact mechanism underlying this process remains unknown, a growing body of evidence indicates that the Wnt signaling pathway is necessary for the skeletal response to loading. Recently, we showed that Wnts produced by osteoblast lineage cells mediate the osteo-anabolic response to tibial loading in adult mice. Here, we report that Wnt1 specifically plays a crucial role in mediating the mechano-adaptive response to loading. Independent of loading, short-term loss of Wnt1 in the Osx-lineage resulted in decreased cortical bone area in the tibias of 5-month old mice. In females, strain-matched loading enhanced periosteal bone formation in Wnt1F/F controls, but not in Wnt1F/F; OsxCreERT2 knockouts. In males, strain-matched loading increased periosteal bone formation in both control and knockout mice; however, the periosteal relative bone formation rate was 65% lower in Wnt1 knockouts versus controls. Together, these findings show that Wnt1 supports adult bone homeostasis and mediates the bone anabolic response to mechanical loading.
A Bayesian approach to single-particle electron cryo-tomography in RELION-4.0
Authors: Zivanov Jasenko , Otón Joaquín , Ke Zunlong , von Kügelgen Andriko , Pyle Euan , Qu Kun , Morado Dustin , Castaño-Díez Daniel , Zanetti Giulia , Bharat Tanmay A. M. , Briggs John A. G. , Scheres Sjors H. W.
Published: February 2022

We present a new approach for macromolecular structure determination from multiple particles in electron cryo-tomography (cryo-ET) data sets. Whereas existing subtomogram averaging approaches are based on 3D data models, we propose to optimise a regularised likelihood target that approximates a function of the 2D experimental images. In addition, analogous to Bayesian polishing and contrast transfer function (CTF) refinement in single-particle analysis, we describe approaches that exploit the increased signal-to-noise ratio in the averaged structure to optimise tilt series alignments, beam-induced motions of the particles throughout the tilt series acquisition, defoci of the individual particles, as well as higher-order optical aberrations of the microscope. Implementation of our approaches in the open-source software package RELION aims to facilitate their general use, in particular for those researchers who are already familiar with its single-particle analysis tools. We illustrate for three applications that our approaches allow structure determination from cryo-ET data to resolutions sufficient for de novo atomic modelling.
Crystal structure of a hypothetical protein from Giardia lamblia. Corrigendum
Authors: Beard Dylan K. , Bristol Seonna , Cosby Kayla , Davis Amber , Manning Courtney , Perry Lionel , Snapp Lauren , Toy Arian , Wheeler Kayla , Young Jeremy , Staker Bart , Arakaki Tracy L. , Abendroth Jan , Subramanian Sandhya , Edwards Thomas E. , Myler Peter J. , Asojo Oluwatoyin A.
Published: February 2022

The name of one of the authors in Beard et al. [(2022), Acta Cryst. F78, 59–65] is corrected.
The omnidirectional runway with infinite heading as a futuristic runway concept for future free route airspace operations
Authors: Aydoğan Emre , Demirel Soner
Published: February 2022

Purpose

The purpose of this paper is to create and analyze the effectiveness of a new runway system, which is totally created for the future free route operations.

Design/methodology/approach

This paper researches and analyses the new generated runway concept with the fast time simulation method. Fuel consumption and environmental effect of the new runway system are calculated based on simulation results.

Findings

According to different traffic density analyses the Omnidirectional Runway with Infinite Heading (ORIH) reduced fuel consumption and CO2 emissions up to 46.97%. Also the total emissions of the ORIH concept, for the hydro carbon (HC), carbon monoxide (CO) and nitrogen oxides (NOx) pollutants were lower than the total emissions with the conventional runway up to 83.13, 74.36 and 51.49%, respectively.

Practical implications

Free route airspaces bring many advantages to air traffic management and airline operations. Direct routes become available from airport to airport thanks to free route airspace concept. However, conventional single runway structure does not allow aircraft operations for every direction. The landing and take-off operations of a conventional airport with a single runway must be executed with only two heading direction. This limitation brings a bottleneck direct approach and departure route usage as convenient with free route airspace concept. This paper suggests and analyzes the omnidirectional runway with infinite heading (ORIH) as a solution for free route airspace.

Originality/value

This paper suggests a new and futuristic runway design and operation for the free route operations. This paper has its originality from the suggested and newly created runway system.
Using new forms of information and communication technologies to empower SMEs
Authors: Jia Shizhen , Tseng Hsiao-Ting , Shanmugam Mohana , Rees Daniel J. , Thomas Roderick , Hajli Nick
Published: February 2022

Purpose

Given the growing importance and demand for online food purchases, this study explores the new advancements in information and communication technologies (ICTs) by examining the key features of social commerce, trust and product’s attributes in the e-commerce environment. The aim is to investigate possible ICTs-related entrepreneurial opportunities in the food and beverage (F&B) industry.

Design/methodology/approach

The study uses a survey to collect data and applies Smart partial least squares to test the model.

Findings

The structural equation modelling results illustrated that social commerce constructs significantly impact trust, leading to customer’s purchase intention. Additionally, product’s attributes was found to have a significant relationship with customer’s purchase intention with trust being the most pertinent driver.

Originality/value

This study contributes to the F&B literature by highlighting the role of new forms of technologies in entrepreneurship activities, especially for small and medium-sized enterprises.