bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dosimetry of [64Cu]FBP8: a fibrin-binding PET probe
Authors: Izquierdo-Garcia David , Désogère Pauline , Philip Anne L. , Sosnovik David E. , Catana Ciprian , Caravan Peter 
Published: June 2024

AbstractPurposeThis study presents the biodistribution, clearance and dosimetry estimates of [64Cu]Fibrin Binding Probe #8 ([64Cu]FBP8) in healthy subjects.ProceduresThis prospective study included 8 healthy subjects to evaluate biodistribution, safety and dosimetry estimates of [64Cu]FBP8, a fibrin-binding positron emission tomography (PET) probe. All subjects underwent up to 3 sessions of PET/Magnetic Resonance Imaging (PET/MRI) 0-2 hours, 4h and 24h post injection. Dosimetry estimates were obtained using OLINDA 2.2 software.ResultsSubjects were injected with ∼400 MBq of [64Cu]FBP8. Subjects did not experience adverse effects due to the injection of the probe. [64Cu]FBP8 PET images demonstrated fast blood clearance (half-life = 67 min) and renal excretion of the probe, showing low background signal across the body. The organs with the higher doses were: the urinary bladder (0.075 vs. 0.091 mGy/MBq for males and females, respectively); the kidneys (0.050 vs. 0.056 mGy/MBq respectively); and the liver (0.027 vs. 0.035 mGy/MBq respectively). The combined mean effective dose for males and females was 0.016 ± 0.0029 mSv/MBq, lower than the widely used [18F]fluorodeoxyglucose ([18F]FDG, 0.020mSv/MBq).ConclusionsThis study demonstrates the following properties of the [64Cu]FBP8 probe: low dosimetry estimates; fast blood clearance and renal excretion; low background signal; and whole-body acquisition within 20 minutes in a single session. These properties provide the basis for [64Cu]FBP8 to be an excellent candidate for whole-body non-invasive imaging of fibrin, an important driver/feature in many cardiovascular, oncological and neurological conditions
Quantitative detection of plant signaling peptides utilizing ELISA
Authors: König Maurice , Sorger Zarah , Doehlemann Gunther , Misas Villamil Johana C. 
Published: June 2024

AbstractPlant signaling peptides, also known as phytocytokines, are involved in a number of signaling mechanisms, including cell-to-cell communication during plant development and immunity. The detection of small peptides in plant tissues is challenging and often relies on time-consuming and cost-intensive approaches. Here, we present an ELISA-based assay as a rapid and cost-effective method for the detection of naturally released peptides in plant tissues. Our ELISA-based method was developed to detect Zip1, a 17-amino-acid phytocytokine derived fromZea maysthat elicits salicylic acid signaling in maize leaves. Using a custom peptide-antibody, we designed an experimental pipeline to achieve peptide specificity, selectivity and sensitivity allowing the detection of the Zip1 peptide in complex biological samples. As a proof of concept, we transfected maize protoplasts to overexpress the precursor molecule PROZIP1 and treated maize leaves with salicylic acid to induce native PROZIP1 expression and Zip1 release. Using ELISA, we were able to quantify native Zip1 signals with a detection limit in the nanogram range, which allowed us to detect different Zip1-containing peptides in plant material. This method can be adapted for the detection and quantification of a variety of plant signaling peptides.
Convergent evolution of sex chromosomes in palms
Authors: Tessarotto H. , Beulé T. , Cherif E. , Orjuela J. , Lindstrom A. , Lemansour A. , Dahme M. , Santoni S. , Käfer J. , Aberlenc F. 
Published: June 2024

AbstractWhile sex chromosomes often evolve in species with separate sexes through similar processes, there are also many differences in their evolutionary dynamics. In palms, a clade with 8-10 independent evolutionary origins of dioecy, sex chromosomes have hitherto been well characterized only in the date palm genusPhoenix. Using genome-wide target capture sequencing, we found that the same region independently became sex-linked both inPhoenixand in the rather distantly related speciesKerriodoxa elegans. Investigating the gene content of this region revealed it contains many genes involved in flower sex differentiation which might be the reason for this case of convergent evolution. This region, which could function as a “genetic toolbox” for the production of unisexual flowers or individuals, may have an ancestral functional importance in palm genomes.
Cryo-electron tomography pipeline for plasma membranes
Authors: Sun Willy W. , Michalak Dennis J. , Sochacki Kem A. , Kunamaneni Prasanthi , Alfonzo-Méndez Marco A. , Arnold Andreas M. , Strub Marie-Paule , Hinshaw Jenny E. , Taraska Justin W. 
Published: June 2024

AbstractCryo-electron tomography (cryoET) provides sub-nanometer protein structure within the dense cellular environment. Existing sample preparation methods are insufficient at accessing the plasma membrane and its associated proteins. Here, we present a correlative cryo-electron tomography pipeline optimally suited to image large ultra-thin areas of isolated basal and apical plasma membranes. The pipeline allows for angstrom-scale structure determination with sub-tomogram averaging and employs a genetically-encodable rapid chemically-induced electron microscopy visible tag for marking specific proteins within the complex cell environment. The pipeline provides fast, efficient, distributable, low-cost sample preparation and enables targeted structural studies of identified proteins at the plasma membrane of cells.
Microflora Danica: the atlas of Danish environmental microbiomes
Authors: Singleton CM , Jensen TBN , Delogu F , Sørensen EA , Jørgensen VR , Karst SM , Yang Y , Knudsen KS , Sereika M , Petriglieri F , Knutsson S , Dall SM , Kirkegaard RH , Kristensen JM , Woodcroft BJ , Speth DR , Aroney STN ,   The Microflora Danica Consortium, Wagner M , Dueholm MKD , Nielsen PH , Albertsen M 
Published: June 2024

SummaryThe last 20 years have witnessed unprecedented advances in revealing the microbiomes underpinning important processes in natural and human associated environments. Recent large-scale metagenome surveys record the variety of microbial life in the oceans1, wastewater2, human gut3,4, and earth5,6, with compilations encompassing thousands of public datasets7–13. So far, large-scale microbiome studies either miss functional information or consistency in sample processing, and although they may cover thousands of locations, these are missing resolution, sparsely located, or lacking metadata. Here, we present Microflora Danica, an atlas of Danish environmental microbiomes, encompassing 10,686 shotgun metagenomes and 449 full-length 16S and 18S rRNA datasets linked to a detailed 5 level habitat classification scheme. We determine that while human-disturbed habitats have high alpha diversity, the same species reoccur, revealing hidden homogeneity and underlining the importance of natural systems for total species (gamma) diversity. In-depth studies of nitrifiers, a functional group closely linked to climate change, challenge existing perceptions regarding habitat preference and discover several novel nitrifiers as more abundant than canonical nitrifiers. Together, the Microflora Danica dataset provides an unprecedented resource and the foundation for answering fundamental questions underlying microbial ecology: what drives microbial diversity, distribution and function.
Spatially resolving how phosphorylation affects ß-cardiac myosin activity in porcine myofibril sarcomeres with single molecule resolution
Authors: Pilagov Matvey , Steczina Sonette , Naim Ateeqa , Regnier Michael , Geeves Michael A. , Kad Neil M. 
Published: June 2024

AbstractCardiac muscle contraction is mediated by myosin binding from the thick filament of the sarcomere to the thin filament in an ATP powered reaction. This process is highly regulated on a beat-to-beat basis by calcium interactions with the thin filament. Additionally, the number of heads available for participation in contraction is also regulated, resulting in a dynamically variable reserve of heads for controlling contractile force. We aimed to discover the size of this reserve and how it is modulated by phosphorylation. Using single molecule imaging of fluorescently labelled ATP molecules binding and releasing myosins within porcine cardiac sarcomeres, we could determine myosin activity with high spatial resolution. We find three kinetic species when examining the myosin ATPase. The fastest is consistent with non-specific ATP binding to myosin’s surface, and the slower two species are consistent with the previously identified DRX and SRX states. The former is thought to represent myosins in an ON state, ready to interact with the thin filament and the latter an OFF state with slowed ATPase that constitutes the cardiac reserve. We find that the cardiac reserve is 50% in the sarcomere and this can be sub-divided into the P-, C- and D-zones, with the D-zone having the least population of OFF heads (44%). Treatment with PKA phosphorylates cardiac myosin binding protein-C (cMyBP-C) leading to a 16% reduction in reserve in the C-zone (where cMyBP-C is found), a 10% reduction in the P-zone, and an unexpected 8% increase in the D-zone. By contrast, myosin regulatory light chain (RLC) phosphorylation with myosin light chain kinase (MLCK) resulted in a large 24% decrease in reserve myosins, interestingly the least affected area of the sarcomere was the C-zone. Altogether these data suggest that cMyBP-C’s interaction with RLC governs the degree of activation due to RLC phosphorylation.
Molecular evolution of the mammalian kinetochore complex
Authors: Arora Uma P. , Dumont Beth L. 
Published: June 2024

AbstractMammalian centromeres are satellite-rich chromatin domains that serve as sites for kinetochore complex assembly. Centromeres are highly variable in sequence and satellite organization across species, but the processes that govern the co-evolutionary dynamics between rapidly evolving centromeres and their associated kinetochore proteins remain poorly understood. Here, we pursue a course of phylogenetic analyses to investigate the molecular evolution of the complete kinetochore complex across primate and rodent species with divergent centromere repeat sequences and features. We show that many protein components of the core centromere associated network (CCAN) harbor signals of adaptive evolution, consistent with their intimate association with centromere satellite DNA and roles in the stability and recruitment of additional kinetochore proteins. Surprisingly, CCAN and outer kinetochore proteins exhibit comparable rates of adaptive divergence, suggesting that changes in centromere DNA can ripple across the kinetochore to drive adaptive protein evolution within distant domains of the complex. Our work further identifies kinetochore proteins subject to lineage-specific adaptive evolution, including rapidly evolving proteins in species with centromere satellites characterized by higher-order repeat structure and lacking CENP-B boxes. Thus, features of centromeric chromatin beyond the linear DNA sequence may drive selection on kinetochore proteins. Overall, our work spotlights adaptively evolving proteins with diverse centromere-associated functions, including centromere chromatin structure, kinetochore protein assembly, kinetochore-microtubule association, cohesion maintenance, and DNA damage response pathways. These adaptively evolving kinetochore protein candidates present compelling opportunities for future functional investigations exploring how their concerted changes with centromere DNA ensure the maintenance of genome stability.
Estimating the potential impact of surveillance test-and-treat posts to reduce malaria in border regions in sub-Saharan Africa: a modelling study
Authors: Topazian Hillary M. , Charles Giovanni D. , Schmit Nora , Pianella Matteo , Marshall John M. , Kleinschmidt Immo , Hauck Katharina , Ghani Azra C. 
Published: June 2024

ABSTRACTThe last malaria cases in near-elimination settings are often found in international border regions due to the presence of hard-to-reach populations, conflict, uneven intervention coverage, and human migration. Test-and-treat border posts are an under-researched form of active case detection used to interrupt transmission chains between countries. We used an individual-based, mathematical metapopulation model ofP. falciparumto estimate the effectiveness of border posts on total cases in malaria-endemic sub-Saharan Africa. We estimated that implementation of international border posts across 401 sub-national administrative units would avert a median of 7,173 (IQR: 1,075 to 23,550) cases per unit over a 10-year period and reducePfPR2-10by a median of 0.21% (IQR: 0.04% to 0.44%). Border posts were most effective in low-transmission settings with high-transmission neighbors. Border posts alone will not allow a country to reach elimination, particularly when considering feasibility and acceptability, but could contribute to broader control packages to targeted populations.
Multi-omic associations of epigenetic age acceleration are heterogeneously shaped by genetic and environmental influences
Authors: Drouard Gabin , Suhonen Sannimari , Heikkinen Aino , Wang Zhiyang , Kaprio Jaakko , Ollikainen Miina 
Published: June 2024

AbstractConnections between the multi-ome and epigenetic age acceleration (EAA), and especially whether these are influenced by genetic or environmental factors, remain underexplored. We therefore quantified associations between the multi-ome comprising four layers – the proteome, metabolome, external exposome, and lifestyle – with six different EAA estimates. Two twin cohorts were used in a discovery-replication scheme, comprising respectively young (N=642; mean age= 22.3) and older (N=354; mean age=62.3) twins. Within-pair twin designs were used to assess genetic and environmental effects on associations. We identified 40 multi-omic factors, of which 28 were proteins, associated with EAA in the young twins while adjusting for sex, smoking, and body mass index. Within-pair analyses showed that genetic confounding heterogeneously affected these associations, with six multi-omic factors remaining significantly associated with EAA independent of genetic effects. Replication in older twins showed that some of these associations persist across adult generations.
An assessment of the Health Information System in Khomas region, Namibia
Authors: Jatileni N J V , Nicol E 
Published: June 2024

AbstractIntroductionA robust and well-functioning Health Information System (HIS) is crucial for managing patient care, monitoring health system performance, and informing public health decisions. However, Namibia, like many developing countries, faces challenges in its HIS, such as limited financial and human resources, knowledge gaps, inadequate infrastructure, and behavioural barriers such as resistance to adopting new systems and a lack of supportive policies. Previous studies have not shown significant improvements since 2012. This study in Namibia’s Khomas region aims to assess human factors affecting the HIS and evaluate progress made from 2012 to 2023. It will use recommendations from a 2012 assessment by USAID to provide insights and propose ways to enhance healthcare delivery and resource allocation.Methods and analysisThis study utilizes a cross-sectional design employing a multi-method approach to evaluate the performance of the Health Information System (HIS). Qualitative methods include conducting 17 in-depth interviews with key informants, a retrospective document review from the Ministry of Health and Social Services headquarters in Windhoek, supplemented by a modified office/facility checklist from all 14 health facilities in the Khomas region. The quantitative methods involve administering a questionnaire to 330 staff members, utilizing an adapted version of the Performance of Routine Information System Management (PRISM)’s Organizational and Behavioural Assessment Tool (OBAT). Descriptive statistics will be applied to analyse the quantitative data, while a deductive interpretive approach will be used for qualitative data analysis.Ethics and disseminationThe protocol was approved by the Stellenbosch University Health Research Ethics Committee (Reference No: S23/05/119), the Namibia ministry of Health and Social Services (Reference No: 22/3/2/1) and will adhere to the principles of the Declaration of Helsinki (1964). The study aims to identify barriers and facilitators for implementing recommendations across different levels of the Health Information System (HIS), with a focus on improving the HIS in the Khomas region. Outputs will include communicating the findings to the study population, presenting at both local and international conferences, and publishing peer-reviewed journal articles.
Evaluating adults’ dental caries burden through the DMFT index: results from the Tanzanian 5thnational oral health survey
Authors: Nyamuryekung’e Kasusu , Mbawalla Hawa , Mlangwa Matilda 
Published: June 2024

AbstractAimDental caries remains the most prevalent chronic disease worldwide, affecting adults and children across all regions. The DMFT index, representing the number of decayed, missing, and filled teeth, serves as a fundamental metric in oral epidemiology, providing an objective quantification of dental caries prevalence and severity. The aim of the current study is to evaluate the dental caries burden of the adult Tanzanian population through the DMFT index.MethodsA national pathfinder survey was conducted in mainland Tanzania using a cross-sectional design. The survey encompassed fourteen districts across thirteen regions. Site selection followed the World Health Organization’s (WHO) basic oral health survey methods, utilizing a modified stratified-cluster sampling approach. Electronic questionnaires were administered to all adult participants prior to their dental examinations. The questionnaires collected data on participants’ sociodemographic information, tooth brushing practices, and dentition status. Dental examinations were conducted in accordance with WHO standard criteria. Data cleaning and analysis were performed using SPSS version 23. Frequencies were calculated to determine the proportions of participants’ mean and separate DMFT (Decayed, Missing, and Filled Teeth) components. Bivariate associations were examined using Student’s t-test and ANOVA to compare participants’ DMFT components with their sociodemographic characteristics and oral health practices.ResultsThe study surveyed a total of 1,386 participants aged 30-34, 35-44 and 50+ comprising 713 females (51.4%) with most participants (49.1%) aged 50 years or older. The mean DMFT in the studied population was 4.63 (SD 5.4) with a dental caries experience of 76.6%. The Missing teeth component constituted the largest portion of the mean DMFT (52.4%), followed closely by the Decayed teeth component (45.8%). Tooth fillings were found in just 3.5% of those with dental caries experience. The mean DMFT score was significantly higher among females (5.31 ± 5.79), those aged 50 or more (5.93 ± 6.26) and with lowest level of education (5.78 ± 6.68). Brushing less than once daily (p<0.001), not using toothpaste (p<0.001) and not using a toothbrush daily (p<0.05) were all associated with increased DMFT scores.ConclusionDental caries is a significant public health issue in Tanzania. The predominance of missing and decayed teeth highlights the critical gaps in treatment and dental care service accessibility. There is a pressing need for increased public health investment in preventive and restorative dental care and enhanced community education on the importance of maintaining dental health.
Effectiveness of a school-based high-intensity interval training intervention in adolescents: study protocol of thePRO-HIITcluster randomised controlled trial
Authors: Liu Yong , Barker Alan R. , Adlam Anna-Lynne R. , Li Minghui , Duncombe Stephanie L. , Agbaje Andrew O. , Gu Yaodong , Zhou Huiyu , Williams Craig A. 
Published: June 2024

ABSTRACTIntroductionHigh-intensity interval training (HIIT) is an effective strategy for improving a variety of health and fitness outcomes within the school settings. Incorporating HIIT into existing physical activity opportunities appears practically feasible, yet the process evaluation and effectiveness of this strategy needs to be further evaluated. Therefore, aPRO-HIITintervention will be conducted to evaluate the effectiveness of a 12-week school-based HIIT intervention on cardiorespiratory fitness, physical activity, body composition, muscular strength, bone health, cognitive function, wellbeing and academic performance among 12-13-year-olds.Methods and analysisEight classes of year 7 students (12-13-year-olds) from a secondary school in Ningbo, China, will be recruited and randomly allocated into an intervention or control group. While the control group maintains their usual activities, a 6 to 10-minute HIIT session will be embedded in the physical education or physical activity lessons five days a week for 12 weeks for the intervention group. Training workshops will be conducted for participants, teachers, and research staff for facilitating the intervention. Outcome data will be collected at three time points: pre- and post-intervention, and two months (summer holiday) upon completion of the intervention. Linear mixed models will be used to analyse the impact of groups (intervention and control), timepoints (pre-, post- and two-month after intervention) and group by time interactions. The implementation process of the intervention will be evaluated with the guidance of MRC process evaluation framework.Ethics and disseminationEthics approval is obtained from the Ningbo University Ethics Committee (TY2024002) and the Public Health and Sport Sciences ethics committee, University of Exeter (5713479). Results fromPRO-HIIT study will be disseminated via peer-reviewed journals, scientific conferences as well as local education system. The study protocol has been retrospectively registered onClinicalTrials.govProtocol Registration and Results System (NCT06374732),https://clinicaltrials.gov/study/NCT06374732.
Human cancer genomes harbor the mutational signature of tobacco-specific nitrosamines NNN and NNK
Authors: Korenjak Michael , Temiz N. Alpay , Keita Stéphane , Chavanel Bérénice , Renard Claire , Sirand Cécilia , Cahais Vincent , Mayel Tanguy , Vevang Karin R. , Jacobs Foster C. , Guo Jiehong , Smith William E. , Oram Marissa K. , Tăbăran Flaviu A. , Ahlat Ozan , Cornax Ingrid , O’Sullivan M. Gerard , Das Samrat , Nandi Shuvro P. , Cheng Yuhe , Alexandrov Ludmil B. , Balbo Silvia , Hecht Stephen S , Senkin Sergey , Virard Francois , Peterson Lisa A. , Zavadil Jiri 
Published: June 2024

ABSTRACTTobacco usage is linked to multiple cancer types and accounts for a quarter of all cancer-related deaths. Tobacco smoke contains various carcinogenic compounds, including polycyclic aromatic hydrocarbons (PAH), though the mutagenic potential of many tobacco-related chemicals remains largely unexplored. In particular, the highly carcinogenic tobacco-specific nitrosamines NNN and NNK form pre-mutagenic pyridyloxobutyl (POB) DNA adducts. In the study presented here, we identified genome-scale POB-induced mutational signatures in cell lines and rat tumors, while also investigating their role in human cancer. These signatures are characterized by T>N and C>T mutations forming from specific POB adducts damaging dT and dC residues. Analysis of 2,780 cancer genomes uncovered POB signatures in ∼180 tumors; from cancer types distinct from the ones linked to smoking-related signatures SBS4 and SBS92. This suggests that, unlike PAH compounds, the POB pathway may contribute uniquely to the mutational landscapes of certain hematological malignancies and cancers of the kidney, breast, prostate and pancreas.