Результаты поиска

Histone Acetyltransferase Activity of MOF Is Required for MLL-AF9 Leukemogenesis.

Chromatin-based mechanisms offer therapeutic targets in acute myeloid leukemia (AML) that are of great current interest. In this study, we conducted an RNAi-based screen to identify druggable chromatin regulator-based targets in leukemias marked by oncogenic rearrangements of the MLL gene. In this manner, we discovered the H4K16 histone acetyltransferase (HAT) MOF to be important for leukemia cell growth. Conditional deletion of Mof in a mouse model of MLL-AF9-driven leukemogenesis reduced tumor burden and prolonged host survival. RNA sequencing showed an expected downregulation of genes withi

H1N1 triggered recurrent acute necrotizing encephalopathy in a family with a T653I mutation in the RANBP2 gene.

A 28-month-old infant presented with fever, vomiting and encephalopathy. Magnetic resonance imaging findings and family history confirmed a diagnosis of recurrent familial acute necrotizing encephalopathy (ANE1). We believe that this is the first description implicating the H1N1 viral strain as a trigger and the second report of a T653I mutation in the RANBP2 gene described in relation to ANE1.

3D Mechanical Response Stem Cell Complex Repairs Spinal Cord Injury by Promoting Neurogenesis and Regulating Tissue Homeostasis.

Spinal cord injury (SCI) leads to acute tissue damage that disrupts the microenvironmental homeostasis of the spinal cord, inhibiting cell survival and function, and thereby undermining treatment efficacy. Traditional stem cell therapies have limited success in SCI, due to the difficulties in maintaining cell survival and inducing sustained differentiation into neural lineages. A new solution may arise from controlling the fate of stem cells by creating an appropriate mechanical microenvironment. In this study, mechanical response stem cell complex (MRSCC) is created as an innovative therapeut

Graphene oxide-functionalized molecular beacon for real-time interference-free detection of Ki-67 mRNA in living cells.

Molecular beacons (MBs) based on hairpin-shaped oligonucleotides are captivating owing to their capability to enable effective real-time det … DNase Ⅱ in lysosomes. Moreover, the size of GO nanosheets was considerably higher than that of the nuclear pore complex (NPC), which prevented nanoprobes from transition through the NPCs, thereby avoiding the generation of false-positive signals in the nucleus. Altogether, the present work affords a convenient approach for the successful detection of Ki-67 mR …

The First Case Report of a Homozygous Consensus Acceptor Splice Variant in the NUP214 Gene Associated With Fetal Hydrops and Arthrogryposis Multiplex.

The NUP214 gene encodes a nuclear pore complex protein (nucleoporin, 214 kilodaltons) which plays a critical role in messenger RNA export to the cytoplasm and import of substrates from the cytoplasm. Biallelic mutations in the NUP214 gene have been associated with susceptibility to acute infection-induced encephalopathy type 9 (ILAE9) (Online Mendelian Inheritance in Man (OMIM), 114350), an autosomal recessive disorder. Herein, we describe for the first time, a fetus with hydrops and arthrogryposis multiplex with a homozygous novel consensus splice site variant in the NUP214 gene, chr9:g.13112…

More Efficient Prussian Blue Nanoparticles for an Improved Caesium Decontamination from Aqueous Solutions and Biological Fluids.

Any release of radioactive cesium-137, due to unintentional accidents in nuclear plants, represents a dangerous threat for human health and the environment. Prussian blue has been widely studied and used as an antidote for humans exposed to acute internal contamination by Cs-137, due to its ability to act as a selective adsorption agent and to its negligible toxicity. In the present work, the synthesis protocol has been revisited avoiding the use of organic solvents to obtain Prussian blue nanoparticles with morphological and textural properties, which positively influence its Cs+ binding capa

Characterisation of Two Toxic Gambierdiscus spp. (Gonyaulacales, Dinophyceae) from the Great Barrier Reef (Australia): G. lewisii sp. nov. and G. holmesii sp. nov.

Ciguatera fish poisoning (CFP) is a human illness caused via consumption of seafood contaminated with neurotoxins produced by some species from the epiphytic dinoflagellate genus Gambierdiscus. In this study, we describe two new species of Gambierdiscus isolated from Heron Island in the Southern Great Barrier Reef, Queensland, Australia. These new species were analysed using light microscopy, scanning electron microscopy, and phylogenetic analyses of nuclear encoded ribosomal ITS, SSU as well as D1-D3 and D8-D10 of the LSU gene regions. Gambierdiscus lewisii sp. nov. (Po, 3', 0a, 7″, 6c,? s, 5

A new genus of proteocephalid tapeworm (Cestoda) from the marbled swamp eel Synbranchus marmoratus Bloch (Synbranchiformes: Synbranchidae) in the River Paraná basin, Argentina.

Synbranchiella gen. n. is proposed to accommodate Synbranchiella mabelae sp. n. (Proteocephalidae: Monticelliinae) from the intestine of the marbled swamp eel Synbranchus marmoratus Bloch, in the River Colastiné, a tributary of the middle River Paraná in Argentina. The new genus is placed in the Monticelliinae because of the cortical position of the genital organs. It differs from all known monticelliine genera by the following combination of characters: (i) scolex robust, with a conical apex, without metascolex; (ii) biloculate suckers with a conspicuous septum separating unequally-sized locu

Механика вирусного Хроматина открывает прессу человеческого аденовируса.

Тщательное содержание обнаженных геномов в некоторых вирусах приводит к высокому внутреннему давлению, которое облегчает их перенос в хозяин. Аденовирус, однако, кодирует гистонеподобные белки, которые ассоциируются с его геномомом, что приводит к замкнутому конденсату ДНК-протеина (core). Клейф этих белков во время созревания уменьшает конденсацию ядра и расщепляет вирион для надлежащего отсоединения с помощью неопознанных механизмов. Здесь мы открываем отдельные, зрелые и незрелые аденовирусные клетки для непосредственного изучения механики их хроматиновых ядер. Мы находим незрелые ядра боле

Совпадение в аннотации оригинала
Tight confinement of naked genomes within some viruses results in high internal pressure that facilitates their translocation into the host. … embly of the mature particle, enabling its escape from the endosome and final genome release at the nuclear pore.

NUP98 gene rearrangements and the clonal evolution of chronic myelogenous leukemia.

The role of the BCR-ABL fusion gene in the pathogenesis of the chronic phase of chronic myelogenous leukemia (CML) has been well established. Several additional genetic changes have been reported to occur, at varying frequencies, during disease progression to "accelerated" and "blast crisis" phases. The NUP98 gene localized to chromosome band 11p15 has been found at the breakpoints of several distinct chromosomal translocations in patients with both de novo and therapy-related myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). Using combined cytogenetic and molecular analyse

NUP98-BPTF promotes oncogenic transformation through PIM1 upregulation.

INTRODUCTION: Nucleoporin 98 (NUP98) fusion proteins are recurrently found in leukemia and are associated with unfavorable clinical outcomes. They are distributed to the nucleus and contribute to leukemogenesis via aberrant transcriptional regulation. We previously identified NUP98-BPTF (NB) fusion in patients with T-cell acute lymphoblastic leukemia (T-ALL) using next-generation sequencing. The FG-repeat of NUP98 and the PHD finger and bromodomain of bromodomain PHD finger transcription factor (BPTF) are retained in the fusion. Like other NUP98 fusion proteins, NB is considered to regulate ge

Rare NUP98::PRRX1 fusion transcript in a therapy-related acute myeloid leukemia associated with del(7q) following chemotherapy for diffuse large B-cell lymphoma.

BACKGROUND: Therapy-related acute myeloid leukemia (t-AML) is increasingly recognized as a treatment complication in patients receiving chemotherapy, radiotherapy, or immunosuppressive agents for primary neoplasms. NUP98::PRRX1 fusion gene, caused by t(1;11)(q23;p15), is a rare recurrent cytogenetic alteration in leukemia, and only seven cases with NUP98::PRRX1 were reported so far. METHODS: A 53-year-old female patient was diagnosed with t-AML after 20 months of complete remission (CR) from diffuse large B-cell lymphoma (DLBCL). Conventional karyotype, fluorescence in situ hybridization (FIS

Exploring the molecular and clinical spectrum of COVID-19-related acute necrotizing encephalopathy in three pediatric cases.

Acute necrotizing encephalopathy (ANE) is a rare disease that predominantly affects children and is associated with a high mortality rate. Here we report three cases of COVID-19-related ANE in children, with the mutation detection in two genes associated with mitochondrial dysfunction. The cases exhibited common ANE symptoms, such as fever, impaired consciousness, positive pathological reflex, increased cerebrospinal fluid protein, and multifocal and symmetric brain lesions identified through MRI. Using genotype-phenotype correlation analysis in trio-whole exome sequencing (WES), four potentia

t(5;12)(q31;p13)/ETV6::ACSL6 and t(6;9)(p23;q34)/DEK::NUP214 concurrence in acute myeloid leukemia: an unusual association of two rare abnormalities.

The translocation t(5;12)(q31;p13)/ETV6::ACSL6 is a rare cytogenetic abnormality, although it is reported in various myeloid malignancies. To date, only 16 cases of t(5;12) and ETV6::ACSL6 rearrangement, confirmed by either molecular or Fluorescence In Situ Hyridization (FISH) analysis, have been reported. Eosinophilia is a distinctive and common feature associated with this rearrangement. Although few cases have been described, the prognosis of patients with ETV6::ACSL6 is considered poor. We report two additional cases of t(5;12)(q31;p13)/ETV6::ACLS6 rearrangement and eosinophilia. Unusually

The genetic basis of triple A (Allgrove) syndrome in a Greek family.

Triple A (or Allgrove) syndrome is an autosomal recessive genetic disorder. Patients typically suffer from chronic adrenal insufficiency due to resistance to ACTH (Addison's disease), achalasia of the cardia, and defective tear formation (alacrima). The syndrome is caused by mutations in the AAAS gene which encodes the protein ALADIN, a constituent of eukaryotic nuclear pore complexes. The multi-systemic nature and variable manifestations of the triple A syndrome often confound its diagnosis and limit our understanding of its exact pathogenesis. We performed mutational screening of the AAAS ge…

NUP85 Mediates Endoplasmic Reticulum Stress through the USP47/ASK1 Signaling Pathway to Regulate the Progression of Liver Fibrosis.

Liver fibrosis is a pathological process caused by excessive deposition of extracellular matrix (ECM) in the liver stimulated by chronic injury or inflammation. Nuclear pore protein 85 (NUP85) has been implicated in the development of various liver diseases. However, its involvement in liver fibrosis remains unclear. The present study aimed to explore the role of NUP85 in liver fibrosis. The expression level of NUP85 was found to be elevated in the liver tissues of liver fibrosis patients and mice. Knockdown of NUP85 not only ameliorated liver injury and collagen deposition, but also suppresse…

Sigma-1R-Pom121 axis preserves nuclear transport and integrity in poly-PR-induced C9orf72 ALS.

Nucleocytoplasmic transport disruption contributes to the pathogenesis of C9orf72-associated amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Among the dipeptide repeat proteins translated from G4C2-repeat RNA, poly-PR is particularly toxic, compromising nuclear envelope integrity and transport. Here, we revealed that poly-PR reduced expression of the nucleoporin Pom121 in NSC-34 cells and in an AAV-mediated poly-PR42 mouse model, resulting in cytoplasmic mislocalization of the neuroprotective transcription factor ATF3 and nuclear envelope damage. Pom121 overexpression restored

Venetoclax-based chemotherapy failure in adult T-cell acute lymphoblastic leukemia with NUP98::ADD3 fusion: a case report.

NUP98 fusions are molecularly rare in T-cell acute lymphoblastic leukemia (T-ALL), with limited data available regarding treatment response and clinical outcomes. Here, we report a case of T-ALL harboring a NUP98::ADD3 fusion (involving NUP98 exon 13 and ADD3 exon 13), representing only the second documented instance of this genetic rearrangement in T-ALL. Notably, the patient demonstrated refractoriness to venetoclax-based chemotherapy. To our knowledge, this is the first report of a T-ALL case with the NUP98::ADD3 fusion exhibiting resistance to venetoclax-containing regimens.

Clinical and genetic characterisation of a series of patients with triple A syndrome.

UNLABELLED: Triple A syndrome (TAS) or Allgrove syndrome (OMIM #231550) is a rare autosomal recessive disorder characterised by adrenocorticotropic hormone-resistant adrenal insufficiency, alacrima, achalasia, and neurological and dermatological abnormalities. Mutations in the AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN have been reported in these patients. Between 2006 and 2017, we evaluated six patients with a clinical diagnosis of TAS, based on the presence of at least two symptoms, usually adrenal insufficiency and alacrima. In all cases, genetic analysis reveale…