bluuebunny/crossref_metadata_2025 huggingface dataset:
Degradation of PET Plastics by Wastewater Bacteria Engineered via Conjugation
Authors: Yip Aaron , McArthur Owen D. , Ho Kalista C. , Aucoin Marc G. , Ingalls Brian P.
Published: February 2024

Microplastics are contaminants of global concern that pose risks to ecosystems and human health. Focusing on PET plastics, we present a proof-of-concept for reduction of microplastic pollution:in situengineering of bacteria in wastewater to degrade PET. Using a broad-host-range conjugative plasmid, we enabled various bacterial species from a municipal wastewater sample to express FAST-PETase, which was released into the extracellular environment. We found that FAST-PETase purified from some isolates could degrade about 40% of a 0.25 mm thick PET film within four days at 50 °C. We then demonstrate partial degradation of post-consumer PET over 5-7 days by exposure to conditioned media from isolates. These results have broad implications for addressing the global plastic pollution problem by enabling environmental bacteria to degrade PET plasticsin situ.
A direct readout mechanism regulates the sequence selectivity of humande novoDNA methyltransferases
Authors: Barlas Ayşe Berçin , Karaca Ezgi
Published: February 2024

De novoDNA methylation is crucial for mammalian gene regulation, and it is mediated by DNMT3A and DNMT3B enzymes. Despite their catalytic domains sharing over 90% sequence similarity, they preferentially methylate different flanking nucleotides adjacent to a classical CG motif. To uncover the basis of this selective methylation pattern, we conducted extensive molecular dynamics simulations of DNMT3A/B bound to eight possible CGX[C/G/T/A] motifs. Our comparative analysis of dynamic enzyme-DNA interactions revealed that single nucleotide substitutions in CGX motifs significantly alter DNMT3A-DNA hydrogen bonding profiles, resulting in a more specific readout for DNMT3A compared to DNMT3B. We found that +2 CGX nucleotide selectivity is driven by Arg/Lys-Guanine base-specific hydrogen bonds formed between DNMT3A/B and DNA. More specifically, Arg836 in DNMT3A reads the guanine complementary to C+2 in its cognate CGC motif, while Lys777 in DNMT3B recognizes two consecutive guanines in its cognate CGG. In DNMT3B, the impact of Arg-to-Lys mutation is mitigated through the cooperative nucleotide recognition directed by Asn779. All in all, our study provides fundamental insights into the molecular mechanisms underlying DNA sequence selectivity inde novoDNA methylation at the atomistic scale, which will have direct implications in understanding other DNA sequence recognition mechanisms.
GenomeFace: a deep learning-based metagenome binner trained on 43,000 microbial genomes
Authors: Lettich Richard , Egan Robert , Riley Robert , Wang Zhong , Tritt Andrew , Oliker Leonid , Yelick Katherine , Buluç Aydın
Published: February 2024

Metagenomic binning, the process of grouping DNA sequences into taxonomic units, is critical for understanding the functions, interactions, and evolutionary dynamics of microbial communities. We propose a deep learning approach to binning using two neural networks, one based on composition and another on environmental abundance, dynamically weighting the contribution of each based on characteristics of the input data. Trained on over 43,000 prokaryotic genomes, our network for composition-based binning is inspired by metric learning techniques used for facial recognition.

Using a task-specific, multi-GPU accelerated algorithm to cluster the embeddings produced by our network, our binner leverages marker genes observed to be universally present in nearly all taxa to grade and select optimal clusters of sequences from a hierarchy of candidates.

We evaluate our approach on four simulated datasets with known ground truth. Our linear time integration of marker genes recovers more near complete genomes than state of the art but computationally infeasible solutions using them, while being over an order of magnitude faster. Finally, we demonstrate the scalability and acuity of our approach by testing it on three of the largest metagenome assemblies ever performed. Compared to other binners, we produced 47%-183% more near complete genomes. From these datasets, we find over the genomes of over 3000 new candidate species which have never been previously cataloged, representing a potential 4% expansion of the known bacterial tree of life.
Multi-genome synteny detection using minimizer graph mappings
Authors: Coombe Lauren , Kazemi Parham , Wong Johnathan , Birol Inanc , Warren René L.
Published: February 2024

In recent years, the landscape of reference-grade genome assemblies has seen substantial diversification. With such rich data, there is pressing demand for robust tools for scalable, multi-species comparative genomics analyses, including detecting genome synteny, which informs on the sequence conservation between genomes and contributes crucial insights into species evolution. Here, we introduce ntSynt, a scalable utility for computing large-scale multi-genome synteny blocks using a minimizer graph-based approach. Through extensive testing utilizing multiple ∼3 Gbp genomes, we demonstrate how ntSynt produces synteny blocks with coverages between 79–100% in at most 2h using 34 GB of memory, even for genomes with appreciable (>15%) sequence divergence. Compared to existing state-of-the-art methodologies, ntSynt offers enhanced flexibility to diverse input genome sequences and synteny block granularity. We expect the macrosyntenic genome analyses facilitated by ntSynt will have broad utility in generating critical evolutionary insights within and between species across the tree of life.
Global diversity, recurrent evolution, and recent selection on amylase structural haplotypes in humans
Authors: Bolognini Davide , Halgren Alma , Lou Runyang Nicolas , Raveane Alessandro , Rocha Joana L. , Guarracino Andrea , Soranzo Nicole , Chin Jason , Garrison Erik , Sudmant Peter H.
Published: February 2024

The adoption of agriculture, first documented ∼12,000 years ago in the Fertile Crescent, triggered a rapid shift toward starch-rich diets in human populations. Amylase genes facilitate starch digestion and increased salivary amylase copy number has been observed in some modern human populations with high starch intake, though evidence of recent selection is lacking. Here, using 52 long-read diploid assemblies and short read data from ∼5,600 contemporary and ancient humans, we resolve the diversity, evolutionary history, and selective impact of structural variation at the amylase locus. We find that amylase genes have higher copy numbers in populations with agricultural subsistence compared to fishing, hunting, and pastoral groups. We identify 28 distinct amylase structural architectures and demonstrate that nearly identical structures have arisen recurrently on different haplotype backgrounds throughout recent human history.AMY1andAMY2Agenes each exhibit multiple duplications/deletions with mutation rates >10,000-fold the SNP mutation rate, whereasAMY2Bgene duplications share a single origin. Using a pangenome graph-based approach to infer structural haplotypes across thousands of humans, we identify extensively duplicated haplotypes present at higher frequencies in modern day populations with traditionally agricultural diets. Leveraging 533 ancient human genomes we find that duplication-containing haplotypes (i.e. haplotypes with moreamylase genecopies than the ancestral haplotype) have increased in frequency more than seven-fold over the last 12,000 years providing evidence for recent selection in West Eurasians. Together, our study highlights the potential impacts of the agricultural revolution on human genomes and the importance of long-read sequencing in identifying signatures of selection at structurally complex loci.
Unified machine learning framework uncovers overlooked bias control in immunogenic neoantigen identification
Authors: Zhang Ziting , Wu Wenxu , Wei Lei , Qi Hai , Wang Xiaowo
Published: February 2024

Neoantigens play a crucial role in tumor immune process and precisely identifying them can greatly contribute to tumor immunotherapy design. There are three main steps in the neoantigen immune process, i.e., binding with MHCs, extracellular presentation, and immunogenicity induction. Various computational methods have been developed, but the overall accuracy of neoantigen identification remains relatively low. Here, we established a unified transformer-based framework ImmuBPI that comprised three tasks. Cross-task model interpretation discovered a counterfactual pattern learned by the immunogenicity prediction model overlooked in previous studies. We demonstrated that this model bias arose from training data imbalance and the neglect of bias control would not only mislead the models but also hinder existing benchmarks from fair evaluation. We further designed a mutual information-based debiasing strategy that showed preliminary potential in alleviating the bias. We believe these observations will provide insightful perspectives for future neoantigen prediction by high-lighting the necessity of bias control.
Study protocol for a pilot clinical trial to understand neural mechanisms of response to a psychological treatment for pain and anxiety in pediatric functional abdominal pain disorders (FAPD)
Authors: Cunningham Natoshia R. , Adler Michelle A. , Barber Garcia Brittany N. , Abounader Taylor , Miller Alaina K. , Monzalvo Mariela , Hashemi Ismaeel , Cox Ryan , Ely Samantha L. , Zhou Yong , DeLano Mark , Mulderink Todd , Reeves Mathew J. , Peugh James L. , Kashikar-Zuck Susmita , Coghill Robert C. , Arnetz Judith E. , Zhu David C.
Published: February 2024

Background

Functional abdominal pain disorders (FAPD) are the most common chronic pain conditions of childhood and are made worse by co-occurring anxiety. Our research team found that the Aim to Decrease Pain and Anxiety Treatment (ADAPT), a six-session coping skills program using cognitive behavioral therapy strategies, was effective in improving pain-related symptoms and anxiety symptoms compared to standard care. In follow-up, this current randomized clinical trial (RCT) aims to test potential neural mechanisms underlying the effect of ADAPT. Specifically, this two-arm RCT will explore changes in amygdalar functional connectivity (primary outcome) following the ADAPT protocol during the water loading symptom provocation task (WL-SPT). Secondary (e.g., changes in regional cerebral blood flow via pulsed arterial spin labeling MRI) and exploratory (e.g., the association between the changes in functional connectivity and clinical symptoms) outcomes will also be investigated.

Methods

We will include patients ages 11 to 16 years presenting to outpatient pediatric gastroenterology care at a midwestern children’s hospital with a diagnosis of FAPD plus evidence of clinical anxiety based on a validated screening tool (the Generalized Anxiety Disorder-7 [GAD-7] measure). Eligible participants will undergo baseline neuroimaging involving the WL-SPT, and assessment of self-reported pain, anxiety, and additional symptoms, prior to being randomized to a six-week remotely delivered ADAPT program plus standard medical care or standard medical care alone (waitlist). Thereafter, subjects will complete a post assessment neuroimaging visit similar in nature to their first visit.

Conclusions

This small scale RCT aims to increase understanding of potential neural mechanisms of response to ADAPT. ClinicalTrials.gov registration:NCT03518216
Effectiveness of Psychosocial care interventions in improving the Quality of Life for Adult Patients with Cancer in low-and middle-income countries (LMICs): A Systematic Review and Meta-Analysis Protocol
Authors: Kavuma David , Namisango Eve , Downing Julia , Niyonzima Nixon , Kinengyere Alison Annet , Kasasa Simon , Makumbi Fredrick Edward , Obuku Ekwaro Anthony , Nuwaha Fred
Published: February 2024

Background

Psychosocial care interventions are part and parcel of cancer care and are known for their significant contribution to the improvement of the quality of life (QoL) for cancer patients and their families. Assessment of the QoL of patients with cancer and their families has become critical in cancer care nowadays since it guides health care providers in making informed decisions during the care process. The aim of this meta-analysis is to synthesise the online literature of primary studies from LMICs in order to understand the effectiveness of psychosocial care interventions towards the improvement of the QoL of adult patients with cancer.

Methods

This study will be done in tandem with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Primary studies that would have investigated the effectiveness of psychosocial care interventions on quality of life of adult cancer patients will be identified through searches in the various electronic databases that are known to produce optimal and efficient searches for systematic reviews and meta-analyses include: Ovid MEDLINE(R), PubMed, EMBASE, APA PsychINFO, Web of Science, PubMed, and Google Scholar. Studies published between 1stJanuary 2002 and 31stDecember 2023 in any LMIC, will be searched. After developing the meta-analysis question, we have developed a search string from the PICOST (population, intervention, comparison, outcome, study design, setting and Time-frame) model with a limitation on study design.

Discussion

This systematic review and meta-analysis will gather evidence from primary studies on the effectiveness of psychosocial care interventions in improving the QoL for adult patients with cancer in LMICs.

Protocol registration

This protocol was registered on 5thJune 2023 and its registration number is CRD42023421561.
HEALTH PROMOTION AND PREVENTIVE INTERVENTIONS FOR SENIOR CITIZENS IN COUNTRIES WITH ACCESSIBLE AND FUNDED HEALTH CARE: STUDY PROTOCOL FOR A SCOPING REVIEW
Authors: Lostelius Petra Vikman , Aromaa Henri , Karlsson Malin Lohela , Revenäs Åsa , Nordgren Lena
Published: February 2024

To improve health in a growing population with increasing life expectancy, a stepwise health care program for citizens aged 65 years and older will be implemented in Region Västmanland in Central Sweden. This scoping review builds on a previous review and aims to map interventions in a larger number of countries and from 2019 to present. The objective of this scoping review is to map the literature on the components of health promotion and preventive interventions in countries that provide accessible and funded health care. The JBI methodology will be employed for good structure. Searches will be conducted in databases and websites, for grey literature. The searches will include health promotion studies, preventive health measures, intervention methods, intervention delivery, outcome measures, or health-economic evaluations for people aged 65 years and older. Two reviewers will individually assess each study and extract data. Data analysis will consist of basic frequencies and percentages. The results will be presented in tables and/or diagrams and a narrative summary.
Perceptual constancy of pareidolias across paper and digital testing formats in neurodegenerative diseases
Authors: Revankar Gajanan S. , Ozono Tatsuhiko , Suzuki Maki , Kanemoto Hideki , Furuya Kota , Kamae Kazue , Yoshiyama Kenji , Yamamoto Yuki , Ogasawara Issei , Yoshida Natsuki , Iwasaki Susumu , Saeki Chizu , Nishio Yoshiyuki , Nakatani Daisaku , Asai Kanako , Kajiyama Yuta , Shimizu Mikito , Hayashi Tatsuya , Taniguchi Seira , Suzuki Yu , Inada Rino , Taminato Tomoya , Nagai Yoshitaka , Hashimoto Mamoru , Ikeda Manabu , Mori Etsuro , Mochizuki Hideki , Nakata Ken
Published: February 2024

Pareidolias refer to visual perceptual deficits where ambiguous shapes take on meaningful appearances. In neurodegenerative diseases, pareidolias are examined via a paper-based neuropsychological tool called the noise pareidolia test. In this study, we present initial findings regarding the utilization of pareidolia test on a digital format to analyze variations between paper-based and digital testing approaches. We performed our experiments on healthy controls, patients diagnosed with Alzheimer’s disease (AD), Dementia with Lewy body disease (DLB) and Parkinson’s disease (PD). Baseline MMSE assessments were conducted, followed by pareidolia testing using both paper-based tools and smartphones. Bland-Altman analysis was performed to evaluate the agreement between the two methods. We found that the illusionary phenomenon of pareidolia is consistent across paper and digital modalities of testing; that perceptual constancy is maintained across patient groups despite variations in image sizes; and pareidolic misperceptions, to some extent, are stabilized on a digital format. Our findings demonstrate a practical way of testing pareidolias on smartphones without compromising on the functionality of the test.
Outcomes of prognostication in people living with advanced cancer: a qualitative study to inform a Core Outcome Set
Authors: Spooner Caitlin , Vivat Bella , White Nicola , Stone Patrick
Published: February 2024

Background

Studies of prognostication in advanced cancer use a wide range of outcomes and outcome measures, making it difficult to compare these studies and their findings. Core Outcome Sets facilitate comparability and standardisation between studies and would benefit future prognostic research. This qualitative study is the second step in developing such a Core Outcome Set, with the aim to explore the perceptions and experiences of patients with advanced cancer, informal caregivers, and clinicians regarding the potential outcomes of prognostication.

Methods

We conducted semi-structured interviews with patients living with advanced cancer (n=8), informal caregivers (n=10), and clinicians (n=10) recruited from palliative care services across three sites in London, United Kingdom. Interviews were conducted in-person, via telephone, or video conferencing, and were audio-recorded. Data were analysed using a thematic framework analysis approach. Findings were compared with outcomes derived from a previously published systematic review.

Results

We identified 33 outcomes, 16 of which were not previously reported in the literature. We grouped outcomes into 10 domains, using a modified COMET taxonomy: 1) mortality/survival; 2) general physiological/clinical outcomes; 3) psychiatric outcomes; 4) spiritual/religious/existential functioning/wellbeing; 5) emotional functioning/wellbeing; 6) social functioning; 7) delivery of care; 8) perceived health status; 9) personal circumstances; 10) societal/carer burden. These findings highlighted discrepancies between the priorities of existing research and those of stakeholders.

Conclusions

This study offers valuable insights into outcomes significant to key stakeholders, underscoring the need for a patient-centred approach in research and clinical practice in prognostication in advanced cancer. These outcomes will play a key role in the development of a Core Outcome Set to assess the impact of prognostication in advanced cancer.
Influenza vaccination allocation in tropical settings under constrained resources
Authors: Servadio Joseph L , Choisy Marc , Thai Pham Quang , Boni Maciej F
Published: February 2024

Influenza virus seasonality, synchronicity, and vaccine supply differ substantially between temperate and tropical settings, and optimal vaccination strategy may differ on this basis. Most national vaccine recommendations focus on high-risk groups, elderly populations, and healthcare workers despite previous analyses demonstrating broad benefits to vaccinating younger high-contact age groups. Here, we parameterized an age-structured non-seasonal asynchronous epidemiological model of influenza virus transmission for a tropical low-income setting. We evaluated timing and age allocation of vaccines across vaccine supplies ranging from 10% to 90% using decade-based age groups. Year-round vaccination was beneficial when comparing to vaccination strategies focused on a particular time of year. When targeting a single age-group for vaccine prioritization, maximum vaccine allocation to the 10-19 high-contact age group minimized annual influenza mortality for all but one vaccine supply. When evaluating across all possible age allocations, optimal strategies always allocated a plurality of vaccines to school-age children (10-19). The converse however was not true as not all strategies allocating a plurality to children aged 10-19 minimized mortality. Allocating a high proportion of vaccine supply to the 10-19 age group is necessary but not sufficient to minimize annual mortality as distribution of remaining vaccine doses to other age groups also needs to be optimized. Strategies focusing on indirect benefits (vaccinating children) showed higher variance in mortality outcomes than strategies focusing on direct benefits (vaccinating the elderly). However, the indirect benefit approaches showed lower mean mortality and lower minimum mortality than vaccination focused on the elderly.

Significance statement

Influenza exhibits strong annual seasonality in temperate countries, but less consistent and predictable patterns in tropical countries. Many tropical countries are low-income countries with low influenza vaccine coverage. Globally, influenza vaccines are recommended for elderly adults and vulnerable groups, though evidence has shown that vaccinating school-age children is beneficial due to their high rates of social contact. Our modeling study evaluated whether age-based vaccine allocations can effectively minimize population influenza mortality in a tropical country with constrained resources and little seasonality. Prioritizing school-aged children for vaccination minimized mortality, with secondary emphasis on elderly adults. These benefits are most apparent under low vaccine supplies and can inform most effective ways to develop or expand influenza vaccination campaigns in low-income tropical settings.
PLAPT: Protein-Ligand Binding Affinity Prediction Using Pretrained Transformers
Authors: Rose Tyler , Monti Nicolò , Anand Navvye , Shen Tianyu
Published: February 2024

Abstract

Predicting protein-ligand binding affinity is crucial for drug discovery, as it enables efficient identification of drug candidates. We introduce PLAPT, a novel model utilizing transfer learning from pre-trained transformers like ProtBERT and ChemBERTa to predict binding affinities with high accuracy. Our method processes one-dimensional protein and ligand sequences, leveraging a branching neural network architecture for feature integration and affinity estimation. We demonstrate PLAPT’s superior performance through validation on multiple datasets, achieving state-of-the-art results while requiring significantly less computational resources for training compared to existing models. Our findings indicate that PLAPT offers a highly effective and accessible approach for accelerating drug discovery efforts.
Mosaic sarbecovirus nanoparticles elicit cross-reactive responses in pre-vaccinated animals
Authors: Cohen Alexander A. , Keeffe Jennifer R. , Schiepers Ariën , Dross Sandra E. , Greaney Allison J. , Rorick Annie V. , Gao Han , Gnanapragasam Priyanthi N.P. , Fan Chengcheng , West Anthony P. , Ramsingh Arlene I. , Erasmus Jesse H. , Pata Janice D. , Muramatsu Hiromi , Pardi Norbert , Lin Paulo J.C. , Baxter Scott , Cruz Rita , Quintanar-Audelo Martina , Robb Ellis , Serrano-Amatriain Cristina , Magneschi Leonardo , Fotheringham Ian G. , Fuller Deborah H. , Victora Gabriel D. , Bjorkman Pamela J.
Published: February 2024

Immunization with mosaic-8b [60-mer nanoparticles presenting 8 SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs)] elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on mosaic-8b efficacy, we evaluated effects of prior COVID-19 vaccinations in non-human primates and mice on anti-sarbecovirus responses elicited by mosaic-8b, admix-8b (8 homotypics), or homotypic SARS-CoV-2 immunizations, finding greatest cross-reactivity for mosaic-8b. As demonstrated by molecular fate-mapping in which antibodies from specific cohorts of B cells are differentially detected, B cells primed by WA1 spike mRNA-LNP dominated antibody responses after RBD-nanoparticle boosting. While mosaic-8b- and homotypic-nanoparticles boosted cross-reactive antibodies, de novo antibodies were predominantly induced by mosaic-8b, and these were specific for variant RBDs with increased identity to RBDs on mosaic-8b. These results inform OAS mechanisms and support using mosaic-8b to protect COVID-19 vaccinated/infected humans against as-yet-unknown SARS-CoV-2 variants and animal sarbecoviruses with human spillover potential.
Geographically widespread and novel hemotropic mycoplasmas and bartonellae in Mexican free-tailed bats and sympatric North American bat species
Authors: Becker Daniel J. , Dyer Kristin E. , Lock Lauren R. , Olbrys Beckett L. , Pladas Shawn A. , Sukhadia Anushka A. , Demory Bret , Nunes Batista Juliana Maria , Pineda Micaela , Simmons Nancy B. , Adams Amanda M. , Frick Winifred F. , O’Mara M. Teague , Volokhov Dmitriy V.
Published: February 2024

Bacterial pathogens remain poorly characterized in bats, especially in North America. We describe novel (and in some cases panmictic) hemoplasmas (10.5% positivity) and bartonellae (25.5% positivity) across three colonies of Mexican free-tailed bats (Tadarida brasiliensis), a partially migratory species that can seasonally travel hundreds of kilometers. Molecular analyses identified three novelCandidatushemoplasma species most similar to another novelCandidatusspecies in Neotropical molossid bats. We also detected novel hemoplasmas in sympatric cave myotis (Myotis velifer) and pallid bats (Antrozous pallidus), with sequences in the latter 96.5% related toC. Mycoplasma haemohominis. We identified nineBartonellagenogroups, including those in cave myotis with 96.7% similarity toC. Bartonella mayotimonensis. We also detectedBartonella rochalimaein migratory Mexican free-tailed bats, representing the first report of this human pathogen in the Chiroptera. The seasonality and diversity of these bacteria observed here suggest that additional longitudinal, genomic, and immunological studies in bats are warranted.
A single giant cell at the origin of an evolutionary innovation
Authors: Badiane Arnaud , Viala Séverine , Armisen David , Mignerey Ilona , Forcet-Vauchel Christelle , De Jesús Villanueva Christina N. , Van Belleghem Steven , Crumière Antonin , Santos Emilia , Francesconi Mirko , Khila Abderrahman
Published: February 2024

Key innovations play a central role in the diversification of lineages, yet our understanding of the mechanisms underlying their emergence remains fragmented. The propelling fan is a key innovation associated with the diversification ofRhagoveliawater striders into fast flowing streams. Here, we show that a single giant cell is responsible for the development of the fan throughout embryogenesis. RNA interference against the fan-specific gene familygsha/mogshadepleted the fan in the embryo but did not alter the giant cell, indicating that these genes are not required for specifying the identity of this cell.gsha/mogshainstead seem to activate the expression of cuticular genes during early development, suggesting a role of these genes in regulating the accumulation of fan structural proteins. We also show that Hox genes act to block the giant cell in the fore- and rear-legs, thus restricting its fate to the mid-legs – the pair of legs that generates movement on water. In addition, Hox expression is specifically excluded from the giant cell, thus allowing the expression of the fan’s developmental genetic program. This study reveals that a single cell can be sufficient to generate innovative traits that have been central for a lineage to acquire new ecological opportunities and burst into diversification.

One-sentence summary

A single giant cell orchestrates the developmental genetic program of a key innovation
Proteomics analysis reveals novel phosphorylated residues and associated proteins of the polyomavirus DNA replication initiation complex
Authors: Dey-Rao Rama , Shen Shichen , Qu Jun , Melendy Thomas
Published: February 2024

Polyomavirus (PyV) Large T-antigen (LT) is the major viral regulatory protein that targets numerous cellular factors/pathways: tumor suppressors, cell cycle regulators, transcription and chromatin regulators, as well as other factors for viral replication. LT directly recruits the cellular replication factors involved in LT’s recognition of the viral origin, origin unwinding, and primer synthesis which is carried out by mutual interactions between LT, DNA polymerase alpha-primase (Polprim), and single strand (ss) DNA binding replication protein A (RPA). The activities as well as interactions of these three with each other as well as other factors, are known to be modulated by post-translational modifications (PTMs); however, modern high-sensitivity proteomic analyses of the PTMs as well as proteins associated with the three have been lacking. Elution from immunoprecipitation (IP) of the three factors were subjected to high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS). We identified 479 novel phosphorylated amino acid residues (PAARs) on the three factors: 82 PAARs on SV40 LT, 305 on the Polprim heterotetrametric complex and 92 on the RPA heterotrimeric complex. LC-MS/MS analysis also identified proteins that co-immunoprecipitated (coIP-ed) with the three factors that were not previously reported: 374 with LT, 453 with Polprim and 183 with RPA. We used a bioinformatic-based approach to analyze the proteomics data and demonstrate a highly significant “enrichment” of transcription-related process associated uniquely with LT, consistent with its role as a transcriptional regulator, as opposed to Polprim and RPA associated proteins which showed no such enrichment. The most significant cell cycle related network was regulated by ETS proto-oncogene 1 (ETS1), indicating its involvement in regulatory control of DNA replication, repair, and metabolism. The interaction between LT and ETS1 is validated and shown to be independent of nucleic acids. One of the novel phosphorylated aa residues detected on LT from this study, has been demonstrated by us to affect DNA replication activities of SV40 Large T-antigen. Our data provide substantial additional novel information on PAARs, and proteins associated with PyV LT, and the cellular Polprim-, RPA- complexes which will benefit research in DNA replication, transformation, transcription, and other viral and host cellular processes.
Direct delivery of stabilized Cas-embedded base editors achieves efficient and accurate editing of clinically relevant targets
Authors: Lee Jeong Min , Zeng Jing , Liu Pengpeng , Nguyen My Anh , Loustaunau Diego Suchenski , Bauer Daniel E. , Yilmaz Nese Kurt , Wolfe Scot A. , Schiffer Celia A.
Published: February 2024

Over the last 5 years, cytosine base editors (CBEs) have emerged as a promising therapeutic tool for specific editing of single nucleotide variants and disrupting specific genes associated with disease. Despite this promise, the currently available CBE’s have the significant liabilities of off-target and bystander editing activities, in part due to the mechanism by which they are delivered, causing limitations in their potential applications. In this study we engineeredhighly stabilized Cas-embedded CBEs (sCE_CBEs) that integrate several recent advances, andthat are highly expressible and soluble for direct delivery into cells as ribonucleoprotein (RNP) complexes. Our resulting sCE_CBE RNP complexes efficiently and specifically target TC dinucleotides with minimal off-target or bystander mutations. Additional uracil glycosylase inhibitor (UGI) protein intransfurther increased C-to-T editing efficiency and target purity in a dose-dependent manner, minimizing indel formation to untreated levels. A single electroporation was sufficient to effectively edit the therapeutically relevant locus for sickle cell disease in hematopoietic stem and progenitor cells (HSPC) in a dose dependent manner without cellular toxicity. Significantly, these sCE_CBE RNPs permitted for the transplantation of edited HSPCs confirming highly efficient editing in engrafting hematopoietic stem cells in mice. The success of the designed sCBE editors, with improved solubility and enhanced on-target editing, demonstrates promising agents for cytosine base editing at other disease-related sites in HSPCs and other cell types.
Freeze-in bino dark matter in high-scale supersymmetry
Authors: Han Chengcheng , Wu Peiwen , Yang Jin Min , Zhang Mengchao
Published: February 2024

We explore a scenario of high-scale supersymmetry where all supersymmetric particles except gauginos stay at a high-energy scale MSUSY that is much larger than the reheating temperature TRH. The dark matter is dominated by a bino component with mass around the electroweak scale and the observed relic abundance is mainly generated by the freeze-in process during the early Universe. Considering the various constraints, we identify two available scenarios in which the supersymmetric sector at an energy scale below TRH consists of (a) bino or (b) bino and wino. Typically, for a bino mass around 0.1–1 TeV and a wino mass around 2 TeV, we find that MSUSY should be around 1013−14  GeV with TRH around 104−6  GeV.

Published by the American Physical Society
2024
Hyperfine Spectroscopy and Fast, All-Optical Arbitrary State Initialization and Readout of a Single, Ten-Level
Ge73
Vacancy Nuclear Spin Qudit in Diamond
Authors: Adambukulam C. , Johnson B. C. , Morello A. , Laucht A.
Published: February 2024

A high-spin nucleus coupled to a color center can act as a long-lived memory qudit in a spin-photon interface. The germanium vacancy (GeV) in diamond has attracted recent attention due to its excellent spectral properties and provides access to the ten-dimensional Hilbert space of the I=9/2 Ge73 nucleus. Here, we observe the GeV73  hyperfine structure, perform nuclear spin readout, and optically initialize the Ge73 spin into any eigenstate on a μs timescale and with a fidelity of up to ∼84%. Our results establish GeV73 as an optically addressable high-spin quantum platform for a high-efficiency spin-photon interface as well as for foundational quantum physics and metrology.

Published by the American Physical Society
2024
Quantum Error Mitigated Classical Shadows
Authors: Jnane Hamza , Steinberg Jonathan , Cai Zhenyu , Nguyen H. Chau , Koczor Bálint
Published: February 2024

Classical shadows enable us to learn many properties of a quantum state ρ with very few measurements. However, near-term and early fault-tolerant quantum computers will only be able to prepare noisy quantum states ρ and it is thus a considerable challenge to efficiently learn properties of an ideal, noise-free state ρid. We consider error mitigation techniques, such as probabilistic error cancelation (PEC), zero noise extrapolation (ZNE), and symmetry verification (SV), which have been developed for mitigating errors in single expected value measurements and generalize them for mitigating errors in classical shadows. We find that PEC is the most natural candidate and thus develop a thorough theoretical framework for PEC shadows with the following rigorous theoretical guarantees: PEC shadows are an unbiased estimator for the ideal quantum state ρid; the sample complexity for simultaneously predicting many linear properties of ρid is identical to that of the conventional shadows approach up to a multiplicative factor, which is the sample overhead due to error mitigation. Due to efficient postprocessing of shadows, this overhead does not depend directly on the number of qubits but rather grows exponentially with the number of noisy gates. The broad set of tools introduced in this work may be instrumental in exploiting near-term and early fault-tolerant quantum computers: we demonstrate in detailed numerical simulations a range of practical applications of quantum computers that will significantly benefit from our techniques.

Published by the American Physical Society
2024
Digital enabled innovation ecosystems: a dual case study of knowledge flows in intellectual property platforms
Authors: Ma Lei , Zhang Ben , Liang Kaitong , Cheng Yang , Yi Chaonan
Published: February 2024

Purpose

The embedding of digital technology and the fuzzy organizational boundary have changed the operation of platform innovation ecosystem (PIE). Specifically, as an important energy of PIE, the internal logic of knowledge flow needs to be reconsidered in the context of digital age, which will be helpful to select the cultivation and governance strategy of PIE.

Design/methodology/approach

A dual case-analysis is applied to open the “black box” of knowledge flow in the PIE from the perspective of enabled by digital technology, by taking the intellectual property (IP) operation platform as cases.

Findings

The research findings are as follow: (1) The knowledge flow mechanism of PIE is mainly demonstrated through the processes of knowledge acquisition, knowledge integration and knowledge spillover. During this process, connectivity empowerment and scenario empowerment realize the digital empowerment of the platform. (2) Connectivity empowerment provides a channel of knowledge acquisition for the digital connection between participants in PIE. In the process of knowledge integration, scenario empowerment improves the opportunities for accurate matching and collaborative innovation between knowledge supplier and demander, and enhance the value of knowledge. The dual effect of connectivity empowerment and scenario empowerment has accelerated the knowledge spillover in PIE. Particularly, connectivity empowerment expands the range of knowledge spillover, and scenario empowerment affects the generativity of the platform, resulting in the enhancement of platform’s capability to embed and expand its value network. (3) Participants have been benefitted from the PIE enabled by digital technology through three key modules (knowledge acquisition, knowledge integration and knowledge spillover), as the result of knowledge flow.

Originality/value

This study focuses on the knowledge flow mechanism of PIE enabled by digital technology, which enriches the PIE theory, and has enlightenments for the cultivation of digital platform ecosystem.
A comparative study on sustainability standards with specific reference to GRI standards and BRSR framework
Authors: Nial Naresh , Parashar Pranay
Published: February 2024

Purpose

The main objective of the study was to compare Business Responsibility and Sustainability Report (BRSR) norms with Global Reporting Initiative (GRI) standards, so as to establish whether BRSR norms match the global standards and best practices or not. Additionally, an effort was made to ascertain and highlight areas where BRSR norms are more comprehensive, just match, or require further refinement to be at par with the GRI standards. The study highlights the similarities and dissimilarities between the internationally accepted GRI standards and the BRSR framework; thereby suggesting areas of improvement for the BRSR framework.

Design/methodology/approach

Scrutinised all the 36 standards of the Global reporting initiative and BRSR format and guidelines of the Securities Exchange Board of India. The Content Analysis Technique was used to ascertain the percentages of similarities between the two frameworks.

Findings

The content analysis found that there are 52.30% similarities between BRSR norms and GRI standards. Further, this study shows the factors that led to the dissimilarities between BRSR and GRI standards. This study found 18 areas where BRSR is more informative than GRI, and 7 areas where BRSR could be further refined.

Originality/value

This study contributes to research in the sustainability reporting framework to be adopted by Indian listed companies. There are a few Indian listed companies who are already reporting as per the GRI framework and might perceive the BRSR as a separate reporting altogether. But as found in this study, more than half of the BRSR framework is similar to the GRI framework; thus, half the work is almost done. As such this study helps Indian firms in developing an understanding of the BRSR and puts in perspective its standing among global sustainability reporting standards. This study shall help institutional investors, rating agencies, and external assurers to better visualize an Indian entity, by referring to its Business Responsibility and Sustainability Reporting.
Weaving emotions: unraveling the emotional significance of Sri Lankan handloom artistry
Authors: Gopura Sumith , Wickramasinghe Ayesha
Published: February 2024

Purpose

This paper examines the socio-emotional identities of handloom artisans in Sri Lanka as a novel technique for new product development.

Design/methodology/approach

Qualitative research methods, including observational research and semi-structured interviews with 27 artisans from different handloom communities in Sri Lanka were conducted and analyzed in thematic approach.

Findings

By highlighting the maker of the craft through their socio-emotional identities in an artisan-oriented approach, this paper provides insight into new product development for handloom in alignment with up-and-coming trends. Ultimately, this can increase the demand for handloom and sustain the sector in both local and international fashion markets.

Originality/value

This research study is one of the first of its kind to propose a novel approach for artisan-oriented product development through the application of artisans’ socio-emotional identities.
The determinants of compliance VAT gap
Authors: Cuceu Ionuţ Constantin , Florescu Decebal Remus , Văidean Viorela Ligia
Published: February 2024

Purpose

This paper aims to analyze the potential variables explaining the compliance value added tax (VAT) gap, which basically represents an estimate of the unpaid VAT in the economy. A major component of compliance VAT Gap is represented by tax fraud; there exist other causes too, like insolvencies, bankruptcies, optimizations practices and maladministration. The objective of our paper is to revisit the main determinants of the VAT compliance gap for the European Union (EU)-27 member states. Using econometric modeling, our study identifies the relationship between the VAT gap and various determinants of it.

Design/methodology/approach

Our work focuses on the shadow economy, final consumption, VAT revenues, standard VAT rates, differences between the standard and reduced rates, economic prosperity, press freedom, political stability and others, as determinants of European VAT compliance gaps, for the 2005–2020 time interval. The methods include panel data analysis through simple and multiple regression modeling, the combinatorial approach, fixed and random effects.

Findings

Our study validates the direct impact of shadow economy and the indirect impact of VAT revenues, economic prosperity and press freedom, upon VAT compliance gaps. Upon subsampling of EU member states within old and new ones, our results estimate a larger positive impact of shadow economy upon old member states, compared to new ones.

Practical implications

The policy implications include leverage effects of governments acting upon a reduction in shadow economy phenomena and boosts of economic development, political stability and press freedom, in order to attain the contraction of compliance VAT gaps.

Originality/value

Our paper sheds light in a poorly explored scientific area, that of the determinants of VAT gap, especially in relationship with financial and economic crime phenomena.
An application of the extended UTAUT model to understand the adoption of cashless transactions: evidence from developing country
Authors: Sakib Md. Nazmus , Akter Mahmuda , Sahabuddin Mohammad , Fahlevi Mochammad
Published: February 2024

Purpose

This study aims to identify the factors influencing cashless transactions toward digital payment systems using the extended UTAUT model in developing countries. This model was extended with perceived usefulness, perceived ease of use, facilitating conditions, perceived security/trust and social influence for assessing consumer behavior toward cashless transactions.

Design/methodology/approach

Using structural equation modeling (SEM), this study conducted a cross-sectional survey to collect data, providing a snapshot of the relationship between exogenous and endogenous variables.

Findings

The results of the study indicate that perceived usefulness, facilitating conditions, perceived trust/security and social influence have a significant influence on consumer intentions toward cashless transactions. Oppositely, leaving the perceived ease of use has no significant influence on consumer intentions toward the usage of cashless transactions.

Originality/value

The contribution of this study is to extend the UTAUT model for adopting cashless transactions in developing countries that will help government agencies, service providers and financial institutions design effective strategies in the future.
Resurgence and transformation: the impact of COVID-19 on Myanmar’s tourism industry and future trends
Authors: Zreik Mohamad
Published: February 2024

Purpose

This paper analyses the impact of the COVID-19 pandemic on Myanmar’s tourism industry, identifying challenges and innovations, and predicting future trends to foster a resilient and sustainable sector.

Design/methodology/approach

The study uses a comprehensive analysis of tourism trends, government and private sector responses and changes in tourist behaviour, employing data, case studies and policy reviews.

Findings

The pandemic significantly disrupted Myanmar’s tourism, causing economic losses and shifts towards sustainable, outdoor and cultural experiences. Effective strategies by the government and private sector are aiding recovery and suggesting a more diverse and resilient future.

Research limitations/implications

The research is limited by the availability of data during the pandemic, highlighting the need for ongoing strategy adaptation.

Practical implications

The study recommends digitalization, health protocols, domestic tourism focus and sustainable practices for a robust post-pandemic industry.

Social implications

The study emphasizes the pandemic’s social impact on tourism-dependent communities and the need for inclusive, sustainable tourism practices.

Originality/value

Itprovides unique insights into COVID-19’s multifaceted impact on Myanmar’s tourism, offering valuable information for future sector strategies.