bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards a new standard in genomic data privacy: a realization of owner-governance
Authors: Zhang Jingcheng , Ren Yingxuan , Au Man Ho , Chow Ka-Ho , Zhou Yekai , Chen Lei , Zhao Yanmin , Su Junhao , Luo Ruibang
Published: July 2024

With the rapid developments in sequencing technologies, individuals now have unprecedented access to their genomic data. However, existing data management systems or protocols are inadequate for protecting privacy, limiting individuals’ control over their genomic information, hindering data sharing, and posing a challenge for biomedical research. To fill the gap, an owner-governed system that fulfills owner authority, lifecycle data encryption, and verifiability at the same time is prompted. In this paper, we realized Governome, an owner-governed data management system designed to empower individuals with absolute control over their genomic data during data sharing. Governome uses a blockchain to manage all transactions and permissions, enabling data owners with dynamic permission management and to be fully informed about every data usage. It uses homomorphic encryption and zero-knowledge proofs to enable genomic data storage and computation in an encrypted and verifiable form for its whole lifecycle. Governome supports genomic analysis tasks, including individual variant query, cohort study, GWAS analysis, and forensics. Query of a variant’s genotype distribution among 2,504 1kGP individuals in Governome can be efficiently completed in under 18 hours on an ordinary server. Governome is an open-source project available athttps://github.com/HKU-BAL/Governome.
Mechanisms of Anammox Adaptation to High Temperatures: Increased Cyclization of Ladderane Lipids and Proteomic Insights
Authors: Christina Karmann , Klára Navrátilová , Adam Behner , Tayyaba Noor , Stella Danner , Anastasia Majchrzak , Jiří Šantrůček , Tomáš Podzimek , Marco A. Marin Lopez , Jana Hajšlová , Petra Lipovová , Jan Bartáček , Vojtěch Kouba
Published: July 2024

Abstract Figure

Graphical abstract

Although anammox-based processes have been widely applied in mesophilic conditions of reject water and recently in mainstream conditions, the potential of their implementation in high-temperature wastewaters remains largely unexplored. Therefore, this study investigated the operation parameters for the successful adaptation of anammox bacteria and the mechanisms involved on the proteomic and cellular level including unique ladderane lipids. For this purpose, the enrichment of ‘CandidatusBrocadia’ was cultivated in two fed-batch reactors (FBRs) at a lab scale. The temperature of one FBR was gradually increased from 30 to 40 °C while the other FBR was maintained at 30 °C with four consecutive replicates of this experiment. For this adaptation to be successful, the original loading rate had to be at least halved, or ideally maintained below half the value of the specific anammox activity at the time. The most notable adaptation mechanisms included: (1) upregulation of chaperones and (2) doubled ladderane cyclization via the replacement of non-ladderane fatty acid by a ladderane fatty acid in ladderane lipids (p-value 0.005). To our best knowledge, this is the first study to describe the novel mechanism of ladderane cyclization which together with other adaptation strategies presents crucial indicators in anammox adaptation to high-temperature wastewaters.
Genetic evolution of keratinocytes to cutaneous squamous cell carcinoma
Authors: Tandukar Bishal , Deivendran Delahny , Chen Limin , Cruz-Pacheco Noel , Sharma Harsh , Xu Albert , Bandari Aravind K. , Chen Daniel B. , George Christopher , Marty Annika , Cho Raymond J. , Cheng Jeffrey , Saylor Drew , Gerami Pedram , Arron Sarah T. , Bastian Boris C. , Shain A. Hunter
Published: July 2024

We performed multi-omic profiling of epidermal keratinocytes, precancerous actinic keratoses, and squamous cell carcinomas to understand the molecular transitions during skin carcinogenesis. Single-cell mutational analyses of normal skin cells showed that most keratinocytes have remarkably low mutation burdens, despite decades of sun exposure, however keratinocytes withTP53orNOTCH1mutations had substantially higher mutation burdens. These observations suggest that wild-type keratinocytes (i.e. without pathogenic mutations) are able to withstand high dosages of cumulative UV radiation, but certain pathogenic mutations break these adaptive mechanisms, priming keratinocytes for transformation by increasing their mutation rate. Mutational profiling of squamous cell carcinomas adjacent to actinic keratoses revealedTERTpromoter andCDKN2Amutations emerging in actinic keratoses, whereas additional mutations inactivatingARID2and activating the MAPK-pathway delineated the transition to squamous cell carcinomas. Surprisingly, actinic keratoses were often not related to their neighboring squamous cell carcinoma, indicating that collisions of unrelated neoplasms are common in the skin. Spatial variation in gene expression patterns was common in both tumor and immune cells, with high expression of checkpoint molecules at the invasive front of tumors. In conclusion, this study catalogues the key events during the evolution of cutaneous squamous cell carcinoma.
Beware of Data Leakage from Protein LLM Pretraining
Authors: Hermann Leon , Fiedler Tobias , Nguyen Hoang An , Nowicka Melania , Bartoszewicz Jakub M.
Published: July 2024

Pretrained protein language models are becoming increasingly popular as a backbone for protein property inference tasks such as structure prediction or function annotation, accelerating biological research. However, related research oftentimes does not consider the effects of data leakage from pretraining on the actual downstream task, resulting in potentially unrealistic performance estimates. Reported generalization might not necessarily be reproducible for proteins highly dissimilar from the pretraining set. In this work, we measure the effects of data leakage from protein language model pretraining in the domain of protein thermostability prediction. Specifically, we compare two different dataset split strategies: a pretraining-aware split, designed to avoid similarity between pretraining data and the held-out test sets, and a commonly-used naive split, relying on clustering the training data for a downstream task without taking the pretraining data into account. Our experiments suggest that data leakage from language model pretraining shows consistent effects on melting point prediction across all experiments, distorting the measured performance. The source code and our dataset splits are available athttps://github.com/tfiedlerdev/pretraining-aware-hotprot.
Expression and characterization of the complete cyanophage genome PP in the heterologous hostSynechococcus elongatusPCC 7942
Authors: Li Guorui , Feng Jia , Zhu Xiaofei , Chai Yujie , Sun Tao , Jiang Jianlan
Published: July 2024

Cyanophages are considered a promising biological management option for treating cyanobacterial blooms. Broadening the host range of cyanophages and/or shortening the lysis cycle by designing and synthesizing artificial cyanophages are potential strategies to enhance their effectiveness and efficiency. However, the rescue of artificial cyanophage genomes remains unexplored. In this study, we achieved the integration of a full-length cyanophage genome, PP, which originally infectsPlectonema boryanumFACHB-240, into the model cyanobacteriumSynechococcus elongatusPCC 7942. Since the integration of these large fragments (∼42 kb) into cyanobacteria depended on conjugation viaEscherichia coli, the toxic open reading frames (ORFs) of PP toE. coliwere first identified, leading to the identification of toxic ORF6, ORF11, and ORF22. The original PP genome was then rearranged, and the three toxic ORFs were controlled using a tandem induction switch. The full length of the PP genome was integrated into the genome ofS. elongatusPCC 7942 via two rounds of homologous recombination.

Interestingly, compared to the control strain, the integration of the PP genome decreased photosynthesis and carbon fixation inS. elongatusPCC 7942, exhibiting cyanophage-like behavior. Transcriptomic analysis revealed that 32 of the 41 ORFs of the PP genome were transcribed inS. elongatusPCC 7942, significantly altering the energy metabolism and carbon fixation pathways. These influences were further demonstrated using metabolomics. This study provides a comprehensive approach for the artificial design and integration of cyanophage genomes in cyanobacteria, laying the foundation for their real rescue in the future.
Seumetry: a versatile and comprehensive R toolkit to accelerate high-dimensional flow and mass cytometry data analysis
Authors: Borggrewe Malte , Flosbach Markus ,   Hamburg Intestinal Tissue Study Group, Bonn Stefan , Bunders Madeleine J.
Published: July 2024

Recent progress in flow and mass cytometry technologies enables the simultaneous measurement of over 50 parameters for an individual cell. The resulting increase in data volume and complexity present challenges, as conventional analysis methods based on manual gating are time-consuming and fail to capture unknown or minor cell populations. Advances in single-cell RNA sequencing (scRNAseq) technologies have prompted the development of sophisticated computational analysis tools specifically designed to process and analyze high-dimensional biological data, some of which could significantly improve certain aspects of cytometry data analysis. Building on these advances, we here present Seumetry, a framework that combines flow and mass cytometry data-specific analysis methods with the capabilities of Seurat, a powerful tool for the analysis of scRNAseq data. Seumetry offers advanced quality control, data visualizations, and differential population abundance and protein expression analysis. We tested Seumetry on an in-house generated complex dataset of immune cells from different layers of human intestines, demonstrating that Seumetry accurately identifies distinct immune cell populations. Furthermore, using a publicly available mass cytometry dataset, Seumetry recapitulates previously published results, further validating its use for high-dimensional flow and mass cytometry data. In summary, Seumetry provides a new scalable framework for the comprehensive analysis of high-dimensional cytometry data with seamless integration into commonly used scRNAseq analysis tools, enabling in-depth analysis methods to facilitate biological interpretations.
A chemical-genetic system to rapidly inhibit the PP2A-B56 phosphatase
Authors: Allan LA , Corno A , Valverde JM , Toth R , Ly T , Saurin AT
Published: July 2024

Abstract

Serine-threonine phosphatases have been challenging to study because of the lack of specific inhibitors. Their catalytic domains are druggable, but these are shared or very similar between individual phosphatase complexes, precluding their specific inhibition. Instead, phosphatase complexes achieve specificity by interacting with short-linear motifs (SLiMs) in substrates or their binding partners. We develop here a chemical-genetic system to rapidly inhibit these interactions within the PP2A-B56 family. Drug-inducible recruitment of ectopic SLiMs (“directSLiMs”) is used to rapidly block the SLiM-binding pocket on the B56 regulatory subunit, thereby displacing endogenous interactors and inhibiting PP2A-B56 activity within seconds. We use this system to characterise PP2A-B56 substrates during mitosis and to identify a novel role for PP2A-B56 in maintaining kinetochore-microtubule attachments at metaphase. The directSLiMs approach can be used to inhibit any other phosphatase, enzyme or protein that uses a critical SLiM-binding interface, providing a powerful strategy to inhibit and characterise proteins once considered .“undruggable”.
Whole-Body Networks: A Holistic Approach for Studying Aging
Authors: Stylianou Orestis , Meixner Johannes M. , Schlick Tilman , Krüger Colin M.
Published: July 2024

Aging is a multiorgan disease, yet the traditional approach is to study each organ in isolation. Such organ-specific studies allowed us to gather invaluable information regarding the pathomechanisms that contribute to senescence. But we believe that a big-picture exploration of the whole-body network (WBN) during aging could be complementary. In this study, we analyzed the functional magnetic resonance imaging (fMRI), breathing rate and heart rate time series of a young and an elderly group during eyes-open resting-state. By exploring the time-lagged coupling between the different organs we constructed WBNs. First, we showed that our analytical pipeline could identify regional differences in the networks of both populations, allowing us to proceed with the remaining of the analysis. By comparing the WBNs of young and elderly, a complex relationship emerged where some connections were stronger and some weaker in the elderly. Finally, the interconnectivity and segregation of the WBNs negatively correlated with the short-term memory of the young participants. This study:i) validated our methods,ii) identified differences between the two groups andiii) showed correlation with behavioral metrics. We are at the edge of a paradigm shift on how aging-related research is conducted and we believe that our methodology should be implemented in more complex mental and/or physical tasks to better demonstrate the alterations of WBNs as we age.
Personality development in wild house mice: Evidence for a nutrition-dependent sensitive period early in life
Authors: Walasek Nicole , Jovicic Milan , Guenther Anja
Published: July 2024

Changing environmental conditions pose serious challenges to organisms, for example, by disrupting access to food. Across species and traits, animals use phenotypic plasticity to rapidly adjust to such changes. Previous work has demonstrated that wild house mice are able to adjust stress coping to changing food quality within just three generations. However, we do not know when during ontogeny changing conditions induce phenotypic adjustments. We tested experimentally when during ontogeny (as fetus, newborn, weanling, or late adolescent) a food switch between standard and high-quality food shapes personality development (stress coping and stress perception) in cage-housed, wild house mice (Mus musculus domesticus). Personality traits were assessed in the Open Field and the Elevated Plus Maze at different time points during ontogeny (weaning, early adolescence, late adolescence, and adulthood). We observed three key findings. First, as mice grow older they tend to use more passive stress-coping strategies, indicating higher risk aversion. This relationship holds irrespective of food quality. However, mice fed with high-quality food show, on average, more active stress coping compared to mice receiving standard-quality food. Second, the fetal life stage might be a sensitive period for stress coping in response to experiencing decreases in nutritional quality. Third, experiencing an increase in nutritional quality may slow the age-related switch towards a passive stress-coping strategy. Our findings contrast previous work observing passive stress coping in mice living in semi-natural enclosures fed with high-quality food. We propose that the social environment of mice living in cages vs mice living in small groups may explain these differences. Our results highlight the need for experiments across the breadth of development comparing captive and semi-free-living animals. Ultimately, such studies will help us understand the complex relationships between development, nutrition, the (social) environment, and personality.
SLC45A4encodes a mitochondrial putrescine transporter that promotes GABAde novosynthesis
Authors: Colson Cecilia , Wang Yujue , Atherton James , Su Xiaoyang
Published: July 2024

Solute carriers (SLC) are membrane proteins that facilitate the transportation of ions and metabolites across either the plasma membrane or the membrane of intracellular organelles. With more than 450 human genes annotated as SLCs, many of them are still orphan transporters without known biochemical functions. We developed a metabolomic-transcriptomic association analysis, and we found that the expression of SLC45A4 has a strong positive correlation with the cellular level of γ-aminobutyric acid (GABA). Using mass spectrometry and the stable isotope tracing approach, we demonstrated that SLC45A4 promotes GABAde novosynthesis through the Arginine/Ornithine/Putrescine (AOP) pathway. SLC45A4 functions as a putrescine transporter localized to the mitochondrial membrane to facilitate GABA production. Taken together, our results revealed a new biochemical mechanism where SLC45A4 controls GABA production.
Δ133p53α and Δ160p53α isoforms of the tumor suppressor protein p53 exert dominant-negative effect primarily by co-aggregation
Authors: Zhao Liuqun , Punga Tanel , Sanyal Suparna
Published: July 2024

p53 is a tumor suppressor protein with multiple isoforms with shared or specific functions. However, two of its isoforms, Δ133p53α and Δ160p53α, with large N-terminal deletions, can cause cancer. These isoforms exert a dominant-negative effect on full-length p53 (FLp53), although the precise molecular mechanisms are unknown. Here, we investigate the mechanisms of action of Δ133p53α and Δ160p53α isoforms using chromatin immunoprecipitation, luciferase expression, subcellular fractionation, immunofluorescence assays, and apoptotic caspase activity assay. Our study elucidates that these DNA-binding deficient p53 isoforms form hetero-tetrameric complexes with FLp53 and disrupt FLp53’s DNA binding and transcriptional activities when present in a higher proportion than FLp53 in the tetramer. However, these structurally unstable isoforms promote vigorous protein aggregation involving FLp53, disrupting its structure and sequestering it in the cytoplasmic and nuclear aggregates, thereby limiting its availability to function as a transcription activator protein. Thus, co-aggregation of Δ133p53α and Δ160p53α with FLp53, rather than hetero-tetramerization, is likely the primary factor contributing to their dominant-negative effect. Modulating the stability and aggregation of p53 isoforms could be a novel strategy for cancer therapy.
Parental-effect gene-drive elements under partial selfing, or why doCaenorhabditisgenomes have hyperdivergent regions?
Authors: Rockman Matthew V.
Published: July 2024

Self-fertileCaenorhabditisnematodes carry a surprising number ofMedeaelements, alleles that act in heterozygous mothers and cause death or developmental delay in offspring that don’t inherit them. At some loci, both alleles in a cross operate as independentMedeas, affecting all the homozygous progeny of a selfing heterozygote. The genomic coincidence ofMedeaelements and ancient, deeply coalescing haplotypes, which pepper the otherwise homogeneous genomes of these animals, raises questions about how these apparent gene-drive elements persist for long periods of time. Here I investigate how mating system affects the evolution ofMedeas, and their paternal-effect counterparts,peels. Despite an intuition that antagonistic alleles should induce balancing selection by killing homozygotes, models show that, under partial selfing, antagonistic elements experience positive frequency dependence: the common allele drives the rare one extinct, even if the rare one is more penetrant. Analytical results for the threshold frequency required for one allele to invade a population show that a very weakly penetrant allele, one whose effects would escape laboratory detection, could nevertheless prevent a much more penetrant allele from invading under high rates of selfing. Ubiquitous weak antagonisticMedeasandpeelscould then act as localized barriers to gene flow between populations, generating genomic islands of deep coalescence. Analysis of gene expression data, however, suggest that this cannot be the whole story. A complementary explanation is that ordinary ecological balancing selection generates ancient haplotypes on whichMedeascan evolve, while high homozygosity in these selfers minimizes the role of gene drive in their evolution.
A nuclear RNA degradation code for eukaryotic transcriptome surveillance
Authors: Soles Lindsey V. , Liu Liang , Zou Xudong , Yoon Yoseop , Li Shuangyu , Tian Lusong , Valdez Marielle Cárdenas , Yu Angela , Yin Hong , Li Wei , Ding Fangyuan , Seelig Georg , Li Lei , Shi Yongsheng
Published: July 2024

The RNA exosome plays critical roles in eukaryotic RNA degradation, but it remains unclear how the exosome specifically recognizes its targets. The PAXT connection is an adaptor that recruits the exosome to polyadenylated RNAs in the nucleus, especially transcripts polyadenylated at intronic poly(A) sites. Here we show that PAXT-mediated RNA degradation is induced by the combination of a 5′ splice site and a poly(A) junction, but not by either sequence alone. These sequences are bound by U1 snRNP and cleavage/polyadenylation factors, which in turn cooperatively recruit PAXT. As the 5′ splice site-poly(A) junction combination is typically not found on correctly processed full-length RNAs, we propose that it functions as a “nuclear RNA degradation code” (NRDC). Importantly, disease-associated single nucleotide polymorphisms that create novel 5′ splice sites in 3′ untranslated regions can induce aberrant mRNA degradation via the NRDC mechanism. Together our study identified the first NRDC, revealed its recognition mechanism, and characterized its role in human diseases.
Coxsackievirus B infection invokes unique cell-type specific responses in primary human pancreatic islets
Authors: Veronese-Paniagua Daniel A. , Hernandez-Rincon Diana C. , Taylor Jared P. , Tse Hubert M. , Millman Jeffrey R.
Published: July 2024

Coxsackievirus B (CVB) infection has long been considered an environmental factor precipitating Type 1 diabetes (T1D), an autoimmune disease marked by loss of insulin-producing β cells within pancreatic islets. Previous studies have shown CVB infection negatively impacts islet function and viability but do not report on how virus infection individually affects the multiple cell types present in human primary islets. Therefore, we hypothesized that the various islet cell populations have unique transcriptional responses to CVB infection. Here, we performed single-cell RNA sequencing on human cadaveric islets treated with either CVB or poly(I:C), a viral mimic, for 24 and 48 hours. Our global analysis reveals CVB differentially induces dynamic transcriptional changes associated with multiple cell processes and functions over time whereas poly(I:C) promotes an immune response that progressively increases with treatment duration. At the single-cell resolution, we find CVB infects all islet cell types at similar rates yet induces unique cell-type specific transcriptional responses with β, α, and ductal cells having the strongest response. Sequencing and functional data suggest that CVB negatively impacts mitochondrial respiration and morphology in distinct ways in β and α cells, while also promoting the generation of reactive oxygen species. We also observe an increase in the expression of the long-noncoding RNAMIR7-3HGin β cells with high viral titers and reveal its knockdown reduces gene expression of viral proteins as well as apoptosis in stem cell-derived islets. Together, these findings demonstrate a cell-specific transcriptional, temporal, and functional response to CVB infection and provide new insights into the relationship between CVB infection and T1D.
Chiral mismatch in collagen-mimetic peptides modulates cell migration through integrin-mediated molecular recognition
Authors: Remson Alexandre , Dellemme David , Luciano Marine , Surin Mathieu , Gabriele Sylvain
Published: July 2024

Chirality influences essential biological processes such as molecular recognition and self- organization, impacting cell proliferation and differentiation mediated by interactions with the extracellular matrix (ECM). Despite extensive research on cell migration, the role of chirality on matrix-cell interactions has been largely overlooked. To explore this aspect, we engineered culture surfaces coated with natural collagen I or collagen-mimetic peptides (CMPs) with opposite chirality, i.e. with either L- or D-amino acids in their sequences. Here we show that D-surfaces impede epithelial keratocyte spreading, making cells more rounded, less adhesive, and slower. Further investigation through integrin inhibition assays and molecular dynamics simulations revealed that a chiral mismatch destabilizes the triple helix of heterochiral CMPs at the L/D junction. This study underscores the profound impact of ECM chirality on cellular behavior, providing new insights into the relationship between matrix (supra)molecular chirality, integrin-mediated molecular recognition, and cell migration dynamics.
Return to work and care use by long-COVID patients on Bonaire, Caribbean Netherlands: Are patients their needs met?
Authors: Berry DSF , Marchena G. , Tiemessen I. , Vegh A. , Jaspers L. , Geubbels E.
Published: July 2024

Background

Symptoms persisting ≥ 4 weeks after an acute SARS-CoV-2 infection (post-COVID condition, PCC) can have substantial consequences for the daily functioning and labor force participation of working age patients. We examined care consultations during PCC among patients on Bonaire, Caribbean Netherlands, identified activity limitations among patients who returned to work (RTW), and described the support that these patients indicated has or would have facilitated them in recovering and re-integrating.

Methods

Bivariate logistic regression was used to examine correlates of care consultations during PCC among 157 PCC patients on Bonaire, and to identify factors related to RTW among a subgroup of working age PCC patients with pre-pandemic employment (n=129). We applied in-depth qualitative analyses to assess patients’ lived experiences related to RTW and care during PCC.

Results

We found 37% of PCC patients consulted at least one (para)medical professional during PCC, of whom one in three consulted multiple professionals. 26% of patients recovered within one month since their acute infection; for patients unrecovered at time of interview, median time since infection was 249 days (IQR 30). Patients with comorbidity (OR=2.90, p<0.01, 95% CI [1.40-5.53]), under care prior to the pandemic (OR=2.52, p<0.01, 95% CI [1.30-4.95]), who had been hospitalized during the acute phase (OR=9.16, p<0.01, 95% CI [3.41, 29.21]), and patients who were aware that their insurance covered certain medical costs related to COVID-19 (after)care (OR=3.99, p<0.01, 95% CI [1.87, 8.81]) were more likely to consult care during PCC. Of patients who RTW (81%), 13% were working reduced hours, 35% experienced worsening of their symptoms after carrying out any physical or cognitive activity, and 40% encountered situations where they were unable to carry out work activities since they had COVID-19. Outside of the workplace, about one in four patients faced issues in sports activities and maintaining social relations since having COVID-19.

Discussion

Our findings highlight various factors related to care use during PCC by patients on Bonaire and patient identified needs related to support in the workplace and COVID-19 aftercare. Improving PCC related occupational and healthcare policies on Bonaire may prove beneficial for recovering patients their vitality and socio-economic vigor.
Clinical performance of cell free DNA for fetal RhD detection in RhD-negative pregnant individuals in the US
Authors: Mateus Nino Julio F. , Wynn Julia , Wiggins-Smith Jenny , Bryant J. Brett , Citty J. Kris , Citty J. Kyle , Ahuja Samir , Newman Roger
Published: July 2024

Objective

We aimed to evaluate the performance of a cell free DNA (cfDNA) assay that uses next generation sequencing (NGS) with quantitative counting templates (QCT) for the clinical detection of the fetal RHD genotype in a diverse RhD-negative pregnant population in the United States (US).

Study Design

This retrospective cohort study was conducted in four US healthcare centers. The same NGS QCT cfDNA fetal RhD assay was offered to non-alloimmunized, RhD-negative pregnant individuals as part of clinical care. Rh immune globulin (RhIG) was administered at the discretion of the provider. The assay’s sensitivity, specificity, and accuracy were calculated considering the neonatal RhD serology results.

Results

A total of 401 non-alloimunized RhD-negative pregnancies who received clinical care in the period from August 2020 to November 2023 were included in the analysis. The D antigen cfDNA result was 100% concordant with the neonatal serology, resulting in 100% sensitivity, 100% positive predictive value (both 95% CI: 98.6%-100%), 100% specificity, and 100% negative predictive value (both 95% CI: 97.4%-100%). There were 10 pregnancies where the cfDNA analysis identified a non-RHD gene deletion, including RhDΨ (n=5) and RHD-CE-D hybrid variants (n=5). RhIG was administered to 93% of pregnant individuals with cfDNA results indicating an RhD-positive fetus compared to 75% of pregnant individuals with cfDNA results indicating an RhD-negative fetus, signifying providers were using the results to guide pregnancy management.

Conclusion

This cfDNA analysis via NGS for detecting fetal RhD status is highly accurate with no false-positive or false-negative results in 401 racially and ethnically diverse pregnancies with 100% follow up of all live births. This study and prior studies of this assay support a recommendation to offer cfDNA screening for fetal Rh status as an alternative option to prophylactic RhIG for all non-alloimmunized RhD-negative individuals, which will result in more efficient and targeted prenatal care with administration of RhIG only when medically indicated.
Assessing Knowledge About Pregnancy Induced Hypertension Among Pregnant Women Attending Antenatal Care at Makole Health Center
Authors: Mrosso Dennis Francis , Dominick Baraka , Machimu Ally , Mwasi Hassan , Ramadhani Rehema , Daniel Tienyi Mnyoro
Published: July 2024

Aim

To assess the knowledge regarding pregnancy induced hypertension among pregnant mothers attending antenatal care at Makole health center.

Methods

Analytical cross-section study design involving 160 participants was conducted at Makole health center. Interviewer and self-administered structured questionnaire was used to assess the objectives of the study. coded, checked and then analyzed using Statistical Package for Social Science (SPSS) version 20 so as to develop descriptive statistical information presented inform of table, pie chart, histogram, and bar charts.

Results

Among 160 participants who were recruited in the study pregnant women aged 25 years or less constituted the majority 53(33.2%) with participants’ mean age of 22.61 with interquartile range of 18 to 43 years. Majority of the respondents had secondary education level 81 (50.6), while majority of the participants 111 (69.4%) were married. A greater proportion 101 (63.1%) of the pregnant women were Christians. With regard to occupational status, majority were self-employed 74(46.2%). While the majority of the respondents 126(78.8%) had low level of knowledge, 12(7.5%) had moderate level of knowledge and 22(13.8%) had high knowledge of pregnancy induced hypertension. The study found that the prevalence of PIH among pregnant women attending at Makole health center to be 8.1%.

Conclusion

Though the prevalence of pregnancy induced hypertension was low, a bigger proportion of these women did not have good knowledge of the disease and its complications. The study found that majority of those participants who were found to have experienced PIH had low level of knowledge. However, older pregnant women were ranging from moderate level of knowledge to high level of knowledge compared to the younger pregnant women whom majority of them had low level of knowledge. Also, health care providers should strengthen the awareness of pregnant women about pregnancy-induced hypertension in antenatal care clinics
The m6A Reader ECT1 Mediates Seed Germination via the DAG2-ECT1-PHYB Regulatory Cascade inArabidopsis
Authors: Li Zenglin , Ma Yuhang , Sun Wen , Ding Pengjun , Bu Yifan , Qi Yuhong , Jia Chengchao , Lei Beilei , Ma Chuang
Published: July 2024

TheN6-methyladenosine (m6A) RNA modification, a significant epitranscriptomic mark, is integral to plant growth and development. m6A reader proteins are capable of recognizing m6A modifications to impact RNA metabolic and biological processes. Here, we discovered ECT1 as an m6A reader protein that directly binds to the m6A site and plays a role in positively regulating seed germination in the context of gibberellins (GAs). ECT1 undergoes m6A modification to ensure its own stability and engages in self-interaction to enhance its protein stability. Moreover, ECT1 establishes a regulatory circuit with DAG2, which has been reported to play a positive regulatory role in GA-mediated seed germination. We found that DAG2 directly binds to theECT1promoter to control its transcription. ECT1 modulates the mRNA stability ofDAG2. Furthermore, we identifiedPHYB, which encodes a key photoreceptor controlling GA-regulated seed germination, as a common downstream target of DAG2 and ECT1. DAG2 and ECT1 regulate the expression ofPHYBat the transcriptional and post-transcriptional levels, respectively. ECT1 binds directly toPHYB, thereby influencing its stability. While DAG2 binds to thePHYBpromoter to regulate its transcription. Together, these results unveil that ECT1 participates in the m6A signaling pathway through complex and multifaceted molecular mechanisms, broadening the spectrum of m6A reader functions and deepening our insight into the m6A signaling network inArabidopsis.
Mapping the space of protein binding sites with sequence-based protein language models
Authors: Oruç Tuğçe , Kadukova Maria , Davies Thomas G. , Verdonk Marcel , Poelking Carl
Published: July 2024

Binding sites are the key interfaces that determine a protein’s biological activity, and therefore common targets for therapeutic intervention. Techniques that help us detect, compare and contextualise binding sites are hence of immense interest to drug discovery. Here we present an approach that integrates protein language models with a 3D tesselation technique to derive rich and versatile representations of binding sites that combine functional, structural and evolutionary information with unprecedented detail. We demonstrate that the associated similarity metrics induce meaningful pocket clusterings by balancing local structure against global sequence effects. The resulting embeddings are shown to simplify a variety of downstream tasks: they help organise the “pocketome” in a way that efficiently contextualises new binding sites, construct performant druggability models, and define challenging train-test splits for believable benchmarking of pocket-centric machine-learning models.
Compromised chronic efficacy of a Glucokinase Activator AZD1656 in mouse models for common humanGCKRvariants
Authors: Ford Brian E , Chachra Shruti S , Alshawi Ahmed , Oakley Fiona , Fairclough Rebecca J. , Smith David M , Tiniakos Dina , Agius Loranne
Published: July 2024

Glucokinase activators (GKAs) have been developed as blood glucose lowering drugs for type 2 diabetes. Despite good short-term efficacy, several GKAs showed a decline in efficacy chronically during clinical trials. The underlying mechanisms remain incompletely understood. We tested the hypothesis that deficiency in the liver glucokinase regulatory protein (GKRP) as occurs with common humanGCKRvariants affects chronic GKA efficacy. We used aGckr-P446L mouse model for theGCKRexonic rs1260326 (P446L) variant and theGckr-del/wt mouse to model transcriptional deficiency to test for chronic efficacy of the GKA, AZD1656 in GKRP-deficient states. In theGckr-P446L mouse, the blood glucose lowering efficacy of AZD1656 (3 mg/kg body wt) after 2 weeks was independent of genotype. However after 19 weeks, efficacy was maintained in wild-type but declined in the LL genotype, in conjunction with raised hepatic glucokinase activity and without raised liver lipids. Sustained blood glucose lowering efficacy in wild-type mice was associated with qualitatively similar but more modest changes in the liver transcriptome compared with the P446L genotype, consistent with GKA therapy representing a more modest glucokinase excess than the P446L genotype. Chronic treatment with AZD1656 in theGckr-del/wt mouse was associated with raised liver triglyceride and hepatocyte microvesicular steatosis. The results show that in mouse models of liver GKRP deficiency in conjunction with functional liver glucokinase excess as occurs in association with common humanGCKRvariants, GKRP-deficiency predisposes to declining efficacy of the GKA in lowering blood glucose and to GKA induced elevation in liver lipids.
Different Roles of D1/D2 Medium Spiny Neurons in the Nucleus Accumbens in Pair Bond Formation of Male Mandarin Voles
Authors: Zhang Lizi , Qu Yishan , Young Larry J , Hou Wenjuan , Liu Limin , Liu Jing , Wang Yuqian , Li Lu , Guo Xing , Li Yin , Huang Caihong , Lv Zijian , Li Yitong , Jia Rui , Lian Ting , Feng Hao , He Zhixiong , Tai Fadao
Published: July 2024

The mesolimbic dopamine (DA) system has been implicated in pair bond formation. However, involvements of DA release, real time activities, and electrophysiological activities of D1/D2 medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell in pair bonding remain unclear. This work verified that male mandarin voles after pair bonding released higher levels of DA in the NAc shell and displayed higher levels of D1 MSNs activity and lower levels of D2 MSNs activity upon sniffing their partners compared to upon sniffing an unknown female. Moreover, pair bonding induced differential alterations in both synaptic plasticity and neuronal intrinsic excitability in both D1 MSNs and D2 MSNs. In addition, chemogenetic inhibition of ventral pallidum (VP) -projecting D2 MSNs in the NAc shell enhanced pair bond formation, while chemogenetic activation of VP-projecting D2 MSNs in the NAc shell inhibited pair bond formation. These findings suggest that different neuronal activity of NAc shell D1 MSNs / D2 MSNs regulated by increasing DA release after pair bonding may be a neurobiological mechanism underlying pair bond formation.
Electron-temperature-gradient-driven ion-scale turbulence in high-performance scenarios in Wendelstein 7-X
Authors: Zocco Alessandro , Podavini Linda , Wilms Felix , Bañón Navarro Alejandro , Jenko Frank
Published: July 2024

Through intercode gyrokinetic numerical simulations, we predict that, for the conditions met during improved performances in the stellarator Wendelstein 7-X, turbulent transport can be dominated by electron-temperature-gradient-driven ion-scale electrostatic turbulence. We find that previously numerically observed large density-gradient-driven turbulence reductions must be attributed to the artificial suppression of the electron temperature gradient. Instead, when electrons have a finite temperature gradient, we observe a moderate turbulence suppression whose quantitative comparison with experimental findings remains challenging. In such partial suppression, the nonlinear dynamics of zonal flows plays a pivotal role as opposed to the underlying most unstable linear modes.

Published by the American Physical Society
2024
Pattern formation in odd viscoelastic fluids
Authors: Floyd Carlos , Dinner Aaron R. , Vaikuntanathan Suriyanarayanan
Published: July 2024

Nonreciprocal interactions fueled by local energy consumption can be found in biological and synthetic active matter at scales where viscoelastic forces are important. Such systems can be described by “odd” viscoelasticity, which assumes fewer material symmetries than traditional theories. Here we study odd viscoelasticity analytically and using lattice Boltzmann simulations. We identify a pattern-forming instability which produces an oscillating array of fluid vortices, and we elucidate which features govern the growth rate, wavelength, and saturation of the vortices. Our observation of pattern formation through odd mechanical response can inform models of biological patterning and guide engineering of odd dynamics in soft active matter systems.

Published by the American Physical Society
2024
Thermometry with a dissipative heavy impurity
Authors: Xie Dong , Xu Chunling
Published: July 2024

Improving the measurement precision of low temperature is significant in fundamental science and advanced quantum technology application. However, the measurement precision of temperature T usually diverges as T tends to zero. Here, by utilizing a heavy impurity to measure the temperature of a Bose gas, we obtain the Landau bound to precision δ2T∝T2 to avoid the divergence. When the initial momentum of the heavy impurity is close to be fixed and nonzero, the measurement precision can be δ2T∝T3 to break the Landau bound. We derive the momentum distribution of the heavy impurity at any moment and obtain the optimal measurement precision of the temperature by calculating the Fisher information. As a result, we find that increasing the expectation value P0 and reducing the variance Δ/2 of the initial momentum can help to improve the measurement precision. Moreover, under certain conditions, Δ/P0 is a relevant parameter, the smallness of which helps improve the thermometric precision of the probe. In addition, the momentum measurement is the optimal measurement of the temperature in the case that the initial momentum is close to be fixed and not equal to zero. The kinetic energy measurement is the optimal measurement in the case that the expectation value of the initial momentum is close to zero. Finally, we obtain that the temperatures of two Bose gases can be measured simultaneously. The simultaneous measurement precision is proportional to T2 when two temperatures are close to T.

Published by the American Physical Society
2024
Directional emission and photon bunching from a qubit pair in waveguide
Authors: Maffei Maria , Pomarico Domenico , Facchi Paolo , Magnifico Giuseppe , Pascazio Saverio , Pepe Francesco V.
Published: July 2024

Waveguide quantum electrodynamics represents a powerful platform to generate entanglement and tailor photonic states. We consider a pair of identical qubits coupled to a parity invariant waveguide in the microwave domain. By working in the one- and two-excitation sectors, we provide a unified view of decay processes and show the common origin of directional single-photon emission and two-photon directional bunching. Unveiling the quantum trajectories, we demonstrate that both phenomena are rooted in the selective coupling of orthogonal Bell states of the qubits with photons propagating in opposite directions. We comment on how to use this mechanism to implement optimized post-selection of Bell states, heralded by the detection of a photon on one side of the system.

Published by the American Physical Society
2024
High-Fidelity, Multiqubit Generalized Measurements with Dynamic Circuits
Authors: Ivashkov Petr , Uchehara Gideon , Jiang Liang , Wang Derek S. , Seif Alireza
Published: July 2024

Generalized measurements, also called positive operator-valued measures (POVMs), can offer advantages over projective measurements in various quantum information tasks. Here, we realize a generalized measurement of one and two superconducting qubits with high fidelity and in a single experimental setting. To do so, we propose a hybrid method, the “Naimark-terminated binary tree,” based on a hybridization of Naimark’s dilation and binary tree techniques that leverages emerging hardware capabilities for midcircuit measurements and feed-forward control. Furthermore, we showcase a highly effective use of approximate compiling to enhance POVM fidelity in noisy conditions. We argue that our hybrid method scales better toward larger system sizes than its constituent methods and demonstrate its advantage by performing detector tomography of symmetric, informationally complete POVM (SIC POVM). Detector fidelity is further improved through a composite error-mitigation strategy that incorporates twirling and a newly devised conditional readout error mitigation. Looking forward, we expect improvements in approximate compilation and hardware noise for dynamic circuits to enable generalized measurements of larger multiqubit POVMs on superconducting qubits.

Published by the American Physical Society
2024
Exploring the psychology of price barriers in Baltic stock markets
Authors: Lobão Júlio , Lopes João G.
Published: July 2024

Purpose

The purpose of this study is to investigate the presence of psychological barriers both in the main stock market indices of the Baltic states and the most actively traded individual stocks. A psychological barrier refers to a specific price point, often at round numbers (i.e. powers of 10), that investors believe is challenging to breach, influencing their behavior and trading decisions.

Design/methodology/approach

We conduct uniformity tests and barrier tests, such as barrier proximity tests and barrier hump tests, to evaluate the presence of psychological barriers. Additionally, we explore variations in means and variances near these potential barriers using regression and GARCH analysis.

Findings

The findings reveal that psychological barriers do exist in the Baltic stock markets, particularly within market indices. The Estonian market index stands out with the most pronounced indications of psychological barriers. Individual stocks also display significant changes in means and variances related to potential barriers, albeit with less uniformity.

Practical implications

Collectively, our findings challenge the traditional assumption of random returns within the Baltic stock markets. For practitioners, the finding that psychological barriers exist opens up opportunities for investment strategies that can capitalize on them.

Originality/value

This study is the first to comprehensively investigate psychological barriers in the Baltic stock markets. Our results provide a valuable contribution to understanding the impact of that phenomenon on pricing dynamics, which is particularly pertinent in less-researched frontier markets like the Baltic states.