bluuebunny/crossref_metadata_2025_split huggingface dataset:
The soluble (pro)renin receptor promotes a preeclampsia-like phenotype both in vitro and in vivo
Authors: Schofield Lachlan G. , Delforce Sarah J. , Pryor Jennifer C. , Endacott Saije K. , Lumbers Eugenie R. , Marshall Sarah A. , Pringle Kirsty G. 
Published: April 2024

AbstractPreeclampsia is classified as new-onset hypertension coupled with gross endothelial dysfunction. Placental (pro)renin receptor ((P)RR) and plasma soluble (P)RR (s(P)RR) are elevated in patients with preeclampsia. Thus, we aimed to interrogate the role (P)RR may play in the pathogenesis of preeclampsia. Human uterine microvascular endothelial cells (HUtMECs, n = 4) were cultured with either; vehicle (PBS), 25–100 nM recombinant s(P)RR, or 10 ng/ml TNF-a (positive control) for 24 h. Conditioned media and cells were assessed for endothelial dysfunction markers via qPCR, ELISA, and immunoblot. Angiogenic capacity was assessed through tube formation and adhesion assays. Additionally, pregnant rats were injected with an adenovirus overexpressing s(P)RR from mid-pregnancy (day 8.5), until term (n = 6–7 dams/treatment). Maternal and fetal tissues were assessed. HUtMECs treated with recombinant s(P)RR displayed increased expression of endothelial dysfunction makers including vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and endothelin-1 mRNA expression (P = 0.003, P = 0.001, P = 0.009, respectively), along with elevated endothelin-1 protein secretion (P < 0.001) compared with controls. Recombinant s(P)RR impaired angiogenic capacity decreasing the number of branches, total branch length, and mesh area (P < 0.001, P = 0.004, and P = 0.009, respectively), while also increasing vascular adhesion (P = 0.032). +ADV rats exhibited increased systolic (P = 0.001), diastolic (P = 0.010), and mean arterial pressures (P = 0.012), compared with -ADV pregnancies. Renal arteries from +ADV-treated rats had decreased sensitivity to acetylcholine-induced relaxation (P = 0.030), compared with -ADV pregnancies. Our data show that treatment with s(P)RR caused hypertension and growth restriction in vivo and caused marked endothelial dysfunction in vitro. These findings demonstrate the significant adverse actions of s(P)RR on vascular dysfunction that is characteristic of the preeclamptic phenotype.
Nardilysin-regulated scission mechanism activates polo-like kinase 3 to suppress the development of pancreatic cancer
Authors: Fu Jie , Ling Jianhua , Li Ching-Fei , Tsai Chi-Lin , Yin Wenjuan , Hou Junwei , Chen Ping , Cao Yu , Kang Ya’an , Sun Yichen , Xia Xianghou , Jiang Zhou , Furukawa Kenei , Lu Yu , Wu Min , Huang Qian , Yao Jun , Hawke David H. , Pan Bih-Fang , Zhao Jun , Huang Jiaxing , Wang Huamin , Bahassi E. I. Mustapha , Stambrook Peter J. , Huang Peng , Fleming Jason B. , Maitra Anirban , Tainer John A. , Hung Mien-Chie , Lin Chunru , Chiao Paul J. 
Published: April 2024

AbstractPancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of KrasG12D-driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find that p41Plk3 is the activated form of Plk3 that regulates a feed-forward mechanism to promote apoptosis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism.
Deficiency of the HGF/Met pathway leads to thyroid dysgenesis by impeding late thyroid expansion
Authors: Fang Ya , Wan Jia-Ping , Wang Zheng , Song Shi-Yang , Zhang Cao-Xu , Yang Liu , Zhang Qian-Yue , Yan Chen-Yan , Wu Feng-Yao , Lu Sang-Yu , Sun Feng , Han Bing , Zhao Shuang-Xia , Dong Mei , Song Huai-Dong 
Published: April 2024

AbstractThe mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes and identify a stop-gain mutation inhgfaand two missense mutations inmetby positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation inhgfaormet. Further studies show that MAPK inhibitor U0126 could mimic thyroid dysgenesis in zebrafish, and the phenotypes are rescued by overexpression of constitutively active MEK or Snail, downstream molecules of the HGF/Met pathway, in thyrocytes. Moreover, HGF promotes thyrocyte migration, which is probably mediated by downregulation ofE-cadherinexpression. The delayed bifurcation of the thyroid primordium is also observed in thyroid-specific Met knockout mice. Together, our findings reveal that HGF/Met is indispensable for the bifurcation of the thyroid primordium during thyroid development mediated by downregulation ofE-cadherinin thyrocytes via MAPK-snail pathway.
Structural basis for dimerization of a paramyxovirus polymerase complex
Authors: Xie Jin , Ouizougun-Oubari Mohamed , Wang Li , Zhai Guanglei , Wu Daitze , Lin Zhaohu , Wang Manfu , Ludeke Barbara , Yan Xiaodong , Nilsson Tobias , Gao Lu , Huang Xinyi , Fearns Rachel , Chen Shuai 
Published: April 2024

AbstractThe transcription and replication processes of non-segmented, negative-strand RNA viruses (nsNSVs) are catalyzed by a multi-functional polymerase complex composed of the large protein (L) and a cofactor protein, such as phosphoprotein (P). Previous studies have shown that the nsNSV polymerase can adopt a dimeric form, however, the structure of the dimer and its function are poorly understood. Here we determine a 2.7 Å cryo-EM structure of human parainfluenza virus type 3 (hPIV3) L–P complex with the connector domain (CD′) of a second L built, while reconstruction of the rest of the second L–P obtains a low-resolution map of the ring-like L core region. This study reveals detailed atomic features of nsNSV polymerase active site and distinct conformation of hPIV3 L with a unique β-strand latch. Furthermore, we report the structural basis of L–L dimerization, with CD′ located at the putative template entry of the adjoining L. Disruption of the L–L interface causes a defect in RNA replication that can be overcome by complementation, demonstrating that L dimerization is necessary for hPIV3 genome replication. These findings provide further insight into how nsNSV polymerases perform their functions, and suggest a new avenue for rational drug design.
Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights
Authors: Sujit Sheeba J. , Aminu Muhammad , Karpinets Tatiana V. , Chen Pingjun , Saad Maliazurina B. , Salehjahromi Morteza , Boom John D. , Qayati Mohamed , George James M. , Allen Haley , Antonoff Mara B. , Hong Lingzhi , Hu Xin , Heeke Simon , Tran Hai T. , Le Xiuning , Elamin Yasir Y. , Altan Mehmet , Vokes Natalie I. , Sheshadri Ajay , Lin Julie , Zhang Jianhua , Lu Yang , Behrens Carmen , Godoy Myrna C. B. , Wu Carol C. , Chang Joe Y. , Chung Caroline , Jaffray David A. , Wistuba Ignacio I. , Lee J. Jack , Vaporciyan Ara A. , Gibbons Don L. , Heymach John , Zhang Jianjun , Cascone Tina , Wu Jia 
Published: April 2024

AbstractWhile we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors. This framework identifies three PET/CT subtypes, which maintain prognostic value after adjusting for clinicopathologic risk factors including tumor volume. Additionally, these subtypes complement ctDNA in predicting disease recurrence. Radiogenomics analysis unveil the molecular underpinnings of these imaging subtypes, highlighting downregulation in interferon alpha and gamma pathways in the high-risk subtype. In summary, our study demonstrates that these habitat imaging subtypes effectively stratify NSCLC patients based on their risk levels for disease recurrence after initial curative surgery or radiotherapy, providing valuable insights for personalized treatment approaches.
KSNP: a fast de Bruijn graph-based haplotyping tool approaching data-in time cost
Authors: Zhou Qian , Ji Fahu , Lin Dongxiao , Liu Xianming , Zhu Zexuan , Ruan Jue 
Published: April 2024

AbstractLong reads that cover more variants per read raise opportunities for accurate haplotype construction, whereas the genotype errors of single nucleotide polymorphisms pose great computational challenges for haplotyping tools. Here we introduce KSNP, an efficient haplotype construction tool based on the de Bruijn graph (DBG). KSNP leverages the ability of DBG in handling high-throughput erroneous reads to tackle the challenges. Compared to other notable tools in this field, KSNP achieves at least 5-fold speedup while producing comparable haplotype results. The time required for assembling human haplotypes is reduced to nearly the data-in time.
Noncanonical assembly, neddylation and chimeric cullin–RING/RBR ubiquitylation by the 1.8 MDa CUL9 E3 ligase complex
Authors: Horn-Ghetko Daniel , Hopf Linus V. M. , Tripathi-Giesgen Ishita , Du Jiale , Kostrhon Sebastian , Vu D. Tung , Beier Viola , Steigenberger Barbara , Prabu J. Rajan , Stier Luca , Bruss Elias M. , Mann Matthias , Xiong Yue , Schulman Brenda A. 
Published: April 2024

AbstractUbiquitin ligation is typically executed by hallmark E3 catalytic domains. Two such domains, ‘cullin–RING’ and ‘RBR’, are individually found in several hundred human E3 ligases, and collaborate with E2 enzymes to catalyze ubiquitylation. However, the vertebrate-specific CUL9 complex with RBX1 (also called ROC1), of interest due to its tumor suppressive interaction with TP53, uniquely encompasses both cullin–RING and RBR domains. Here, cryo-EM, biochemistry and cellular assays elucidate a 1.8-MDa hexameric human CUL9–RBX1 assembly. Within one dimeric subcomplex, an E2-bound RBR domain is activated by neddylation of its own cullin domain and positioning from the adjacent CUL9–RBX1 in trans. Our data show CUL9 as unique among RBX1-bound cullins in dependence on the metazoan-specific UBE2F neddylation enzyme, while the RBR domain protects it from deneddylation. Substrates are recruited to various upstream domains, while ubiquitylation relies on both CUL9’s neddylated cullin and RBR domains achieving self-assembled and chimeric cullin–RING/RBR E3 ligase activity.
A document-level information extraction pipeline for layered cathode materials for sodium-ion batteries
Authors: Gou Yuxiao , Zhang Yiping , Zhu Jian , Shu Yidan 
Published: April 2024

AbstractNatural language processing techniques enable extraction of valuable information from large amounts of published literature for the application of data science and technology, i.e. machine learning in the field of materials science. Nevertheless, the automated extraction of data from full-text documents remains a complex task. We propose a document-level natural language processing pipeline for literature extraction of comprehensive information on layered cathode materials for sodium-ion batteries. The pipeline enhances entity recognition with contextual supplementary information while capturing the article structure. Finally, a heuristic multi-level relationship extraction algorithm is employed in relation extraction to extract experimental parameters and complex performance relationships respectively. We successfully extracted a comprehensive dataset containing 5265 records from 1747 documents, encompassing essential information such as chemical composition, synthesis parameters, and electrochemical properties. By implementing our pipeline, we have made significant progress in overcoming the challenges associated with data scarcity in battery informatics. The extracted datasets provide a valuable resource for further research and development in the field of layered cathode materials.
A bicoherence approach to analyze multi-dimensional cross-frequency coupling in EEG/MEG data
Authors: Basti Alessio , Nolte Guido , Guidotti Roberto , Ilmoniemi Risto J. , Romani Gian Luca , Pizzella Vittorio , Marzetti Laura 
Published: April 2024

AbstractWe introduce a blockwise generalisation of the Antisymmetric Cross-Bicoherence (ACB), a statistical method based on bispectral analysis. The Multi-dimensional ACB (MACB) is an approach that aims at detecting quadratic lagged phase-interactions between vector time series in the frequency domain. Such a coupling can be empirically observed in functional neuroimaging data, e.g., in electro/magnetoencephalographic signals. MACB is invariant under orthogonal trasformations of the data, which makes it independent, e.g., on the choice of the physical coordinate system in the neuro-electromagnetic inverse procedure. In extensive synthetic experiments, we prove that MACB performance is significantly better than that obtained by ACB. Specifically, the shorter the data length, or the higher the dimension of the single data space, the larger the difference between the two methods.
Anticancer, antioxidant, and antibacterial activity of chemically fingerprinted extract from Cyclamen persicum Mill.
Authors: Al-Rimawi Fuad , Khalid Mahmoud , Salah Zaidoun , Zawahreh Malak A. A. , Alnasser Sulaiman Mohammed , Alshammari Shifaa O. , Wedian Fadel , Karimulla Shaik , Almutairi Abdulrahman , Alanazi Fadi Ibrahim B. , Alanazi Hamad Owijan , Al-Mazaideh Ghassab M. , Nafidi Hiba-Allah , Salamatullah Ahmad Mohammad , Mekonnen Amare Bitew , Bourhia Mohammed 
Published: April 2024

AbstractIn the last few decades, researchers have thoroughly studied the use of plants in Palestine, one of them is Cyclamen persicum Mill. (C. persicum). Cyclamen persicum has been historically cultivated since the 1700s due to its tuber. The tuber is known to stimulate the nasal receptors, thus triggering the sensory neurons. Cyclamen persicum has anti-inflammatory effects, reduces cholesterol levels, treats diabetes, and inhibits tumor growth. In this respect, in-vitro examination of antibacterial and anticancer activities and antioxidative potency of C. persicum ethanolic extract were evaluated. The antioxidative potency of the extracted plant material was determined spectrophotometrically using the DPPH free radical scavenging method and the HPLC–PDA method to evaluate its total phenolic content (TPC) and total flavonoid content (TFC). The experimental results demonstrated limited antibacterial activity of C. persicum extract against both gram negative (E. coli) and gram positive (Streptococcus and S. aureus) bacterial strains, with the observed zones of inhibition measuring less than 8 mm. On the other hand, powerful activity against MCF7 breast cancer as well as HT29 colon cancer cell lines was obtained. The findings also revealed potent inhibition of free radicals and the presence of maximal levels of natural products such as phenolic compounds and flavonoids, which supportits biological activities and powerful ability to scavenge free radicals. HPLC results showed the presence of numerous flavonoid and phenolic compounds such as rutin, chlorogenic acid, kaempferol, trans-cinnamic acid, quercetin, sinapic acid, and p-coumaric acid.
Using Mendelian randomization provides genetic insights into potential targets for sepsis treatment
Authors: Xia Rui , Sun Meng , Yin Jing , Zhang Xu , Li Jianhua 
Published: April 2024

AbstractSepsis is recognized as a major contributor to the global disease burden, but there is a lack of specific and effective therapeutic agents. Utilizing Mendelian randomization (MR) methods alongside evidence of causal genetics presents a chance to discover novel targets for therapeutic intervention. MR approach was employed to investigate potential drug targets for sepsis. Pooled statistics from IEU-B-4980 comprising 11,643 cases and 474,841 controls were initially utilized, and the findings were subsequently replicated in the IEU-B-69 (10,154 cases and 454,764 controls). Causal associations were then validated through colocalization. Furthermore, a range of sensitivity analyses, including MR-Egger intercept tests and Cochran's Q tests, were conducted to evaluate the outcomes of the MR analyses. Three drug targets (PSMA4, IFNAR2, and LY9) exhibited noteworthy MR outcomes in two separate datasets. Notably, PSMA4 demonstrated not only an elevated susceptibility to sepsis (OR 1.32, 95% CI 1.20–1.45, p = 1.66E−08) but also exhibited a robust colocalization with sepsis (PPH4 = 0.74). According to the present MR analysis, PSMA4 emerges as a highly encouraging pharmaceutical target for addressing sepsis. Suppression of PSMA4 could potentially decrease the likelihood of sepsis.
Design of efficient binary multiplier architecture using hybrid compressor with FPGA implementation
Authors: Thamizharasan V. , Parthipan V. 
Published: April 2024

AbstractIn signal processing applications, the multipliers are essential component of arithmetic functional units in many applications, like digital signal processors, image/video processing, Machine Learning, Cryptography and Arithmetic & Logical units (ALU). In recent years, Profuse multipliers are there. In that, Vedic multiplier is one of the high-performance multiplications and it is used to signal/image processing applications. In order to ameliorate the performance of this multiplier further, by proposed a novel multiplier using hybrid compressor. The proposed hybrid compressor-based multiplier is designed and implemented in Field programmable Gate Array (FPGA—spartan 6). The synthesis result shows that the speed of proposed hybrid compressor-based multiplier gets improved as compared to Array multiplier (35.83%), Wallace tree multiplier (34.58%), Vedic Multiplier based on Carry look ahead adder (CLA) (28.49%), Vedic Multiplier based on Ripple carry adder (RCA) (20.65%), Booth Multiplication (21.65%) and Vedic Multiplication based on Han-Carlson Adder (HCA) (20.10%) and Hybrid multiplier using Carry Select Adder (CSELA) (17.81%) and Hybrid Vedic Multiplier (7.15%).
Slow response of surface water temperature to fast atmospheric variability reveals mixing heterogeneity in a deep lake
Authors: Amadori Marina , Bresciani Mariano , Giardino Claudia , Dijkstra Henk A. 
Published: April 2024

AbstractSlow and long-term variations of sea surface temperature anomalies have been interpreted as a red-noise response of the ocean surface mixed layer to fast and random atmospheric perturbations. How fast the atmospheric noise is damped depends on the mixed layer depth. In this work we apply this theory to determine the relevant spatial and temporal scales of surface layer thermal inertia in lakes. We fit a first order auto-regressive model to the satellite-derived Lake Surface Water Temperature (LSWT) anomalies in Lake Garda, Italy. The fit provides a time scale, from which we determine the mixed layer depth. The obtained result shows a clear spatial pattern resembling the morphological features of the lake, with larger values (7.18± 0.3 m) in the deeper northwestern basin, and smaller values (3.18 ± 0.24 m) in the southern shallower basin. Such variations are confirmed by in-situ measurements in three monitoring points in the lake and connect to the first Empirical Orthogonal Function of satellite-derived LSWT and chlorophyll-a concentration. Evidence from our case study open a new perspective for interpreting lake-atmosphere interactions and confirm that remotely sensed variables, typically associated with properties of the surface layers, also carry information on the relevant spatial and temporal scales of mixed-layer processes.
Identifying influential nodes based on the disassortativity and community structure of complex network
Authors: Wang Zuxi , Huang Ruixiang , Yang Dian , Peng Yuqiang , Zhou Boyun , Chen Zhong 
Published: April 2024

AbstractThe complex networks exhibit significant heterogeneity in node connections, resulting in a few nodes playing critical roles in various scenarios, including decision-making, disease control, and population immunity. Therefore, accurately identifying these influential nodes that play crucial roles in networks is very important. Many methods have been proposed in different fields to solve this issue. This paper focuses on the different types of disassortativity existing in networks and innovatively introduces the concept of disassortativity of the node, namely, the inconsistency between the degree of a node and the degrees of its neighboring nodes, and proposes a measure of disassortativity of the node (DoN) by a step function. Furthermore, the paper analyzes and indicates that in many real-world network applications, such as online social networks, the influence of nodes within the network is often associated with disassortativity of the node and the community boundary structure of the network. Thus, the influential metric of node based on disassortativity and community structure (mDC) is proposed. Extensive experiments are conducted in synthetic and real networks, and the performance of the DoN and mDC is validated through network robustness experiments and immune experiment of disease infection. Experimental and analytical results demonstrate that compared to other state-of-the-art centrality measures, the proposed methods (DoN and mDC) exhibits superior identification performance and efficiency, particularly in non-disassortative networks and networks with clear community structures. Furthermore, we find that the DoN and mDC exhibit high stability to network noise and inaccuracies of the network data.