bluuebunny/crossref_metadata_2025_split huggingface dataset:
An extended interaction site determines binding between AP180 and AP2 in clathrin mediated endocytosis
Authors: Naudi-Fabra Samuel , Elena-Real Carlos A. , Vedel Ida Marie , Tengo Maud , Motzny Kathrin , Jiang Pin-Lian , Schmieder Peter , Liu Fan , Milles Sigrid 
Published: July 2024

AbstractThe early phases of clathrin mediated endocytosis are organized through a highly complex interaction network mediated by clathrin associated sorting proteins (CLASPs) that comprise long intrinsically disordered regions (IDRs). AP180 is a CLASP exclusively expressed in neurons and comprises a long IDR of around 600 residues, whose function remains partially elusive. Using NMR spectroscopy, we discovered an extended and strong interaction site within AP180 with the major adaptor protein AP2, and describe its binding dynamics at atomic resolution. We find that the 70 residue-long site determines the overall interaction between AP180 and AP2 in a dynamic equilibrium between its bound and unbound states, while weaker binding sites contribute to the overall affinity at much higher concentrations of AP2. Our data suggest that this particular interaction site might play a central role in recruitment of adaptors to the clathrin coated pit, whereas more transient and promiscuous interactions allow reshaping of the interaction network until cargo uptake inside a coated vesicle.
Kdm4a is an activity downregulated barrier to generate engrams for memory separation
Authors: Guo Xiuxian , Hong Pengfei , Xiong Songhai , Yan Yuze , Xie Hong , Guan Ji-Song 
Published: July 2024

AbstractMemory engrams are a subset of learning activated neurons critical for memory recall, consolidation, extinction and separation. While the transcriptional profile of engrams after learning suggests profound neural changes underlying plasticity and memory formation, little is known about how memory engrams are selected and allocated. As epigenetic factors suppress memory formation, we developed a CRISPR screening in the hippocampus to search for factors controlling engram formation. We identified histone lysine-specific demethylase 4a (Kdm4a) as a negative regulator for engram formation. Kdm4a is downregulated after neural activation and controls the volume of mossy fiber boutons. Mechanistically, Kdm4a anchors to the exonic region of Trpm7 gene loci, causing the stalling of nascent RNAs and allowing burst transcription of Trpm7 upon the dismissal of Kdm4a. Furthermore, the YTH domain containing protein 2 (Ythdc2) recruits Kdm4a to the Trpm7 gene and stabilizes nascent RNAs. Reducing the expression of Kdm4a in the hippocampus via genetic manipulation or artificial neural activation facilitated the ability of pattern separation in rodents. Our work indicates that Kdm4a is a negative regulator of engram formation and suggests a priming state to generate a separate memory.
Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity
Authors: Quach Henry , Farrell Spencer , Wu Ming Jia Michael , Kanagarajah Kayshani , Leung Joseph Wai-Hin , Xu Xiaoqiao , Kallurkar Prajkta , Turinsky Andrei L. , Bear Christine E. , Ratjen Felix , Kalish Brian , Goyal Sidhartha , Moraes Theo J. , Wong Amy P. 
Published: July 2024

AbstractStudying human fetal lungs can inform how developmental defects and disease states alter the function of the lungs. Here, we sequenced >150,000 single cells from 19 healthy human pseudoglandular fetal lung tissues ranging between gestational weeks 10–19. We capture dynamic developmental trajectories from progenitor cells that express abundant levels of the cystic fibrosis conductance transmembrane regulator (CFTR). These cells give rise to multiple specialized epithelial cell types. Combined with spatial transcriptomics, we show temporal regulation of key signalling pathways that may drive the temporal and spatial emergence of specialized epithelial cells including ciliated and pulmonary neuroendocrine cells. Finally, we show that human pluripotent stem cell-derived fetal lung models contain CFTR-expressing progenitor cells that capture similar lineage developmental trajectories as identified in the native tissue. Overall, this study provides a comprehensive single-cell atlas of the developing human lung, outlining the temporal and spatial complexities of cell lineage development and benchmarks fetal lung cultures from human pluripotent stem cell differentiations to similar developmental window.
Ethylene electrosynthesis from low-concentrated acetylene via concave-surface enriched reactant and improved mass transfer
Authors: Chen Fanpeng , Li Li , Cheng Chuanqi , Yu Yifu , Zhao Bo-Hang , Zhang Bin 
Published: July 2024

AbstractElectrocatalytic semihydrogenation of acetylene (C2H2) provides a facile and petroleum-independent strategy for ethylene (C2H4) production. However, the reliance on the preseparation and concentration of raw coal-derived C2H2 hinders its economic potential. Here, a concave surface is predicted to be beneficial for enriching C2H2 and optimizing its mass transfer kinetics, thus leading to a high partial pressure of C2H2 around active sites for the direct conversion of raw coal-derived C2H2. Then, a porous concave carbon-supported Cu nanoparticle (Cu-PCC) electrode is designed to enrich the C2H2 gas around the Cu sites. As a result, the as-prepared electrode enables a 91.7% C2H4 Faradaic efficiency and a 56.31% C2H2 single-pass conversion under a simulated raw coal-derived C2H2 atmosphere (~15%) at a partial current density of 0.42 A cm−2, greatly outperforming its counterpart without concave surface supports. The strengthened intermolecular π conjugation caused by the increased C2H2 coverage is revealed to result in the delocalization of π electrons in C2H2, consequently promoting C2H2 activation, suppressing hydrogen evolution competition and enhancing C2H4 selectivity.
Transient shuttle for a widespread neural probe with minimal perturbation
Authors: Roh Yeonwook , Kim Hyeongseok , Kim Eun-A , Ji Kyungbin , Kang Minji , Gong Dohyeon , Im Sunghoon , Hong Insic , Park Jieun , Park Soo Jung , Bae Yiseul , Park Jae-Il , Koh Je-Sung , Han Seungyong , Lee Eun Jeong , Kang Daeshik 
Published: July 2024

AbstractBioelectronic implants in the deep brain provide the opportunity to monitor deep brain activity with potential applications in disease diagnostics and treatment. However, mechanical mismatch between a probe and brain tissue can cause surgical trauma in the brain and limit chronic probe-based monitoring, leading to performance degradation. Here, we report a transient shuttle-based probe consisting of a PVA and a mesh-type probe. A rigid shuttle based on PVA implants an ultrathin mesh probe in the target deep brain without a tangle, while creating both a sharp edge for facile penetration into the brain and an anti-friction layer between the probe and brain tissue through dissolving its surface. The capability to shuttle dissolved materials can exclude the retracted process of the shuttle in the brain. Complete dissolution of the shuttle provides a dramatic decrease (~1078-fold) in the stiffness of the probe, which can therefore chronically monitor a wide area of the brain. These results indicate the ability to use a simplistic design for implantation of wide and deep brain probes while preventing unnecessary damage to the brain and probe degradation during long-term use.
Reassortment incompetent live attenuated and replicon influenza vaccines provide improved protection against influenza in piglets
Authors: Graaf-Rau Annika , Schmies Kathrin , Breithaupt Angele , Ciminski Kevin , Zimmer Gert , Summerfield Artur , Sehl-Ewert Julia , Lillie-Jaschniski Kathrin , Helmer Carina , Bielenberg Wiebke , grosse Beilage Elisabeth , Schwemmle Martin , Beer Martin , Harder Timm 
Published: July 2024

AbstractSwine influenza A viruses (swIAV) cause an economically important respiratory disease in modern pig production. Continuous virus transmission and antigenic drift are difficult to control in enzootically infected pig herds. Here, antibody-positive piglets from a herd enzootically infected with swIAV H1N2 (clade 1 A.3.3.2) were immunized using a homologous prime-boost vaccination strategy with novel live attenuated influenza virus (LAIV) based on a reassortment-incompetent bat influenza-swIAV chimera or a vesicular stomatitis virus-based replicon vaccine. Challenge infection of vaccinated piglets by exposure to H1N2 swIAV-infected unvaccinated seeder pigs showed that both LAIV and replicon vaccine markedly reduced virus replication in the upper and lower respiratory tract, respectively, compared to piglets immunized with commercial heterologous or autologous adjuvanted whole-inactivated virus vaccines. Our novel vaccines may aid in interrupting continuous IAV transmission chains in large enzootically infected pig herds, improve the health status of the animals, and reduce the risk of zoonotic swIAV transmission.
Towards an Interoperability Landscape for a National Research Data Infrastructure for Personal Health Data
Authors: Vorisek Carina Nina , Klopfenstein Sophie Anne Inès , Löbe Matthias , Schmidt Carsten Oliver , Mayer Paula Josephine , Golebiewski Martin , Thun Sylvia 
Published: July 2024

AbstractThe German initiative “National Research Data Infrastructure for Personal Health Data” (NFDI4Health) focuses on research data management in health research. It aims to foster and develop harmonized informatics standards for public health, epidemiological studies, and clinical trials, facilitating access to relevant data and metadata standards. This publication lists syntactic and semantic data standards of potential use for NFDI4Health and beyond, based on interdisciplinary meetings and workshops, mappings of study questionnaires and the NFDI4Health metadata schema, and literature search. Included are 7 syntactic, 32 semantic and 9 combined syntactic and semantic standards. In addition, 101 ISO Standards from ISO/TC 215 Health Informatics and ISO/TC 276 Biotechnology could be identified as being potentially relevant. The work emphasizes the utilization of standards for epidemiological and health research data ensuring interoperability as well as the compatibility to NFDI4Health, its use cases, and to (inter-)national efforts within these sectors. The goal is to foster collaborative and inter-sectoral work in health research and initiate a debate around the potential of using common standards.
A high-quality chromosome-level genome assembly of the endangered tree Kmeria septentrionalis
Authors: Shi Chen-Yu , Qin Guo-Le , Qin Ying-Can , Lu Lin-Yuan , Guan De-Long , Gao Li-Xia 
Published: July 2024

AbstractKmeria septentrionalis is a critically endangered tree endemic to Guangxi, China, and is listed on the International Union for Conservation of Nature’s Red List. The lack of genetic information and high-quality genome data has hindered conservation efforts and studies on this species. In this study, we present a chromosome-level genome assembly of K. septentrionalis. The genome was initially assembled to be 2.57 Gb, with a contig N50 of 11.93 Mb. Hi-C guided genome assembly allowed us to anchor 98.83% of the total length of the initial contigs onto 19 pseudochromosomes, resulting in a scaffold N50 of 135.08 Mb. The final chromosome-level genome, spaning 2.54 Gb, achieved a BUSCO completeness of 98.9% and contained 1.67 Gb repetitive elements and 35,927 coding genes. This high-quality genome assembly provides a valuable resource for understanding the genetic basis of conservation-related traits and biological properties of this endangered tree species. Furthermore, it lays a critical foundation for evolutionary studies within the Magnoliaceae family.
Asymptomatic malaria and predictors among migrant farmworkers East Shewa zone Oromia Ethiopia
Authors: Legesse Gudeta , Tafesse Weynshet , Kenea Dagaga , Subussa Bereket Wake , Alemayehu Gezahegn Solomon , Kebede Tadesse , Golassa Lemu , Ali Musa Mohammed , Hailu Asrat 
Published: July 2024

AbstractAsymptomatic malaria can impact existing malaria control and elimination efforts around the world, particularly in Africa, where the majority of malaria cases and death occurs. This is a cross-sectional study aimed to determine the prevalence and predictors of asymptomatic malaria among migrant farmworkers from June to July 2020 in the Upper Awash Agro-industry, East Shewa zone, Oromia Regional State, Ethiopia. A total of 254 migrant farmworkers without signs and symptoms of malaria were enrolled. Data on socio-demographic characteristics and malaria prevention practices were obtained through a structured questionnaire. Venous blood samples were collected and diagnosed using microscopy, rapid diagnostic tests, and polymerase chain reaction (PCR). Data were coded, entered, and analyzed using SPSS version-21 statistical software. Multivariable logistic regression was used to assess associated factors. A p < 0.05 was considered statistically significant. The overall prevalence of asymptomatic malaria among farmworkers in this study was 5.1% [95% CI 1.6, 6.7]. The proportions of Plasmodium falciparum was 90.0% (9/10) while it was 10.0% (1/10) for Plasmodium vivax. Out of the microscopy and/or RDT-confirmed malaria cases, (n = 9; 100%) were confirmed to be P. falciparum by nested PCR, while (n = 3/122; 2.46%) were found to be P. falciparum among 50% negative cases with the microscopy and/or RDT. The gametocyte stage was detected in 40% of microscopically positive cases out of which 44.4% belongs to P. falciparum. Home area/origin of migrant laborers [AOR = 6.08, (95% CI 1.08, 34.66)], family history of malaria [AOR = 8.15, (95% CI 1.43, 46.44)], and outdoor sleeping [AOR = 10.14, (95% CI 1.15, 89.14)] were significantly associated with asymptomatic malaria. In conclusion, asymptomatic malaria was detected among farmworkers in the study area and it was significantly associated with outdoor sleeping, home area, and family history of malaria. Prevention tools and control strategies, particularly focusing on migrant farmworkers, should be considered to support the ongoing malaria control and elimination effort in Ethiopia.
Breast cancer, viruses, and human leukocyte antigen (HLA)
Authors: James Lisa M. , Georgopoulos Apostolos P. 
Published: July 2024

AbstractSeveral viruses have been implicated in breast cancer, including human herpes virus 4 (HHV4), human herpes virus 5 (HHV5), human papilloma virus (HPV), human JC polyoma virus (JCV), human endogenous retrovirus group K (HERVK), bovine leukemia virus (BLV) and mouse mammary tumor virus (MMTV). Human leukocyte antigen (HLA) is involved in virus elimination and has been shown to influence breast cancer protection/susceptibility. Here we investigated the hypothesis that the contribution of a virus to development of breast cancer would depend on the presence of the virus, which, in turn, would be inversely related to the success of its elimination. For that purpose, we estimated in silico predicted binding affinities (PBA) of proteins of the 7 viruses above to 127 common HLA alleles (69 Class I [HLA-I] and 58 Class II HLA-II]) and investigated the association of these binding affinities to the breast cancer—HLA (BC-HLA) immunogenetic profile of the same alleles. Using hierarchical tree clustering, we found that, for HLA-I, viruses BLV, JCV and MMTV were grouped with the BC-HLA, whereas, for HLA-II, viruses BLV, HERVK, HPV, JCV, and MMTV were grouped with BC-HLA. Finally, for both HLA classes, the average PBAs of the viruses grouped with the BC-HLA profile were significantly lower than those of the other, non BC-HLA associated viruses. Assuming that low PBAs are likely associated with slower viral elimination, these findings support the hypothesis that a defective/slower elimination and, hence, longer persistence and inefficient/delayed production of antibodies against them underlies the observed association of the low-PBA group with breast cancer.
Role of serum complement C3 and C4 on kidney outcomes in IgA nephropathy
Authors: Tringali Edoardo , Vetrano Daniele , Tondolo Francesco , Maritati Federica , Fabbrizio Benedetta , Pasquinelli Gianandrea , Provenzano Michele , La Manna Gaetano , Baraldi Olga 
Published: July 2024

AbstractIgA Nephropathy (IgAN) is the most prevalent glomerular disease worldwide. Complement system activation is crucial in its pathogenesis. Few studies correlated serum C3 and C4 with disease activity and prognosis. This retrospective study investigated the prognostic value of serum complement at the time of diagnosis in patients with IgAN. Specifically we evaluated whether adding serum C3 and C4 levels to established predictive models-one based on variables related to chronic kidney disease (CKD) progression and another incorporating variables from the International IgA Prediction Tool (IntIgAPT)-enhances the accuracy of outcome prediction. A composite renal outcome was defined as 50% decline in eGFR or onset of kidney failure. 101 patients were stratified according to baseline C3 levels in three groups (Low, Medium and High). During a median follow-up of 54 months, the Low group exhibited higher incidence of primary outcome (16.3 events vs 2.9 and 1.7 events × 100 pts/year, p = 0.0026). Model-1 (M1), consisting of CKD progression variables, and Model-3 (M3), comprising IntIgANPT variables, were implemented with baseline C3 and C4 to create Model-2 (M2) and Model-4 (M4), respectively. M2 demonstrated better predictive performance over M1, showing higher discrimination (lower AIC and BIC, higher C-index and NR2). Similarly, M4 outperformed M3, showing enhanced outcome prediction when C3 and C4 levels were added. Implementation of serum C3 and C4 can enhance prediction accuracy of already-validated prognostic models in IgAN. Lower C3 and higher C4 levels were associated with poorer prognosis, highlighting a more 'Complement-Pathic' subset of patients.
A comprehensive analysis of germline predisposition to early-onset ovarian cancer
Authors: Horackova Klara , Zemankova Petra , Nehasil Petr , Vocka Michal , Hovhannisyan Milena , Matejkova Katerina , Janatova Marketa , Cerna Marta , Kleiblova Petra , Jelinkova Sandra , Stastna Barbora , Just Pavel , Dolezalova Tatana , Nemcova Barbora , Urbanova Marketa , Koudova Monika , Hazova Jana , Machackova Eva , Foretova Lenka , Stranecky Viktor , Zikan Michal , Kleibl Zdenek , Soukupova Jana 
Published: July 2024

AbstractThe subset of ovarian cancer (OC) diagnosed ≤ 30yo represents a distinct subgroup exhibiting disparities from late-onset OC in many aspects, including indefinite germline cancer predisposition. We performed DNA/RNA-WES with HLA-typing, PRS assessment and survival analysis in 123 early-onset OC-patients compared to histology/stage-matched late-onset and unselected OC-patients, and population-matched controls. Only 6/123(4.9%) early-onset OC-patients carried a germline pathogenic variant (GPV) in high-penetrance OC-predisposition genes. Nevertheless, our comprehensive germline analysis of early-onset OC-patients revealed two divergent trajectories of potential germline susceptibility. Firstly, overrepresentation analysis highlighted a connection to breast cancer (BC) that was supported by the CHEK2 GPV enrichment in early-onset OC(p = 1.2 × 10–4), and the presumably BC-specific PRS313, which successfully stratified early-onset OC-patients from controls(p = 0.03). The second avenue pointed towards the impaired immune response, indicated by LY75-CD302 GPV(p = 8.3 × 10–4) and diminished HLA diversity compared with controls(p = 3 × 10–7). Furthermore, we found a significantly higher overall GPV burden in early-onset OC-patients compared to controls(p = 3.8 × 10–4). The genetic predisposition to early-onset OC appears to be a heterogeneous and complex process that goes beyond the traditional Mendelian monogenic understanding of hereditary cancer predisposition, with a significant role of the immune system. We speculate that rather a cumulative overall GPV burden than specific GPV may potentially increase OC risk, concomitantly with reduced HLA diversity.
Green method for 17-hydroxyprogesterone extraction and determination using PDMS stir bar sorptive extraction coupled with HPLC: optimization by response surface methodology
Authors: Noori Maedeh , Talebpour Zahra 
Published: July 2024

AbstractQuantifying small amounts of the 17-hydroxyprogesterone in various matrix is crucial for different purposes. In this study, a commercial polydimethylsiloxane stir bar was used to extract hormone from water and urine samples. Analysis was performed by high-performance liquid chromatography using a UV detector. The response surface methodology was used to optimize the desorption and extraction steps, with predicted optimal point relative errors of 1.25% and 6.40%, respectively. The optimized method was validated with a linear range of 1.21–1000.00 for aqueous and 2.43–2000.00 ng mL–1 for urine samples. The coefficient of determination was 0.9998 and 0.9967, and the detection limit of the proposed method was obtained to be 0.40 and 0.80 ng mL–1 for aqueous and urine samples, respectively. The recovery percentage and relative standard deviation within a day and between three days after the addition of three different concentration levels of the standard to the control sample were 87–103% and 0.4–3.6% for aqueous and 87.5–101% and 0.1–5.2% for urine samples, respectively. The results show that the proposed method can be appropriate and cost-effective for extracting and analyzing this hormone. In addition, using three different tools, the greenness of the proposed method was proven.
Effects of different afforestation years on soil moisture and nutrient content in Maxian Mountain of the Loess Plateau
Authors: Mao Liang , Miao Yugu , Ge Yiru , Wei Shaochong , Yang Xuanyi , Li Shijie , Si Li , Gou Yu-Ping , Quandahor Peter 
Published: July 2024

AbstractIn the area of “returning farmland to forest” on the Loess Plateau in China, it is difficult to cultivate artificially planted trees into forests. In the current study, abandoned cultivated land after 10 years of natural restoration served as controls (CK), while the treatments included afforestation periods of 2, 4, 6, 8, and 10 years. Soil samples were collected from various depths: 0–20, 20–40, 40–60, 60–80, to 80–100 cm. The findings revealed that with increasing years of artificial afforestation, soil pH gradually increased, and soil moisture content rose in the 0–20 cm layer while declining in deeper layers (20–100 cm) in the Maxian Mountain region of the Loess Plateau. Moreover, the total carbon, nitrogen, phosphorus, and potassium content initially increased and then decreased with the duration of artificial afforestation, reaching peak values after 8 years. Contents of organic matter, ammonium nitrogen, nitrate nitrogen, available phosphorus, and available potassium in the same soil layer increased with each year of afforestation. However, upon reaching 10 years of artificial afforestation, the effective nutrient content in the 60–80 and 80–100 cm soil layers exhibited a decrease. The values of Integrated Fertility Index (IFI) in different afforestation years were ranked as follows: 8 years > 6 years > 10 years > 4 years > 2 year, but all of them were significantly smaller than those of natural restoration plot CK (P < 0.05). Overall, soil fertility in the Maxian Mountain area of the Loess Plateau increases with each additional year of artificial afforestation. However, when the artificial afforestation period is 10 years, soil fertility decreases and marking a shift from enhancement to decline beyond this duration.