bluuebunny/crossref_metadata_2025 huggingface dataset:
Network for Knowledge Organization (NEKO): an AI knowledge mining workflow for synthetic biology research
Authors: Xiao Zhengyang , Pakrasi Himadri B. , Chen Yixin , Tang Yinjie J.
Published: July 2024

Large language models (LLMs) can complete general scientific question-and-answer, yet they are constrained by their pretraining cut-off dates and lack the ability to provide specific, cited scientific knowledge. Here, we introduceNetwork forKnowledgeOrganization (NEKO), a workflow that uses LLM Qwen to extract knowledge through scientific literature text mining. When user inputs a keyword of interest, NEKO can generate knowledge graphs and comprehensive summaries from PubMed search. NEKO has immediate applications in daily academic tasks such as education of young scientists, literature review, paper writing, experiment planning/troubleshooting, and new hypothesis generation. We exemplified this workflow’s applicability through several case studies on yeast fermentation and cyanobacterial biorefinery. NEKO’s output is more informative, specific, and actionable than GPT-4’s zero-shot Q&A. NEKO offers flexible, lightweight local deployment options. NEKO democratizes artificial intelligence (AI) tools, making scientific foundation model more accessible to researchers without excessive computational power.
Eruptive insect outbreaks from endemic populations under climate change
Authors: Brush Micah , Lewis Mark A.
Published: July 2024

Insects, especially forest pests, are frequently characterized by eruptive dynamics. These types of species can stay at low, endemic population densities for extended periods of time before erupting in large-scale outbreaks. We here present a mechanistic model of these dynamics for mountain pine beetle. This extends a recent model that describes key aspects of mountain pine beetle biology coupled with a forest growth model by additionally including a fraction of low-vigor trees. These low-vigor trees, which may represent hosts with weakened defenses from drought, disease, other bark beetles, or other stressors, give rise to an endemic equilibrium in biologically plausible parameter ranges. The mechanistic nature of the model allows us to study how each model parameter affects the existence and size of the endemic equilibrium. We then show that under certain parameter shifts that are more likely under climate change, the endemic equilibrium can disappear entirely, leading to an outbreak.
Development and validation of the Emotion Regulation Questionnaire – Positive/Negative (ERQ-PN): Does the target of emotion regulation matter?
Authors: De Jesús-Romero Robinson , Chimelis-Santiago José R. , Rutter Lauren A. , Lorenzo-Luaces Lorenzo
Published: July 2024

The Emotion Regulation Questionnaire (ERQ) assesses emotion regulation strategies, particularly expressive suppression and cognitive reappraisal. However, the ERQ does not discern between regulating positive vs. negative emotions. Recent research suggests that suppression and reappraisal can impact mental health differently when targeting positive vs negative emotions. We developed and validated the Emotion Regulation Questionnaire - Positive/Negative (ERQ-PN), designed to measure positive and negative forms of suppression and reappraisal strategies. We recruited 963 participants (female = 478) through Prolific.com and administered the ERQ-PN. Participants had an average age of 45 years and were predominantly White (74%) and heterosexual (84%). Structural validity was assessed through confirmatory factor analyses. Model fit was estimated using the comparative fit index and the root-mean-square error of approximation. We also used the Bayesian information criterion to compare the fit of different models. Overall, participants used reappraisal more often to decrease negative emotions (vs. increasing positive) and leaned toward using suppression more for negative (vs. positive) emotions. These analyses revealed that the four-factor model (Model 2) delineating four latent variables (positive reappraisal, negative reappraisal, positive suppression, and negative suppression) had a good fit (RMSEA = 0.07, CFI = 0. 97, TLI = 0.96,χ2(98) = 531.28,p< 0.001). An incremental validity assessment revealed that positive and negative reappraisal correlated similarly with related mental health constructs. By contrast, suppression of negative vs. positive emotions was differentially associated to the validators tested. The ERQ-PN represents a valid measure of emotion regulation that accounts for both positive and negative emotions.
Behavioral state regulates the dynamics of memory consolidation
Authors: Silva N. Tatiana , Ribeiro Maria Inês , Carey Megan R.
Published: July 2024

Long-term memories are consolidated over time, progressively becoming more stable and resistant to interference. Memory consolidation occurs offline and often involves transfer of memories from one brain site to another. For many motor memories, consolidation is thought to involve early learning in cerebellar cortex that is subsequently transferred to the cerebellar nuclei. Here we report that in mice, engaging in locomotor activity during training in a classical conditioning task shifts the critical time window for memory consolidation, from just after training sessions, to between trials, within sessions. This temporal shift requires natural patterns of cerebellar granule cell activity during intertrial intervals and is accompanied by earlier involvement of the downstream cerebellar nucleus. These results reveal that the critical time window for cerebellar memory consolidation can be surprisingly brief, on a timescale from seconds to minutes, and that it is dynamically regulated by behavioral state.
PINK1-G411S mutant increases kinase stability and enhances mitochondrial-linked functions
Authors: Gonçalves Filipa B. , Enguita Francisco J. , Morais Vanessa A.
Published: July 2024

PINK1, a mitochondria targeted Serine/Threonine kinase, regulates ATP production by phosphorylating the Complex I subunit NdufA10. However, when in the presence of depolarized mitochondria, PINK1 phosphorylates ubiquitin and Parkin triggering mitochondria clearance. Mutations in PINK1 have been linked to early-onset recessive familial forms of Parkinson’s disease (PD). Deficits in Complex I enzymatic activity and an increase in oxidative damage have been identified in multiple brain regions of PD patients. Unravelling how PINK1 activity regulates mitochondria fate is pivotal. In the present study we characterized how human PD-related PINK1 mutants affect major PINK1 functions. Using molecular dynamics, we gain mechanistic insight into how specific mutations alter the tertiary structure and stability of PINK1’s ATP-binding pocket, leading to an increased rigidity and stability. More importantly, we report a structural explanation for the enhanced kinase function of the PINK1-G411S mutant.
Denoising Longitudinal Social Media for Pandemic Monitoring
Authors: Lin Shixu , Garay Lucas , Hua Yining , Guo Zhijiang , Xu Xiaolin , Yang Jie
Published: July 2024

Objective

Current studies leveraging social media data for disease monitoring face challenges like noisy colloquial language and insufficient tracking of user disease progression in longitudinal data settings. This study aims to develop a pipeline for collecting, cleaning, and analyzing large-scale longitudinal social media data for disease monitoring, with a focus on COVID-19 pandemic.

Materials and Methods

This pipeline initiates by screening COVID-19 cases from tweets spanning February 1, 2020, to April 30, 2022. Longitudinal data is collected for each patient, two months before and three months after self-reporting. Symptoms are extracted using Name Entity Recognition (NER), followed by denoising with a combination of Graph Convolutional Network (GCN) and Bidirectional Encoder Representations from Transformers (BERT) model to retain only User Symptom Mentions (USM). Subsequently, symptoms are mapped to standardized medical concepts using the Unified Medical Language System (UMLS). Finally, this study conducts symptom pattern analysis and visualization to illustrate temporal changes in symptom prevalence and co-occurrence.

Results

This study identified 191,096 self-reported COVID-19-positive cases from COVID-19-related tweets and retrospectively collected 811,398,280 historical tweets, of which 2,120,964 contained symptoms information. After denoising, 39% (832,287) of symptom-sharing tweets reflected user-related mentions. The trained USM model achieved an F1 score of 0.926. Further analysis revealed a higher prevalence of upper respiratory tract symptoms during the Omicron period compared to the Delta and wild-type periods. Additionally, there was a pronounced co-occurrence of lower respiratory tract and nervous system symptoms in the wild-type strain and Delta variant.

Conclusion

This study established a robust framework for pandemic monitoring via social media, integrating denoising of user-related symptom mentions and longitudinal data. The findings underscore the importance of denoising procedures in revealing accurate prevalence trends, thereby minimizing biases in symptom analysis.
Effective coverage for maternal health: operationalizing effective coverage cascades for antenatal care and nutrition interventions for pregnant women in seven low- and middle-income countries
Authors: Sheffel Ashley , Carter Emily , Heidkamp Rebecca , Hossain Aniqa Tasnim , Katz Joanne , Kim Sunny , Lama Tsering Pema , Marchant Tanya , Perin Jamie , Requejo Jennifer ,   Global Financing Facility, World Bank, Walton Shelley , Munos Melinda K.
Published: July 2024

Background

Efforts to improve maternal health have focused on measuring health and nutrition service coverage. However, high maternal mortality rates, despite improved service coverage, suggests that coverage indicators alone that do not account for quality can overestimate the health benefits of a service. Effective coverage (EC) cascades have been proposed as an approach to capture service quality within population-based coverage measures, but the proposed maternal health EC cascades have not been operationalized. This study aims to operationalize the effective coverage cascades for antenatal care (ANC) and maternal nutrition services using existing data from low- and middle-income countries (LMICs).

Methods

We used household surveys and health facility assessments from seven LMICs to estimate EC cascades for ANC and maternal nutrition services provided during ANC visits. We developed theoretical coverage cascades, defined health facility readiness and provision/experience of care scores and linked the facility-based scores to household survey data based on geographic domain and facility type. We then estimated the coverage cascade steps for each service by country.

Findings

Service contact coverage for at least one ANC visit (ANC1) was high, ranging from 80% in Bangladesh to 99% in Sierra Leone. However, there was a substantial drop in coverage from service contact to readiness-adjusted coverage, and a further drop to quality-adjusted coverage for all countries. For ANC1, from service contact to quality-adjusted coverage, there was an average net decline of 52 percentage points. For ANC1 maternal nutrition services, there was an average net decline of 48 percentage points from service contact to quality-adjusted coverage. This pattern persisted across cascades. Further exploration revealed that gaps in service readiness including lack of provider training, and gaps in provision/experience of care such as limited nutrition counseling were core contributors to the drops in coverage observed.

Conclusions

The cascade approach provided useful summary measures that identified major barriers to EC. However, detailed measures underlying the steps of the cascade are likely needed to support evidence-based decision-making with more actionable information. This analysis highlights the importance of understanding bottlenecks in achieving health outcomes and the inter-connectedness of service access and service quality to improve health in LMICs.
Guilt by association: Plant-based foods can be incorporated into both healthy and unhealthy plant-based diet indices associated with coronary heart disease
Authors: Jamshidi-Naeini Yasaman , Henschel Beate , Shikany James M. , Allison David B. , Brown Andrew W.
Published: July 2024

Background

One approach to test for differential associations between plant foods with health uses a scoring approach: foods categorized into animal or ‘healthy’ plant-based or ‘unhealthy’ plant-based groups to construct a plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI).

Objective

To evaluate robustness of associations between diet indices and incident coronary heart disease (CHD) risk when recategorizing food groups in indices.

Methods

Using REasons for Geographic and Racial Differences in Stroke (REGARDS) data, we replicated a published use of the scoring approach. Using Cox proportional hazards regression, we assessed ramifications of the following on associations between diet indices and CHD risk: 1) reconfiguring foods within and among food groups, using potatoes as an example, 2) leave-one-out analysis for each of 12 plant-based food groups, and 3) agnostically redefining each food group as ‘healthy’ or ‘unhealthy’.

Results

Over 153,286 person-years of follow-up, there were 868 cases of CHD. Replication analyses did not reach statistical significance. General patterns of magnitude of hazard ratios (HRs) in replication and reconfiguration models were PDI HRs < hPDI HRs < uPDI HRs for women, and hPDI < PDI < uPDI for men. Five models reconfiguring potatoes resulted in small, varied differences in PDI, hPDI, and uPDI associations. Leave-one-out analyses resulted in greater variation of associations between indices and CHD. In agnostic models, each plant-based food group was classified in indices as ‘healthy’ and ‘unhealthy’ with statistically significant beneficial or deleterious associations with CHD. Averaged over 4,096 models, HRs’ shifts were small when food groups were moved between ‘healthy’ and ‘unhealthy’.

Conclusion

Statistically significant associations between hPDI, uPDI, and PDI and incident CHD were not replicated. Small perturbations of the scoring approach had varied impacts on HRs. Agnostically constructing diet indices demonstrated the potential for guilt (or benefit) by association: any of the food groups we studied could be categorized with others in an index showing beneficial or deleterious associations.
Cell membrane glycan contents are biochemical factors that constitute a kinetic barrier to viral particle uptake in a protein-nonspecific manner
Authors: Kaizuka Yoshihisa , Machida Rika
Published: July 2024

Various types of glycoproteins have been suggested to inhibit viral infection of cells via steric repulsion. However, it is difficult to evaluate such physical actions genetically, simply because they are nonspecific and can be caused by any molecule. Therefore, we investigated a method to compare this nonspecific action among cells with diverse membrane protein profiles. We found that a wide range of glycoproteins individually had a strong inhibitory effect on infection, while on the other hand, the total amount of glycans was negatively correlated with the infection level in each cell. Thus, the infection-inhibitory effect of glycoproteins was molecularly nonspecific, but was additively enhanced according to the amount of glycans on the cell surface. In this correlation, glycans function as a fundamental factor. Further investigating the mechanism by which glycans function as a factor in infection control, we conclude that the repulsion between proteins created by branched glycans forms a kinetic energy barrier against packing the virus into the region of protein interstitial space. As a result, the formation of the adhesive interface between the virus and the cell membrane, which is necessary for infection, is inhibited. This study attempted to link the cell’s nonspecific physical properties with intracellular biochemicals. A similar approach may be applied to quantify other nonspecific biological phenomena.
Quiescent cells maintain active degradation-mediated protein quality control requiring proteasome, autophagy and nucleus-vacuole junctions
Authors: Franić Dina , Pravica Mihaela , Zubčić Klara , Miles Shawna , Bedalov Antonio , Boban Mirta
Published: July 2024

Many cells spend a major part of their life in quiescence, a reversible state characterized by a distinct cellular organization and metabolism. In glucose-depleted quiescent yeast cells, there is a metabolic shift from glycolysis to mitochondrial respiration, and a large fraction of proteasomes are reorganized into cytoplasmic granules containing disassembled particles. Given these changes, the operation of protein quality control (PQC) in quiescent cells, in particular the reliance on degradation-mediated PQC and the specific pathways involved, remains unclear. By examining model misfolded proteins expressed in glucose-depleted quiescent yeast cells, we found that misfolded proteins are targeted for selective degradation requiring functional 26S proteasomes. This indicates that a significant pool of proteasomes remains active in degrading quality control substrates. Misfolded proteins were degraded in a manner dependent on the E3 ubiquitin ligases Ubr1 and San1, with Ubr1 playing a dominant role. In contrast to exponentially growing cells, the efficient clearance of certain misfolded proteins additionally required intact nucleus-vacuole junctions (NVJ) and Cue5-independent selective autophagy. Our findings suggest that proteasome activity, autophagy, and NVJ-dependent degradation operate in parallel. Together the data demonstrate that quiescent cells maintain active PQC that relies primarily on selective protein degradation. The necessity of multiple degradation pathways for the removal of misfolded proteins during quiescence underscores the importance of misfolded protein clearance in this cellular state.
Elucidating the Transport Mechanisms and Metabolic Roles of Serine, Threonine, and Glycine inTrypanosoma cruzi
Authors: Alencar Mayke Bezerra , Bruno Moreira Girard Richard Marcel , Crispim Marcell , Baptista Carlos Gustavo , Biran Marc , Bringaud Frederic , Silber Ariel Mariano
Published: July 2024

l-Serine (l-Ser) andl-Threonine (l-Thr) have versatile roles in metabolism. In addition to their use in protein synthesis, these amino acids participate in the biosynthesis pathways of other amino acids and even phospholipids. Furthermore,l-Ser andl-Thr can be substrates for a Ser/Thr dehydratase (Ser/ThrDH), resulting in pyruvate (Pyr) and 2-oxobutyrate, respectively, thus being amino acids with anaplerotic potential.Trypanosoma cruzi, the etiological agent of Chagas disease, uses amino acids in several biological processes: metacyclogenesis, infection, resistance to nutritional and oxidative stress, osmotic control, etc. In this study, we investigated the import and metabolism ofl-Ser,l-Thr, and Gly inT. cruzi. Our results demonstrate that these amino acids are transported from the extracellular environment intoT. cruzicells through a saturable transport system that fits the Michaelis-Menten model. Our results show thatl-Ser andl-Thr can sustain epimastigote (Epi) cell viability under nutritional stress (NS) conditions and can stimulate oxygen consumption to maintain intracellular ATP levels. Additionally, our findings indicate thatl-Ser plays a role in establishing the mitochondrial membrane potential (ΔΨm) inT. cruzi.l-Ser is also involved in energy metabolism via the Ser-Pyr pathway, which stimulates the production and subsequent excretion of acetate and alanine. Our results demonstrate the importance ofl-Ser andl-Thr in the energy metabolism ofT. cruziand provide new insights into the metabolic adaptations of this parasite during its life cycle.
Colicin Receptor CirA EnhancesSalmonellaTyphimurium’s Resistance to Colicin Ib in the Absence of the Cognate Immunity Protein
Authors: Gollan BC , Luo L , Li Yan , Clark-Corrigall J , Qadri B , Alshuwaier A , Hinton J , Khan CMA
Published: July 2024

Intestinal microbiota play a central role in colonisation resistance providing a fundamental barrier to infection to enteric pathogens. An important mechanism of colonisation resistance involves the production of antimicrobial peptides, such as colicins. Pore-forming colicins, synthesised byEscherichia coli(E. coli) strains, target competing bacteria in their environmental niche, whilst the producing cells are safeguarded by specific immunity proteins. Notably, non-typhoidalSalmonellaTyphimurium strains can produce a narrow-spectrum protein toxin colicin IB (ColIb) providing a competitive edge against susceptibleEnterobacteriaceaestrains. However, the multi-drug resistant and systemically invasive iNTS (invasive non-TyphoidalSalmonella)S. Typhimurium D23580 strain poses an interesting case. The strain lacks colicin Ib production and the corresponding immunity protein, but its potential vulnerability in a colicin-rich gastrointestinal milieu remains uninvestigated. In this study,S. Typhimurium D23580 exhibited resistance to colicin Ib under tested conditions, despite the absence of the immunity geneimm. Intriguingly, in colicin Ib-producingS. Typhimurium strains, theimmgene appeared functionally redundant in contrast to our current understanding. ColIb binds to the outer membrane protein CirA and is translocated to the inner membrane where it forms a pore in sensitive bacteria dissipating the electrochemical potential. Through a series of experimental approaches, including the use ofEscherichia coliandS. TyphimuriumcirAdeletion mutants, promoter-swap techniques, and gene complementation, we identified that the colicin resistance phenotype inS. Typhimurium was partly attributable to the CirA receptor. This finding suggests a complex interplay in the microbial resistance to colicins, highlighting the intricacies of microbial interactions within the gastrointestinal environment.
Care delivery in the context of district mental healthcare plans (DMHP) in Ghana: experiences of primary health care workers and service users
Authors: Sakyi L , Ae-Ngibise KA , Adwan-Kamara L , Weobong Ben , Lund Crick
Published: July 2024

Background

The integration of mental healthcare into primary healthcare services is an effective way to addressing the substantial treatment gap for mental health conditions in low- and middle-income (LMIC) countries. In Ghana, District Mental Healthcare Plans (DMHPs) were developed and implemented in three districts over a 2-year period. This study aimed to explore the perceptions and experiences of mental health service users and primary healthcare workers regarding the implementation of the DMHPs.

Methods

The study employed a qualitative design involving in-depth interviews with 32 service users and 28 primary healthcare providers in the three demonstration districts. Participants were purposively sampled. Interview data were analysed using reflexive thematic analysis combining inductive and deductive approaches.

Results

Three main themes were identified: 1) Factors supporting DMHP implementation, including capacity building, collaboration, awareness creation, and acceptability; 2) Challenges impacting DMHP implementation, such as inadequate resources and medication shortages; and 3) Impacts of the DMHPs, including improved access to care, reduced relapse, enhanced daily functioning, and reduced stigma. Some district-level variations were noted in the intensity of challenges and impacts.

Conclusion

The DMHPs showed promise in improving mental healthcare in primary care settings in Ghana. However, addressing resource constraints and medication shortages, and sustaining capacity building and awareness creation efforts, will be crucial for successful scale-up. The perspectives of service users and healthcare providers offer valuable insights for policy makers and practitioners aiming to enhance integrated mental healthcare.

Strengths and limitations of this study

⇒ This study is the first in Ghana to explore in-depth the experiences of healthcare workers and service users in implementation of DMHPs.

⇒ Using qualitative design provide more nuanced understanding of factors supporting implementation of DMHP which would have been more difficult to do using quantitative methods.

⇒ The study reported from a relatively small sample size from only 3 districts from 261 districts in Ghana. While this sample size provided valuable insights, it may not cover the wide and diverse experiences of healthcare workers and service users involved in the DMHPs.
Single-cell analysis of human diversity in circulating immune cells
Authors: Kock Kian Hong , Tan Le Min , Han Kyung Yeon , Ando Yoshinari , Jevapatarakul Damita , Chatterjee Ankita , Lin Quy Xiao Xuan , Buyamin Eliora Violain , Sonthalia Radhika , Rajagopalan Deepa , Tomofuji Yoshihiko , Sankaran Shvetha , Park Mi-So , Abe Mai , Chantaraamporn Juthamard , Furukawa Seiko , Ghosh Supratim , Inoue Gyo , Kojima Miki , Kouno Tsukasa , Lim Jinyeong , Myouzen Keiko , Nguantad Sarintip , Oh Jin-Mi , Rayan Nirmala Arul , Sarkar Sumanta , Suzuki Akari , Thungsatianpun Narita , Venkatesh Prasanna Nori , Moody Jonathan , Nakano Masahiro , Chen Ziyue , Tian Chi , Zhang Yuntian , Tong Yihan , Tan Crystal T.Y. , Tizazu Anteneh Mehari ,   SG10K_Health Consortium, Loh Marie , Hwang You Yi , Ho Roger C , Larbi Anis , Ng Tze Pin , Won Hong-Hee , Wright Fred A. , Villani Alexandra-Chloé , Park Jong-Eun , Choi Murim , Liu Boxiang , Maitra Arindam , Pithukpakorn Manop , Suktitipat Bhoom , Ishigaki Kazuyoshi , Okada Yukinori , Yamamoto Kazuhiko , Carninci Piero , Chambers John C. , Hon Chung-Chau , Matangkasombut Ponpan , Charoensawan Varodom , Majumder Partha P. , Shin Jay W. , Park Woong-Yang , Prabhakar Shyam
Published: July 2024

Lack of diversity and proportionate representation in genomics datasets and databases contributes to inequity in healthcare outcomes globally1,2. The relationships of human diversity with biological and biomedical phenotypes are pervasive3, yet remain understudied, particularly in a single-cell genomics context. Here we present the Asian Immune Diversity Atlas (AIDA), a multi-national single-cell RNA-sequencing (scRNA-seq) healthy reference atlas of human immune cells. AIDA comprises 1,265,624 circulating immune cells from 619 healthy donors and 6 controls, spanning 7 population groups across 5 countries. AIDA is one of the largest healthy blood datasets in terms of number of cells, and also the most diverse in terms of number of population groups. Though population groups are frequently compared at the continental level, we identified a pervasive impact of sub-continental diversity on cellular and molecular properties of immune cells. These included cell populations and genes implicated in disease risk and pathogenesis as well as those relevant for diagnostics. We detected single-cell signatures of human diversity not apparent at the level of cell types, as well as modulation of the effects of age and sex by self-reported ethnicity. We discovered functional genetic variants influencing cell type-specific gene expression, including context-dependent effects, which were under-represented in analyses of non-Asian population groups, and which helped contextualise disease-associated variants. We validated our findings using multiple independent datasets and cohorts. AIDA provides fundamental insights into the relationships of human diversity with immune cell phenotypes, enables analyses of multi-ancestry disease datasets, and facilitates the development of precision medicine efforts in Asia and beyond.
Aspartic proteases are abundant and active in acidified wound fluid
Authors: Barbosa da Silva Elany , Crane Meredith J. , Liu Lawrence , Gelsinger Danielle J. , Jordon Alexander R.D. , McKinney Robin L. , Eberson Craig P. , Jamieson Amanda M. , O’Donoghue Anthony J.
Published: July 2024

Wound healing necessitates a balance between synthesis and breakdown of extracellular matrix components, which is tightly regulated by proteases and their inhibitors. Studies have shown that treatment of poorly healing wounds with acid results in improved healing. In this study, we systematically evaluated changes in proteolytic activity of murine wound fluid upon acidification. A library of 228 synthetic peptides served as reporters of protease activity at pH 7.4, pH 5.0 and pH 3.5. The peptide digestion patterns differed at each pH, revealing that proteases active at pH 7.4 are inactivated at pH 3.5. Notably, aspartic acid proteases emerged as the dominant active enzymes at pH 3.5 and their activity was inhibited by pepstatin. Using a fluorogenic substrate, we quantified aspartic protease activity across varying pH levels and demonstrated optimal activity between pH 3.0 and 3.8. This activity was detectable as early as one day post-injury and persisted over the following ten days. Importantly, human wound fluid exhibited the same activity profile, validating the mouse model as a relevant system for studying acid-mediated wound healing processes.
A side-by-side comparison of variant function measurements using deep mutational scanning and base editing
Authors: Sokirniy Ivan , Inam Haider , Tomaszkiewicz Marta , Reynolds Joshua , McCandlish David , Pritchard Justin Robert
Published: July 2024

Variant annotation is a crucial objective in mammalian functional genomics. Deep Mutational Scanning (DMS) is a well-established method for annotating human gene variants, but CRISPR base editing (BE) is emerging as an alternative. However, questions remain about how well high-throughput base editing measurements can annotate variant function and the extent of downstream experimental validation required. This study presents the first direct comparison of DMS and BE in the same lab and cell line. Results indicate that focusing on the most likely edits and highest efficiency sgRNAs enhances the agreement between a "gold standard" DMS dataset and a BE screen. A simple filter for sgRNAs making single edits in their window could sufficiently annotate a large proportion of variants directly from sgRNA sequencing of large pools. When multi-edit guides are unavoidable, directly measuring the variants created in the pool, rather than sgRNA abundance, can recover high-quality variant annotation measurements in multiplexed pools. Taken together, our data show a surprising degree of correlation between base editor data and gold standard deep mutational scanning.
Boosting biomolecular switch efficiency with quantum coherence
Authors: Burkhard Mattheus , Pusuluk Onur , Farrow Tristan
Published: July 2024

The resource theory of quantum thermodynamics has emerged as a powerful tool for exploring the out-of-equilibrium dynamics of microscopic and highly correlated systems. Recently, it has been employed in photoisomerization, a mechanism facilitating vision through the isomerism of the photoreceptor protein rhodopsin, to elucidate the fundamental limits of efficiency inherent in this physical process. Limited attention has been given to the impact of energetic quantum coherences in this process, as these coherences do not influence the energy-level populations within an individual molecule subjected to thermal operations. However, a specific type of energetic quantum coherences can impact the energy-level populations in the scenario involving two or more molecules. In this study, we examine the case of two molecules undergoing photoisomerization to show that energetic quantum coherence can function as a resource that amplifies the efficiency of photoisomerization. These insights offer evidence for the role of energetic quantum coherence as a key resource in the realm of quantum thermodynamics at mesoscopic scales.

Published by the American Physical Society
2024
Multimode physics of the unimon circuit
Authors: Tuohino Sasu , Vadimov Vasilii , Teixeira Wallace , Malmelin Tommi , Silveri Matti , Möttönen Mikko
Published: July 2024

We consider a superconducting half-wavelength resonator that is grounded at its both ends and contains a single Josephson junction. Previously this circuit was considered as a unimon qubit in the single-mode approximation where dc-phase-biasing the junction to π leads to increased anharmonicity and 99.9% experimentally observed single-qubit gate fidelity. Inspired by the promising first experimental results, we develop here a theoretical and numerical model for the detailed understanding of the multimode physics of the unimon circuit. To this end, first, we consider the high-frequency modes of the unimon circuit and find that even though these modes are at their ground state, they imply a significant renormalization to the Josephson energy. We introduce an efficient method to fully account for the relevant modes and show that unexcited high-lying modes lead to corrections in the qubit energy and anharmonicity. Interestingly, provided that the junction is offset from the middle of the circuit, we find strong cross-Kerr coupling strengths between a few low-lying modes. This observation paves the way for the utilization of the multimode structure, for example, as several qubits embedded into a single unimon circuit.

Published by the American Physical Society
2024
High-dimensional two-photon quantum controlled phase-flip gate
Authors: Chen Mingyuan , Tang Jiang-Shan , Cai Miao , Lu Yanqing , Nori Franco , Xia Keyu
Published: July 2024

High-dimensional quantum systems have been used to reveal interesting fundamental physics and to improve information capacity and noise resilience in quantum information processing. However, it remains a significant challenge to realize universal two-photon quantum gates in high dimensions with high success probability. Here, by considering an ion-cavity QED system, we theoretically propose, to the best of our knowledge, the first high-dimensional, deterministic, and universal two-photon quantum gate. By using an optical cavity embedded with a single trapped Ca+40 ion, we achieve a high average fidelity larger than 98% for a quantum controlled phase-flip gate in four-dimensional space, spanned by photonic spin angular momenta and orbital angular momenta. Our proposed system can be an essential building block for high-dimensional quantum information processing, and also provides a platform for studying high-dimensional cavity QED.

Published by the American Physical Society
2024
Comprehensive encoding of conformational and compositional protein structural ensembles through the mmCIF data structure
Authors: Wankowicz Stephanie A. , Fraser James S.
Published: July 2024

In the folded state, biomolecules exchange between multiple conformational states crucial for their function. However, most structural models derived from experiments and computational predictions only encode a single state. To represent biomolecules accurately, we must move towards modeling and predicting structural ensembles. Information about structural ensembles exists within experimental data from X-ray crystallography and cryo-electron microscopy. Although new tools are available to detect conformational and compositional heterogeneity within these ensembles, the legacy PDB data structure does not robustly encapsulate this complexity. We propose modifications to the macromolecular crystallographic information file (mmCIF) to improve the representation and interrelation of conformational and compositional heterogeneity. These modifications will enable the capture of macromolecular ensembles in a human and machine-interpretable way, potentially catalyzing breakthroughs for ensemble–function predictions, analogous to the achievements of AlphaFold with single-structure prediction.
The impact of exchanging the light and heavy chains on the structures of bovine ultralong antibodies
Authors: Clarke John D. , Douangamath Alice , Mikolajek Halina , Bonnet-Di Placido Marie , Ren Jingshan , Fry Elizabeth E. , Stuart Dave I. , Hammond John A. , Owens Raymond J.
Published: July 2024

The third complementary-determining regions of the heavy-chain (CDR3H) variable regions (VH) of some cattle antibodies are highly extended, consisting of 48 or more residues. These `ultralong' CDR3Hs form β-ribbon stalks that protrude from the surface of the antibody with a disulfide cross-linked knob region at their apex that dominates antigen interactions over the other CDR loops. The structure of the Fab fragment of a naturally paired bovine ultralong antibody (D08), identified by single B-cell sequencing, has been determined to 1.6 Å resolution. By swapping the D08 native light chain with that of an unrelated antigen-unknown ultralong antibody, it is shown that interactions between the CDR3s of the variable domains potentially affect the fine positioning of the ultralong CDR3H; however, comparison with other crystallographic structures shows that crystalline packing is also a major contributor. It is concluded that, on balance, the exact positioning of ultralong CDR3H loops is most likely to be due to the constraints of crystal packing.
Effect of different sealers on the properties of phosphate conversion coatings on 30CrMnSi alloys
Authors: Guo Haonan , Wang Chunxia , Liu Hui
Published: July 2024

Purpose

This study aims to investigate a chromium-free sealing treatment process to replace the chromate sealing process in response to the environmental hazards caused by chromate in the Phosphate chemical conversion (PCC) coating post-treatment sealing process.

Design/methodology/approach

In this paper, chromium-free sealing technology was used to post-treat PCC coatings. Scanning electron microscopy was used to investigate the structure of the surface of the PCC coatings after the sealing treatment, and the corrosion resistance, hydrophobicity and bonding were tested using an electrochemical workstation, a copper sulfate spot-drop test, a lacquer bonding test, a contact angle meter and a neutral salt spray test.

Findings

Chromium-free closure makes the grain distribution on the surface of the PCC coating more uniform and dense, and forms an organic film on the surface of the coating, which significantly improves the corrosion resistance and hydrophobicity of the PCC coating, does not affect the coating film bonding force and has similar performance with potassium dichromate solution.

Originality/value

The results show that the corrosion resistance of PCC coatings after chromium-free sealing treatment is improved, and chromium-free sealing has the potential to replace chromium sealing.
Housing price determinants in Ecuador: a spatial hedonic analysis
Authors: Valdez Gómez de la Torre Felipe Miguel , Chen Xuwei
Published: July 2024

Purpose

This paper aims to compare the efficiency of spatial and nonspatial hedonic price models in capturing housing submarkets dynamics for cities in developing countries. This study expects to contribute to a better understanding of the housing price determinants from both nonspatial and spatial perspectives. In addition, this paper fills a gap in the literature on the study of housing prices from a spatial perspective in Latin American cities.

Design/methodology/approach

This study uses a comparative analysis between an ordinary least squares regression and a geographical weighted regression, GWR. The study also assesses the performance of two distinct data sources: the city’s cadastral records and a real estate sales web portal.

Findings

The results suggest that compared to the traditional regression model, the spatial regression models are more effective at capturing housing market variations on a fine scale. Moreover, they reveal interesting findings on the spatial varying, sometimes contradictory effects of some housing attributes on housing prices in different areas of the city, suggesting the potential impact from segregation.

Research limitations/implications

The availability of data on housing prices and characteristics in Latin American cities is fragmented and complex. The level of detail, granularity and coverage is not consistent over time. For this reason, this study combines and compares data sets from official and unofficial sources in an effort to close this gap. Likewise, the socioeconomic variables that come from the census must be carefully analyzed, knowing the historical context in which they were constructed, what they represent and their interpretation.

Practical implications

This paper suggests that despite the improvement on the spatial models, the selection of a specific one should always be based on the diagnosis of it as it highly depends on the data used and the objectives of the study.

Originality/value

This study enriches the limited body of literature on spatial hedonic price models of housing in Latin American cities. It also shed light on the importance of spatial approaches to identify complex housing submarkets.
Human-following task without a prior map
Authors: Zhou Zhiqiang , Fu Yong , Wu Wei
Published: July 2024

Purpose

The human-following task is a fundamental function in human–robot collaboration. It requires a robot to recognize and locate a target person, plan a path and avoid obstacles. To enhance the applicability of the human-following task in various scenarios, it should not rely on a prior map. This paper aims to introduce a human-following method that meets these requirements.

Design/methodology/approach

For the identification and localization of the target person (ILTP), this paper proposes an approach that integrates data from a camera, a light detection and ranging (LiDAR) and a ultra-wideband (UWB) anchor. For path planning and obstacle avoidance, a modified timed-elastic-bands (TEB) algorithm is introduced.

Findings

Compared to the UWB-only method, where only UWB is used to locate the target person, the proposed ILTP method in this paper reduces the localization error by 41.82%. Experimental results demonstrate the effectiveness of the ILTP and the modified TEB method under various challenging conditions. Such as crowded environments, multiple obstacles, the target person being occluded and the target person moving out of the robot’s field of view. The complete experimental videos are available for viewing on https://youtu.be/ZKbrNE1sePM.

Originality/value

This paper offers a novel solution for human-following tasks. The proposed ILTP method can recognize the target person among multiple individuals, determine whether the target person is lost and publish the target person’s position at a frequency of 20 Hz. The modified TEB algorithm does not rely on a prior map. It can plan paths and avoid obstacles effectively.
Information search process model based on costs and benefits: a behavioural economics perspective
Authors: Qi Jinglin , Han Zhengbiao , Hansen Preben
Published: July 2024

Purpose

This study constructed an information search process model based on costs and benefits to reflect different information search processes under different decisions from a behavioural economics perspective.

Design/methodology/approach

This study used a deductive approach to conceptualise the costs, benefits, and uncertainties of the information search process. Subsequently, we constructed an information search process model based on the costs and benefits using graphical reasoning, loss aversion theory, bounded rationality theory, the satisficing theory of behavioural economics, and the uncertainty changes of information search process.

Findings

The model revealed four types of user behaviours in the information search process: (1) avoiding search at the initiation of the search process; (2) exiting in the middle of a search; (3) stopping at the point of satisficing; and (4) continuing the search until experiencing physical discomfort.

Originality/value

The model constructed in this study treats the information search as a process based on costs and benefits with uncertainty. This model integrates information search avoidance and stopping into an information search process model. The model identifies users’ bounded rationality by evaluating ideal and real situations. Moreover, the model explains relative and absolute information overloads and the area beyond the user’s bounded rationality. These findings could help improve users’ information literacy and optimise information systems.
Demographic, forensic and service involvement characteristics related to adults referred to a community-based learning disability forensic team pre- and post-COVID-19
Authors: Mir Rebecca , Power Niall
Published: July 2024

Purpose

To ensure health, social and criminal justice services are suited to the complex and dynamic needs of people with learning/intellectual disabilities (LD) at risk of offending, it is important to systematically analyse the needs and characteristics of this population. This study aimed to analyse the patterns of referrals to a single community forensic LD service before and during the COVID-19 pandemic.

Design/methodology/approach

A structured audit was conducted on all referrals to the service (n = 37) across a three-year period (May 2019 – end of July 2022).

Findings

The majority of the overall sample were male (36, 97%) and Caucasian (24, 65%) with a mean age of 32.9 years and mild LD. The most prevalent current offending type was sexual offending (17, 44%), whereas the most prevalent historical offending type was violence (17, 35%). The most common service/function offered by the service was advice and consultation to other professionals and agencies (10, 19%). The service user and forensic/legal characteristics measured did not differ significantly before and during COVID-19.

Originality/value

To the best of the authors’ knowledge, the project is the first to systematically analyse and compare community forensic LD service referral patterns before and during the COVID-19 pandemic. This study also provides an example of how a structured audit tool can be used to benefit individual services and the wider literature on assessing the needs and characteristics of adults with LD who live in the community and are at risk of [re]offending.
Why and how does the Dark Triad personality influence knowledge hiding? A generativity perspective
Authors: Yan Aimin , Sun Yicong , Brooks Sarah , Zhang Yinghui , Duan Jinyun
Published: July 2024

Purpose

Drawing on the generativity framework, this study aims to investigate the relationship between the Dark Triad personalities (Machiavellianism, narcissism, and psychopathy) and knowledge hiding. This study also identifies the mediating role of generativity motivation and the moderating role of focus on opportunities.

Design/methodology/approach

Using a convenience sample, a two-wave time-lagged study collected survey responses from 498 employees from manufacturing industries in China, and the data was analyzed using hierarchal regression and bootstrapping methods.

Findings

This study found that Machiavellianism and psychopathy are both positively related to generativity motivation. The generativity motivation plays a mediating role in the paths of Machiavellianism and psychopathy on knowledge hiding, and a focus on opportunities positively moderates the direct and indirect effect of Machiavellianism and psychopathy on knowledge hiding.

Originality/value

Based on the generativity framework, we find a new underlying mechanism between the Dark Triad personalities and knowledge hiding, thereby further enriching the literature in relation to their influence over knowledge management. Moreover, it also finds that a focus on opportunities can weaken the negative relationships between the Dark Triad personalities and knowledge hiding.