bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ubiquitin ligase RNF5 determines acute myeloid leukemia growth and susceptibility to histone deacetylase inhibitors
Authors: Khateb Ali , Deshpande Anagha , Feng Yongmei , Finlay Darren , Lee Joo Sang , Lazar Ikrame , Fabre Bertrand , Li Yan , Fujita Yu , Zhang Tongwu , Yin Jun , Pass Ian , Livneh Ido , Jeremias Irmela , Burian Carol , Mason James R. , Almog Ronit , Horesh Nurit , Ofran Yishai , Brown Kevin , Vuori Kristiina , Jackson Michael , Ruppin Eytan , Deshpande Aniruddha J. , Ronai Ze’ev A. 
Published: September 2021

AbstractAcute myeloid leukemia (AML) remains incurable, largely due to its resistance to conventional treatments. Here, we find that increased abundance of the ubiquitin ligase RNF5 contributes to AML development and survival. High RNF5 expression in AML patient specimens correlates with poor prognosis. RNF5 inhibition decreases AML cell growth in culture, in patient-derived xenograft (PDX) samples and in vivo, and delays development of MLL-AF9–driven leukemogenesis in mice, prolonging their survival. RNF5 inhibition causes transcriptional changes that overlap with those seen upon histone deacetylase (HDAC)1 inhibition. RNF5 induces the formation of K29 ubiquitin chains on the histone-binding protein RBBP4, promoting its recruitment to and subsequent epigenetic regulation of genes involved in AML maintenance. Correspondingly, RNF5 or RBBP4 knockdown enhances AML cell sensitivity to HDAC inhibitors. Notably, low expression of both RNF5 and HDAC coincides with a favorable prognosis. Our studies identify an ERAD-independent role for RNF5, demonstrating that its control of RBBP4 constitutes an epigenetic pathway that drives AML, and highlight RNF5/RBBP4 as markers useful to stratify patients for treatment with HDAC inhibitors.
Genetic variations of DNA bindings of FOXA1 and co-factors in breast cancer susceptibility
Authors: Wen Wanqing , Chen Zhishan , Bao Jiandong , Long Quan , Shu Xiao-ou , Zheng Wei , Guo Xingyi 
Published: September 2021

AbstractIdentifying transcription factors (TFs) whose DNA bindings are altered by genetic variants that regulate susceptibility genes is imperative to understand transcriptional dysregulation in disease etiology. Here, we develop a statistical framework to analyze extensive ChIP-seq and GWAS data and identify 22 breast cancer risk-associated TFs. We find that, by analyzing genetic variations of TF-DNA bindings, the interaction of FOXA1 with co-factors such as ESR1 and E2F1, and the interaction of TFs with chromatin features (i.e., enhancers) play a key role in breast cancer susceptibility. Using genetic variants occupied by the 22 TFs, transcriptome-wide association analyses identify 52 previously unreported breast cancer susceptibility genes, including seven with evidence of essentiality from functional screens in breast relevant cell lines. We show that FOXA1 and co-factors form a core TF-transcriptional network regulating the susceptibility genes. Our findings provide additional insights into genetic variations of TF-DNA bindings (particularly for FOXA1) underlying breast cancer susceptibility.
Relief of excited-state antiaromaticity enables the smallest red emitter
Authors: Kim Heechan , Park Woojin , Kim Younghun , Filatov Michael , Choi Cheol Ho , Lee Dongwhan 
Published: September 2021

AbstractIt is commonly accepted that a large π-conjugated system is necessary to realize low-energy electronic transitions. Contrary to this prevailing notion, we present a new class of light-emitters utilizing a simple benzene core. Among different isomeric forms of diacetylphenylenediamine (DAPA), o- and p-DAPA are fluorescent, whereas m-DAPA is not. Remarkably, p-DAPA is the lightest (FW = 192) molecule displaying red emission. A systematic modification of the DAPA system allows the construction of a library of emitters covering the entire visible color spectrum. Theoretical analysis shows that their large Stokes shifts originate from the relief of excited-state antiaromaticity, rather than the typically assumed intramolecular charge transfer or proton transfer. A delicate interplay of the excited-state antiaromaticity and hydrogen bonding defines the photophysics of this new class of single benzene fluorophores. The formulated molecular design rules suggest that an extended π-conjugation is no longer a prerequisite for a long-wavelength light emission.
Structure and function relationship of OqxB efflux pump from Klebsiella pneumoniae
Authors: Bharatham Nagakumar , Bhowmik Purnendu , Aoki Maho , Okada Ui , Sharma Sreevalli , Yamashita Eiki , Shanbhag Anirudh P. , Rajagopal Sreenath , Thomas Teby , Sarma Maitrayee , Narjari Riya , Nagaraj Savitha , Ramachandran Vasanthi , Katagihallimath Nainesh , Datta Santanu , Murakami Satoshi 
Published: September 2021

AbstractOqxB is an RND (Resistance-Nodulation-Division) efflux pump that has emerged as a factor contributing to the antibiotic resistance in Klebsiella pneumoniae. OqxB underwent horizontal gene transfer and is now seen in other Gram-negative bacterial pathogens including Escherichia coli, Enterobacter cloacae and Salmonella spp., further disseminating multi-drug resistance. In this study, we describe crystal structure of OqxB with n-dodecyl-β-D-maltoside (DDM) molecules bound in its substrate-binding pocket, at 1.85 Å resolution. We utilize this structure in computational studies to predict the key amino acids contributing to the efflux of fluoroquinolones by OqxB, distinct from analogous residues in related transporters AcrB and MexB. Finally, our complementation assays with mutated OqxB and minimum inhibitory concentration (MIC) experiments with clinical isolates of E. coli provide further evidence that the predicted structural features are indeed involved in ciprofloxacin efflux.
Emergence and expansion of highly infectious spike protein D614G mutant SARS-CoV-2 in central India
Authors: Sharma Shashi , Dash Paban Kumar , Sharma Sushil Kumar , Srivastava Ambuj , Kumar Jyoti S. , Karothia B. S. , Chelvam K. T. , Singh Sandeep , Gupta Abhaydeep , Yadav Ram Govind , Yadav Ruchi , Greeshma T. S. , Kushwaha Pramod Kumar , Kumar Ravi Bhushan , Nagar D. P. , Nandan Manvendra , Kumar Subodh , Thavaselvam Duraipandian , Dubey Devendra Kumar 
Published: September 2021

AbstractCOVID-19 has emerged as global pandemic with largest damage to the public health, economy and human psyche.The genome sequence data obtained during the ongoing pandemic are valuable to understand the virus evolutionary patterns and spread across the globe. Increased availability of genome information of circulating SARS-CoV-2 strains in India will enable the scientific community to understand the emergence of new variants and their impact on human health. The first case of COVID-19 was detected in Chambal region of Madhya Pradesh state in mid of March 2020 followed by multiple introduction events and expansion of cases within next three months. More than 5000 COVID-19 suspected samples referred to Defence Research and Development Establishment, Gwalior, Madhya Pradesh were analyzed during the nation -wide lockdown and unlock period. A total of 136 cases were found positive over a span of three months that included virus introduction to the region and its further spread. Whole genome sequences employing Oxford nanopore technology were generated for 26 SARS-CoV-2 circulating in 10 different districts in Madhya Pradesh state of India. This period witnessed index cases with multiple travel histories responsible for introduction of COVID-19 followed by remarkable expansion of virus. The genome wide substitutions including in important viral proteins were identified. The detailed phylogenetic analysis revealed the circulating SARS-CoV-2 clustered in multiple clades including A2a, A4 and B. The cluster-wise segregation was observed, suggesting multiple introduction links and subsequent evolution of virus in the region. This is the first comprehensive whole genome sequence analysis from central India, which revealed the emergence and evolution of SARS-CoV-2 during thenation-wide lockdown and unlock.
Lactobacillus crispatus thrives in pregnancy hormonal milieu in a Nigerian patient cohort
Authors: Odogwu Nkechi Martina , Onebunne Chinedum Amara , Chen Jun , Ayeni Funmilola A. , Walther-Antonio Marina R. S. , Olayemi Oladapo O. , Chia Nicholas , Omigbodun Akinyinka O. 
Published: September 2021

AbstractSteroid hormones are one of the presumed modulators ofLactobacillusabundance in the vaginal epithelium. We set out to characterize the vaginal microbiome (VMB) and also provide an in-depth understanding of the relative contribution of estradiol (E2) and progesterone (P1) in shaping the vaginal microbiome of Nigerian women (n = 38) who experienced both uncomplicated term delivery and preterm delivery using samples longitudinally collected during pregnancy (17–21, 27–31, 36–41 weeks gestation) and 6 weeks postpartum. Vaginal swabs and blood samples were aseptically collected. Vaginal swabs were used for microbiome assessment using 16S ribosomal RNA (rRNA) gene sequencing. Blood samples were used for hormonal measurement using a competitive-based enzyme-linked immunosorbent assay (ELISA). Across several maternal covariates, maternal age, pregnancy status and delivery mode were not significantly associated with the vaginal microbiota whereas maternal E2 level (pE2 = 0.006, Omnibus), and P1 level (pP1 = 0.001, Omnibus) were significantly associated with the vaginal microbiome. E2 and P1 concentrations increased throughout pregnancy commensurately with increasing proportions ofL. crispatus(pE2 = 0.036, pP1 = 0.034, Linear Mixed Model). An increasing trend of α-diversity was also observed as pregnancy progressed (pobserved ASV = 0.006, LMM). A compositional microbiome shift fromLactobacillusprofile to non-Lactobacillusprofile was observed in most postnatal women (pCST IV < 0.001, LMM). Analysis of our data shows a species-specific link between pregnancy steroid hormone concentration andL. crispatusabundance.
Paraquat-induced cholesterol biosynthesis proteins dysregulation in human brain microvascular endothelial cells
Authors: Tatjana Vujić , Domitille Schvartz , Jean-Charles Sanchez 
Published: September 2021

AbstractDespite Paraquat (PQ) being banned in several countries, it is still one of the most commonly used herbicides in agriculture. This compound is known to induce damaging effects on human and animal brain cells by generating Reactive Oxygen Species (ROS). However, there is few evidence of PQ effect on Human Brain Microvascular Endothelial Cells (HBMECs), one of the major component of the Blood–Brain Barrier (BBB). The present study aimed at unraveling biological mechanisms associated to the exposure of 1, 10 and 100 µM of PQ for 24 h on HBMECs. High-throughput mass spectrometry-based proteomics using data-independent acquisition (DIA) was applied. Biological pathway enrichment and cellular assays such as mitochondrial respiration and cholesterol level were performed to verify proteomics results. A total of 3753 proteins were quantified out of which 419 were significantly modulated by paraquat exposure. Biological pathway enrichment revealed the ubiquinone metabolism, a pathway directly linked to mitochondrial complex I proteins, confirming the well-known mechanism of PQ inducing oxidative stress. Additionally, this study also described the cholesterol biosynthesis modulation on HBMECs not yet described. In conclusion, our data indicate the toxic effect of PQ on HBMECs by downregulating proteins involved in mitochondrial complex I and cholesterol pathways.
Evaluation of graphene/crosslinked polyethylene for potential high voltage direct current cable insulation applications
Authors: Li Yuan , Zhu Guangya , Zhou Kai , Meng Pengfei , Wang Guodong 
Published: September 2021

AbstractThis paper evaluates the potential usage of graphene/crosslinked polyethylene (graphene/XLPE) as the insulating material for high voltage direct current (HVDC) cables. Thermal, mechanical and electrical properties of blends with/without graphene were evaluated by differential scanning calorimetry (DSC), tensile strength, DC conductivity, space charge measurements and water tree aging test. The results indicate that 0.007–0.008% weight amount of graphene can improve the mechanical and electrical insulation properties of XLPE blends, namely higher tensile/yield strength, improved space charge distribution, and shorter/fewer water tree branches. The improvements mainly attribute to the high stiffness of graphene, deep traps introduced by the interaction zones of graphene and XLPE, and the blockage effect of graphene within XLPE. For thermal performance of XLPE blends, graphene nano-fillers have but limited improvement. The crystallinity of the blends barely changes with the addition of graphene. However, the crosslinking degree increases as the additive-like amounts of graphene doped. The above findings provide a guide for tailoring lightweight XLPE materials with excellent mechanical and electrical performances by doping them with a small amount of graphene.
Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS
Authors: Zhu Xiaoyang , Guo Yangyang , Liu Zhigang , Yang Jingyi , Tang Huiru , Wang Yulan 
Published: September 2021

AbstractItaconic acid is produced by immune responsive gene 1 (IRG1)-coded enzyme in activated macrophages and known to play an important role in metabolism and immunity. In this study, mechanism of itaconic acid functioning as an anti-inflammatory metabolite was investigated with molecular biology and immunology techniques, by employing IRG1-null (prepared with CRISPR) and wild-type macrophages. Experimental results showed that itaconic acid significantly promoted the pentose phosphate pathway (PPP), which subsequently led to significantly higher NADPH oxidase activity and more reactive oxygen species (ROS) production. ROS production increased the expression of anti-inflammatory gene A20, which in turn decreased the production of inflammatory cytokines IL-6, IL-1β and TNF-α. NF-κB, which can up-regulate A20, was also vital in controlling IRG1 and itaconic acid involved immune-modulatory responses in LPS-stimulated macrophage in this study. In addition, itaconic acid inhibited the growth of Salmonella typhimurium in cell through increasing ROS production from NADPH oxidase and the hatching of Schistosoma japonicum eggs in vitro. In short, this study revealed an alternative mechanism by which itaconic acid acts as an anti-inflammatory metabolite and confirmed the inhibition of bacterial pathogens with itaconic acid via ROS in cell. These findings provide the basic knowledge for future biological applications of itaconic acid in anti-inflammation and related pathogens control.
Flexural band gaps and vibration control of a periodic railway track
Authors: Iqbal Mohd , Kumar Anil , Murugan Jaya Mahesh , Bursi Oreste Salvatore 
Published: September 2021

AbstractPeriodic structures exhibit unique band gap characteristics by virtue of which they behave as vibro-acoustic filters thereby allowing only waves within a certain frequency range to pass through. In this paper, lateral and vertical flexural wave propagation and vibration control of a railway track periodically supported on rigid sleepers using fastenings are studied in depth. The dispersion relations in both lateral and vertical directions are obtained using the Floquet-Bloch theorem and the resulting dispersion curves are verified using finite element models. Afterwards, tuned mass dampers (TMDs) with different mass ratios are designed to control vibrations of the examined rail in both the directions. Moreover, the influence of damping of rail and resonators on band gap characteristics is investigated. As a replacement to the conventional TMD, a novel possibility to control vibration relies on using another existing rail as a lateral distributed resonator (LDR). Although the effectiveness of LDR is lower than that of localized resonators, the former represents a simple and promising way to control vibrations. Efficacy of the proposed control methods is finally verified by applying a random Gaussian white noise input. The study presented here is useful to understand the propagation and attenuation behavior of flexural waves and to develop efficient and novel vibration control strategies for track structures.
Efficient biallelic knock-in in mouse embryonic stem cells by in vivo-linearization of donor and transient inhibition of DNA polymerase θ/DNA-PK
Authors: Arai Daisuke , Nakao Yoichi 
Published: September 2021

AbstractCRISPR/Cas9-mediated homology-directed repair (HDR) is used for error-free targeted knock-in of foreign donor DNA. However, the low efficiency of HDR-mediated knock-in hinders establishment of knock-in clones. Double-strand breaks (DSBs) induced by CRISPR/Cas9 are preferentially repaired by non-homologous end joining (NHEJ) or microhomology-mediated end joining (MMEJ) before HDR can occur, thereby preventing HDR-mediated knock-in. NHEJ/MMEJ also cause random integrations, which give rise to false-positive knock-in events, or silently disrupt the genome. In this study, we optimized an HDR-mediated knock-in method for mouse embryonic stem cells (mESCs). We succeeded in improving efficiency of HDR-mediated knock-in of a plasmid donor while almost completely suppressing NHEJ/MMEJ-based integration by combining in vivo-linearization of the donor plasmid, transient knockdown of DNA polymerase θ, and chemical inhibition of DNA-dependent protein kinase (DNA-PK) by M3814. This method also dramatically improved the efficiency of biallelic knock-in; at theRosa26alocus, 95% of HDR-mediated knock-in clones were biallelic. We designate this method BiPoD (Biallelic knock-in assisted byPol θ andDNA-PK inhibition). BiPoD achieved simultaneous efficient biallelic knock-in into two loci. BiPoD, therefore, enables rapid and easy establishment of biallelic knock-in mESC lines.
Thermosensitive collagen/fibrinogen gels loaded with decorin suppress lesion site cavitation and promote functional recovery after spinal cord injury
Authors: Matthews Jacob , Surey Sarina , Grover Liam M. , Logan Ann , Ahmed Zubair 
Published: September 2021

AbstractThe treatment of spinal cord injury (SCI) is a complex challenge in regenerative medicine, complicated by the low intrinsic capacity of CNS neurons to regenerate their axons and the heterogeneity in size, shape and extent of human injuries. For example, some contusion injuries do not compromise the dura mater and in such cases implantation of preformed scaffolds or drug delivery systems may cause further damage. Injectable in situ thermosensitive scaffolds are therefore a less invasive alternative. In this study, we report the development of a novel, flowable, thermosensitive, injectable drug delivery system comprising bovine collagen (BC) and fibrinogen (FB) that forms a solid BC/FB gel (Gel) immediately upon exposure to physiological conditions and can be used to deliver reparative drugs, such as the naturally occurring anti-inflammatory, anti-scarring agent Decorin, into adult rat spinal cord lesion sites. In dorsal column lesions of adult rats treated with the Gel + Decorin, cavitation was completely suppressed and instead lesion sites became filled with injury-responsive cells and extracellular matrix materials, including collagen and laminin. Decorin increased the intrinsic potential of dorsal root ganglion neurons (DRGN) by increasing their expression of regeneration associated genes (RAGs), enhanced local axon regeneration/sprouting, as evidenced both histologically and by improved electrophysiological, locomotor and sensory function recovery. These results suggest that this drug formulated, injectable hydrogel has the potential to be further studied and translated into the clinic.
Interrogating the haemodynamic effects of haemodialysis arteriovenous fistula on cardiac structure and function
Authors: Stoumpos Sokratis , Rankin Alastair , Hall Barrientos Pauline , Mangion Kenneth , McGregor Ellon , Thomson Peter C. , Stevenson Karen , Welsh Paul , Kasthuri Ram , Kingsmore David B. , Roditi Giles , Mark Patrick B. 
Published: September 2021

AbstractArteriovenous fistula (AVF) is the preferred type of vascular access for maintenance haemodialysis but it may contribute to maladaptive cardiovascular remodelling. We studied the effect of AVF creation on cardiac structure and function in patients with chronic kidney disease (CKD). In this prospective cohort study patients with CKD listed for first AVF creation underwent cardiac magnetic resonance (CMR) imaging at baseline and at 6 weeks. All participants had ultrasound measurements of fistula blood flow at 6 weeks. The primary outcome was the change in left ventricular (LV) mass. Secondary outcomes included changes in LV volumes, LV ejection fraction, cardiac output, LV global longitudinal strain and N-terminal-pro B-type natriuretic peptide (NT-proBNP). A total of 55 participants were enrolled, of whom 40 (mean age 59 years) had AVF creation and completed both scans. On the second CMR scan, a mean increase of 7.4 g (95% CI 1.1–13.7, p = 0.02) was observed in LV mass. Significant increases in LV end-diastolic volumes (p = 0.04) and cardiac output (p = 0.02) were also seen after AVF creation. No significant changes were observed in LV end-systolic volumes, LV ejection fraction, NT-proBNP and LV global longitudinal strain. In participants with fistula blood flows ≥ 600 mL/min (n = 22) the mean increase in LV mass was 15.5 g (95% CI 7.3–23.8) compared with a small decrease of 2.5 g (95% CI − 10.6 to 5.6) in participants with blood flows < 600 mL/min (n = 18). Creation of AVF for haemodialysis resulted in a significant increase of LV myocardial mass within weeks after surgery, which was proportional to the fistula flow.
Synthesis of axially chiral biaryl thioglycosides through thiosugar-directed Pd-catalyzed asymmetric C–H activation
Authors: Fatthalla Maha , Grimblat Nicolas , Brachet Etienne , Alami Mouad , Gandon Vincent , Le Bideau Franck , Messaoudi Samir 
Published: September 2021

An atroposelective Fujiwara–Moritani reaction towards the synthesis of alkenylthioglycoside is reported. β-thioglucose moiety is used both as a directing group for the C–H bond activation and as a chiral source inducing axial chirality.