Core Domain Research Articles

Effects of a Learning Trajectory for statistical inference on 9th-grade students’ statistical literacy

AbstractIn our data-driven society, it is essential for students to become statistically literate. A core domain within Statistical Literacy is Statistical Inference, the ability to draw inferences from sample data. Acquiring and applying inferences is difficult for students and, therefore, usually not included in the pre-10th-grade curriculum. However, recent studies suggest that developing a good understanding of key statistical concepts at an early age facilitates the understanding of Statistical Inference later on. This study evaluates the effects of a Learning Trajectory for Statistical Inference on Dutch 9th-grade students’ Statistical Literacy. Theories on informal Statistical Inference and repeated sampling guided the Learning Trajectory’s design. For the evaluation, we used a pre-post research design with an intervention group (n = 267). The results indicated that students made significant progress on Statistical Literacy and on the ability to make inferences in particular, but also on the other domains of Statistical Literacy. To further interpret the learning gains of this group, we compared students’ results with national baseline achievements from a comparison group (n = 217) who followed the regular 9th-grade curriculum, and with international studies using similar test items. Both comparisons confirmed a significant positive effect on all domains of Statistical Literacy. These findings suggest that current statistics curricula for grades 7–9, usually with a strong descriptive focus, can be enriched with an inferential focus.

Adhesin domains responsible for binding bacteria to surfaces they colonize project outwards from companion split domains.

Bacterial adhesins attach their hosts to surfaces that the bacteria will colonize. This surface adhesion occurs through specific ligand-binding domains located towards the distal end of the long adhesin molecules. However, recognizing which of the many adhesin domains are structural and which are ligand binding has been difficult up to now. Here we have used the protein structure modeling program AlphaFold2 to predict structures for these giant 0.2- to 1.5-megadalton proteins. Crystal structures previously solved for several adhesin regions are in good agreement with the models. Whereas most adhesin domains are linked in a linear fashion through their N- and C-terminal ends, ligand-binding domains can be recognized by budding out from a companion core domain so that their ligand-binding sites are projected away from the axis of the adhesin for maximal exposure to their targets. These companion domains are "split" in their continuity by projecting the ligand-binding domain outwards. The "split domains" are mostly β-sandwich extender modules, but other domains like a β-solenoid can serve the same function. Bioinformatic analyses of Gram-negative bacterial sequences revealed wide variety ligand-binding domains are used in their Repeats-in-Toxin adhesins. The ligands for many of these domains have yet to be identified but known ligands include various cell-surface glycans, proteins, and even ice. Recognizing the ligands to which the adhesins bind could lead to ways of blocking colonization by bacterial pathogens. Engineering different ligand-binding domains into an adhesin has the potential to change the surfaces to which bacteria bind.

Structural packing of the non-amyloid component core domain in α-synuclein plays a role in the stability of the fibrils

Parkinson's disease (PD) is one of many neurodegenerative diseases. The protein associated with PD is α-synuclein (AS). Aggregation of AS protein into oligomers, protofilaments, and finally to fibrils yields to the development of PD. The aggregation process of AS leads to the formation of polymorphic AS fibrils. Herein, we compared four polymorphic full-length AS1–140 fibrils, using extensive computational tools. The main conclusion of this study emphasizes the role of the structurally packed non-amyloid component (NAC) core domain in AS fibrils. Polymorphic AS fibrils that presented a packed NAC core domain, exhibited more β-sheets and fewer fluctuations in the NAC domain. Hence, these AS fibrils are more stable and populated than the AS fibrils, by which the NAC domains are more exposed, more fluctuate and less packed in the fibrillary structure. Therefore, this study emphasizes the importance of the NAC domain packing in the morphology of AS fibrils. The results obtained in this study will initiate future studies to develop compounds to prevent and inhibit AS aggregation.

Association of clinical response criteria and disease activity levels with axial spondyloarthritis core domains: results from two phase 3 randomised studies, BE MOBILE 1 and 2

ObjectiveTo assess how achievement of increasingly stringent clinical response criteria and disease activity states at week 52 translate into changes in core domains in patients with non-radiographic (nr-) and radiographic...

Concerns beyond ankle symptoms predominate healthcare professionals’ views of patients with ankle osteoarthritis: A qualitative study

ObjectivesExplore healthcare professionals’ perspectives on the main problems that their patients with ankle osteoarthritis experience and to propose health-related domains. MethodsA qualitative study using semi-structured interviews was conducted with an international multidisciplinary group of healthcare professionals identified as ankle experts. Eligibility criteria were aged ≥18 years, and a certified healthcare professional with ≥ 5-year experience post-qualification in working with ankle osteoarthritis and/or chronic ankle pain. Interviews were recorded, transcribed verbatim and thematically analysed. ResultsTwenty-one healthcare professionals (20 males; mean (range) age 49 (34–72) years) from four professions (orthopaedic surgeons (n = 9), athletic trainers (n = 5), physiotherapists (n = 4) and podiatrists (n = 3)) were interviewed. Four main themes were identified: 1) people with ankle osteoarthritis have difficulty with weight-bearing activities; 2) symptoms of pain and stiffness predominate, alongside swelling, instability, weakness and poor balance; 3) chronic pain in ankle osteoarthritis has psychosocial consequences; and 4) the loss of activities of daily living and independence compromises quality of life. We proposed 15 health-related domains that emerge from the interview data. ConclusionHealthcare professionals recognise that ankle osteoarthritis patients have difficulty in physical, sporting, and occupational weight-bearing activities, and they live with persistent ankle pain, stiffness and other symptoms that have physical and psychosocial consequences. The health-related domains derived from interviews with expert healthcare professionals will contribute to the development of a core domain set for ankle osteoarthritis.

Species Abundance Modelling of Arctic-Boreal Zone Ducks Informed by Satellite Remote Sensing

The Arctic-Boreal zone (ABZ) covers over 26 million km2 and is home to numerous duck species; however, understanding the spatiotemporal distribution of their populations across this vast landscape is challenging, in part due to extent and data scarcity. Species abundance models for ducks in the ABZ commonly use static (time invariant) habitat covariates to inform predictions, such as wetland type and extent maps. For the first time in this region, we developed species abundance models using high-resolution, time-varying wetland inundation data produced using satellite remote sensing methods. This data captured metrics of surface water extent and inundated vegetation in the Peace Athabasca Delta, Canada, which is within the NASA Arctic Boreal Vulnerability Experiment core domain. We used generalized additive mixed models to demonstrate the improved predictive value of this novel data set over time-invariant data. Our findings highlight both the potential complementarity and efficacy of dynamic wetland inundation information for improving estimation of duck abundance and distribution at high latitudes. Further, these data can be an asset to spatial targeting of biodiversity conservation efforts and developing model-based metrics of their success under rapidly changing climatic conditions.

A hybrid attention-guided ConvNeXt-GRU network for action recognition

In the digital age, with the continuous emergence of large-scale video data, video understanding has become increasingly important. As a core domain, action recognition has garnered widespread attention. However, video exhibits high-dimensional properties and contains human action information at multiple scales, which makes conventional attention mechanisms difficult to capture complex action information. To improve the performance of action recognition, a Hybrid Attention-guided ConvNeXt-GRU Network (HACG) is proposed. Specifically, a Novel Attention Mechanism (ANM) is constructed by integrating a parameter-free attention module into ConvNeXt, enabling the preliminary extraction of important features without the addition of extra parameters. Then, a Multiscale Hybrid Attention Module (MHAM) adopts an improved and efficient Selective Kernel Network (SKNet) to adaptively calibrate channel features. In this way, the module enhances the model’s ability to perceive features at different scales while improving the correlation between channels. Furthermore, MHAM incorporates an Atrous Spatial Pyramid Pooling (ASPP) to extract local and global information from different regions. Finally, MHAM is integrated with the Gated Recurrent Unit (GRU) to capture the interdependence between space and time. Experimental results show that HACG exhibits superior competitiveness compared with the state-of-the-art on the UCF-101, HMDB-51, and Kinetics-400 datasets. This indicates that HACG can more effectively capture important features to suppress noise interference while also having a lower computational load, which makes HACG a highly promising choice for action recognition tasks.

Neoproterozoic low-T/P metamorphism in the Yangtze Block manifests a long-lived subduction girdle around Rodinia

Identifying long-lived subduction at the periphery of supercontinents provides insights into the processes of block assembly and dispersal within the supercontinent cycle. The Yangtze Block of South China stands as a key component during the transition from Rodinia to Gondwana, characterized by active tectono-magmatic processes throughout the early to middle Neoproterozoic. However, the lack of metamorphic records associated with accretionary orogenesis results in ambiguity about the tectonic regime and its evolution in Rodinia during this period. Here, we present evidence of low-temperature/pressure ratio (low-T/P) metamorphism in phengite-bearing orthogneisses from the western margin of the Yangtze Block (WYB). Through petrographic investigations and zircon U–Pb–Hf–O isotopic analysis in core and rim domains, we identify two distinct metamorphic rock types, with protolith ages of 1419 ± 19 Ma and 831 ± 9 Ma. Both rock types record metamorphism at ca. 830–820 Ma, accompanied by infiltration of externally-derived melts with high-δ18O and unradiogenic Hf isotopes. Our phase equilibria modeling, combined with mineral thermometry and Si-in-phengite content, shows peak metamorphic conditions of ∼550 °C and ∼8.2–8.6 kbar, corresponding to a cold geothermal gradient (19.0–20.5 °C/km). The low-T/P metamorphism is interpreted to occur either in a subduction zone accretionary wedge or in an overriding forearc continental crust, providing robust evidence for Neoproterozoic orogenesis of the WYB within a subduction framework. Based on petrological, isotopic, and paleomagnetic data, we conclude that the WYB represents part of a long-lived subduction girdle (at least ca. 970–750 Ma) at the periphery of Rodinia. Since the early stage of Rodinia breakup, this girdle was involved in alternating advance and retreat accretionary orogenesis as the Yangtze Block continuously drifted away from a mantle upwelling toward the degree-2 girdle of mantle downwelling. Our study provides a snapshot of the evolution of a complete long-lived circum-Rodinian subduction girdle during the transition from Rodinia to Gondwana.

An efficient peptide ligase engineered from a bamboo asparaginyl endopeptidase.

In recent years, a few asparaginyl endopeptidases (AEPs) from certain higher plants have been identified as efficient peptide ligases with wide applications in protein labeling and cyclic peptide synthesis. Recently, we developed a NanoLuc Binary Technology (NanoBiT)-based peptide ligase activity assay to identify more AEP-type peptide ligases. Herein, we screened 61 bamboo species from 16 genera using this assay and detected AEP-type peptide ligase activity in the crude extract of all tested bamboo leaves. From a popular bamboo species, Bambusa multiplex, we identified a full-length AEP-type peptide ligase candidate (BmAEP1) via transcriptomic sequencing. After its zymogen was overexpressed in Escherichia coli and self-activated in vitro, BmAEP1 displayed high peptide ligase activity, but with considerable hydrolytic activity. After site-directed mutagenesis of its ligase activity determinants, the mutant zymogen of [G238V]BmAEP1 was normally overexpressed in E. coli, but failed to activate itself. To resolve this problem, we developed a novel protease-assisted activation approach in which trypsin was used to cleave the mutant zymogen and was then conveniently removed via ion-exchange chromatography. After the noncovalently bound cap domain was dissociated from the catalytic core domain under acidic conditions, the recombinant [G238V]BmAEP1 displayed high peptide ligase activity with much lower hydrolytic activity and could efficiently catalyze inter-molecular protein ligation and intramolecular peptide cyclization. Thus, the engineered bamboo-derived peptide ligase represents a novel tool for protein labeling and cyclic peptide synthesis.

Network analysis of smoking-related sleep characteristics in Chinese adults

The associations between multiple sleep characteristics and smoking behavior are inconsistent, and it is unclear which sleep characteristics are most crucial for tobacco prevention. This study aimed to explore the associations between smoking status/intensity and multiple sleep characteristics and to identify the potential core domain of smoking-related sleep using network analysis. Data were obtained from a survey of cancer-related risk factors among Chinese adults. Logistic regression models were used to quantify the associations between sleep characteristics and smoking status/intensity. Network analyses were employed to identify the core sleep characteristics. A total of 5,228 participants with a median age of 44 years old were included in the study. Current smoking was significantly positively associated with long nap time, difficulty falling asleep, late bedtime, getting up after 7 am, and waking up earlier than expected. There was significant positive association between current smoking and short sleep duration in young adults under 45 years old. Late bedtime and getting up after 7 am were only associated with current heavy smoking, but not current light smoking. Network analyses showed that multiple smoking-related sleep characteristics were interconnected, with difficulty falling asleep and late bedtime as central characteristics in the network. The study found that the associations between sleep characteristics and smoking varied by age and smoking intensity and highlights the potential benefits of sleep health promotion in smoking cessation, with a particular focus on difficulty falling asleep and late bedtime.

Abstract 1314: SCHEQ Foundation (STEMM & Cancer Health Equity): Increasing STEMM diversity and outcomes for patients navigating cancer

Abstract Health inequities are estimated to cost $320B annually, while racial and ethnic disparities are estimated to cost $42B in productivity. There are systemic issues at play that contribute to these disparities. These include lack of diversity in Science, Technology, Engineering, Mathematics, and Medicine (STEMM) fields; bias in healthcare delivery and access; underinsurance in patients from low-income backgrounds; and lack of training that advances those from historically underrepresented groups. The SCHEQ Foundation (STEMM & Cancer Health Equity) is a black-founded nonprofit organization that seeks to increase STEMM workforce diversity and improve outcomes for underrepresented, underserved, marginalized, and invisible populations across the cancer care continuum. Herein we describe the formation of SCHEQ Foundation and our core domains that we seek to make change. We seek to increase STEMM access and exposure, increase STEMM workforce diversity, and improve outcomes for underserved populations navigating the cancer care continuum. This will be accomplished in part by 1) engaging professional in STEMM from their lived background and experiences, 2) developing training, mentoring, and professional developing programs across the academic continuum to increase success of minoritized scholars; and 3) providing information and resources in culturally responsive manners to help underserved patient navigate cancer and advocate for the standard of care they deserve. We will change how we convey content, information, and resources to underserved populations by utilizing a combination of multimedia, infographics, webinars, info sheets, and community engagement. The goal is to increase survival for groups that historically have the greatest cancer disparities. Citation Format: Eugene Manley. SCHEQ Foundation (STEMM & Cancer Health Equity): Increasing STEMM diversity and outcomes for patients navigating cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1314.

Abstract 4694: In charge: Targeting neddylation of UBE2M for anticancer therapy

Abstract Post-translational modification of proteins with ubiquitin and ubiquitin-like molecules orchestrates a vast number of processes in the cell. Consequently, post-translational modification pathways are considered major targets for therapeutic intervention of many diseases, including cancers. Neddylation is a post-translational mechanism like ubiquitination, but instead of ubiquitin, NEDD8 is conjugated to protein targets via an E1-E2-E3 multi-enzymatic cascade. Neddylation is upregulated in multiple cancer types and the development of therapeutics targeting neddylation pathways are gaining increasing popularity. UBE2M, one of the two E2 neddylation conjugation enzymes, takes part in two types of reactions: transthiolation-transfer of NEDD8 from a thioester to a thiol group and aminolysis-transfer of NEDD8 from a thioester to an amino group. These activities require both a 26-residue N-terminal docking peptide and a conserved E2 catalytic core domain, which is the basis for the transfer of NEDD8. Here, we describe findings in the quest to understand the UBE2M interaction with NEDD8 and effects on cancer cells by modifying UBE2M at the N-terminal docking peptide or at the catalytic site. Cancer cells were transfected with ΔN or catalytic site UBE2M mutant constructs and analyzed by immunoprecipitation for charging of NEDD8 onto UBE2M. The catalytic site mutants are deficient in charging (C111A) or discharging (C111S) of UBE2M by NEDD8, which leads to a decrease in neddylation of downstream substrates, such as CULLIN family members. Elimination of the N-terminal docking peptide by introduction of catalytically competent ΔN UBE2M mutant constructs resulted in reduced reaction kinetics. Structural modeling suggests that the loss of the N-terminal docking region likely weakens protein-protein interactions between UBE2M and the UBA3-APPBP1 E1 complex. Interestingly, ΔN UBE2M mutants were observed to be slightly charged with NEDD8, but appeared to have a defect in NEDD8 discharge, resulting in reduced neddylation of substrates. Moreover, further phenotypic evaluation of UBE2M mutant transfected cancer cells revealed a divergence in phenotypic effect: while both mutant types led to a deficiency in NEDD8 charge or discharge from UBE2M, only the manipulation of the active site of UBE2M led to a DNA re-replication phenotype with subsequent cell death. These observations reveal the complexity of the neddylation cascade and raise the question if slowing down discharge of NEDD8 from UBE2M is a more viable therapeutic option than slowing down the charging of UBE2M. Citation Format: Alex G. Batrouni, Jacob P. Matson, Andressa L. Mota, Archna Ravi, Marcus O'Hara, Micholas D. Smith, Jeremy C. Smith, Vivek K. Vishnudas, Anjan Thakurta, Stephane Gesta, Maria D. Nastke. In charge: Targeting neddylation of UBE2M for anticancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4694.

Assessing the mechanism of fast-cycling cancer-associated mutations of Rac1 small Rho GTPase.

Rho-GTPases proteins function as molecular switches alternating from an active to an inactive state upon Guanosine triphosphate (GTP) binding and hydrolysis to Guanosine diphosphate (GDP). Among them, Rac subfamily regulates cell dynamics, being overexpressed in distinct cancer types. Notably, these proteins are object of frequent cancer-associated mutations at Pro29 (P29S, P29L, and P29Q). To assess the impact of these mutations on Rac1 structure and function, we performed extensive all-atom molecular dynamics simulations on wild-type (wt) and oncogenic isoforms of this protein in GDP- and GTP-bound states. Our results unprecedentedly elucidate that P29Q/S-induced structural and dynamical perturbations of Rac1 core domain weaken the binding of the catalytic site Mg2+ ion, and reduce the GDP residence time within protein, enhancing the GDP/GTP exchange rate and Rac1 activity. This broadens our knowledge of the role of cancer-associated mutations on small GTPases mechanism supplying valuable information for future drug discovery efforts targeting specific Rac1 isoforms.

C-terminal Domain of T4 gene 32 Protein Enables Rapid Filament Reorganization and Dissociation

Bacteriophage T4 gene 32 protein (gp32) is a single-stranded DNA (ssDNA) binding protein essential for DNA replication. gp32 forms stable protein filaments on ssDNA through cooperative interactions between its core and N-terminal domain. gp32′s C-terminal domain (CTD) is believed to primarily help coordinate DNA replication via direct interactions with constituents of the replisome. However, the exact mechanisms of these interactions are not known, and it is unclear how tightly-bound gp32 filaments are readily displaced from ssDNA as required for genomic processing. Here, we utilized truncated gp32 variants to demonstrate a key role of the CTD in regulating gp32 dissociation. Using optical tweezers, we probed the binding and dissociation dynamics of CTD-truncated gp32, *I, to an 8.1 knt ssDNA molecule and compared these measurements with those for full-length gp32. The *I-ssDNA helical filament becomes progressively unwound with increased protein concentration but remains significantly more stable than that of full-length, wild-type gp32. Protein oversaturation, concomitant with filament unwinding, facilitates rapid dissociation of full-length gp32 from across the entire ssDNA segment. In contrast, *I primarily unbinds slowly from only the ends of the cooperative clusters, regardless of the protein density and degree of DNA unwinding. Our results suggest that the CTD may constrain the relative twist angle of proteins within the ssDNA filament such that upon critical unwinding the cooperative interprotein interactions largely vanish, facilitating prompt removal of gp32. We propose a model of CTD-mediated gp32 displacement via internal restructuring of its filament, providing a mechanism for rapid ssDNA clearing during genomic processing.

The eukaryotic-like characteristics of small GTPase, roadblock and TRAPPC3 proteins from Asgard archaea

Membrane-enclosed organelles are defining features of eukaryotes in distinguishing these organisms from prokaryotes. Specification of distinct membranes is critical to assemble and maintain discrete compartments. Small GTPases and their regulators are the signaling molecules that drive membrane-modifying machineries to the desired location. These signaling molecules include Rab and Rag GTPases, roadblock and longin domain proteins, and TRAPPC3-like proteins. Here, we take a structural approach to assess the relatedness of these eukaryotic-like proteins in Asgard archaea, the closest known prokaryotic relatives to eukaryotes. We find that the Asgard archaea GTPase core domains closely resemble eukaryotic Rabs and Rags. Asgard archaea roadblock, longin and TRAPPC3 domain-containing proteins form dimers similar to those found in the eukaryotic TRAPP and Ragulator complexes. We conclude that the emergence of these protein architectures predated eukaryogenesis, however further adaptations occurred in proto-eukaryotes to allow these proteins to regulate distinct internal membranes.

Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson’s disease

Parkinson’s disease (PD) starts at the molecular and cellular level long before motor symptoms appear, yet there are no early-stage molecular biomarkers for diagnosis, prognosis prediction, or monitoring therapeutic response. This lack of biomarkers greatly impedes patient care and translational research—l-DOPA remains the standard of care more than 50 years after its introduction. Here, we performed a large-scale, multi-tissue, and multi-platform proteomics study to identify new biomarkers for early diagnosis and disease monitoring in PD. We analyzed 4877 cerebrospinal fluid, blood plasma, and urine samples from participants across seven cohorts using three orthogonal proteomics methods: Olink proximity extension assay, SomaScan aptamer precipitation assay, and liquid chromatography–mass spectrometry proteomics. We discovered that hundreds of proteins were upregulated in the CSF, blood, or urine of PD patients, prodromal PD patients with DAT deficit and REM sleep behavior disorder or anosmia, and non-manifesting genetic carriers of LRRK2 and GBA mutations. We nominate multiple novel hits across our analyses as promising markers of early PD, including DOPA decarboxylase (DDC), also known as l-aromatic acid decarboxylase (AADC), sulfatase-modifying factor 1 (SUMF1), dipeptidyl peptidase 2/7 (DPP7), glutamyl aminopeptidase (ENPEP), WAP four-disulfide core domain 2 (WFDC2), and others. DDC, which catalyzes the final step in dopamine synthesis, particularly stands out as a novel hit with a compelling mechanistic link to PD pathogenesis. DDC is consistently upregulated in the CSF and urine of treatment-naïve PD, prodromal PD, and GBA or LRRK2 carrier participants by all three proteomics methods. We show that CSF DDC levels correlate with clinical symptom severity in treatment-naïve PD patients and can be used to accurately diagnose PD and prodromal PD. This suggests that urine and CSF DDC could be a promising diagnostic and prognostic marker with utility in both clinical care and translational research.

(221) Anatomical Transcriptome Atlas of the Male Mouse Reproductive System During Aging

Abstract Introduction The elderly males undergo degenerative fertility and testicular endocrine function that jeopardize the reproductive health and well-being. However, the mechanisms underlying reproductive aging are unclear. Objective This study aims to investigate the phenotypes and transcriptomes of seven regions of the male mouse reproductive tract: the testis, efferent ductules, initial segment, caput, corpus and cauda epididymidis, and vas deferens, in adult (3 months) and aged (21 months) mice. Methods Quantitative PCR, immunohistochemistry, immunofluorescent staining, and enzyme-linked immunosorbent assay were performed for the analysis of gene expression in mice, human tissues, and semen samples. Aged male mice showed both systematic and reproductive changes, and remarkable histological changes were detected in the testis and proximal epididymis. Transcriptomes of the male reproductive tract were mapped, and a series of region-specific genes were identified and validated in mouse and/or human tissues, including Protamine 1 (Prm2), ADAM metallopeptidase domain 28 (Adam28), Ribonuclease A family member 13 (Rnase13), WAP four-disulfide core domain 13 (Wfdc13), and Wfdc9. Meanwhile, age-related transcriptome changes of different regions of the male reproductive tract were characterized. Results Notably, increased immune response was functionally related to the male reproductive aging, especially the T cell activation. An immune response-associated factor, phospholipase A2 group IID (Pla2g2d), was identified as a potential biomarker for reproductive aging in mice. And the PLA2G2D level in human seminal plasma surged at approximately 35 years of age. Furthermore, we highlighted Protein tyrosine phosphatase receptor type C (Ptprc), Lymphocyte protein tyrosine kinase (Lck), Microtubule associated protein tau (Mapt), and Interferon induced protein with tetratricopeptide repeats 3 (Ifit3) as critical molecules in the aging of initial segment, caput, caput, and cauda epididymidis, respectively. Conclusions This study provides an RNA-seq resource for the male reproductive system during aging in mice, and is expected to improve our understanding of male reproductive aging and infertility. Disclosure No.

Wenlanzhangite–(Y) from the Yushui deposit, South China: a potential proxy for tracing the redox state of ore formation

Abstract Mineral phases in which vanadium (V) and heavy–rare–earth elements (HREEs) coexist are rarely documented. Here, we report a new V–HREE–bearing silicate mineral species, wenlanzhangite–(Y), which is a vanadiferous derivate of jingwenite–(Y) [Y2Al2V4+2(SiO4)2O4(OH)4] coexisting with jingwenite–(Y) in bedded/massive ores at Yushui, South China. Wenlanzhangite–(Y) forms as a dark brown, 70–100 μm–thick rim on a core domain of jingwenite–(Y), which occurs as 100–200 μm columnar crystals. The colour, streak, lustre, and hardness (Mohs) are dark brown, yellow grey, vitreous, and ~4, respectively. Compared to jingwenite–(Y), wenlanzhangite–(Y) has higher vanadium and lower aluminium contents. Calculated on the basis of 8 cations, the empirical formula is (Y1.26Dy0.17Er0.11Gd0.09Yb0.09Nd0.09Sm0.06Sc0.04Ho0.03Ce0.02Tb0.02Tm0.02Pr0.01)Σ2.00(V3+1.46Al0.54)Σ2.00V4+2(SiO4)2O4(OH)4, which can be simplified to the ideal formula Y2V3+2V4+2(SiO4)2O4(OH)4. Wenlanzhangite–(Y) is triclinic, with space group P–1(#2), Z = 2, and unit–cell parameters a = 5.9632(7) Å, b = 9.599(1) Å, c = 9.9170(9) Å, α = 90.033(8)°, β = 98.595(2)°, γ = 90.003(9)°, and V = 561.28(10) Å3. Wenlanzhangite–(Y) is approved by the International Mineralogical Association Commission on New Minerals, Nomenclature and Classification (IMA2022–142). The structure of wenlanzhangite–(Y) is composed of a–axis–oriented chains of [VO6] octahedra consisting of edge–sharing octahedra linked by insular [SiO4] tetrahedra, leaving open channels occupied by rare earth elements. Observed compositional variation and crystal structure demonstrate that V3+ can substitute for Al3+ in jingwenite–(Y), forming wenlanzhangite–(Y). The occurrence of wenlanzhangite–(Y) indicates a relatively more reducing hydrothermal environment causing reduction of V5+ in oxidized fluids to V3+ and thus represents a useful proxy for tracing the redox state of ore formation.

Defining domains: developing consensus-based definitions for foundational domains in OMERACT core outcome sets

ObjectiveTo develop a set of detailed definitions for foundational domains commonly used in OMERACT (Outcome Measures in Rheumatology) core domain sets. MethodsWe identified candidate domain definitions from prior OMERACT publications and websites and publications of major organizations involved in outcomes research for six domains commonly used in OMERACT Core Domain Sets: pain intensity, pain interference, physical function, fatigue, patient global assessment, and health-related quality of life. We conducted a two-round survey of OMERACT working groups, patient research partners, and then the OMERACT Technical Advisory Group to establish their preferred domain definitions. Results were presented at the OMERACT 2023 Methodology Workshop, where participants discussed their relevant lived experience and identified potential sources of variability giving the needed detail in our domain definitions. ResultsOne-hundred four people responded to both rounds of the survey, and a preferred definition was established for each of the domains except for patient global assessment for which no agreement was reached. Seventy-five participants at the OMERACT 2023 Methodology Workshop provided lived experience examples, which were used to contextualise domain definition reports for each of the five domains. ConclusionUsing a consensus-based approach, we have created a detailed definition for five of the foundational domains in OMERACT core domain sets; patient global assessment requires further research. These definitions, although not mandatory for working groups to use, may facilitate the initial domain-match assessment step of instrument selection, and reduce the time and resources required by future OMERACT groups when developing core outcome sets.

Influence of Spider Silk Protein Structure on Mechanical and Biological Properties for Energetic Material Detection.

Spider silk protein, renowned for its excellent mechanical properties, biodegradability, chemical stability, and low immune and inflammatory response activation, consists of a core domain with a repeat sequence and non-repeating sequences at the N-terminal and C-terminal. In this review, we focus on the relationship between the silk structure and its mechanical properties, exploring the potential applications of spider silk materials in the detection of energetic materials.