Translocation

Systemic mastocytosis (SM) is a rare haematological neoplasm associated with the gain of function mutation KIT D816V in 90% of adult patients. Classically, cytogenetic aberrations are not common except in cases of SM associated with another haematological neoplasm. We highlight here an unusual clinical presentation of SM and demonstrate the utility of advanced cytogenetic analysis (optical genome mapping, OGM) in detecting a novel cytogenetic abnormality resulting in an unusual mechanism of DNMT3A and TET2 loss of function...

INTRODUCTION: Microglia are the main phagocytes in the brain and can induce neuroinflammation. Moreover, they are critical to alpha-synuclein (α-syn) aggregation and propagation. Plasma exosomes derived from patients diagnosed with Parkinson's disease (PD-exo) reportedly evoked α-syn aggregation and inflammation in microglia. In turn, microglia internalized and released exosomal α-syn, enhancing α-syn propagation. However, the specific mechanism through which PD-exo influences α-syn degradation remains unknown...

BACKGROUND: Subarachnoid hemorrhage (SAH), a severe subtype of stroke, is characterized by notably high mortality and morbidity, largely due to the lack of effective therapeutic options. Although the neuroprotective potential of PPARg and Nrf2 has been recognized, investigative efforts into oroxin A (OA), remain limited in preclinical studies. METHODS: SAH was modeled in vivo through filament perforation in male C57BL/6 mice and in vitro by exposing HT22 cells to hemin to induce neuronal damage...

Hepatocellular carcinoma (HCC) is the main histological subtype of primary liver cancer and remains one of the most common solid malignancies globally. Ferroptosis was recently defined as an iron-catalyzed form of regulated necrosis. Because cancer cells exhibit higher iron requirements than noncancer cells, treatment with ferroptosis-inducing compounds may be a feasible strategy for cancer therapy. However, cancer cells develop acquired resistance to evade ferroptosis, and the mechanisms responsible for ferroptosis resistance are not fully clarified...

Fruit crops are frequently subjected to biotic and abiotic stresses that can significantly reduce the absorption and translocation of essential elements, ultimately leading to a decrease in crop yield. It is imperative to grow fruits and vegetables in areas prone to drought, salinity, and extreme high, and low temperatures to meet the world's minimum nutrient demand. The use of integrated approaches, including supplementation of beneficial elements like silicon (Si), can enhance plant resilience under various stresses...

The current pharmacological approaches to multiple sclerosis (MS) target its inflammatory and autoimmune components, but effective treatments to foster remyelination and axonal repair are still lacking. We therefore selected two targets known to be involved in MS pathogenesis: N-acylethanolamine-hydrolyzing acid amidase (NAAA) and glycogen synthase kinase-3β (GSK-3β). We tested whether inhibiting these targets exerted a therapeutic effect against experimental autoimmune encephalomyelitis (EAE), an animal model of MS...

BACKGROUND: Previous in vivo and in vitro studies have demonstrated that estrogen receptor agonist G-1 regulates glucose and lipid metabolism. This study focused on the effects of G-1 on cardiometabolic syndrome and anti-obesity under a high fat diet (HFD). METHODS: Bilateral ovariectomized female mice were fed an HFD for 6 weeks, and treated them with G-1. A cardiomyocyte insulin resistance model was used to simulate the in vivo environment. The main outcome measures were blood glucose, body weight, and serum insulin levels to assess insulin resistance, while cardiac function and degree of fibrosis were assessed by cardiac ultrasound and pathological observations...

Despite therapeutic advancements, GVHD is a major complication of HSCT. In current models of GVHD, tissue injury induced by cytotoxic conditioning regimens, along with translocation of microbes expressing Pathogen Associated Molecular Patterns (PAMPs), result in activation of host antigen-presenting cells (APC) to stimulate alloreactive donor T lymphocytes. Recent studies have demonstrated that in many pathologic states, tissue injury results in the release of mitochondria from the cytoplasm to the extracellular space...

BACKGROUND: Dementia is a major public health challenge for aging societies worldwide. Neuroinflammation is thought to be a key factor in dementia development. The aim of this study was to comprehensively assess translocator protein (TSPO) expression by positron emission tomography (PET) imaging to reveal the characteristics of neuroinflammation in dementia. METHODS: We used a meta-analysis to retrieve literature on TSPO expression in dementia using PET imaging technology, including but not limited to the quality of the study design, sample size, and the type of TSPO ligand used in the study...

Enzymes of the ten-eleven translocation (TET) family play a key role in the regulation of gene expression by oxidizing 5-methylcytosine (5mC), a prominent epigenetic mark in many species. Yet, TET proteins also have less characterized noncanonical modes of action, notably in Drosophila , whose genome is devoid of 5mC. Here, we show that Drosophila TET activates the expression of genes required for larval central nervous system (CNS) development mainly in a catalytic-independent manner. Genome-wide profiling shows that TET is recruited to enhancer and promoter regions bound by Polycomb group complex (PcG) proteins...

The concentration of inorganic phosphate (Pi) in the chloroplast stroma must be maintained within narrow limits to sustain photosynthesis and to direct the partitioning of fixed carbon. However, it is unknown if these limits or the underlying contributions of different chloroplastic Pi transporters vary throughout the photoperiod or between chloroplasts in different leaf tissues. To address these questions, we applied live Pi imaging to Arabidopsis (Arabidopsis thaliana) wild-type plants and two loss-of-function transporter mutants: triose phosphate/phosphate translocator (tpt), phosphate transporter 2; 1 (pht2; 1), and tpt pht2; 1...

The fine control of synaptic function requires robust trans-synaptic molecular interactions. However, it remains poorly understood how trans-synaptic bridges change to reflect the functional states of the synapse. Here, we develop optical tools to visualize in firing synapses the molecular behavior of two trans-synaptic proteins, LGI1 and ADAM23, and find that neuronal activity acutely rearranges their abundance at the synaptic cleft. Surprisingly, synaptic LGI1 is primarily not secreted, as described elsewhere, but exo- and endocytosed through its interaction with ADAM23...

The cytosolic detection of pathogen-derived nucleic acids has evolved as an essential strategy for host innate immune defense in mammals. One crucial component in this process is the stimulator of IFN genes (STING), which acts as a vital signaling adaptor, connecting the cytosolic detection of DNA by cyclic GMP-AMP (cGAMP) synthase (cGAS) to the downstream type I IFN signaling pathway. However, this process remains elusive in invertebrates. In this study, we present evidence demonstrating that STING, an ortholog found in a marine invertebrate (shrimp) called Litopenaeus vannamei, can directly detect DNA and initiate an IFN-like antiviral response...

Sequencing of biomacromolecules is a crucial cornerstone in life sciences. Glycans, one of the fundamental biomolecules, derive their physiological and pathological functions from their structures. Glycan sequencing faces challenges due to its structural complexity and current detection technology limitations. As a highly sensitive sensor, nanopores can directly convert nucleic acid sequence information into electrical signals, spearheading the revolution of third-generation nucleic acid sequencing technologies...

Splenic gas gangrene caused by  Clostridium perfringens  is rare. A 73-year-old woman was referred to our hospital because of fatigue, dyspnea, and left hypochondrial pain. She had a history of blunt trauma to the left abdomen eight days ago. She presented with hypoxemia and a high inflammatory response on blood tests. A CT showed left pleural effusion and gas in the spleen. She was treated with antimicrobials and underwent splenectomy.  C. perfringens  was identified from blood and intraoperative ascites cultures...

BACKGROUND: Ischemic postconditioning (IPostC) has been reported as a promising method for protecting against myocardial ischemia-reperfusion (MI/R) injury. Our previous study found that the infarct-limiting effect of IPostC is abolished in the heart of diabetes whose cardiac expression of DJ-1 (also called PARK7, Parkinsonism associated deglycase) is reduced. However, the role and in particular the underlying mechanism of DJ-1 in the loss of sensitivity to IPostC-induced cardioprotection in diabetic hearts remains unclear...

An adult plant gene for resistance to stripe rust was narrowed down to the proximal one-third of the 2Nv S segment translocated from Aegilops ventricosa to wheat chromosome arm 2AS, and based on the gene expression analysis, two candidate genes were identified showing a stronger response at the adult plant stage compared to the seedling stage. The 2Nv S translocation from Aegilops ventricosa, known for its resistance to various diseases, has been pivotal in global wheat breeding for more than three decades...

Uterine luminal epithelia (LE), the first layer contacting with the blastocyst, acquire receptivity for normal embryo implantation. Besides the well-accepted transcriptional regulation dominated by ovarian estrogen and progesterone for receptivity establishment, the involvement of epigenetic mechanisms remains elusive. This study systematically profiles the transcriptome and genome-wide H3K27me3 distribution in the LE throughout the preimplantation. Combining genetic and pharmacological approaches targeting the PRC2 core enzyme Ezh1/2, we demonstrate that the defective remodeling of H3K27me3 in the preimplantation stage disrupts the differentiation of LE, and derails uterine receptivity, resulting in implantation failure...

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a dynamic chronic liver disease closely related to metabolic abnormalities, such as diabetes and obesity. MASLD can further progress to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis and even hepatocellular carcinoma (HCC). However, the mechanisms underlying the progression of MASLD and further progression to liver fibrosis and liver cancer are unknown. METHODS: In this study, we performed transcriptome analysis in livers from mice with MASLD and found suppression of a potential anti-oncogene, RAS association domain protein 4 (RASSF4)...

AIMS: CD4+ T cells are activated during inflammatory dilated cardiomyopathy (iDCM) development to induce immunogenic responses that damage the myocardium. Low-intensity pulsed ultrasound (LIPUS), a novel physiotherapy for cardiovascular diseases, has recently been shown to modulate inflammatory responses. However, its efficacy in iDCM remains unknown. Here, we investigated whether LIPUS could improve the severity of iDCM by orchestrating immune responses and explored its therapeutic mechanisms...