bluuebunny/crossref_metadata_2025_split huggingface dataset:
RAB14 promotes epithelial-mesenchymal transition in bladder cancer through autophagy‑dependent AKT signaling pathway
Authors: Deng Huanhuan , Deng Leihong , Chao Haichao , Yu Zhaojun , Huang Jianbiao , Song Zhen , Peng Lifen , Zeng Tao 
Published: August 2023

AbstractBladder cancer (BLCA) is the 9th most common cancer of mortality. Autophagy and epithelial to mesenchymal transition (EMT) have an essential role in cancer invasion and metastasis. However, the relationship between autophagy and EMT is still poorly understood in BLCA. Functional enrichment and pathway network analysis were carried out. Comprehensive protein-protein interactions (PPI) networks were proposed to prioritize candidate autophagy-related genes. Furthermore, an autophagy-related signature and a nomogram model were established by integrating clinical information and this signature risk score to evaluate candidate autophagy-related genes. RAB14 expression and its association with pathological information and survival were evaluated in samples from TCGA dataset. Knocking down RAB14 in T24 cells was constructed, and immunofluorescence staining, transmission electron microscopy, immunohistochemistry and western blotting and a series of functional assays were performed to evaluate the migration, invasion, EMT and autophagy abilities of BLCA cells. The autophagy-related gene RAB14 was the only candidate gene identified by three kinds of analytic approaches. RAB14 was highly upregulated in BLCA and correlated with clinical outcomes based on TCGA BLCA datasets. Knocking down RAB14 was found to inhibit EMT and autophagy in T24 cells. RAB14 levels were positively related to those of LC3B and Beclin1, two genes with critical roles in the autophagy process, and the correlation was further confirmed in clinical tissue specimens by IHC and western blot analysis. In addition, RAB14-promoted EMT, migration, and invasion in T24 cells could be partially reversed by autophagy activator, rapamycin. The effects of RAB14 on autophagy was associated with level of p-Akt, indicating that they were possibly mediated via PI3K/AKT signaling. These findings indicated that autophagy-related gene RAB14-promoted EMT, migration and invasion of bladder cancer via the Akt-associated autophagic pathway.
Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase/transferase
Authors: Wang Chongyang , Liu Changshui , Zhu Xiaochuan , Peng Quancai , Ma Qingjun 
Published: August 2023

AbstractAlthough enzyme catalysis is typified by high specificity, enzymes can catalyze various substrates (substrate promiscuity) and/or different reaction types (catalytic promiscuity) using a single active site. This interesting phenomenon is widely distributed in enzyme catalysis, with both fundamental and applied importance. To date, the mechanistic understanding of enzyme promiscuity is very limited. Herein, we report the structural mechanism underlying the substrate and catalytic promiscuity of Vibrio dual lipase/transferase (VDLT). Crystal structures of the VDLT from Vibrio alginolyticus (ValDLT) and its fatty acid complexes were solved, revealing prominent structural flexibility. In particular, the “Ser−His−Asp” catalytic triad machinery of ValDLT contains an intrinsically flexible oxyanion hole. Analysis of ligand-bound structures and mutagenesis showed that the flexible oxyanion hole and other binding residues can undergo distinct conformational changes to facilitate substrate and catalytic promiscuity. Our study reveals a previously unknown flexible form of the famous catalytic triad machinery and proposes a “catalytic site tuning” mechanism to expand the mechanistic paradigm of enzyme promiscuity.
Molecular insights into intrinsic transducer-coupling bias in the CXCR4-CXCR7 system
Authors: Sarma Parishmita , Carino Carlo Marion C. , Seetharama Deeksha , Pandey Shubhi , Dwivedi-Agnihotri Hemlata , Rui Xue , Cao Yubo , Kawakami Kouki , Kumari Poonam , Chen Yu-Chih , Luker Kathryn E. , Yadav Prem N. , Luker Gary D. , Laporte Stéphane A. , Chen Xin , Inoue Asuka , Shukla Arun K. 
Published: August 2023

AbstractChemokine receptors constitute an important subfamily of G protein-coupled receptors (GPCRs), and they are critically involved in a broad range of immune response mechanisms. Ligand promiscuity among these receptors makes them an interesting target to explore multiple aspects of biased agonism. Here, we comprehensively characterize two chemokine receptors namely, CXCR4 and CXCR7, in terms of their transducer-coupling and downstream signaling upon their stimulation by a common chemokine agonist, CXCL12, and a small molecule agonist, VUF11207. We observe that CXCR7 lacks G-protein-coupling while maintaining robust βarr recruitment with a major contribution of GRK5/6. On the other hand, CXCR4 displays robust G-protein activation as expected but exhibits significantly reduced βarr-coupling compared to CXCR7. These two receptors induce distinct βarr conformations even when activated by the same agonist, and CXCR7, unlike CXCR4, fails to activate ERK1/2 MAP kinase. We also identify a key contribution of a single phosphorylation site in CXCR7 for βarr recruitment and endosomal localization. Our study provides molecular insights into intrinsic-bias encoded in the CXCR4-CXCR7 system with broad implications for drug discovery.
Diastereo- and atroposelective synthesis of N-arylpyrroles enabled by light-induced phosphoric acid catalysis
Authors: Dai Lei , Zhou Xueting , Guo Jiami , Dai Xuan , Huang Qingqin , Lu Yixin 
Published: August 2023

AbstractThe C−N axially chiral N-arylpyrrole motifs are privileged scaffolds in numerous biologically active molecules and natural products, as well as in chiral ligands/catalysts. Asymmetric synthesis of N-arylpyrroles, however, is still challenging, and the simultaneous creation of contiguous C−N axial and central chirality remains unknown. Herein, a diastereo- and atroposelective synthesis of N-arylpyrroles enabled by light-induced phosphoric acid catalysis has been developed. The key transformation is a one-pot, three-component oxo-diarylation reaction, which simultaneously creates a C−N axial chirality and a central quaternary stereogenic center. A broad range of unactivated alkynes were readily employed as a reaction partner in this transformation, and the N-arylpyrrole products are obtained in good yields, with excellent enantioselectivities and very good diastereoselectivities. Notably, the N-arylpyrrole skeletons represent interesting structural motifs that could be used as chiral ligands and catalysts in asymmetric catalysis.
Unreprogrammed H3K9me3 prevents minor zygotic genome activation and lineage commitment in SCNT embryos
Authors: Xu Ruimin , Zhu Qianshu , Zhao Yuyan , Chen Mo , Yang Lingyue , Shen Shijun , Yang Guang , Shi Zhifei , Zhang Xiaolei , Shi Qi , Kou Xiaochen , Zhao Yanhong , Wang Hong , Jiang Cizhong , Li Chong , Gao Shaorong , Liu Xiaoyu 
Published: August 2023

AbstractSomatic cell nuclear transfer (SCNT) can be used to reprogram differentiated somatic cells to a totipotent state but has poor efficiency in supporting full-term development. H3K9me3 is considered to be an epigenetic barrier to zygotic genomic activation in 2-cell SCNT embryos. However, the mechanism underlying the failure of H3K9me3 reprogramming during SCNT embryo development remains elusive. Here, we perform genome-wide profiling of H3K9me3 in cumulus cell-derived SCNT embryos. We find redundant H3K9me3 marks are closely related to defective minor zygotic genome activation. Moreover, SCNT blastocysts show severely indistinct lineage-specific H3K9me3 deposition. We identify MAX and MCRS1 as potential H3K9me3-related transcription factors and are essential for early embryogenesis. Overexpression of Max and Mcrs1 significantly benefits SCNT embryo development. Notably, MCRS1 partially rescues lineage-specific H3K9me3 allocation, and further improves the efficiency of full-term development. Importantly, our data confirm the conservation of deficient H3K9me3 differentiation in Sertoli cell-derived SCNT embryos, which may be regulated by alternative mechanisms.
Emergent layer stacking arrangements in c-axis confined MoTe2
Authors: Hart James L. , Bhatt Lopa , Zhu Yanbing , Han Myung-Geun , Bianco Elisabeth , Li Shunran , Hynek David J. , Schneeloch John A. , Tao Yu , Louca Despina , Guo Peijun , Zhu Yimei , Jornada Felipe , Reed Evan J. , Kourkoutis Lena F. , Cha Judy J. 
Published: August 2023

AbstractThe layer stacking order in 2D materials strongly affects functional properties and holds promise for next-generation electronic devices. In bulk, octahedral MoTe2 possesses two stacking arrangements, the ferroelectric Weyl semimetal Td phase and the higher-order topological insulator 1T′ phase. However, in thin flakes of MoTe2, it is unclear if the layer stacking follows the Td, 1T′, or an alternative stacking sequence. Here, we use atomic-resolution scanning transmission electron microscopy to directly visualize the MoTe2 layer stacking. In thin flakes, we observe highly disordered stacking, with nanoscale 1T′ and Td domains, as well as alternative stacking arrangements not found in the bulk. We attribute these findings to intrinsic confinement effects on the MoTe2 stacking-dependent free energy. Our results are important for the understanding of exotic physics displayed in MoTe2 flakes. More broadly, this work suggests c-axis confinement as a method to influence layer stacking in other 2D materials.
Multifunctional IgG/IgM antibodies and cellular cytotoxicity are elicited by the full-length MSP1 SumayaVac-1 malaria vaccine
Authors: Rosenkranz Micha , Fürle Kristin , Hibbert Julia , Ulmer Anne , Ali Arin , Giese Thomas , Blank Antje , Haefeli Walter E. , Böhnlein Ernst , Lanzer Michael , Thomson-Luque Richard 
Published: August 2023

AbstractRadical control of malaria likely requires a vaccine that targets both the asymptomatic liver stages and the disease-causing blood stages of the human malaria parasite Plasmodium falciparum. While substantial progress has been made towards liver stage vaccines, the development of a blood stage vaccine is lagging behind. We have recently conducted a first-in-human clinical trial to evaluate the safety and immunogenicity of the recombinant, full-length merozoite surface protein 1 (MSP1FL) formulated with GLA-SE as adjuvant. Here, we show that the vaccine, termed SumayaVac-1, elicited both a humoral and cellular immune response as well as a recall T cell memory. The induced IgG and IgM antibodies were able to stimulate various Fc-mediated effector mechanisms associated with protection against malaria, including phagocytosis, release of reactive oxygen species, production of IFN-γ as well as complement activation and fixation. The multifunctional activity of the humoral immune response remained for at least 6 months after vaccination and was comparable to that of naturally acquired anti-MSP1 antibodies from semi-immune adults from Kenya. We further present evidence of SumayaVac-1 eliciting a recallable cellular cytotoxicity by IFN-γ producing CD8+ T cells. Our study revitalizes MSP1FL as a relevant blood stage vaccine candidate and warrants further evaluation of SumayaVac-1 in a phase II efficacy trial.
Reversed Holocene temperature–moisture relationship in the Horn of Africa
Authors: Baxter A. J. , Verschuren D. , Peterse F. , Miralles D. G. , Martin-Jones C. M. , Maitituerdi A. , Van der Meeren T. , Van Daele M. , Lane C. S. , Haug G. H. , Olago D. O. , Sinninghe Damsté J. S. 
Published: August 2023

AbstractAnthropogenic climate change is predicted to severely impact the global hydrological cycle1, particularly in tropical regions where agriculture-based economies depend on monsoon rainfall2. In the Horn of Africa, more frequent drought conditions in recent decades3,4 contrast with climate models projecting precipitation to increase with rising temperature5. Here we use organic geochemical climate-proxy data from the sediment record of Lake Chala (Kenya and Tanzania) to probe the stability of the link between hydroclimate and temperature over approximately the past 75,000 years, hence encompassing a sufficiently wide range of temperatures to test the ‘dry gets drier, wet gets wetter’ paradigm6 of anthropogenic climate change in the time domain. We show that the positive relationship between effective moisture and temperature in easternmost Africa during the cooler last glacial period shifted to negative around the onset of the Holocene 11,700 years ago, when the atmospheric carbon dioxide concentration exceeded 250 parts per million and mean annual temperature approached modern-day values. Thus, at that time, the budget between monsoonal precipitation and continental evaporation7 crossed a tipping point such that the positive influence of temperature on evaporation became greater than its positive influence on precipitation. Our results imply that under continued anthropogenic warming, the Horn of Africa will probably experience further drying, and they highlight the need for improved simulation of both dynamic and thermodynamic processes in the tropical hydrological cycle.
Coral reefs benefit from reduced land–sea impacts under ocean warming
Authors: Gove Jamison M. , Williams Gareth J. , Lecky Joey , Brown Eric , Conklin Eric , Counsell Chelsie , Davis Gerald , Donovan Mary K. , Falinski Kim , Kramer Lindsey , Kozar Kelly , Li Ning , Maynard Jeffrey A. , McCutcheon Amanda , McKenna Sheila A. , Neilson Brian J. , Safaie Aryan , Teague Christopher , Whittier Robert , Asner Gregory P. 
Published: August 2023

AbstractCoral reef ecosystems are being fundamentally restructured by local human impacts and climate-driven marine heatwaves that trigger mass coral bleaching and mortality1. Reducing local impacts can increase reef resistance to and recovery from bleaching2. However, resource managers lack clear advice on targeted actions that best support coral reefs under climate change3 and sector-based governance means most land- and sea-based management efforts remain siloed4. Here we combine surveys of reef change with a unique 20-year time series of land–sea human impacts that encompassed an unprecedented marine heatwave in Hawai‘i. Reefs with increased herbivorous fish populations and reduced land-based impacts, such as wastewater pollution and urban runoff, had positive coral cover trajectories predisturbance. These reefs also experienced a modest reduction in coral mortality following severe heat stress compared to reefs with reduced fish populations and enhanced land-based impacts. Scenario modelling indicated that simultaneously reducing land–sea human impacts results in a three- to sixfold greater probability of a reef having high reef-builder cover four years postdisturbance than if either occurred in isolation. International efforts to protect 30% of Earth’s land and ocean ecosystems by 2030 are underway5. Our results reveal that integrated land–sea management could help achieve coastal ocean conservation goals and provide coral reefs with the best opportunity to persist in our changing climate.
No evidence for magnetic field effects on the behaviour of Drosophila
Authors: Bassetto Marco , Reichl Thomas , Kobylkov Dmitry , Kattnig Daniel R. , Winklhofer Michael , Hore P. J. , Mouritsen Henrik 
Published: August 2023

AbstractMigratory songbirds have the remarkable ability to extract directional information from the Earth’s magnetic field1,2. The exact mechanism of this light-dependent magnetic compass sense, however, is not fully understood. The most promising hypothesis focuses on the quantum spin dynamics of transient radical pairs formed in cryptochrome proteins in the retina3–5. Frustratingly, much of the supporting evidence for this theory is circumstantial, largely because of the extreme challenges posed by genetic modification of wild birds. Drosophila has therefore been recruited as a model organism, and several influential reports of cryptochrome-mediated magnetic field effects on fly behaviour have been widely interpreted as support for a radical pair-based mechanism in birds6–23. Here we report the results of an extensive study testing magnetic field effects on 97,658 flies moving in a two-arm maze and on 10,960 flies performing the spontaneous escape behaviour known as negative geotaxis. Under meticulously controlled conditions and with vast sample sizes, we have been unable to find evidence for magnetically sensitive behaviour in Drosophila. Moreover, after reassessment of the statistical approaches and sample sizes used in the studies that we tried to replicate, we suggest that many—if not all—of the original results were false positives. Our findings therefore cast considerable doubt on the existence of magnetic sensing in Drosophila and thus strongly suggest that night-migratory songbirds remain the organism of choice for elucidating the mechanism of light-dependent magnetoreception.
Europeans’ support for refugees of varying background is stable over time
Authors: Bansak Kirk , Hainmueller Jens , Hangartner Dominik 
Published: August 2023

AbstractProtracted global conflicts during the past decade have led to repeated major humanitarian protection crises in Europe. During the height of the Syrian refugee crisis at the end of 2015, Europe hosted around 2.3 million people requesting asylum1. Today, the ongoing war in Ukraine has resulted in one of the largest humanitarian emergencies in Europe since World War II, with more than eight million Ukrainians seeking refuge across Europe2. Here we explore whether repeated humanitarian crises threaten to exhaust solidarity and whether Europeans welcome Ukrainian asylum seekers over other asylum seekers3,4. We conducted repeat conjoint experiments during the 2015–2016 and 2022 refugee crises, asking 33,000 citizens in 15 European countries to evaluate randomly varied profiles of asylum seekers. We find that public preferences for asylum seekers with specific attributes have remained remarkably stable and general support has, if anything, increased slightly over time. Ukrainian asylum seekers were welcomed in 2022, with their demographic, religious and displacement profile having a larger role than their nationality. Yet, this welcome did not come at the expense of support for other marginalized refugee groups, such as Muslim refugees. These findings have implications for our theoretical understanding of the drivers and resilience of public attitudes towards refugees and for policymakers tasked to find effective responses to the enduring stress on the asylum system5–8.
Validation of the Idylla GeneFusion assay to detect fusions and MET exon-skipping in non-small cell lung cancers
Authors: Gilson Pauline , Pouget Celso , Belmonte Richard , Fadil Smahane , Demange Jessica , Rouyer Marie , Lacour Julien , Betz Margaux , Dardare Julie , Witz Andréa , Merlin Jean-Louis , Harlé Alexandre 
Published: August 2023

AbstractGene fusions and MET exon skipping drive oncogenesis in 8–9% and 3% of non-small cell lung cancers (NSCLC) respectively. Their detection are essential for the management of patients since they confer sensitivity to specific targeted therapies with significant clinical benefit over conventional chemotherapy. Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) account for historical reference techniques however molecular-based technologies (RNA-based sequencing and RT-PCR) are emerging as alternative or complementary methods. Here, we evaluated the analytical performance of the fully-automated RT-PCR Idylla GeneFusion assay compared to reference methods using 35 fixed NSCLC samples. Idylla demonstrated overall agreement, sensitivity and specificity of 100% compared to RNASeq. Interestingly, it succeeded in retrieving 10 out of 11 samples with inconclusive results due to insufficient RNA quality for sequencing. Idylla showed an overall agreement, sensitivity and specificity of 90.32%, 91.67% and 89.47% compared to IHC/FISH respectively. Using commercial standards, the limit of detection of the Idylla system for the most frequent fusions and exon skipping ranges between 5 and 10 ng RNA input. These results support that the Idylla assay is a reliable and rapid option for the detection of these alterations, however a particular attention is needed for the interpretation of the expression imbalance.
Medication-related osteonecrosis of the jaw without osteolysis on computed tomography: a retrospective and observational study
Authors: Sakamoto Yuki , Sawada Shunsuke , Kojima Yuka 
Published: August 2023

AbstractMedication-related osteonecrosis of the jaw (MRONJ) is a refractory osteonecrosis caused by antiresorptive agents such as bisphosphonate and denosumab (DMB). In MRONJ surgery, computed tomography (CT) is generally used to determine the extent of bone resection. However, in some recent MRONJ cases, no abnormal findings were detected on CT. Therefore, we aimed to clarify the characteristics of MRONJ without osteolysis. This retrospective and observational study included 18 patients diagnosed with MRONJ between October 2020 and October 2022 at Department of Dentistry and Oral Surgery, Kansai Medical University Medical Center. In four of 18 patients with MRONJ, no abnormal findings such as osteolysis, separation of sequestrum, and periosteal reaction were observed on CT images at the first visit. All four patients with non-osteolytic MRONJ had malignant tumors and received high-dose DMB, and in the four patients there were no preceding dental infections such as apical lesions or periodontal disease and the trigger of MRONJ was unknown. Surgery was performed in three of the four patients. The extent of bone resection was determined using magnetic resonance imaging and intraoperative gross findings. In the future, it is necessary to establish a method for diagnosing non osteolytic MRONJ and determining the extent of bone resection.
Synthesis of trimetallic oxide (Fe2O3–MgO–CuO) nanocomposites and evaluation of their structural and optical properties
Authors: Al-Hammadi A. H. , Alnehia Adnan , Al-Sharabi Annas , Alnahari Hisham , Al-Odayni Abdel-Basit 
Published: August 2023

AbstractIn this paper, tri-phase Fe2O3–MgO–CuO nanocomposites (NCs) and pure CuO, Fe2O3 and MgO nanoparticles (NPs) were prepared using sol–gel technique. The physical properties of the prepared products were examined using SEM, XRD, and UV–visible. The XRD data indicated the formation of pure CuO, Fe2O3 and MgO NPs, as well as nanocomposite formation with Fe2O3 (cubic), MgO (cubic), and CuO (monoclinic). The crystallite size of all the prepared samples was calculated via Scherrer's formula. The energy bandgap of CuO, Fe2O3 and MgO and Fe2O3–MgO–CuO NCs were computed from UV–visible spectroscopy as following 2.13, 2.29, 5.43 and 2.96 eV, respectively. The results showed that Fe2O3–MgO–CuO NCs is an alternative material for a wide range of applications as optoelectronics devices due to their outstanding properties.