bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Silico Analysis Of The Effects Of Omicron Spike Amino Acid Changes On The Interactions With Human ACE2 Receptor And Structurally Characterized Complexes With Human Antibodies
Authors: D’Arminio Nancy , Giordano Deborah , Scafuri Bernardina , Biancaniello Carmen , Petrillo Mauro , Facchiano Angelo , Marabotti Anna 
Published: January 2022

AbstractThe new SARS-CoV-2 variant Omicron is characterised, among others, by more than 30 amino acid changes (including 4 deletions and 1 insertion) occurring on the spike glycoprotein.We report a comprehensive analysis of the effects of the Omicron spike amino acid changes in the interaction with human ACE2 receptor or with human antibodies, obtained by analysing the publicly available resolved 3D structures. Our analysis predicts that amino acid changes occurring on amino acids interacting with the ACE2 receptor may increase Omicron transmissibility. The interactions of Omicron spike with human antibodies can be both negatively and positively affected by amino acid changes, with a predicted total loss of interactions only in few complexes. We believe that such an approach can be used to better understand SARS-CoV-2 transmissibility, detectability, and epidemiology, especially when extended to other than spike proteins.
Engineered bacterial swarm patterns as spatial records of environmental inputs
Authors: Doshi Anjali , Shaw Marian , Tonea Ruxandra , Moon Soonhee , Doshi Anish , Laine Andrew , Guo Jia , Danino Tal 
Published: January 2022

AbstractA diverse array of bacteria species naturally self-organize into durable macroscale patterns on solid surfaces via swarming motility—a highly coordinated, rapid movement of bacteria powered by flagella1–5. Engineering swarming behaviors is an untapped opportunity to increase the scale and robustness of coordinated synthetic microbial systems. Here we engineer Proteus mirabilis, which natively forms centimeter-scale bullseye patterns on solid agar through swarming, to “write” external inputs into a visible spatial record. Specifically, we engineer tunable expression of swarming-related genes that accordingly modify pattern features, and develop quantitative approaches to decode input conditions. Next, we develop a two-input system that modulates two swarming-related genes simultaneously, and show the resulting patterns can be interpreted using a deep learning classification model. Lastly, we show a growing colony can record dynamic environmental changes, which can be decoded from endpoint images using a segmentation model. This work creates an approach for building a macroscale bacterial recorder and expands the framework for engineering emergent microbial behaviors.
Broadly-recognized, cross-reactive SARS-CoV-2 CD4 T cell epitopes are highly conserved across human coronaviruses and presented by common HLA alleles
Authors: Becerra-Artiles Aniuska , Calvo-Calle J. Mauricio , Co Marydawn , Nanaware Padma P. , Cruz John , Weaver Grant C. , Lu Liying , Forconi Catherine , Finberg Robert W. , Moormann Ann M. , Stern Lawrence J. 
Published: January 2022

SummarySequence homology between SARS-CoV-2 and common-cold human coronaviruses (HCoVs) raises the possibility that memory responses to prior HCoV infection can impact the T cell response in COVID-19. We studied T cells recognizing SARS-CoV-2 and HCoVs in convalescent COVID-19 donors, and identified a highly conserved SARS-CoV-2 sequence S811-831, with two overlapping epitopes presented by common MHC-II proteins HLA-DQ5 and HLA-DP4. These epitopes were recognized by CD4+T cells from convalescent COVID-19 donors, mRNA vaccine recipients, and by low-abundance CD4+T cells in uninfected donors. TCR sequencing revealed a diverse repertoire with public TCRs. CD4+T cell cross-reactivity was driven by the remarkably strong conservation of T cell contact residues in both HLA-DQ5 and HLA-DP4 binding frames, with distinct patterns of HCoV cross-reactivity explained by MHC-II binding preferences and substitutions at secondary TCR contact sites. These data highlight S811-831as a highly-conserved CD4+T cell epitope broadly recognized across human populations.
High efficiency multiplex biallelic heritable editing in Arabidopsis using an RNA virus
Authors: Nagalakshmi Ugrappa , Meier Nathan , Liu Jau-Yi , Voytas Daniel F. , Dinesh-Kumar Savithramma P 
Published: January 2022

AbstractDelivery of gene editing components such as the Cas nuclease and single guide RNAs (sgRNAs) into plant cells is commonly accomplished by agrobacterium-mediated transformation. Although Arabidopsis is easy to transform, generation of biallelic edited plants requires screening a large number of plants in subsequent generations. Here, we describe optimization of the Tobacco rattle virus (TRV) for in planta delivery of sgRNAs fused to a tRNAIleu that induces efficient multiplex somatic and biallelic heritable editing in Arabidopsis. Inclusion of tRNAIleu enhances the systemic movement of TRV and the mutant phenotype is visible in the initial TRV::sgRNA-tRNAIleu infected Arabidopsis, which allows for the uncovering of lethal phenotypes. Mutant progeny are recovered in the next generation (M1) at frequencies ranging from 30-60%, with 100% mutant recovery in the following (M2) generation. TRV::tRNAIleu system described here allows generation of biallelic edited plants in a single generation and is amenable for large-scale high throughput CRISPR screens.
Overdiagnosis and treatment of COPD in nonagenarians
Authors: Tole Mateo , Ascoli Christian J. , Joo Min , Rubinstein Israel 
Published: January 2022

AbstractBackgroundThe prevalence of COPD is increasing with age. However, the effects of age-dependent decline in lung function on diagnosis and treatment of COPD in nonagenarians are uncertain.ObjectivesTo determine performance of spirometry, prescription of COPD medications, and COPD-related acute care visits and hospitalizations in patients 90 years and older with physician-diagnosed COPD.MethodsHealth records of 166 consecutive patients 90 years and older with physician-diagnosed COPD at a university-affiliated medical center in Chicago were reviewed. Pertinent demographic, clinical, and physiological data were extracted.ResultsPatients were predominantly ex-smoker (96%), African American (52%) males (96%). Sixty patients (36%) had no spirometry testing on record. Of the remaining 106 patients, 11 (10%) had baseline FEV1/FVC≥0.70, 24 (23%) had post-bronchodilator FEV1/FVC ≥0.70, 28 (26%) had FEV1/FVC <0.70 and ≥LLN, and 43 (41%) had FEV1/FVC <0.70 and <LLN. Thus, only 71 of 166 patients 90 years and older (43%) fulfilled the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations. Nonetheless, COPD medications, predominantly short-acting β2 agonists and long-acting muscarinic antagonists, were prescribed to 95 of the 166 patients (57%). No significant differences in prevalence of co-morbidities and prescribed COPD medications, including systemic corticosteroids and anti-infectives prescribed during unscheduled healthcare visits and hospitalizations, were found between the four groups.ConclusionsThese data suggest that a large proportion of nonagenarians at our medical center are overdiagnosed with and treated for COPD. A larger, multi-center, prospective study is warranted to support or refute these retrospective observations.
Rapid prototyping of metabolites detection by bacterial biosensors in human fecal samples
Authors: Zuñiga Ana , Boivineau Lucile , Mayonove Pauline , Conejero Ismael , Pageaux Georges-Philippe , Altwegg Romain , Bonnet Jerome 
Published: January 2022

AbstractGut metabolites are pivotal mediators of host-microbiome interactions and provide an important window on human physiology and disease. However, current methods to monitor gut metabolites rely on heavy and expensive technologies such as liquid chromatography-mass spectrometry (LCMS). In that context, robust, fast, field-deployable, and cost-effective strategies for monitoring fecal metabolites would support large-scale functional studies and routine monitoring of metabolites biomarkers associated with pathological conditions. Living cells are an attractive option to engineer biosensors due to their ability to detect and process many environmental signals and their self-replicating nature. Here we optimized a protocol for feces processing and gut metabolites detection using bacterial biosensors (bactosensors), enabling rapid evaluation of their operational capacity in these samples. We show that a simple filtration step is enough to remove host microbes and reproducibly obtain a physiological-derived media retaining important characteristics of human feces, such as matrix effects and endogenous metabolites. We measured how fecal samples affect the performance of biosensors for benzoate, lactate, anhydrotetracycline, and bile acids, and found that bactosensors are highly sensitive to fecal matrices. Sensitivity to the matrix is biosensor-dependent but also varies between individuals, highlighting the need for case-by-case optimization for bactosensors operation in feces. Finally, by detecting endogenous bile acids, we demonstrate that bactosensor can be used for metabolites monitoring in feces. This work lays the foundation for the optimization and use of bacterial biosensors for fecal metabolites monitoring. In the future, our method could also allow rapid pre-prototyping of engineered bacteria designed to operate in the gut, with applications to in situ diagnostics and therapeutics.
Structure and Protein-Protein Interactions of Ice Nucleation Proteins Drive Their Activity
Authors: Hartmann Susan , Ling Meilee , Dreyer Lasse S.A. , Zipori Assaf , Finster Kai , Grawe Sarah , Jensen Lasse Z. , Borck Stella , Reicher Naama , Drace Taner , Niedermeier Dennis , Jones Nykola C. , Hoffmann Søren V. , Wex Heike , Rudich Yinon , Boesen Thomas , Šantl-Temkiv Tina 
Published: January 2022

ABSTRACTMicrobially-produced ice nucleating proteins (INpro) are unique molecular structures with the highest known catalytic efficiency for ice formation. Their critical role in rain formation and frost damage of crops together with their diverse commercial applications warrant an in-depth under-standing of their inherent ice nucleation mechanism. We used the machine-learning based software Al-phaFold to develop the first ab initio structural model of a bacterial INpro which is a novel beta-helix structure consisting of repeated stacks of two beta strands connected by two sharp turns. Using the synchrotron radiation circular dichroism, we validated the β-strand content of the model. Combining functional studies of purified recombinant INpro, electron microscopy and modeling, we further demonstrate that the formation of dimers and higher-order oligomers is key to INpro activity. This work presents a major advance in understanding the molecular foundation for bacterial ice-nucleation activity and the basis for investigating the mechanistic role of INpro-induced ice formation in the atmosphere, and for commercial design and production of ice-nucleating particles for industrial applications.
Metal cofactor stabilization by a partner protein is a widespread strategy employed for amidase activation
Authors: Page Julia E. , Skiba Meredith A. , Do Truc , Kruse Andrew C. , Walker Suzanne 
Published: January 2022

ABSTRACTConstruction and remodeling of the bacterial peptidoglycan (PG) cell wall must be carefully coordinated with cell growth and division. Central to cell wall construction are hydrolases that cleave bonds in peptidoglycan. These enzymes also represent potential new antibiotic targets. One such hydrolase, the amidase LytH inStaphylococcus aureus, acts to remove stem peptides from PG, controlling where substrates are available for insertion of new PG strands and consequently regulating cell size. When it is absent, cells grow excessively large and have division defects. For activity, LytH requires a protein partner, ActH, that consists of an intracellular domain, a large rhomboid protease domain, and three extracellular tetratricopeptide repeats (TPRs). Here we demonstrate that the amidase-activating function of ActH is entirely contained in its extracellular TPRs. We show that ActH binding stabilizes metals in the LytH active site, and that LytH metal binding in turn is needed for stable complexation with ActH. We further present a structure of a complex of the extracellular domains of LytH and ActH. Our findings suggest that metal cofactor stabilization is a general strategy used by amidase activators and that ActH houses multiple functions within a single protein.SIGNIFICANCE STATEMENTThe Gram-positive pathogenStaphylococcus aureusis a leading cause of antibiotic resistance-associated death in the United States. Many antibiotics used to treatS. aureus, including the beta-lactams, target biogenesis of the essential peptidoglycan (PG) cell wall. Some hydrolases play important roles in cell wall construction and are potential antibiotic targets. The amidase LytH, which requires a protein partner, ActH, for activity, is one such hydrolase. Here, we uncover how the extracellular domain of ActH binds to LytH to stabilize metals in the active site for catalysis. This work advances our understanding of how hydrolase activity is controlled to contribute productively to cell wall synthesis.
Nanoformulated Remdesivir with Extremely Low Content of Poly(2-oxazoline) - Based Stabilizer for Aerosol Treatment of COVID-19
Authors: Ramsey Jacob D. , Stewart Ian E. , Madden Emily A. , Lim Chaemin , Hwang Duhyeong , Heise Mark T. , Hickey Anthony J. , Kabanov Alexander V. 
Published: January 2022

AbstractThe rise of the novel virus SARS-CoV2 which causes the disease known as COVID-19 has led to a global pandemic claiming millions of lives. With no clinically approved treatment for COVID-19, physicians initially struggled to treat the disease and there is still need for improved anti-viral therapies in this area. We conceived early in the pandemic that an inhalable formulation of the drug Remdesivir which directly targets the virus at the initial site of infection could improve therapeutic outcomes in COVID-19. We developed a set of requirements that would be conducive to rapid drug approval: 1) try to use GRAS or GRAS similar reagents 2) minimize excipient concentration and 3) achieve a working concentration of 5 mg/mL Remdesivir to achieve a deliverable dose which is 5-10% of the IV dose. In this work, we discovered that Poly(2-oxazoline) block copolymers can stabilize drug nanocrystal suspensions and provide suitable formulation characteristics for aerosol delivery while maintaining anti-viral efficacy. We believe POx block copolymers can be used as a semi-ubiquitous stabilizer for the rapid development of nanocrystal formulations for new and existing diseases.
GLH/VASA helicases promote germ granule formation to ensure the fidelity of piRNA-mediated transcriptome surveillance
Authors: Chen Wenjun , Brown Jordan S , He Tao , Wu Wei-Sheng , Tu Shikui , Weng Zhiping , Zhang Donglei , Lee Heng-Chi 
Published: January 2022

ABSTRACTThe ability to distinguish non-self from self is the key characteristic for any defense system. piRNAs function as guardians of the genome by silencing non- self nucleic acids and transposable elements in animals. Many piRNA factors are enriched in perinuclear germ granules, but whether their localization is required for piRNA biogenesis or function is not known. Here we show that GLH/VASA helicase mutants exhibit defects in forming perinuclear condensates containing PIWI and other small RNA cofactors. These mutant animals produce largely normal levels of piRNA but are defective in triggering piRNA silencing. Strikingly, while many piRNA targets are activated in GLH mutants, we observed that hundreds of endogenous genes are aberrantly silenced by piRNAs. This defect in self versus non-self recognition was also observed in other mutants where perinuclear P granules are disrupted. Together, our results argue that perinuclear germ granules function critically to promote the fidelity of piRNA- based transcriptome surveillance in C. elegans and preserve self versus non-self distinction.
What influences Vietnamese Airbnb travelers’ positive electronic word-of-mouth intentions? An extension of the Mehrabian – Russell model
Authors: Do Thuc Thi Mai Doan , Pinto Patrícia , Silva Joao Albino , Pereira Luis Nobre 
Published: January 2022

Purpose
This study aims to investigate the relationship between environmental stimuli of Airbnb experience, customers’ perceived enjoyment and positive electronic word-of-mouth (eWOM) intentions through an extension of the Mehrabian–Russell model.

Design/methodology/approach
A quantitative methodology was adopted using a web-based survey. Data were collected from a sample of 162 Vietnamese Airbnb consumers who had stayed at the platform accommodations. A two-stage procedure with the partial least squares approach to structural equation modeling was conducted to evaluate the measurement model and structural model.

Findings
The results confirmed the significant positive effect of home benefits and social interaction on Airbnb customers’ perceived enjoyment, which subsequently inspires them to develop intentions to spread positive comments toward this platform. Moreover, these relationships remain unchanged among the different groups of customers, except Airbnb travelers with business purposes.

Practical implications
The findings will provide Airbnb stakeholders in emerging markets with insights into identifying the important environmental factors that are more likely to stimulate consumers’ enjoyment and encourage them to spread positive WOM on social network outlets.

Originality/value
This research provides a deeper comprehension of Airbnb users’ emotional states and positive eWOM intentions by exploring the possible antecedents. Moreover, to the best of the authors’ knowledge, this is the first study to propose the moderating role of gender, purpose of the trip and type of accommodation in the hypothesized relationships. The contradictory findings of this study also highlight the cultural difference in Airbnb customers’ perception and behavioral intentions.
Integrated project delivery in the Nigerian construction sector: an unexplored approach from the stakeholders’ perspective
Authors: Ebekozien Andrew , Aigbavboa Clinton Ohis , Aigbedion Marvelous , Ogbaini Iliye Faith , Aginah Ibeabuchi Lawrence 
Published: January 2022

PurposeOver the past years, high waste and inefficiencies in the construction industry may have contributed to many projects failing to meet clients’ expectations. Among the new project delivery mechanisms to tackle this problem is integrated project delivery (IPD). IPD has been proved as a mechanism that increases stakeholders’ collaboration at the early stage and delivers the highest value-for-money projects. In Nigeria, research regarding practitioners in the application of IPD in construction delivery is scarce. Thus, this study aims to investigate the level of awareness, issues hindering the implementation of IPD and proffer solutions to promote the use of IPD in project delivery.Design/methodology/approachQualitative research was adopted. Twenty virtual interviews via Zoom and Whatsapp Videos were used to collect data from the selected participants and analysed via a thematic method. This is because of the unexplored dimension of the issues.FindingsResults show that practitioners are aware of IPD but lax in the application. The emerged issues hindering the adoption and implementation of IPD were grouped into technological, legal, financial and cultural in Nigeria’s context.Research limitations/implicationsThis study is restricted to the relevance and hindrances facing the usage of IPD in the Nigerian built environment. The study proffers solutions to promote the use of IPD in the built environment via a qualitative approach.Practical implicationsThis paper will contribute towards stirring Nigeria’s stakeholders to create an enabling environment within the industry via IPD friendly policies and promote the use of IPD on construction projects.Originality/valueThis paper is one of the few papers that attempted to uncover issues that hinder the use of IPD on construction projects in Nigeria via a qualitative approach.
Exploring users' adoption intentions in the evolution of artificial intelligence mobile banking applications: the intelligent and anthropomorphic perspectives
Authors: Lee Jung-Chieh , Chen Xueqing 
Published: January 2022

PurposeThe development of mobile technology has changed the traditional financial industry and banking sector. While traditional banks have adopted artificial intelligence (AI) techniques to deepen the development of mobile banking applications (apps), the current literature lacks research on the use of AI-based constructs to explore users' mobile banking app adoption intentions. To fill this gap, based on stimulus-organism-response (SOR) theory, two AI feature constructs as stimuli are considered, namely, perceived intelligence and anthropomorphism. This study then develops a research model to investigate how intelligence and anthropomorphism affect task-technology fit (TTF), perceived cost, perceived risk and trust (organism), which in turn influence users' AI mobile banking app adoption (response).Design/methodology/approachThis study used a convenience nonprobability sampling approach; a total of 451 responses were collected to examine the model. The partial least squares technique was utilized for data analysis.FindingsThe results show that intelligence and anthropomorphism increase users' willingness to adopt mobile banking apps through TTF and trust. However, higher levels of anthropomorphism enhance users' perceived cost. In addition, both intelligence and anthropomorphism have insignificant effects on perceived risk. The results provide theoretical contributions for AI-based mobile banking app adoption and offer practical guidance for bank planning to use AI to retain users.Originality/valueBased on SOR theory, this study reveals that as features, AI-enabled intelligence and anthropomorphism help us further understand users' perceptions regarding cost, risk, TTF and trust in the context of AI-enabled app adoption intentions.