bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catalytic enantioselective reductive domino alkyl arylation of acrylates via nickel/photoredox catalysis
Authors: Qian Pengcheng , Guan Haixing , Wang Yan-En , Lu Qianqian , Zhang Fan , Xiong Dan , Walsh Patrick J. , Mao Jianyou 
Published: November 2021

AbstractNonsteroidal anti-inflammatory drug derivatives (NSAIDs) are an important class of medications. Here we show a visible-light-promoted photoredox/nickel catalyzed approach to construct enantioenriched NSAIDs via a three-component alkyl arylation of acrylates. This reductive cross-electrophile coupling avoids preformed organometallic reagents and replaces stoichiometric metal reductants by an organic reductant (Hantzsch ester). A broad range of functional groups are well-tolerated under mild conditions with high enantioselectivities (up to 93% ee) and good yields (up to 90%). A study of the reaction mechanism, as well as literature precedence, enabled a working reaction mechanism to be presented. Key steps include a reduction of the alkyl bromide to the radical, Giese addition of the alkyl radical to the acrylate and capture of the α-carbonyl radical by the enantioenriched nickel catalyst. Reductive elimination from the proposed Ni(III) intermediate generates the product and forms Ni(I).
mTOR-mediated phosphorylation of VAMP8 and SCFD1 regulates autophagosome maturation
Authors: Huang Hong , Ouyang Qinqin , Zhu Min , Yu Haijia , Mei Kunrong , Liu Rong 
Published: November 2021

AbstractThe mammalian target of rapamycin (mTORC1) has been shown to regulate autophagy at different steps. However, how mTORC1 regulates the N-ethylmaleimide-sensitive protein receptor (SNARE) complex remains elusive. Here we show that mTORC1 inhibits formation of the SNARE complex (STX17-SNAP29-VAMP8) by phosphorylating VAMP8, thereby blocking autophagosome-lysosome fusion. A VAMP8 phosphorylation mimic mutant is unable to promote autophagosome-lysosome fusion in vitro. Furthermore, we identify SCFD1, a Sec1/Munc18-like protein, that localizes to the autolysosome and is required for SNARE complex formation and autophagosome-lysosome fusion. VAMP8 promotes SCFD1 recruitment to autolysosomes when dephosphorylated. Consistently, phosphorylated VAMP8 or SCFD1 depletion inhibits autophagosome-lysosome fusion, and expression of phosphomimic VAMP8 leads to increased lipid droplet accumulation when expressed in mouse liver. Thus, our study supports that mTORC1-mediated phosphorylation of VAMP8 blocks SCFD1 recruitment, thereby inhibiting STX17-SNAP29-VAMP8 complex formation and autophagosome-lysosome fusion.
Full spectrum fluorescence lifetime imaging with 0.5 nm spectral and 50 ps temporal resolution
Authors: Williams Gareth O. S. , Williams Elvira , Finlayson Neil , Erdogan Ahmet T. , Wang Qiang , Fernandes Susan , Akram Ahsan R. , Dhaliwal Kev , Henderson Robert K. , Girkin John M. , Bradley Mark 
Published: November 2021

AbstractThe use of optical techniques to interrogate wide ranging samples from semiconductors to biological tissue for rapid analysis and diagnostics has gained wide adoption over the past decades. The desire to collect ever more spatially, spectrally and temporally detailed optical signatures for sample characterization has specifically driven a sharp rise in new optical microscopy technologies. Here we present a high-speed optical scanning microscope capable of capturing time resolved images across 512 spectral and 32 time channels in a single acquisition with the potential for ~0.2 frames per second (256 × 256 image pixels). Each pixel in the resulting images contains a detailed data cube for the study of diverse time resolved light driven phenomena. This is enabled by integration of system control electronics and on-chip processing which overcomes the challenges presented by high data volume and low imaging speed, often bottlenecks in previous systems.
Mechanism of actin-dependent activation of nucleotidyl cyclase toxins from bacterial human pathogens
Authors: Belyy Alexander , Merino Felipe , Mechold Undine , Raunser Stefan 
Published: November 2021

AbstractBacterial human pathogens secrete initially inactive nucleotidyl cyclases that become potent enzymes by binding to actin inside eukaryotic host cells. The underlying molecular mechanism of this activation is, however, unclear. Here, we report structures of ExoY from Pseudomonas aeruginosa and Vibrio vulnificus bound to their corresponding activators F-actin and profilin-G-actin. The structures reveal that in contrast to the apo-state, two flexible regions become ordered and interact strongly with actin. The specific stabilization of these regions results in an allosteric stabilization of the nucleotide binding pocket and thereby to an activation of the enzyme. Differences in the sequence and conformation of the actin-binding regions are responsible for the selective binding to either F- or G-actin. Other nucleotidyl cyclase toxins that bind to calmodulin rather than actin undergo a similar disordered-to-ordered transition during activation, suggesting that the allosteric activation-by-stabilization mechanism of ExoY is conserved in these enzymes, albeit the different activator.
Associations between patterns in comorbid diagnostic trajectories of individuals with schizophrenia and etiological factors
Authors: Krebs Morten Dybdahl , Themudo Gonçalo Espregueira , Benros Michael Eriksen , Mors Ole , Børglum Anders D. , Hougaard David , Mortensen Preben Bo , Nordentoft Merete , Gandal Michael J. , Fan Chun Chieh , Geschwind Daniel H. , Schork Andrew J. , Werge Thomas , Thompson Wesley K. 
Published: November 2021

AbstractSchizophrenia is a heterogeneous disorder, exhibiting variability in presentation and outcomes that complicate treatment and recovery. To explore this heterogeneity, we leverage the comprehensive Danish health registries to conduct a prospective, longitudinal study from birth of 5432 individuals who would ultimately be diagnosed with schizophrenia, building individual trajectories that represent sequences of comorbid diagnoses, and describing patterns in the individual-level variability. We show that psychiatric comorbidity is prevalent among individuals with schizophrenia (82%) and multi-morbidity occur more frequently in specific, time-ordered pairs. Three latent factors capture 79% of variation in longitudinal comorbidity and broadly relate to the number of co-occurring diagnoses, the presence of child versus adult comorbidities and substance abuse. Clustering of the factor scores revealed five stable clusters of individuals, associated with specific risk factors and outcomes. The presentation and course of schizophrenia may be associated with heterogeneity in etiological factors including family history of mental disorders.
A potent and protective human neutralizing antibody targeting a novel vulnerable site of Epstein-Barr virus
Authors: Zhu Qian-Ying , Shan Sisi , Yu Jinfang , Peng Si-Ying , Sun Cong , Zuo Yanan , Zhong Lan-Yi , Yan Shu-Mei , Zhang Xiao , Yang Ziqing , Peng Yong-Jian , Shi Xuanling , Cao Su-Mei , Wang Xinquan , Zeng Mu-Sheng , Zhang Linqi 
Published: November 2021

AbstractEpstein-Barr virus (EBV) is associated with a range of epithelial and B cell malignancies as well as autoimmune disorders, for which there are still no specific treatments or effective vaccines. Here, we isolate EBV gH/gL-specific antibodies from an EBV-infected individual. One antibody, 1D8, efficiently neutralizes EBV infection of two major target cell types, B cells and epithelial cells. In humanized mice, 1D8 provides protection against a high-dose EBV challenge by substantially reducing viral loads and associated tumor burden. Crystal structure analysis reveals that 1D8 binds to a key vulnerable interface between the D-I/D-II domains of the viral gH/gL protein, especially the D-II of the gH, thereby interfering with the gH/gL-mediated membrane fusion and binding to target cells. Overall, we identify a potent and protective neutralizing antibody capable of reducing the EBV load. The novel vulnerable site represents an attractive target that is potentially important for antibody and vaccine intervention against EBV infection.
Abemaciclib is a potent inhibitor of DYRK1A and HIP kinases involved in transcriptional regulation
Authors: Kaltheuner Ines H. , Anand Kanchan , Moecking Jonas , Düster Robert , Wang Jinhua , Gray Nathanael S. , Geyer Matthias 
Published: November 2021

AbstractHomeodomain-interacting protein kinases (HIPKs) belong to the CMGC kinase family and are closely related to dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs). HIPKs are regulators of various signaling pathways and involved in the pathology of cancer, chronic fibrosis, diabetes, and multiple neurodegenerative diseases. Here, we report the crystal structure of HIPK3 in its apo form at 2.5 Å resolution. Recombinant HIPKs and DYRK1A are auto-activated and phosphorylate the negative elongation factor SPT5, the transcription factor c-Myc, and the C-terminal domain of RNA polymerase II, suggesting a direct function in transcriptional regulation. Based on a database search, we identified abemaciclib, an FDA-approved Cdk4/Cdk6 inhibitor used for the treatment of metastatic breast cancer, as potent inhibitor of HIPK2, HIPK3, and DYRK1A. We determined the crystal structures of HIPK3 and DYRK1A bound to abemaciclib, showing a similar binding mode to the hinge region of the kinase as observed for Cdk6. Remarkably, DYRK1A is inhibited by abemaciclib to the same extent as Cdk4/Cdk6 in vitro, raising the question of whether targeting of DYRK1A contributes to the transcriptional inhibition and therapeutic activity of abemaciclib.
Horizontally arranged zinc platelet electrodeposits modulated by fluorinated covalent organic framework film for high-rate and durable aqueous zinc ion batteries
Authors: Zhao Zedong , Wang Rong , Peng Chengxin , Chen Wuji , Wu Tianqi , Hu Bo , Weng Weijun , Yao Ying , Zeng Jiaxi , Chen Zhihong , Liu Peiying , Liu Yicheng , Li Guisheng , Guo Jia , Lu Hongbin , Guo Zaiping 
Published: November 2021

AbstractRechargeable aqueous zinc-ion batteries (RZIBs) provide a promising complementarity to the existing lithium-ion batteries due to their low cost, non-toxicity and intrinsic safety. However, Zn anodes suffer from zinc dendrite growth and electrolyte corrosion, resulting in poor reversibility. Here, we develop an ultrathin, fluorinated two-dimensional porous covalent organic framework (FCOF) film as a protective layer on the Zn surface. The strong interaction between fluorine (F) in FCOF and Zn reduces the surface energy of the Zn (002) crystal plane, enabling the preferred growth of (002) planes during the electrodeposition process. As a result, Zn deposits show horizontally arranged platelet morphology with (002) orientations preferred. Furthermore, F-containing nanochannels facilitate ion transport and prevent electrolyte penetration for improving corrosion resistance. The FCOF@Zn symmetric cells achieve stability for over 750 h at an ultrahigh current density of 40 mA cm−2. The high-areal-capacity full cells demonstrate hundreds of cycles under high Zn utilization conditions.
Rhodium-catalyzed intermolecular enantioselective Alder–ene type reaction of cyclopentenes with silylacetylenes
Authors: Zhang Dongquan , Li Miaomiao , Li Jiajia , Lin Aijun , Yao Hequan 
Published: November 2021

AbstractThe Alder–ene type reaction between alkenes and alkynes provides an efficient and atom-economic method for the construction of C-C bond, which has been widely employed in the synthesis of natural products and other functional molecules. The intramolecular enantioselective Alder-ene cycloisomerization reactions of 1,n-enynes have been extensively investigated. However, the intermolecular asymmetric version has not been reported, and remains a challenging task. Herein, we describe a rhodium-catalyzed intermolecular enantioselective Alder-ene type reaction of cyclopentenes with silylacetylenes. A variety of chiral (E)-vinylsilane tethered cyclopentenes bearing one quaternary carbon and one tertiary carbon stereocenters are achieved in high yields and enantioselectivities. The reaction undergoes carbonyl-directed migratory insertion, β-H elimination and desymmetrization of prochiral cyclopentenes processes.
Low-dimensional non-metal catalysts: principles for regulating p-orbital-dominated reactivity
Authors: Zhou Si , Pei Wei , Zhao Yanyan , Yang Xiaowei , Liu Nanshu , Zhao Jijun 
Published: November 2021

AbstractActivation ofp-block elements to replace the rare and precious transition metals for renewable energy applications is highly desirable. In this review, we go over recent experimental and theoretical progress on the low-dimensional non-metal materials for clean energy production, including carbon, silicon, oxide, boron, and phosphorus-based nanostructures, with thep-block elements serving as active sites. We aim to elucidate the mechanism for triggering activity in different kinds of non-metal systems, and extract general principles for controlling thep-orbital-mediated reactivity from a theoretical point of view. The perspectives and challenges for developing high-efficiency non-metal catalysts are provided in the end.
Mapping cis-regulatory elements in the midgestation mouse placenta
Authors: Starks Rebekah R. , Kaur Haninder , Tuteja Geetu 
Published: November 2021

AbstractThe placenta is a temporary organ that provides the developing fetus with nutrients, oxygen, and protection in utero. Defects in its development, which may be caused by misregulated gene expression, can lead to devastating outcomes for the mother and fetus. In mouse, placental defects during midgestation commonly lead to embryonic lethality. However, the regulatory mechanisms controlling expression of genes during this period have not been thoroughly investigated. Therefore, we generated and analyzed ChIP-seq data for multiple histone modifications known to mark cis-regulatory regions. We annotated active and poised promoters and enhancers, as well as regions generally associated with repressed gene expression. We found that poised promoters were associated with neuronal development genes, while active promoters were largely associated with housekeeping genes. Active and poised enhancers were associated with placental development genes, though only active enhancers were associated with genes that have placenta-specific expression. Motif analysis within active enhancers identified a large network of transcription factors, including those that have not been previously studied in the placenta and are candidates for future studies. The data generated and genomic regions annotated provide researchers with a foundation for future studies, aimed at understanding how specific genes in the midgestation mouse placenta are regulated.
Declining methane emissions and steady, high leakage rates observed over multiple years in a western US oil/gas production basin
Authors: Lin John C. , Bares Ryan , Fasoli Benjamin , Garcia Maria , Crosman Erik , Lyman Seth 
Published: November 2021

AbstractMethane, a potent greenhouse gas, is the main component of natural gas. Previous research has identified considerable methane emissions associated with oil and gas production, but estimates of emission trends have been inconsistent, in part due to limited in-situ methane observations spanning multiple years in oil/gas production regions. Here we present a unique analysis of one of the longest-running datasets of in-situ methane observations from an oil/gas production region in Utah’s Uinta Basin. The observations indicate Uinta methane emissions approximately halved between 2015 and 2020, along with declining gas production. As a percentage of gas production, however, emissions remained steady over the same years, at ~ 6–8%, among the highest in the U.S. Addressing methane leaks and recovering more of the economically valuable natural gas is critical, as the U.S. seeks to address climate change through aggressive greenhouse emission reductions.
The performance of a flapping foil for a self-propelled fishlike body
Authors: Paniccia Damiano , Padovani Luca , Graziani Giorgio , Piva Renzo 
Published: November 2021

AbstractSeveral fish species propel by oscillating the tail, while the remaining part of the body essentially contributes to the overall drag. Since in this case thrust and drag are in a way separable, most attention was focused on the study of propulsive efficiency for flapping foils under a prescribed stream. We claim here that the swimming performance should be evaluated, as for undulating fish whose drag and thrust are severely entangled, by turning to self-propelled locomotion to find the proper speed and the cost of transport for a given fishlike body. As a major finding, the minimum value of this quantity corresponds to a locomotion speed in a range markedly different from the one associated with the optimal efficiency of the propulsor. A large value of the feathering parameter characterizes the minimum cost of transport while the optimal efficiency is related to a large effective angle of attack. We adopt here a simple two-dimensional model for both inviscid and viscous flows to proof the above statements in the case of self-propelled axial swimming. We believe that such an easy approach gives a way for a direct extension to fully free swimming and to real-life configurations.
The trajectory of putative astroglial dysfunction in first episode schizophrenia: a longitudinal 7-Tesla MRS study
Authors: Jeon Peter , Mackinley Michael , Théberge Jean , Palaniyappan Lena 
Published: November 2021

AbstractMyo-inositol is mainly found in astroglia and its levels has been shown to be reduced in the anterior cingulate cortex (ACC) of patients with schizophrenia. We investigate the status of astroglial integrity indexed by ACC myo-inositol at the onset and over the first 6 months of treatment of first episode schizophrenia. We employed 7 T magnetic resonance spectroscopy (1H-MRS) and quantified myo-inositol spectra at the dorsal ACC in 31 participants; 21 patients with schizophrenia with median lifetime antipsychotic exposure of less than 3 days, followed up after 6 months of treatment, and 10 healthy subjects scanned twice over the same period. We studied the time by group interaction for myo-inositol after adjusting for gender and age. We report significant reduction in myo-inositol concentration in the ACC in schizophrenia at an early, untreated state of acute illness that becomes insignificant over time, after instituting early intervention. This trajectory indicates that dynamic astroglial changes are likely to operate in the early stages of schizophrenia. MRS myo-inositol may be a critical marker of amelioration of active psychosis in early stages of schizophrenia.
Spatiotemporal endometrial transcriptome analysis revealed the luminal epithelium as key player during initial maternal recognition of pregnancy in the mare
Authors: Rudolf Vegas Alba , Podico Giorgia , Canisso Igor F. , Bollwein Heinrich , Almiñana Carmen , Bauersachs Stefan 
Published: November 2021

AbstractDuring the period of maternal recognition of pregnancy (MRP) in the mare, the embryo needs to signal its presence to the endometrium to prevent regression of the corpus luteum and prepare for establishment of pregnancy. This is achieved by mechanical stimuli and release of various signaling molecules by the equine embryo while migrating through the uterus. We hypothesized that embryo’s signals induce changes in the endometrial gene expression in a highly cell type-specific manner. A spatiotemporal transcriptomics approach was applied combining laser capture microdissection and low-input-RNA sequencing of luminal and glandular epithelium (LE, GE), and stroma of biopsy samples collected from days 10–13 of pregnancy and the estrous cycle. Two comparisons were performed, samples derived from pregnancies with conceptuses ≥ 8 mm in diameter (comparison 1) and conceptuses ≤ 8 mm (comparison 2) versus samples from cyclic controls. The majority of gene expression changes was identified in LE and much lower numbers of differentially expressed genes (DEGs) in GE and stroma. While 1253 DEGs were found for LE in comparison 1, only 248 were found in comparison 2. Data mining mainly focused on DEGs in LE and revealed regulation of genes related to prostaglandin transport, metabolism, and signaling, as well as transcription factor families that could be involved in MRP. In comparison to other mammalian species, differences in regulation of genes involved in epithelial barrier formation and conceptus attachment and implantation reflected the unique features of equine reproduction at the time of MRP at the molecular level.
X-ray computed tomography (CT) and ESEM-EDS investigations of unusual subfossilized juniper cones
Authors: Mohamed Wafaa A. , Mansour Maisa M. A. , Salem Mohamed Z. M. , Ali Hayssam M. , Böhm Martin 
Published: November 2021

AbstractRecent investigations of a Greco-Roman site at Sais have provided well-preserved archaeobotanical remains within a pile of metal fragments. The remains are compared with comparable modern taxa. The morphology and anatomy are studied using Light microscope (LM), Environmental scanning electron microscope (ESEM) and X-ray computed tomography (CT). To investigate the preservation mode, Energy dispersive spectroscopy (EDS) analysis and elemental mapping are conducted. Results revealed that the archaeobotanical remains are exhibiting close affinity with modern juniper cones. Although, the studied archaeobotanical remains are buried for more than 2 millenniums, they underwent early stages of silicification and copper mineralization. These results are discussed in relation to other excavated objects in the find and to our knowledge and understanding of daily life in the Greco-Roman period.