Three-dimensional structured illumination microscopy (3D-SIM) provides excellent optical sectioning and doubles the resolution in all dimensions compared with wide-field microscopy. However, its much lower axial resolution results in blurred fine details in that direction and overall image distortion. Here we present 4Pi-SIM, a substantial revamp of IS that synergizes 3D-SIM with interferometric microscopy to achieve isotropic optical resolution through interference in both the illumination and detection wavefronts.
View Article and Find Full Text PDFThe current reference genome of , GRCm39, has major gaps in both euchromatic and heterochromatic regions associated with repetitive sequences. In this work, we have sequenced and assembled the telomere-to-telomere genome of mouse haploid embryonic stem cells. The results reveal more than 7.
View Article and Find Full Text PDFOver the past few decades, unbiased approaches such as genetic screening and protein affinity purification have unveiled numerous proteins involved in DNA double-strand break (DSB) repair and maintaining genome stability. However, despite our knowledge of these protein factors, the underlying molecular mechanisms governing key cellular events during DSB repair remain elusive. Recent evidence has shed light on the role of non-protein factors, such as RNA, in several pivotal steps of DSB repair.
View Article and Find Full Text PDFAlthough DNA-PK inhibitors (DNA-PK-i) have been applied in clinical trials for cancer treatment, the biomarkers and mechanism of action of DNA-PK-i in tumor cell suppression remain unclear. Here, we observed that a low dose of DNA-PK-i and PARP inhibitor (PARP-i) synthetically suppresses BRCA-deficient tumor cells without inducing DNA double-strand breaks (DSBs). Instead, we found that a fraction of DNA-PK localized inside of nucleoli, where we did not observe obvious DSBs.
View Article and Find Full Text PDFRAD51-associated protein 1 (RAD51AP1) is known to promote homologous recombination (HR) repair. However, the precise mechanism of RAD51AP1 in HR repair is unclear. Here, we identify that RAD51AP1 associates with pre-rRNA.
View Article and Find Full Text PDFThe elevated occurrence of debilitating neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD) and Machado-Joseph disease (MJD), demands urgent disease-modifying therapeutics. Owing to the evolutionarily conserved molecular signalling pathways with mammalian species and facile genetic manipulation, the nematode () emerges as a powerful and manipulative model system for mechanistic insights into neurodegenerative diseases. Herein, we review several representative models established for five common neurodegenerative diseases, which closely simulate disease phenotypes specifically in the gain-of-function aspect.
View Article and Find Full Text PDFObjective: To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHR), and explore preliminarily the mediating role of cholinergic anti-inflammatory pathway (CAP) and its downstream nuclear factor κB (NF-κB) signaling pathway.
Methods: Six 12-week-old WKY male rats were employed as the normal group. Eighteen 12-week-old SHR were randomly divided into 3 groups, i.
The BRCA1/BARD1 complex plays a key role in the repair of DNA double-strand breaks (DSBs) in both somatic cells and germ cells. However, the underlying molecular mechanism by which this complex mediates DSB repair is not fully understood. Here, we examined the XY body of male germ cells, where DSBs are accumulated.
View Article and Find Full Text PDFIn response to genotoxic stress-induced DNA damage, TopBP1 mediates ATR activation for signaling transduction and DNA damage repair. However, the detailed molecular mechanism remains elusive. Here, using unbiased protein affinity purification and RNA sequencing, it is found that TopBP1 is associated with pre-ribosomal RNA (pre-rRNA).
View Article and Find Full Text PDFMono-ADP-ribosylation (MARylation) is a post-translational modification that regulates a variety of biological processes, including DNA damage repair, cell proliferation, metabolism, and stress and immune responses. In mammals, MARylation is mainly catalyzed by ADP-ribosyltransferases (ARTs), which consist of two groups: ART cholera toxin-like (ARTCs) and ART diphtheria toxin-like (ARTDs, also known as PARPs). The human ARTC (hARTC) family is composed of four members: two active mono-ADP-ARTs (hARTC1 and hARTC5) and two enzymatically inactive enzymes (hARTC3 and hARTC4).
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
January 2023
Objectives: Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms.
View Article and Find Full Text PDFObjective: The objective is to observe the synergistic and attenuating effect of electroacupuncture (EA) on aconitine (ACO) in improving heart failure (HF) and to explore its underlying mechanism for calcium regulation.
Methods: Twenty-four male Sprague-Dawley rats were randomly divided into four groups: normal control (NC) ( = 6), HF( = 6), ACO ( = 6), and ACO + EA ( = 6). The maximum rates of left ventricular pressure rising and declining (±dp/dtmax), arrhythmia, the left ventricular systolic pressure (LVSP), ejection fraction (LVEF), and fractional shortening (LVFS) were measured by physiological recorder and ultrasound, respectively.
Objective: To investigate the effect of electroacupuncture (EA) at Neiguan (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHRs), and to explore the contribution of interleukin-1 β (IL-1 β), insulin-like growth factor 1 (IGF-1), and transforming growth factor β 1 (TGF- β 1) to the effects.
Methods: Nine 12-weeks-old Wistar Kyoto (WKY) male rats were employed as the normal group. Twenty-seven SHRs were equally randomized into SHR, SHR+EA, and SHR + sham groups.
Objective: To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function of ventriculus sinister in rats with spontaneously hypertensive (SHR), and to explore the mediation effect of endothelin-1 (ET-1)/endothelial nitric oxide synthase (eNOS).
Methods: Six 12-week-old male Wistar Kyoto (WKY) rats were taken as the normal group. Eighteen 12-week-old SHR were randomly divided into a model group, an EA group and a sham EA group, 6 rats in each group.
Noncoding RNAs are known to associate with mitotic chromosomes, but the identities and functions of chromosome-associated RNAs in mitosis remain elusive. Here, we show that rRNA species associate with condensed chromosomes during mitosis. In particular, pre-rRNAs such as 45S, 32S, and 30S are highly enriched on mitotic chromosomes.
View Article and Find Full Text PDFMediator of DNA damage checkpoint protein 1 (MDC1) serves as a docking platform to promote the localization of various DNA damage response (DDR) components to DNA double-strand break (DSB) sites. MDC1 is vital in controlling proper DDR and maintaining genomic stability. In cancers, genomic instability results from mutations in DNA repair genes and drives cancer development.
View Article and Find Full Text PDFTea (, ) is one of the most widely consumed beverages in the world. The three major types of tea, green tea, oolong tea, and black tea, differ in terms of the manufacture and chemical composition. Catechins, theaflavins, and thearubigins have been identified as the major components in tea.
View Article and Find Full Text PDFAcupuncture is recommended for the relief of chronic tinnitus in traditional Chinese medicine, but the underlying neural mechanism remains unclear. The human brain is a dynamic system, and it's unclear about acupuncture's effects on the dynamic functional connectivity (DFC) of chronic tinnitus. Therefore, this study based on resting-state functional magnetic resonance imaging (fMRI) investigates abnormal DFC in chronic tinnitus patients and the neural activity change evoked by acupuncture treatment for tinnitus.
View Article and Find Full Text PDFA novel photo-thermo-mechanochemical approach to assembling quinolines catalyzed by iron(II) phthalocyanine has been realized for the first time. This transformation features a cost-efficient catalytic system and operational simplicity, is free of solvent, and shows good substrate tolerance, providing a green alternative to existing thermal approaches. Mechanistic experiments demonstrate that the in-situ-formed secondary amine may be the key intermediate for the further cyclization/aromatization process.
View Article and Find Full Text PDFCaspase-mediated cleavage of PARP1 is a surrogate marker for apoptosis. However, the biological significance of PARP1 cleavage during apoptosis is still unclear. Here, using unbiased protein affinity purification, we show that truncated PARP1 (tPARP1) recognizes the RNA polymerase III (Pol III) complex in the cytosol.
View Article and Find Full Text PDFIn response to DNA double-strand breaks (DSBs), DNA damage repair factors are recruited to DNA lesions and form nuclear foci. However, the underlying molecular mechanism remains largely elusive. Here, by analyzing the localization of DSB repair factors in the XY body and DSB foci, we demonstrate that pre-ribosomal RNA (pre-rRNA) mediates the recruitment of DSB repair factors around DNA lesions.
View Article and Find Full Text PDFObjective: To investigate the mechanism of electroacupuncture (EA) with the involvement of sarcoplasmic reticulum Ca-ATPase2a (SERCA2a)/phospholamban (PLB) on the synergistic and attenuated effect of aconitine for heart failure.
Methods: Thirty SPF-ranked SD rats were randomly divided into a control group, a model group, an EA group, an aconitine group and an EA plus aconitine group, with 6 rats in each group. The rat model of acute heart failure was established by infusion of high-dose propranolol hydrochloride solution into the right femoral vein.
Objective: To observe the influence of electroacupuncture(EA) combined with aconitine on the hemodyna-mics, echocardiogram, and arrhythmias in heart failure rats, so as to explore the facilitation and attenuation effects of EA combined with aconitine.
Methods: SD rats were randomly divided into control, model, aconitine and aconitine+EA groups, with 6 rats in each group. Propranolol hydrochloride was used to establish the heart failure model.
ADP-ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage and viral infection and is involved in intra- and extracellular signaling, chromatin and transcriptional regulation, protein biosynthesis, and cell death. ADP-ribosylation is catalyzed by ADP-ribosyltransferases (ARTs), which transfer ADP-ribose from NAD onto substrates. The modification, which occurs as mono- or poly-ADP-ribosylation, is reversible due to the action of different ADP-ribosylhydrolases.
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