Biology subjects

Qiang, J.

Publications and source records attributed to Qiang, J..

7 recordsLinked to original sources

bioRxiv2024

N-acetylation of α-synuclein enhances synaptic vesicle clustering mediated by α-synuclein and lysophosphatidylcholine

Post-translational modifications (PTMs) of -synuclein (-syn) such as acetylation and phosphorylation play important yet distinct roles in regulating -syn conformation, membrane binding, and amyloid aggregation. However, how PTMs regulate -syn function in presynaptic terminals remains unclear. Previously, we reported that -syn clusters synaptic vesicles (SV)1, and neutral phospholipid lysophosphatidylcholine (LPC) can mediate this clustering2. Here, based on our previous findings, we further demonstrate that N-terminal acetylation, which occurs under physiological conditions and is irreversible in mammalian cells, significantly enhances the functional activity of -syn in clustering SVs. Mechanistic studies reveal that this enhancement is caused by the N-acetylation-promoted insertion of -syns N-terminus and increased intermolecular interactions on the LPC-containing membrane. Our work demonstrates that N-acetylation fine-tunes -syn-LPC interaction for mediating -syns function in SV clustering.

biophysics↗

bioRxiv2022

Indigenous Cultural Safety Training for Applied Health, Social Work and Education Professionals: A PRISMA Scoping Review

BackgroundAnti-Indigenous racism is a widespread social problem in health, social work, and education systems in English-speaking Colonized countries such as Canada, with profound negative impacts to the health and education of Indigenous peoples. In 2015, Canadas Truth and Reconciliation Commission recognized the legacy and impact of Colonization and recommended training programs for these professions on cultural competency and curricula, and on the colonial history of Canada. Yet there is little evidence on best practices for such training, highlighting the need to synthesize existing findings on how these training programs are developed, implemented, and evaluated. MethodsThis scoping review explored the academic literature on Indigenous cultural safety and competence training in the health, social work, and education fields. Medline, EMBASE, CINAHL, ERIC and ASSIA were searched for articles published between 1996-2020 in Canada, United States, Australia, and New Zealand. The Joanna Briggs Institutes three-step search strategy was used as was the PRISMA extension for Scoping Reviews. Data was charted and synthesized in three stages. Results134 were included in this review. Data was extracted on four themes: 1) Article Characteristic; 2) Cultural Safety Concepts, Critiques and Rationale; 3) Characteristics of Cultural Safety Training; and 4) Evaluation Details of Cultural Safety Training. Findings suggest that research on cultural safety training programs in health, social work and education has grown significantly. Nursing and medicine professions have received a significant proportion of cultural training programs, compared with general/allied health, social work, and education. Across fields, professionals and students were targeted equally by training programs. Only half of evaluations of cultural safety and related intervention identified methodological limitations. ImplicationsConsidering, comparing, and contrasting literature on cultural safety and related concepts and how they are applied in practice would advance this scholarly work, as would more robust evaluations of cultural safety and similar training interventions to understand their impact at the individual level. Finally, commitment to meaningfully engage Indigenous communities to develop, implement and evaluate such programs is urgently needed.

scientific communication and education↗

bioRxiv2022

Specific binding of Hsp27 and phosphorylated Tau mitigates abnormal Tau aggregation-induced pathology

Amyloid aggregation of phosphorylated Tau (pTau) into neurofibrillary tangles is closely associated with Alzheimers disease (AD). Several molecular chaperones have been reported to bind Tau and impede its pathological aggregation. Recent findings of elevated levels of Hsp27 in the brains of patients with AD suggested its important role in pTau pathology. However, the molecular mechanism of Hsp27 in pTau aggregation remains poorly understood. Here, we show that Hsp27 partially co-localizes with pTau tangles in the brains of patients with AD. Notably, phosphorylation of Tau by microtubule affinity regulating kinase 2 (MARK2), dramatically enhances the binding affinity of Hsp27 to Tau. Moreover, Hsp27 efficiently prevents pTau fibrillation in vitro and mitigates neuropathology of pTau aggregation in a Drosophila tauopathy model. Further mechanistic study reveals that Hsp27 employs its N-terminal domain to directly interact with multiple phosphorylation sites of pTau for specific binding. Our work provides the structural basis for the specific recognition of Hsp27 to pathogenic pTau, and highlights the important role of Hsp27 in preventing abnormal aggregation and pathology of pTau in AD.

biochemistry↗

bioRxiv2020

Hypoxia-induced miR-92a regulates p53 signalling pathway and apoptosis by targeting calcium-sensing receptor in Genetically Improved Farmed Tilapia (Oreochromis niloticus)

miR-92a miRNAs are immune molecules that regulate apoptosis (programmed cell death) during the immune response. Apoptosis helps to maintain the dynamic balance in tissues of fish under hypoxia stress. The aim of this study was to explore the role and potential mechanisms of miR-92a in the liver of tilapia under hypoxia stress. We first confirmed that CaSR (encoding a calcium-sensing receptor) is a target gene of miR-92a in genetically improved farmed tilapia (GIFT) using luciferase reporter gene assays. In GIFT under hypoxia stress, miR-92a was up-regulated and CaSR was down-regulated in a time-dependent manner. Knocked-down CaSR expression led to inhibited expression of p53, TP53INP1 and caspase-3/8, reduced the proportion of apoptotic hepatocytes, and decreased the activity of calcium ions induced by hypoxia in hepatocytes. GIFT injected in the tail vein with an miR-92a agomir showed up-regulation of miR-92a and down-regulation of CaSR, p53, TP53INP1, and caspase-3/8 genes in the liver, resulting in lower serum alanine aminotransferase and aspartate aminotransferase activities under hypoxia stress. These findings suggest that stimulation of miR-92a interferes with hypoxia-induced apoptosis in hepatocytes of GIFT by targeting CaSR, thereby alleviating liver damage. These results provide new insights into the adaptation mechanisms of GIFT to hypoxia stress.

molecular biology↗

bioRxiv2019

Mechanistic insights into NAD synthase NMNAT chaperoning phosphorylated Tau from pathological aggregation

Tau hyper-phosphorylation and deposition into neurofibrillary tangles have been found in brains of patients with Alzheimers disease (AD) and other tauopathies. Molecular chaperones are involved in regulating the pathological aggregation of phosphorylated Tau (pTau) and modulating disease progression. Here, we report that nicotinamide mononucleotide adenylyltransferase (NMNAT), a well-known NAD synthase, serves as a chaperone of pTau to prevent its amyloid aggregation in vitro as well as mitigate its pathology in a fly tauopathy model. By combining NMR spectroscopy, crystallography, single-molecule and computational approaches, we revealed that NMNAT adopts its enzymatic pocket to specifically bind the phosphorylated sites of pTau, which can be competitively disrupted by the enzymatic substrates of NMNAT. Moreover, we found that NMNAT serves as a co-chaperone of Hsp90 for the specific recognition of pTau over Tau. Our work uncovers a dedicated chaperone of pTau and suggests NMNAT as a key node between NAD metabolism and Tau homeostasis in aging and neurodegeneration.

biochemistry↗

bioRxiv2018

Zebrafish DANA retroposon can form large zebrafish sequence in human Hepg2 and 293T cell lines

In this study, we cloned small zebrafish retroposon DANA from zebrafish genome and constructed the lentiviral expression vector pEB-GFP (T2A)PURO. Three human cell lines including 293T, Hepg2 and LO2 were selected as infection targets. After detecting the expression of DANA, we found that the expression of DANA retroposon in three cells had different effects on cell lines through chromosome walking. Among these cells, LO2 showed no DANA retrotrans-position, while 293T and Hepg2 cell lines displayed retrotrans-position with the formation of some zebrafish genome fragments. Thereafter, we constructed a mutant of DANA retroposon and infected it in 293T cells, but no retrotrans-position was found after chromosome walking. Re-sequencing of the two cell lines (293T and Hepg2) showed that a large number of zebrafish genome fragments were found in the genomes of both cell lines, which could be divided into four types. The first type was zebrafish microsatellite sequence, accounting for 79.23% and 74.45% in 293T cell line and Hepg2 cell line, respectively. The second type was the sequence with a small amount of poly A or T, and the third type was the sequence with poly G or C, and the second and third types accounted very low proportion. The fourth type was composed of coding sequence and non-coding sequence, with large difference and very low proportion of common sequences between the two cell lines. Taken together, this study indicated that zebrafish DANA retroposon can result in retrotrans-position using the retrotrans system of human cell lines.

cell biology↗

bioRxiv2018

Rearranged zebrafish genomic DNA induces zebrafish mutant after microinjection into fertilized egg and preliminary study of the mechanism

Genomic DNA of zebrafish was first digested incompletely with Msp I, and then the fragments were joined to form rearranged genomic DNA. This rearranged genomic DNA was incompletely digested with EcoR I, and the fragments were linked with a long adaptor. Two primers (Gmprimer1 and Gmprimer2) were designed according to the adaptor sequence for two-step amplification. The Gmprimer1-amplified products were microinjected into fertilized zebrafish eggs after purification and a red flesh mutant was observed among 42 surviving zebrafish. We obtained several introduced sequences by two-step amplification. The second set of Gmprimer2-amplified products were purified and microinjected into fertilized zebrafish eggs; all 37 surviving fish were red flesh mutants. We found that the largest amplified band from the mutant from the first microinjection was also present in the amplified pattern from six mutants from the second microinjection. The length of the sequence was 2,565 bp, but it did not encode any proteins. Microinjecting this sequence into fertilized zebrafish eggs produced the red flesh mutant. The sequences differed slightly among different individuals from the second microinjection. Most regions of these sequences were the same, with the exception of a hypervariable region. We mixed 10 such sequences equally and microinjected them into zebrafish zygotes; the findings showed that most zygotes died and the surviving zebrafish were almost all mutants. By genome walking, we found that the site of insertion of the fragment was the same, beginning at position 41,365,003 of the eighth chromosome, and that downstream of the introduced fragment is a conservative sequence of 6,536 bp (named Cao-sequence), starting from a small reverse repeat sequence, not encoding any gene, nor similar to any known regulatory sequence. It has 322 homologous sequences in the zebrafish genome, which are distributed in all chromosomes. We designed two primers within Cao-sequence and several primers specific for different locations upstream of it. Compared with normal zebrafish, we found that the amplified patterns of all mutants in Cao-sequence regions changed to varying degrees. To further understand the effect of the introduced sequence on the zebrafish genomes, we selected six mutants for whole-genome resequencing. The results showed that numerous Cao-sequences from these six mutants were partially deleted and the lengths of the deletions was mostly approximately 6,100 bp, being located at the 5' end of Cao-sequences. Among them, 43 Cao-sequence loci were commonly deleted from the six mutants (with slightly different locations), and the other deletion sites were not identical. We think that different deletion combinations of Cao-sequence may show different mutation characteristics. The tail part from four red flesh mutants and three individuals of wild type were collected for transcriptome sequencing. TopGO analysis showed that the 4 most significant enrichment nodes were sequence specific DNA binding proteins, sequence specific transcription factors, chromatin proteins and zinc binding proteins. The results of KEGG enrichment analysis showed that the top four affected KEGG-pathways were metabolic pathways, oxidative phosphorylation, citrate cycle and 2-oxocarboxylic acid metabolism.We conclude that deletion of Cao-sequence can affect the expression of a series of transcription regulators and specific DNA binding proteins, then many basic metabolic processes were disturbed which led to mutations.

genetics↗