bluuebunny/crossref_metadata_2025_split huggingface dataset:
Replacement of the Alpha variant of SARS-CoV-2 by the Delta variant in Lebanon between April and June 2021
Authors: Merhi Georgi , Trotter Alexander J. , de Oliveira Martins Leonardo , Koweyes Jad , Le-Viet Thanh , Naja Hala Abou , Buaini Mona Al , Prosolek Sophie J. , Alikhan Nabil-Fareed , Lott Martin , Tohmeh Tatiana , Badran Bassam , Jupp Orla J. , Gardner Sarah , Felgate Matthew W. , Makin Kate A. , Wilkinson Janine M. , Stanley Rachael , Sesay Abdul K. , Webber Mark A. , Davidson Rose K. , Ghosn Nada , Pallen Mark , Hasan Hamad , Page Andrew J. , Tokajian Sima 
Published: August 2021

AbstractBackgroundThe COVID-19 pandemic continues to expand globally, with case numbers rising in many areas of the world, including the Eastern Mediterranean Region. Lebanon experienced its largest wave of COVID-19 infections from January to April 2021. Limited genomic surveillance was undertaken, with just twenty six SARS-CoV-2 genomes available for this period, nine of which were from travellers from Lebanon detected by other countries. Additional genome sequencing is thus needed to allow surveillance of variants in circulation.MethodsNine hundred and five SARS-CoV-2 genomes were sequenced using the ARTIC protocol. The genomes were derived from SARS-CoV-2-positive samples, selected retrospectively from the sentinel COVID-19 surveillance network, to capture diversity of location, sampling time, gender, nationality and age.ResultsAlthough sixteen PANGO lineages were circulating in Lebanon in January 2021, by February there were just four, with the Alpha variant accounting for 97% of samples. In the following two months, all samples contained the Alpha variant. However, this had changed dramatically by June and July, when all samples belonged to the Delta variant.DiscussionThis study provides a ten-fold increase in the number of SARS-CoV-2 genomes available from Lebanon. The Alpha variant, first detected in the UK, rapidly swept through Lebanon, causing the country’s largest wave to date, which peaked in January 2021. The Alpha variant was introduced to Lebanon multiple times despite travel restrictions, but the source of these introductions remains uncertain. The Delta variant was detected in Gambia in travellers from Lebanon in mid-May, suggesting community transmission in Lebanon several weeks before this variant was detected in the country. Prospective sequencing in June/July 2021 showed that the Delta variant had completely replaced the Alpha variant in under six weeks.
Modeling and Multiobjective Optimization of Indoor Airborne Disease Transmission Risk and Associated Energy Consumption for Building HVAC Systems
Authors: Risbeck Michael J. , Bazant Martin Z. , Jiang Zhanhong , Lee Young M. , Drees Kirk H. , Douglas Jonathan D. 
Published: August 2021

AbstractThe COVID-19 pandemic has renewed interest in assessing how the operation of HVAC systems influences the risk of airborne disease transmission in buildings. Various processes, such as ventilation and filtration, have been shown to reduce the probability of disease spread by removing or deactivating exhaled aerosols that potentially contain infectious material. However, such qualitative recommendations fail to specify how much of these or other disinfection techniques are needed to achieve acceptable risk levels in a particular space. An additional complication is that application of these techniques inevitably increases energy costs, the magnitude of which can vary significantly based on local weather. Moreover, the operational flexibility available to the HVAC system may be inherently limited by equipment capacities and occupant comfort requirements. Given this knowledge gap, we propose a set of dynamical models that can be used to estimate airborne transmission risk and energy consumption for building HVAC systems based on controller setpoints and a forecast of weather conditions. By combining physics-based material balances with phenomenological models of the HVAC control system, it is possible to predict time-varying airflows and other HVAC variables, which are then used to calculate key metrics. Through a variety of examples involving real and simulated commercial buildings, we show that our models can be used for monitoring purposes by applying them directly to transient building data as operated, or they may be embedded within a multi-objective optimization framework to evaluate the tradeoff between infection risk and energy consumption. By combining these applications, building managers can determine which spaces are in need of infection risk reduction and how to provide that reduction at the lowest energy cost. The key finding is that both the baseline infection risk and the most energy-efficient disinfection strategy can vary significantly from space to space and depend sensitively on the weather, thus underscoring the importance of the quantitative predictions provided by the models.
Cleavage of histone H2A during embryonic stem cell differentiation destabilizes nucleosomes to counteract gene activation
Authors: Coradin Mariel , Cesare Joseph , Lan Yemin , Zhu Zhexin , Lund Peder J. , Sidoli Simone , Perez Yekaterina , Lu Congcong , Porter Elizabeth G. , Robert Charles W. M. , Garcia Benjamin A. 
Published: August 2021

AbstractHistone proteolysis is a poorly understood phenomenon in which the N-terminal tails of histones are irreversibly cleaved by intracellular proteases. During development, histone post-translational modifications are known to orchestrate gene expression patterns that ultimately drive cell fate decisions. Therefore, deciphering the mechanisms of histone proteolysis is necessary to enhance the understanding of cellular differentiation. Here we show that H2A is cleaved by the lysosomal protease Cathepsin L during ESCs differentiation. Using quantitative mass spectrometry (MS), we identified L23 to be the primary cleavage site that gives rise to the clipped form of H2A (cH2A), which reaches a maximum level of ~1% of total H2A after four days of differentiation. Using ChIP-seq, we found that preventing proteolysis leads to an increase in acetylated H2A at promoter regions in differentiated ES cells. We also identified novel readers of different acetylated forms of H2A in pluripotent ES cells, such as members of the PBAF remodeling complex. Finally, we showed that H2A proteolysis abolishes this recognition. Altogether, our data suggests that proteolysis serves as an efficient mechanism to silence pluripotency genes and destabilize the nucleosome core particle.
Cryo-EM reveals disrupted human p97 allosteric activation by disease mutations and inhibitor binding
Authors: Caffrey Brian , Zhu Xing , Berezuk Alison , Tuttle Katharine , Chittori Sagar , Subramaniam Sriram 
Published: August 2021

ABSTRACTThe human AAA ATPase p97, a potential cancer target, plays a vital role in clearing misfolded proteins. p97 dysfunction is also known to play a crucial role in several neurodegenerative disorders. Here, we present cryo-EM structural analyses of four disease mutants p97R155H, p97R191Q, p97A232E, p97D592N, as well as p97E470D, implicated in resistance to the drug CB-5083. These structures demonstrate that the mutations affect nucleotide-driven p97 allosteric activation by predominantly interfering with either the coupling between the D1 and N-terminal domains (p97R155H and p97R191Q), the inter-protomer interactions (p97A232E), or the coupling between D1 and D2 nucleotide domains (p97D592N, p97E470D). We also show that binding of the competitive inhibitor CB-5083 to the D2 domain prevents conformational changes similar to that seen for mutations that affect coupling between D1 and D2 domains. Our studies enable tracing of the path of allosteric activation across p97 and establish a common mechanistic link between active site inhibition and defects in allosteric activation by disease-causing mutations.
Age and sex dependent variability of type 2 dopamine receptors in the human brain: A large-scale PET cohort
Authors: Malén Tuulia , Karjalainen Tomi , Isojärvi Janne , Vehtari Aki , Bürkner Paul-Christian , Putkinen Vesa , Kaasinen Valtteri , Hietala Jarmo , Nuutila Pirjo , Rinne Juha , Nummenmaa Lauri 
Published: August 2021

AbstractBACKGROUNDThe dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved.METHODSIn this cross-sectional register-based study we investigated how age, sex, body mass index (BMI), as well as cerebral hemisphere and regional volume influence striatal type 2 dopamine receptor (D2R) availability in the human brain. We analyzed a large historical dataset (n=156, 120 males and 36 females) of [11C]raclopride PET scans performed between 2004 and 2018.RESULTSStriatal D2R availability decreased through age for both sexes and was higher in females versus males throughout age. BMI and striatal D2R availability were weakly associated. There was no consistent lateralization of striatal D2R. The observed effects were independent of regional volumes. These results were validated using two different spatial normalization methods, and the age and sex effects also replicated in an independent sample (n=135).CONCLUSIONSD2R density is dependent on age and sex, which may contribute to the vulnerability of neurological and psychiatric conditions involving altering D2R expression.
Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF
Authors: Aljahani Abrar , Hua Peng , Karpinska Magdalena A. , Quililan Kimberly , Davies James O.J. , Oudelaar A. Marieke 
Published: August 2021

ABSTRACTEnhancers and promoters predominantly interact within large-scale topologically associating domains (TADs), which are formed by loop extrusion mediated by cohesin and CTCF. However, it is unclear whether complex chromatin structures exist at sub-kilobase-scale and to what extent fine-scale regulatory interactions depend on loop extrusion. To address these questions, we present an MNase-based chromosome conformation capture (3C) approach, which has enabled us to generate the most detailed local interaction data to date and precisely investigate the effects of cohesin and CTCF depletion on chromatin architecture. Our data reveal that cis-regulatory elements have distinct internal nano-scale structures, within which local insulation is dependent on CTCF, but which are independent of cohesin. In contrast, we find that depletion of cohesin causes a subtle reduction in longer-range enhancer-promoter interactions and that CTCF depletion can cause rewiring of regulatory contacts. Together, our data show that loop extrusion is not essential for enhancer-promoter interactions, but contributes to their robustness and specificity and to precise regulation of gene expression.
Dysregulation of Hepatitis B Virus Nucleocapsid Assembly with RNA-directed Small Ligands
Authors: Patel Nikesh , Abulwerdi Fardokht , Fatehi Farzad , Manfield Iain , Grice Stuart Le , Schneekloth John S. , Twarock Reidun , Stockley Peter G. 
Published: August 2021

AbstractRNA sequences/motifs dispersed across the pre-genomic copy of the Hepatitis B Virus genome regulate formation of nucleocapsidsin vitroin an epsilon/polymerase independent fashion. These multiple RNA Packaging Signals (PSs) form stem-loops presenting in each loop a core protein recognition motif, -RGAG-. Small, drug-like molecules binding these motifs were identified by screening an immobilized library with a fluorescently-labelled RNA oligonucleotide encompassing the most conserved of these sites. This identified 66 “hits”, with affinities ranging from low nanomolar to high micromolar in SPR assays. High affinity ligand binding is dependent on the presence of the -RGAG-motif, which also appears to be the common element in cross-binding to other PS sites. Some of these compounds are potent inhibitors ofin vitrocore protein assembly around the HBV pre-genome. Mathematical modelling confirms the potential of these novel anti-viral drug targets for disrupting replication of this major human pathogen. Preliminary structure-activity relationships of the highest affinity compound reveal critical functional groups for PS-binding. PS-regulated assembly is easily adapted to high-throughput screening allowing future development of pharmacologically active compounds.
Upregulation of C4 characteristics does not consistently improve photosynthetic performance in intraspecific hybrids of a grass
Authors: Bianconi Matheus E. , Sotelo Graciela , Curran Emma V. , Milenkovic Vanja , Samaritani Emanuela , Dunning Luke T. , Bertolino Lígia T. , Osborne Colin P. , Christin Pascal-Antoine 
Published: August 2021

AbstractC4 photosynthesis is thought to have evolved via intermediate stages, with changes towards the C4 phenotype gradually enhancing photosynthetic performance. This hypothesis is widely supported by modelling studies, but experimental tests are missing. Mixing of C4 components to generate artificial intermediates can be achieved via crossing, and the grass Alloteropsis semialata represents an outstanding system since it includes C4 and non-C4 populations. Here, we analyse F1 hybrids between C3 and C4, and C3+C4 and C4 genotypes to determine whether the acquisition of C4 characteristics increases photosynthetic performance. The hybrids have leaf anatomical characters and C4 gene expression profiles that are largely intermediate between those of their parents. Carbon isotope ratios are similarly intermediate, which suggests that a partial C4 cycle coexists with C3 carbon fixation in the hybrids. This partial C4 phenotype is associated with C4-like photosynthetic efficiency in C3+C4 x C4, but not in C3 x C4 hybrids, which are overall less efficient than both parents. Our results support the hypothesis that the photosynthetic gains from the upregulation of C4 characteristics depend on coordinated changes in anatomy and biochemistry. The order of acquisition of C4 components is thus constrained, with C3+C4 species providing an essential step for C4 evolution.
Nucleated Fish Erythrocyte Extracellular Traps (FEETs) release is an evolutionary conserved immune defence process
Authors: Rinaldi Giulia , de Haro Neila Álvarez , Desbois Andrew P. , Robb Calum T. , Rossi Adriano G. 
Published: August 2021

AbstractFish erythrocytes remain nucleated for their life-span, unlike mammalian erythrocytes which undergo enucleation. Asides transportation of oxygen, fish erythrocytes are capable of several immune defence processes. Nucleated fish erythrocytes represent prime candidates for carrying out ETotic responses. ETosis is an evolutionary conserved innate immune defence process found in both vertebrates and invertebrates, which involves the extrusion of DNA studded with antimicrobial proteins into the extracellular space serving to trap and kill microorganisms. In this report, we demonstrate that fish erythrocytes isolated from Danio rerio (zebrafish) produce ETotic-like responses when exposed to chemical and physiological stimuli. Furthermore, we found Salmo salar (Atlantic salmon) erythrocytes produce similar ETotic responses. We have termed these ET-like formations Fish Erythrocyte Extracellular Traps (FEETs). Interestingly, we discovered that mammalian inducers of NETosis, such as the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate and the calcium ionophore ionomycin, induced FEETs. Moreover, we found that FEETs are dependent upon activation of PKC and generation of mitochondrial reactive oxygen species. Thus, this brief report represents the first demonstration that fish erythrocytes can exhibit ETotic-like responses, unveiling a previously unknown function of nucleated erythrocytes, which sheds new light on the innate immune arsenal of erythrocytes.
Genetic risk estimates for offspring of patients with Stargardt disease
Authors: Cornelis Stéphanie S. , Runhart Esmee H. , Bauwens Miriam , Corradi Zelia , de Baere Elfride , Roosing Susanne , Haer-Wigman Lonneke , Dhaenens Claire-Marie , Vulto-van Silfhout Anneke T. , Cremers Frans P.M. 
Published: August 2021

AbstractBACKGROUNDGenetic counseling in autosomal recessive Stargardt disease (STGD1) is complicated because of unknown frequencies of pathogenicABCA4alleles across populations, variable and unknown severity ofABCA4alleles, and incomplete penetrance.METHODSIn this cross-sectional study, publishedABCA4variants were categorized by severity based on previous functional and clinical studies and current statistical comparisons of their frequencies in patients versus the general population, their observed versus expected homozygous occurrence in patients, and their occurrence in combination with established mild alleles in patients. The sum allele frequencies of these severity categories were used to estimate inheritance risks for offspring of STGD1 patients and carriers of pathogenicABCA4variants.RESULTSThe risk for offspring of a STGD1 patient with the ‘severe|severe’ genotype or a ‘severe|mild with complete penetrance’ genotype to develop STGD1 at some moment in life was estimated at 2.8-3.1% (1 in 35-32 individuals) and 1.6-1.8% (1 in 62-57 individuals), respectively. The risk to develop STGD1 in childhood was estimated to be 2 to 4-fold lower: 0.7-0.8% (1 in 148-124) and 0.3-0.4% (1 in 295-248), respectively. For offspring of an unaffectedABCA4variant carrier from a STGD1 family who carries one severe or one mildABCA4variant with complete penetrance, the risk to develop STGD1 throughout life is 1.4-1.6% (1 in 71-64) and 0.19-0.21% (1 in 516-487), respectively.CONCLUSIONWe propose a genotype-based personalized counseling approach to appreciate the large differences in inheritance risk between individuals. We advocate considering the lower risk of early-onset STGD1 compared with the total STGD1 risk.
Microphaser - a small-scale phasing approach for improved personalized neopeptidome creation
Authors: Forster Jan , Lähnemann David , Paschen Annette , Schramm Alexander , Schuler Martin , Köster Johannes 
Published: August 2021

AbstractMotivationHaplotype phasing approaches have been shown to improve accuracy of the search space of neoantigen prediction by determining if adjacent variants are located on the same chromosomal copy. However, the aneuploid nature of cancer cells as well as the admixture of different clones in tumor bulk sequencing data are challenging the current diploid based phasing algorithms. We present microphaser, a small-scale phasing approach to improve haplotyping variants in cancer samples. Microphaser aims to create a more accurate neopeptidome for downstream neoantigen prediction.ResultsMicrophaser achieves large concordance with state-of-the-art phasing-aware neoantigen prediction pipeline neoepiscope, with differences in edge cases and an improved filtering step.AvailabilityMicrophaser is written in the Rust programming language. It is made available via Github (https://github.com/koesterlab/microphaser)and Bioconda. The corresponding prediction pipeline (https://github.com/snakemake-workflows/dna-seq-neoantigen-prediction) has been written within the Snakemake workflow management system and can be deployed as part of the snakemake-workflows project.
Fostering ethical consumption in food sector: Insights from the Italian Solidarity Purchasing Groups
Authors: Sciarelli Mauro , Tani Mario , Prisco Anna , Caputo Francesco 
Published: August 2021

PurposeThe paper aims at investigating antecedents and predictors of consumers' buying and consumption processes within the Italian Solidarity Purchasing Groups (SPGs) to enrich current debate about drivers and levers on which act for fostering ethical consumption in food sector.Design/methodology/approachBuilding upon the theory of planned behavior (TPB) a theoretical model is proposed for depicting possible antecedents and predictors of consumers' buying and consumption processes in food sector. The validity of the model has been tested via partial least squares structural equation modeling (PLS-SEM) using SmartPLS for analyzing primary data collected through a structured questionnaire from 354 consumers engaged in SPGs.FindingsWithin the domain of food buying and consumptions through SPGS, results show that consumers' behavior intention (BI) is influenced by consumers' attitude (ATT) and perceived behavioral control (PBC). Moreover, the research also demonstrates that consumers' ATT is influenced by consumers' ethical self-identity (ETH), consumers' willingness to support local economy (SLE), and food safety concern (FSC).Originality/valueThe study contributes to the ongoing debate on sustainable consumerism focusing the attention on SPGs as emerging social organizations inspired by ethical food consumption. Both theoretical development and empirical evidences enrich current knowledge about drivers and levers on which act for fostering ethical consumption in food sector.
A look into user’s privacy perceptions and data practices of IoT devices
Authors: Al-Ameen Mahdi Nasrullah , Chauhan Apoorva , Ahsan M.A. Manazir , Kocabas Huzeyfe 
Published: August 2021

Purpose
With the rapid deployment of internet of things (IoT) technologies, it has been essential to address the security and privacy issues through maintaining transparency in data practices. The prior research focused on identifying people's privacy preferences in different contexts of IoT usage and their mental models of security threats. However, there is a dearth in existing literature to understand the mismatch between user's perceptions and the actual data practices of IoT devices. Such mismatches could lead users unknowingly sharing their private information, exposing themselves to unanticipated privacy risks. The paper aims to identify these mismatched privacy perceptions in this work.

Design/methodology/approach
The authors conducted a lab study with 42 participants, where they compared participants’ perceptions with the data practices stated in the privacy policy of 28 IoT devices from different categories, including health and exercise, entertainment, smart homes, toys and games and pets.

Findings
The authors identified the mismatched privacy perceptions of users in terms of data collection, sharing, protection and storage period. The findings revealed the mismatches between user's perceptions and the data practices of IoT devices for various types of information, including personal, contact, financial, heath, location, media, connected device, online social media and IoT device usage.

Originality/value
The findings from this study lead to the recommendations on designing simplified privacy notice by highlighting the unexpected data practices, which in turn, would contribute to the secure and privacy-preserving use of IoT devices.