bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 and Mycobacterium tuberculosis co-infection in vitro
Authors: de Lucena Thays Maria Costa , de Oliveira Miranda Débora Elienai , de Barros Arcoverde Juliana Vieira , Bezerra Cavalcanti Mariana Souza , da Silva Rabello Michelle Christiane , de Azevêdo Silva Jaqueline
Published: August 2024

In less than a year, SARS-CoV-2 (SARS2) has managed to displaceMycobacterium tuberculosis(Mtb) as the leading cause of death worldwide due to a single infectious agent. Both pathogens affect the respiratory tract, mainly the lungs. However, the impact that a possible Mtb + SARS2 co-infection can have on the host response is still unknown. Herein we propose (depict) a rigorous system to evaluate the complex interaction between the two infectionsin vitroin a lung epithelial cell line (A549). Overall, the process includes eight steps: (I) Mtb culture, (II) cell maintenance, (III) preparation of viral stocks, (IV) determination of infectious titers, (V) Mtb and SARS2 co-infection, (VI) determination of intracellular bacterial load, (VII) SARS2 viability test, and (VIII) decontamination of supernatants. This comprehensive protocol will allow experimentalists to study the pathogenesis of co-infectionin vitro, and facilitate collaborative work in the literature.
Dopaminergic modulation of behavioral and electrocortical markers of interpersonal performance monitoring in Parkinson’s Disease: insights from multivariate and univariate analyses
Authors: Era V. , Pesci U.G. , Moreau Q. , Pezzetta R. , Zabberoni S. , Peppe A. , Costa A. , Taglieri S. , Candidi M. , Aglioti S.M.
Published: August 2024

Effective interpersonal interaction necessitates constant monitoring and adaptation to others’ actions, a process known as interpersonal performance monitoring, which is influenced by the dopaminergic system and marked by specific electrocortical signatures. To explore the connection between deficits in interpersonal performance monitoring and altered neural markers, we assessed patients with Parkinson’s Disease (PD) performing coordination tasks with a virtual partner (VP) under two conditions: on dopaminergic medication (PD ON) and after withdrawal (PD OFF). In Interactive trials, which required adaptation to the VP’s actions, PD OFF performance was impaired compared to PD ON. EEG analysis revealed in PD OFF increased midfrontal Delta-Theta activity during Interactive trials. Higher Delta-Theta synchronization was associated with improved performance, suggesting compensatory mechanisms. Multivariate EEG analysis distinguished Interactive from Cued trials, especially in PD OFF. Our findings highlight dopamine’ s role in modulating electrocortical markers of interpersonal performance monitor, with significant implications for understanding and treating PD.
Precision Network Modeling of Transcranial Magnetic Stimulation Across Individuals Suggests Therapeutic Targets and Potential for Improvement
Authors: Sun Wendy , Billot Anne , Du Jingnan , Wei Xiangyu , Lemley Rachel A. , Daneshzand Mohammad , Nummenmaa Aapo , Buckner Randy L. , Eldaief Mark C.
Published: August 2024

Higher-order cognitive and affective functions are supported by large-scale networks in the brain. Dysfunction in different networks is proposed to associate with distinct symptoms in neuropsychiatric disorders. However, the specific networks targeted by current clinical transcranial magnetic stimulation (TMS) approaches are unclear. While standard-of-care TMS relies on scalp-based landmarks, recent FDA-approved TMS protocols use individualized functional connectivity with the subgenual anterior cingulate cortex (sgACC) to optimize TMS targeting. Leveraging previous work on precision network estimation and recent advances in network-level TMS targeting, we demonstrate that clinical TMS approaches target different functional networks between individuals. Homotopic scalp positions (left F3 and right F4) target different networks within and across individuals, and right F4 generally favors a right-lateralized control network. We also modeled the impact of targeting the dorsolateral prefrontal cortex (dlPFC) zone anticorrelated with the sgACC and found that the individual-specific anticorrelated region variably targets a network coupled to reward circuitry. Combining individualized, precision network mapping and electric field (E-field) modeling, we further illustrate how modeling can be deployed to prospectively target distinct closely localized association networks in the dlPFC with meaningful spatial selectivity and E-field intensity and retrospectively assess network engagement. Critically, we demonstrate the feasibility and reliability of this approach in an independent cohort of participants (including those with Major Depressive Disorder) who underwent repeated sessions of TMS to distinct networks, with precise targeting derived from a low-burden single session of data. Lastly, our findings emphasize differences between selectivity and maximal intensity, highlighting the need to consider both metrics in precision TMS efforts.
Availability, Price and Nutritional Assessment of Plant-Based Meat Alternatives in Hypermarkets and Supermarkets in Petaling, the Most Populated District in Malaysia
Authors: Qi Lou Katty Jia , Rajaram Nadia Nantheni , Say Yee-How
Published: August 2024

This study investigated the availability, price, nutritional composition, and quality of PBMAs in supermarkets and hypermarkets in Petaling, the most populated district in Malaysia. The survey covered 85 stores through on-site visits, identifying 251 unique PBMA products from 42 brands. The PBMAs were categorized into nine groups: Burgers/Patties, Coated Meat, Luncheon Meat, Minced Meat, Pastries, Pieces/Chunks/Fillets/Strips, Prepacked Cooked Meals, Sausages, and Seafood Balls/Cakes/Meatballs. The survey indicated widespread availability of PBMAs in Petaling, with premium supermarkets offering the most extensive selection. The median prices of PBMAs across categories were below MYR 7 (∼USD 1.6) per 100 grams, with Pieces/Chunks/Fillets/Strips being the most affordable. Nutritionally, PBMAs exhibited lower energy, total fat, saturated fat, sodium, and protein levels than meat equivalents, while showing higher carbohydrate content. Nutri-Score profiling revealed generally favourable scores (Grade A to C), indicating moderate to good nutritional quality. These findings suggest that PBMAs offer a viable alternative for consumers in Malaysia seeking healthier and more sustainable food options, particularly for those aiming to reduce their intake of fat and sodium. However, PBMAs may not be recommended for individuals seeking a higher protein and lower carbohydrate diet. Further research is recommended to explore micronutrient profiles to enhance dietary decision-making.
“Implementing a policy is something else”: Governance of complex health information systems in Tanzania
Authors: Unkels Regine , Mkumbo Elibariki , Kapologwe Ntuli A , Manzi Fatuma , Hanson Claudia , Alvesson Helle Mølsted , Pembe Andrea B
Published: August 2024

Introduction

Health management information systems are crucial for a country’s health service planning and monitoring. Research indicates that generated data is often of low quality or not used for decision-making in low-resource settings. Digitalization potentially alleviates these problems, but scale-up in these countries is hampered by unreliable availability of resources.

We aimed to understand how health policymakers perceive and experience working with data, data systems and the introduction of digital technology related to the governance of health management information systems in Tanzania.

Methods

We conducted 16 interviews with national, regional and district health care managers experienced in using health information systems in Tanzania. Reflexive thematic analysis was used. Themes were developed underpinned by complexity theory and M. Lipsky’s theory of street-level bureaucracy.

Results

Health care managers experienced challenges in health management information system governance in an unpredictable environment. Different power practices for system governance and implementation were used: Institutional power was applied to areas with existing international guidance and strategic examples. Subnational managers contextualized implementation through discretionary power practices where uncertainties prevailed. This led to transformed agendas in some cases, but also allowed for innovations to make policies work.

Conclusions

Acknowledging the complexity of health management information system governance with constant adaptation can allow policymakers and senior managers to direct discretionary power where policy implementation would otherwise fail in the Tanzanian context. This can be achieved by identifying a set of social values around data processes that resonates with all actor groups and may support governance of this complex system.
Research Priorities of Individuals and Families with Sex Chromosome Aneuploidies
Authors: Carl Alexandra , Bothwell Samantha , Farah Fathia , Swenson Karli , Hong David , Prakash Siddharth , Strang John , Tartaglia Nicole , Raznahan Armin , Ross Judith ,   INSIGHTS Consortium,   GALAXY Consortium, Davis Shanlee
Published: August 2024

Sex chromosome aneuploidies (SCAs) are chromosomal variations that result from an atypical number of X and/or Y chromosomes. Combined, SCAs affect ~1/400 live births, including individuals with Klinefelter syndrome (47,XXY), Turner syndrome (45,X and variants), Double Y syndrome (47,XYY), Trisomy X (47,XXX), and rarer tetrasomies and pentasomies. Individuals with SCAs experience a wide variety of physical health, mental health, and healthcare experiences that differ from the standard population. To understand the priorities of the SCA community we surveyed participants in two large SCA registries, the Inspiring New Science in Guiding Healthcare in Turner Syndrome (INSIGHTS) Registry and the Generating Advancements in Longitudinal Analysis in X and Y Variations (GALAXY) Registry. 303/629 (48.1% response rate) individuals from 13 sites across the United States responded to the survey, including 251 caregivers and 52 self-advocates, with a range of ages from 3 weeks to 73 years old and represented SCAs including Turner syndrome, XXX, XXY, XYY, XXYY, and combined rare tetrasomies and pentasomies. Results demonstrate the priorities for physical health and emotional/behavioral health identified by the SCA community, as well as preferred types of research. All SCA subtypes indicated intervention studies as the top priority, emphasizing the need for researchers to focus on clinical treatments in response to priorities of the SCA community.

STATEMENTS RELATING TO ETHICS AND INTEGRITY POLICIES

The data that support the findings of this study are available on request from the corresponding author. This study was funded by the Turner Syndrome Global Alliance, Association for X and Y Chromosome Variations, Living with XXY, the XXYY Project, and the University of Colorado School of Medicine Department of Pediatrics. Data collection and storage was supported by NIH/NCATS Colorado CTSA Grant Number UM1 TR004399. The authors do not have any conflicts of interest to disclose. This study was reviewed and approved by the Colorado Multiple Institutional Review Board (COMIRB # 20-0482 and # 19-3027). All participants provided informed consent for participation - participants under 18 years old provided assent along with parental informed consent prior to any study procedures. Contents are the authors’ sole responsibility and do not necessarily represent official NIH views.
Self-reported access to specialty clinics and receipt of health surveillance among U.S. patients with neurofibromatosis 1: A national survey
Authors: Merker Vanessa L. , Ma Yidan , Chibnik Lori B. , Radtke Heather B. , Kelts Kate , Yohay Kaleb , Ullrich Nicole J. , Plotkin Scott R. , Jordan Justin T.
Published: August 2024

Background

Neurofibromatosis 1 (NF1) is a rare, neurogenetic disorder predisposing individuals to central and peripheral nervous system tumors, as well as a wide range of other physical, neurocognitive, and psychosocial issues. Regular health monitoring throughout the lifespan is needed to identify these heterogenous disease complications, but the degree to which this is implemented in routine clinical practice is unknown. This, this study aimed to investigate U.S. patients’ access to specialized NF1 clinics and receipt of evidence-informed health surveillance.

Methods

An online cross-sectional survey was distributed in May 2021 to adults with NF1 and parents of children with NF1 enrolled in the NF Registry (n=6908). Rate of NF1 clinic attendance and self-reported receipt of health surveillance amongst all NF Registry participants was estimated using inverse propensity scores. Differences in these outcomes based on participant demographics were assessed using weighted logistic regression and robust linear regression, respectively.

Results

322 individuals responded (160 adults, 162 parents; 4.7% overall response rate). We estimate that 51.7% of children and 35.6% of adults attend NF1 clinics. Younger children were more likely to attend an NF1 clinic, as were adults living in urban areas, with a college degree or higher, or with a household income ≥$130,000 (all ps<0.05). Completion rates for each individual health surveillance evaluation ranged from 41%-79% for children and 33%-61% for adults. Higher rates of recommended evaluations were reported by both adults and children who attend a specialized NF1 clinic, non-Hispanic White adults, and adults with commercial or Medicare insurance (all ps<0.05).

Discussion

Adults with NF1 experience significant sociodemographic disparities in care, and patients of all ages attending NF1 specialty clinics receive more recommended health surveillance. Given the limited access to specialty NF clinics, quality improvement efforts are needed to increase access for underserved adults and improve provision of recommended health surveillance outside specialty clinics.
Centimeter-scale, physiologically relevant intestinal organoids generated entirely from pluripotent stem cells
Authors: Qi Zhen , Zuo Zhanguang , Dong Yi , Shao Jingyu , Wang Chong , Zhang Rosanna
Published: August 2024

Over the past decade, intestinal organoids have shown great promise as a platform to study the development of intestine, elucidate the pathogenesis of diseases such as inflammatory bowel disease (IBD), and model physiological features of intestinal tissue for high-throughput drug screening. However, intestinal organoids derived from adult epithelial stem cells lack cellular diversity, especially those resides in the lamina propria. Intestinal organoids derived from embryonic stem (ES) cells or induced-pluripotent stem cells (iPSCs) has greater cellular diversity, but are still limited in size and physiological features such as peristalsis. In this study, we generated centimeter-scale, full-thickness, and physiologically relevant intestinal organoids in suspension culture without usage of Matrigel. Using a series of optimized culture media, multiple lineages of cells were differentiated from iPSCs and spontaneously assembled to achieve the intestinal architecture. These bubble-like organoids have a thickness of 500 microns, exhibit a mature vasculature network, and have smooth muscle-like cells to conduct regular peristalsis. In addition, adipocyte-like cells and granulocyte-like cells are also observed in these organoids, which are important in immune homeostasis. Lastly, these organoids show mature crypt structures, response to lipopolysaccharides (LPS), and increases luminal influx upon forskolin treatment, suggesting the organoids have intact epithelial integrity. Thus, this study provides a highly reproducible approach to produce large and physiologically relevant intestinal organoids that are suitable for different biomedical applications.
DNAAF9 (Shulin) and ARL3 regulate the transport and activation of ciliary Outer Dynein Arms (ODAs)
Authors: Issa Karim Housseini B , Ren Muyang , Burnet Bradley , Melia Charlotte , Heesom Kate , Mali Girish R.
Published: August 2024

Multiciliogenesis requires large-scale biosynthesis of motility-powering axonemal inner and outer dynein arm motors (IDA and ODA) prior to their intraflagellar transport (IFT) into cilia. ODAs are inhibited by the packaging chaperone Shulin during ciliogenesis inT. thermophila.How Shulin is released for ODAs to become active inside cilia remains unclear. We establish interactions between DNAAF9 (human Shulin) and mammalian ODA subunits, IFT proteins and the ciliary small GTPase ARL3 using proteomics andin vitroreconstitutions. Mutagenesis combined with biochemical and structural studies reveal that DNAAF9 and Shulin preferentially bind the active Arl3-GTP state. GTP-loaded Arl3 can access, bind and displace Shulin from the packaged ODA-Shulin complex. We propose that once the inhibited ODA complex enters growing cilia, Arl3-GTP displaces Shulin (DNAAF9) and sequesters it away from ODAs promoting activation of their motility specifically inside cilia.
Competition and Compromise between Exogenous Probiotics and Native Microbiota
Authors: Han Zhe , Sun Zheng , Zhao Qian , Du Lingwei , Zhen Dongyu , Liu Xinlei , Jiang Shuaiming , Liu Yang-Yu , Zhang Jiachao
Published: August 2024

Probiotic interventions are effective strategies to modulate the gut microbiome, but how exogenous probiotics compete with native gut microbiota remains elusive. Here, we use a mouse model and a well-documented probioticBifidobacterium animalissubsp. lactisV9 (BV9) to mechanistically investigate its competitive strategies. We perform metagenomic and whole genome sequencing of stool samples and isolated BV9, longitudinally collected from 24 mice orally administered with BV9 and different diets. Results show that a high-fiber diet most effectively supports the colonization of BV9, where BV9 selectively competes withParabacteroides distasonis(P. distasonis), rather than extensively with other gut bacteria. By comparing the genomic structures of BV9 andP. distasonisisolated during the washout period, we infer their co-evolution mechanisms, highlighting their competition and compromise in utilizing inulin-derived glucose. Finally, ourin vitroco-culture experiments validate such competitive dynamics. This study fills a critical gap in our understanding of niche competition in colonization.
Enhanced auxin signaling hub triggers root hair growth at moderate low temperature inArabidopsis thaliana
Authors: Gabarain Victoria Berdion , Núñez-Lillo Gerardo , Pěnčík Aleš , Ibeas Miguel Angel , Pacheco Javier Martínez , Lopez Leonel , Carignani Sardoy Mariana , Zhongtao Jia , Novák Ondřej , Giehl Ricardo F.H. , von Wiren Nicolaus , Meneses Claudio , Estevez José M.
Published: August 2024

Root hairs (RH) as a mixed tip- and non-tip growing protrusions that develop from root epidermal cells are important for nutrient and water uptake, root anchoring, and interaction with soil microorganisms. Although nutrient availability and temperature are critical interlinked factors for sustained plant growth, the molecular mechanisms underlying their sensing and downstream signaling pathways remain unclear. Here, we identified a moderate low temperature (10°C) condition that triggers a strong RH elongation response involving several molecular components of the auxin pathway. Then, we have determined that auxin biosynthesis carried out by YUCCAs/TAA1, the auxin transport conducted by PIN2/PIN4 and AUX1/PGP4, and the auxin signaling controlled by TIR1/AFB2 coupled to four specific ARFs (ARF6/ARF8 and ARF7/ARF19), are all crucial for the RH response at moderate low temperature. These results uncover the auxin pathway as one central hub under moderate low temperature in the roots to trigger RH growth. Our work highlights the importance of moderate low temperature stimulus as a complex nutritional signal from the media soil into the roots that may be fine-tuned for future biotechnological applications to enhance nutrient uptake.
Whole-brain dynamics of articulatory, acoustic and semantic speech representations
Authors: Verwoert Maxime , Amigó-Vega Joaquín , Gao Yingming , Ottenhoff Maarten C. , Kubben Pieter L. , Herff Christian
Published: August 2024

Speech production is a complex process that traverses several representations, from the meaning of spoken words (semantic), through the movement of articulatory muscles (articulatory) and, finally, to the produced audio waveform (acoustic). In our study, we aimed to identify how these different representations of speech are spatially and temporally distributed throughout the depth of the brain. By considering multiple representations from the same exact data, we can limit potential con-founders to better understand the different aspects of speech production and acquire crucial complementary information for speech brain-computer interfaces (BCIs). Intracranial speech production data was collected of 15 participants, recorded from 1647 electrode contacts, while they overtly spoke 100 unique words. The electrodes were distributed across the entire brain, including sulci and subcortical areas. We found a bilateral spatial distribution for all three representations, although there was a stronger tuning in the left hemisphere with a more widespread and temporally dynamic distribution than in the right hemisphere. The articulatory and acoustic representations share a similar spatial distribution surrounding the Sylvian fissure, while the semantic representation appears to be widely distributed across the brain in a mostly distinct network. These results highlight the distributed nature of the speech production process and the potential of non-motor representations for speech BCIs.
Coupling of secondary metabolite production inBacillus subtilis
Authors: Dinesen Caja , Vertot Manca , Jarmusch Scott A. , Lozano-Andrade Carlos N. , Andersen Aaron J.C. , Kovács Ákos T.
Published: August 2024

Although not essential for their growth, the production of secondary metabolites increases the fitness of the producing microorganisms in their natural habitat by enhancing establishment, competition and nutrient acquisition. The Gram-positive soil-dwelling bacterium,Bacillus subtilisproduces a variety of secondary metabolites. Here, we investigated the regulatory relationship between the non-ribosomal peptide surfactin and the sactipeptide bacteriocin subtilosin A. We discovered thatB. subtilismutants lacking surfactin production exhibited higher production of subtilosin A compared to their parental wild-type strain. Additionally, spatial visualization ofB. subtilisproduction of metabolites demonstrated that surfactin secreted by a wild-type colony could suppress subtilosin A production in an adjacent mutant colony lacking surfactin production. Reporter assays were performed using mutants in specific transcriptional regulators that confirmed the role of ResD as an activator of the subtilosin A encoding BGC, while removal or Rok and AbrB repressors increased expression of the BGC that was further enhanced by additional deletion of surfactin, suggesting that a so far unidentified regulator might mediate the influence of surfactin on production of subtilosin A. Our study reveals a regulatory influence of one secondary metabolite on another, highlighting that the function of secondary metabolites could be more complex than its influence on other organisms and interactions among secondary metabolites could also contribute to their ecological significance.

Importance

Secondary metabolites play an important role in the life of microorganisms facilitating their fitness in the environment, including competing against other microorganisms, interacting with their host or environment, and allowing expansion in their environment. However, secondary metabolites also function as cue molecules influencing gene expression between and within species. Here, we describe that the non-ribosomally synthesized peptide surfactin repress the production of ribosomally synthesized and post translationally modified peptide, subtilosin A inBacillus subtilis, revealing an ecological interaction between two secondary metabolites that could potentially influence the biocontrol efficiency ofB. subtilisstrain that depends on the production of these secondary metabolites against plant pathogen microorganisms.
Gray matter correlates of childhood maltreatment: searching for replicability in a multi-cohort brain-wide association study
Authors: Goltermann Janik , Winter Nils R , Meinert Susanne , Grotegerd Dominik , Kraus Anna , Flinkenflügel Kira , Altegoer Luisa , Krieger Judith , Leehr Elisabeth J , Böhnlein Joscha , Bonnekoh Linda M , Richter Maike , Hahn Tim , Fisch Lukas , Gruber Marius , Hermesdorf Marco , Berger Klaus , Arolt Volker , Brosch Katharina , Stein Frederike , Thomas-Odenthal Florian , Usemann Paula , Teutenberg Lea , Hammes Vincent , Jamalabadai Hamidreza , Alexander Nina , Straube Benjamin , Jansen Andreas , Nenadić Igor , Kircher Tilo , Opel Nils , Dannlowski Udo
Published: August 2024

Childhood maltreatment effects on cerebral gray matter have been frequently discussed as a neurobiological pathway for depression. However, localizations are highly heterogeneous, and recent reports have questioned the replicability of mental health neuroimaging findings. Here, we investigate the replicability of gray matter correlates of maltreatment (measured retrospectively via the Childhood Trauma Questionnaire) across three large adult cohorts (total N=3225). Pooling cohorts revealed maltreatment-related gray matter reductions, with most extensive effects when not controlling for depression diagnosis (maximum partial R2=.022). However, none of these effects significantly replicated across cohorts. Non-replicability was consistent across a variety of maltreatment subtypes and operationalizations, as well as subgroup analyses with and without depression, and stratified by sex. In this work we show that there is little evidence for the replicability of gray matter correlates of childhood maltreatment, when adequately controlling for psychopathology. This underscores the need to focus on replicability research in mental health neuroimaging.
Morpho-physiological and transcriptomic responses of field pennycress to waterlogging
Authors: Combs-Giroir Rachel , Shah Manesh , Chhetri Hari , Morgan Mallory , Prates Erica , Townsend Alice , Phippen Mary E. , Phippen Winthrop B. , Jacobson Daniel A. , Gschwend Andrea R.
Published: August 2024

Field pennycress (Thlaspi arvense) is a new biofuel winter annual crop with extreme cold hardiness and a short life cycle, enabling off-season integration into corn and soybean rotations across the Midwest. Pennycress fields are susceptible to winter snow melt and spring rainfall, leading to waterlogged soils. The objective of this research was to determine if waterlogging during the reproductive stage had a significant effect on gene expression, morphology, physiology, recovery, and yield of two pennycress lines (SP32-10 and MN106). In a controlled environment, total pod number, shoot/root dry weight, and total seed count/weight were significantly reduced in SP32-10 in response to waterlogging, whereas primary branch number, shoot dry weight, and single seed weight were significantly reduced in MN106. This indicated waterlogging had a greater negative impact on seed yield in SP32-10 than MN106. The number of differentially expressed genes (DEGs) between waterlogged and control roots were doubled in MN106 (3,424) compared to SP32-10 (1,767). Functional enrichment analysis of upregulated DEGs revealed Gene Ontology (GO) terms associated with hypoxia and decreased oxygen, with genes in these categories involved in alcoholic fermentation and glycolysis. Interestingly, MN106 waterlogged roots exhibited significant stronger upregulation of these genes than SP32-10. Additionally, downregulated DEGs revealed GO terms associated with cell wall biogenesis and secondary metabolite biogenesis, indicating suppressed growth and energy conservation. Together, these results reveal the reconfiguration of cellular and metabolic processes in response to the severe energy crisis invoked by waterlogging in pennycress.
Implementation and calibration of spectroscopic single-molecule localization microscopy
Authors: Brenner Benjamin , Yeo Wei-Hong , Lee Youngseop , Kweon Junghun , Sun Cheng , Zhang Hao F.
Published: August 2024

Spectroscopic single-molecule localization microscopy (sSMLM) allows multi-color super-resolution images with high spectral sensitivity. In this protocol, we provide essential information for researchers to implement sSMLM in a laboratory setting. We describe how to assemble and align the illumination and detection paths of a 3D dual-wedge prism (DWP)-based sSMLM instrument. We provide detailed step-by-step instructions for performing spectral and axial calibration using fluorescent beads and a nanohole array, respectively. We also discuss using sSMLM to image fluorescently labeled cells and report a new MATLAB package, RainbowSTORM v2, to reconstruct super-resolution 3D images. Further, we present representative images as typical anticipated results for users to validate.
Allele-specific transcription factor binding across human brain regions offers mechanistic insight into eQTLs
Authors: Anderson Ashlyn G. , Moyers Belle A. , Loupe Jacob M. , Rodriguez-Nunez Ivan , Felker Stephanie A. , Lawlor James M.J. , Bunney William E. , Bunney Blynn G. , Cartagena Preston M. , Sequeira Adolfo , Watson Stanley J. , Akil Huda , Mendenhall Eric M. , Cooper Gregory M. , Myers Richard M.
Published: August 2024

Transcription factors (TFs) regulate gene expression by facilitating or disrupting the formation of transcription initiation machinery at particular genomic loci. Because TF occupancy is driven in part by recognition of DNA sequence, genetic variation can influence TF–DNA associations and gene regulation. To identify variants that impact TF binding in human brain tissues, we assessed allele-specific binding (ASB) at heterozygous variants for 94 TFs in nine brain regions from two donors. Leveraging graph genomes constructed from phased genomic sequence data, we compared ChIP-seq signals between alleles at heterozygous variants within each brain region and identified thousands of variants exhibiting ASB for at least one TF. ASB reproducibility was measured by comparisons between independent experiments both within and between donors. We found that rare alleles in the general population more frequently led to reduced TF binding, whereas common alleles had an equal likelihood of increasing or decreasing binding. Further, for ASB variants in predicted binding motifs, the favored allele tended to be the one with the stronger expected motif match, but this concordance was not observed within highly occupied sites. We also found that neuron-specificcis-regulatory elements (cCREs), in contrast with oligodendrocyte-specific cCREs, showed depletion of ASB variants. We identified 2670 ASB variants associated with evidence for allele-specific gene expression in the brain from GTEx data and observed increasing eQTL effect direction concordance as ASB significance increases. These results provide a valuable and unique resource for mechanistic analysis ofcis-regulatory variation in human brain tissue.
Widespread natural selection on metabolite levels in humans
Authors: Timasheva Yanina , Lepik Kaido , Liska Orsolya , Papp Balázs , Kutalik Zoltán
Published: August 2024

Natural selection acts ubiquitously on complex human traits, predominantly constraining the occurrence of extreme phenotypes (stabilizing selection). These constraints propagate to DNA sequence variants associated with traits under selection. The genetic signatures of such evolutionary events can thus be detected via combining effect size estimates from genetic association studies and the corresponding allele frequencies. Although this approach has been successfully applied to high-level traits, the prevalence and mode of selection acting on molecular traits remain poorly understood. Here, we estimate the action of natural selection on genetic variants associated with metabolite levels, an important layer of molecular traits. By leveraging summary statistics of published genome-wide association studies with large sample sizes, we find strong evidence of stabilizing selection for 15 out of 97 plasma metabolites, with nonessential amino acids displaying especially strong selection signatures. Mendelian randomization analysis reveals that metabolites under stronger stabilizing selection display larger effects on a range of clinically relevant complex traits, suggesting that maintaining a disease-free profile may be an important source of selective constraints on the metabolome. Metabolites under strong stabilizing selection in humans are also more conserved in their concentrations among diverse mammalian species, suggesting shared selective forces across micro- and macroevolutionary timescales. Overall, this study demonstrates that variation in metabolite levels among humans is frequently shaped by natural selection and this may act through their causal impact on disease susceptibility.
Colibactin leads to a bacteria-specific mutation pattern and self-inflicted DNA damage
Authors: Lowry Emily , Wang Yiqing , Dagan Tal , Mitchell Amir
Published: August 2024

Colibactin produced primarily byEscherichia colistrains of the B2 phylogroup cross-links DNA and can promote colon cancer in human hosts. Here, we investigate the toxin's impact on colibactin producers and on bacteria cocultured with producing cells. Using genome-wide genetic screens and mutation accumulation experiments, we uncover the cellular pathways that mitigate colibactin damage and reveal the specific mutations it induces. We discover that although colibactin targets A/T-rich motifs, as observed in human colon cells, it induces a bacteria-unique mutation pattern. Based on this pattern, we predict that long-term colibactin exposure will culminate in a genomic bias in trinucleotide composition. We test this prediction by analyzing thousands ofE. coligenomes and find that colibactin-producing strains indeed show the predicted skewness in trinucleotide composition. Our work reveals a bacteria-specific mutation pattern and suggests that the resistance protein encoded on the colibactin pathogenicity island is insufficient in preventing self-inflicted DNA damage.
Chicken Immunization followed by RNA Extraction and cDNA Synthesis for Antibody Library Preparation
Authors: Yang Hyunji , Chae Jisu , Kim Hyori , Noh Jinsung , Chung Junho
Published: August 2024

Effective isolation of specific antibodies from immunological repertoires requires the generation of a diverse library against a specific antigen of interest, as well as efficient selection procedures, such as bio-panning and phage ELISA. Key to this is the generation of a good immune response in the host, followed by preparation of high-quality RNA and cDNA from which a library can be constructed by the amplification and cloning of immunoglobulin heavy and light chain genes. The first step in the construction of such an “immune library” is a successful course of immunization. Detection of a strong serum antibody titer will theoretically then result in a pool of extracted RNA that is enriched for transcripts of genes encoding the antibody of interest. Chicken antibodies have been widely used for research and diagnostic purposes, largely because of both their cross-reactivity to epitopes shared by humans, mice, primates, and other mammals, and their simple characteristics, with chickens featuring single functional copies ofVH/JHandVλ/Jλgene pairs. In chickens, antibodies against an antigen of interest can be detected in the serum as soon as 5–7 d after immunization. Once the antibody titer reaches an appropriate level in the serum, the spleen, bursa of Fabricius, and bone marrow are then harvested, and antibody libraries can be prepared from extracted RNA. Here, we describe a protocol for chicken immunization with an antigen of interest, followed by RNA extraction from the relevant tissues and cDNA synthesis, which users can use for antibody library construction.
Preparation of VCSM13 Helper Phage for Display Library Reamplification and Bio-Panning
Authors: Yang Hyunji , Chae Jisu , Kim Hyori , Noh Jinsung , Chung Junho
Published: August 2024

Phage-displayed antibody libraries can be constructed using any species that is easily immunized. The pComb3XSS phagemid vector is commonly used for library cloning and phage display. This phagemid encodes the origin of replication of the filamentous bacteriophage f1 but lacks all the genes required for replication and assembly of phage particles. The replication and the assembly of phage from these phagemids thus requires a “helper” phage that provides the genes essential for those steps during library production and bio-panning. One of those helper phages is VCSM13. In this protocol, we describe the preparation of VCSM13 helper phage. Users should prepare VCSM13 helper phage for library reamplification and for bio-panning.
Measuring differential particle correlations in relativistic nuclear collisions
Authors: Magdy Niseem
Published: August 2024

This study explores the transverse momentum (pT) dependencies of symmetric and asymmetric correlations (SC and ASC) with one and two particles of interest in Au+Au collisions at 200 GeV. Leveraging a multiphase transport (AMPT) model, the investigation delves into the sensitivity of these correlations to the final state effects, providing valuable insights into their potential for constraining the final state effects' pT dependencies. The HIJING model is employed as a benchmark for nonflow correlations, shedding light on their impact on interpreting SC and ASC data. Moreover, the study points out that differential SC and ASC with one and two particles of interest (POIs) typically incorporate contributions from event-plane angle fluctuations. Consequently, this work highlights the significance of SC and ASC with one and two POIs as valuable tools for investigating the pT nature of the final state effects and advocates for comprehensive experimental measurements across various beam energies and system sizes to enhance understanding and provide additional constraints for theoretical models.

Published by the American Physical Society
2024
From area metric backgrounds to the cosmological constant and corrections to the Polyakov action
Authors: Borissova Johanna , Ho Pei-Ming
Published: August 2024

Area metrics and area metric backgrounds provide a unified framework for quantum gravity. They encode physical degrees of freedom beyond those of a metric. These nonmetric degrees of freedom must be suppressed by a potential at sufficiently high energy scales to ensure that in the infrared regime classical gravity is recovered. On this basis, we first study necessary and sufficient algebraic conditions for an area metric to be induced by a metric. Second, we consider candidate potentials for the area metric and point out a possible connection between the reduction of area metric geometry to metric geometry on the one hand, and the smallness of the cosmological constant on the other. Finally, we consider modifications of the Nambu-Goto action for a string from a metric background to an area metric background. We demonstrate that area metric perturbations introduce an interaction corresponding to a singular vertex operator in the classically equivalent Polyakov action. The implications of these types of vertex operators for the quantum theory remain to be understood.

Published by the American Physical Society
2024
Lattice Realization of Complex Conformal Field Theories: Two-Dimensional Potts Model with
Q>4
States
Authors: Jacobsen Jesper Lykke , Wiese Kay Jörg
Published: August 2024

The two-dimensional Q-state Potts model with real couplings has a first-order transition for Q>4. We study a loop-model realization in which Q is a continuous parameter. This model allows for the collision of a critical and a tricritical fixed point at Q=4, which then emerge as complex conformally invariant theories at Q>4, or even complex Q, for suitable complex coupling constants. All critical exponents can be obtained as analytic continuation of known exact results for Q≤4. We verify this scenario in detail for Q=5 using transfer-matrix computations.

Published by the American Physical Society
2024
Bilayer Crystals of Trapped Ions for Quantum Information Processing
Authors: Hawaldar Samarth , Shahi Prakriti , Carter Allison L. , Rey Ana Maria , Bollinger John J. , Shankar Athreya
Published: August 2024

Trapped-ion systems are a leading platform for quantum information processing, but they are currently limited to 1D and 2D arrays, which imposes restrictions on both their scalability and their range of applications. Here, we propose a path to overcome this limitation by demonstrating that Penning traps can be used to realize remarkably clean bilayer crystals, wherein hundreds of ions self-organize into two well-defined layers. These bilayer crystals are made possible by the inclusion of an anharmonic trapping potential, which is readily implementable with current technology. We study the normal modes of this system and discover salient differences compared to the modes of single-plane crystals. The bilayer geometry and the unique properties of the normal modes open new opportunities—in particular, in quantum sensing and quantum simulation—that are not straightforward in single-plane crystals. Furthermore, we illustrate that it may be possible to extend the ideas presented here to realize multilayer crystals with more than two layers. Our work increases the dimensionality of trapped-ion systems by efficiently utilizing all three spatial dimensions, and it lays the foundation for a new generation of quantum information processing experiments with multilayer 3D crystals of trapped ions.

Published by the American Physical Society
2024
What decision-making process do mHealth users go through when faced with privacy disclosure behaviors? A dual trade-off perspective
Authors: Xin Hao , Liu FengTao , Wei ZiXiang
Published: August 2024

Purpose

This paper proposes that the trade-off between medical benefits and privacy concerns among mHealth users extends to their disclosure intentions, manifested as individuals simultaneously holding intentions to tend to disclose in the near future and to reduce disclosure in the distant future. Consequently, this paper aims to explore the privacy decision-making process of mHealth users from the perspective of a dual trade-off.

Design/methodology/approach

This paper constructs the model using the privacy calculus theory and the antecedent-privacy concern-outcome framework. It employs the construal level theory to evaluate the impact of privacy calculus on two types of disclosure intentions. The study empirically tests the model using a data sample of 386 mHealth users.

Findings

The results indicate that perceived benefits positively affect both near-future and distant-future disclosure intentions. In contrast, perceived risks just negatively affect distant-future disclosure intention. Additionally, perceived benefits, near-future and distant-future disclosure intentions positively affect disclosure behavior. The findings also reveal that privacy management perception positively affects perceived benefits. Personalized services and privacy invasion experience positively affect perceived benefits and risks, while trust negatively affects perceived risks.

Originality/value

This paper considers the trade-off in the privacy calculus phase as the first trade-off. On this basis, this trade-off will extend to the disclosure intention. The individuals’ two times of trade-offs between privacy concerns and medical benefits constitute the dual trade-off perspective. This paper first uses this perspective to explore the privacy decision-making process of mHealth users. This paper employs the construal level theory to effectively evaluate the impact of privacy calculus on both disclosure intentions in mHealth, extending the theory’s applicability. Moreover, we introduce antecedents of privacy calculus from the perspectives of platform, society, and individuals, enhancing the study’s realism. The research findings provide a basis for mHealth platforms to better cater to users’ privacy needs.
When the well is full, it will run over: the double-edged sword effect of corporate lobbying activities on firm performance
Authors: Xiao Shufeng , Jiménez Alfredo , Jung Sukyoon , Park Byung Il , Choi Seong Jin
Published: August 2024

Purpose

How much variance in firm performance can be attributed to firms’ corporate political activities (CPA)? Under what conditions does CPA contribute to firm performance? To theorize and empirically tackle these questions, we build on the resource-based view (RBV) to theorize how CPA might improve or hinder firm performance, and specifically examine the direct relationship between firms’ investments in lobbying activities and their performance. We also expect firm growth rate to moderate the relationship between lobbying and performance.

Design/methodology/approach

We empirically test our hypotheses using large-scale longitudinal panel data from publicly traded US firms from 2008 to 2018.

Findings

Our analyses support our predictions of the double-edged sword effect of lobbying on firm performance. Moreover, our results show that this effect is steeper for firms with higher growth rates.

Originality/value

Our study contributes meaningful insights to strategy scholarship on the influence of nonmarket strategies, highlighting the relevance of firm-specific conditions in shaping the performance outcomes of such strategies. In particular, we make a contribution by identifying a nonlinear relationship between lobbying and firm performance, which is amplified in fast-growing firms compared to stagnant ones.
ConjunctiveNet: an improved deep learning-based conjunctive-eyes segmentation and severity detection model
Authors: Pahwa Seema , Kaur Amandeep , Dhiman Poonam , Damaševičius Robertas
Published: August 2024

Purpose

The study aims to enhance the detection and classification of conjunctival eye diseases' severity through the development of ConjunctiveNet, an innovative deep learning framework. This model incorporates advanced preprocessing techniques and utilizes a modified Otsu’s method for improved image segmentation, aiming to improve diagnostic accuracy and efficiency in healthcare settings.

Design/methodology/approach

ConjunctiveNet employs a convolutional neural network (CNN) enhanced through transfer learning. The methodology integrates rescaling, normalization, Gaussian blur filtering and contrast-limited adaptive histogram equalization (CLAHE) for preprocessing. The segmentation employs a novel modified Otsu’s method. The framework’s effectiveness is compared against five pretrained CNN architectures including AlexNet, ResNet-50, ResNet-152, VGG-19 and DenseNet-201.

Findings

The study finds that ConjunctiveNet significantly outperforms existing models in accuracy for detecting various severity stages of conjunctival eye conditions. The model demonstrated superior performance in classifying four distinct severity stages – initial, moderate, high, severe and a healthy stage – offering a reliable tool for enhancing screening and diagnosis processes in ophthalmology.

Originality/value

ConjunctiveNet represents a significant advancement in the automated diagnosis of eye diseases, particularly conjunctivitis. Its originality lies in the integration of modified Otsu’s method for segmentation and its comprehensive preprocessing approach, which collectively enhance its diagnostic capabilities. This framework offers substantial value to the field by improving the accuracy and efficiency of conjunctival disease severity classification, thus aiding in better healthcare delivery.