Search results for " Cell"
showing 10 items of 14074 documents
Ethical Aspects of Nuclear and Mitochondrial DNA Transfer
2016
Somatic cell nuclear transfer (SCNT) (cloning), as a reproductive or therapeutic method, and mitochondrial DNA transfer, as a method to prevent the transmission of mitochondrial diseases, are analyzed in this paper from a bioethics perspective. The licit purpose of being able to treat certain diseases, as in the case of SCNT, cannot justify, in any case, resorting to illicit means such as the manipulation, selection, and elimination of human embryos in the blastocyst phase, by using cell lines obtained from them. Crossing this line paves the way (as utilitarian ethics advocates) to assuming any cost in scientific experimentation so long as satisfactory results are obtained. With mitochondr…
Transcriptional and Epigenetic Control of Astrogliogenesis
2017
Abstract Astrocytes exert pivotal functions in the brain ranging from homeostasis to plasticity and their malfunctioning may contribute to neurodegenerative diseases. With increased recognition of their importance, more efforts are being dedicated to decoding the molecular mechanisms that control the generation of astrocytes from neural stem cells, a process referred to as astrogliogenesis. In this chapter, we highlight the discoveries that have shed light on the role of transcription factors, DNA methylation, histone modifications, and microRNAs in driving the transcriptional programs that underlie astrocyte generation. We further discuss the current understanding of gene regulatory pathwa…
Identification and Successful Negotiation of a Metabolic Checkpoint in Direct Neuronal Reprogramming
2016
Despite the widespread interest in direct neuronal reprogramming, the mechanisms underpinning fate conversion remain largely unknown. Our study revealed a critical time point after which cells either successfully convert into neurons or succumb to cell death. Co-transduction with Bcl-2 greatly improved negotiation of this critical point by faster neuronal differentiation. Surprisingly, mutants with reduced or no affinity for Bax demonstrated that Bcl-2 exerts this effect by an apoptosis-independent mechanism. Consistent with a caspase-independent role, ferroptosis inhibitors potently increased neuronal reprogramming by inhibiting lipid peroxidation occurring during fate conversion. Genome-w…
Complete Genome Sequence of an Aquaculture-Associated Phage, FL-1, Infecting Flavobacterium spp
2017
Flavobacterium spp. are abundant and widespread in freshwater environments (1, 2). Despite the prevalence of the members in this genus, the phages infecting Flavobacterium spp. are less known. So far, most of the phages studied in detail infect fish pathogenic members of the genus, such as F. psychrophilum (3). The phage FL-1 and its Flavobacterium sp. host strain B183 were previously isolated from a water sample from a fish farm in Central Finland. Transmission electron microscopy revealed FL-1 to be a member of the family Myoviridae (4). In addition to the isolation host, FL-1 also infects multiple Flavobacterium sp. isolates and strains of the fish pathogen F. columnare, the causative ag…
Antioxidant role of microvesicles, activated by genistein, in stem cells
2018
Intercellular communication is an essential hallmark of multicellular organisms. Microvesicles (MVs), which are released from and taken up by most types of cells are involved in intercellular communication. The nutrients we ingest from food contact with immune cells in the bloodstream and can promote the formation of MVs. Some foods contain molecules with regulatory activity, such as genistein, a polyphenol found in soy. We aimed to study the effects of MVs released from genistein-treated immune cells on dental pulp stem cells (DPSC). We obtained peripheral blood mononuclear cells (PBMC) from 5 young women (aged 18–25). Cells were cultured and treated with 0.5 μM genistein or 0.01% DMSO as …
miR-22 suppresses DNA ligase III addiction in multiple myeloma
2019
Multiple myeloma (MM) is a hematologic malignancy characterized by high genomic instability. Here we provide evidence that hyper-activation of DNA ligase III (LIG3) is crucial for genomic instability and survival of MM cells. LIG3 mRNA expression in MM patients correlates with shorter survival and even increases with more advanced stage of disease. Knockdown of LIG3 impairs MM cells viability in vitro and in vivo, suggesting that neoplastic plasmacells are dependent on LIG3-driven repair. To investigate the mechanisms involved in LIG3 expression, we investigated the post-transcriptional regulation. We identified miR-22-3p as effective negative regulator of LIG3 in MM. Enforced expression of…
RINT1 Loss Impairs Retinogenesis Through TRP53-Mediated Apoptosis
2020
Genomic instability in the central nervous system (CNS) is associated with defective neurodevelopment and neurodegeneration. Congenital human syndromes that affect the CNS development originate from mutations in genes of the DNA damage response (DDR) pathways. RINT1 (Rad50-interacting protein 1) is a partner of RAD50, that participates in the cellular responses to DNA double-strand breaks (DSB). Recently, we showed that Rint1 regulates cell survival in the developing brain and its loss led to premature lethality associated with genomic stability. To bypass the lethality of Rint1 inactivation in the embryonic brain and better understand the roles of RINT1 in CNS development, we conditionally…
A dual role of caspase-8 in triggering and sensing proliferation-associated DNA damage, a key determinant of liver cancer development.
2017
Summary Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis. Proliferation-associated DNA damage is sensed by a complex comprising caspase-8, FADD, c-FLIP, and a kinase-dependent function of RIPK1. This platform requires a non-apop…
FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability
2021
Common fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability involves transcription- and replication-dependent mechanisms. Here, we uncover a role for the mitochondrial stress response pathway in the regulation of CFS stability in human cells. We show that FANCD2, a master regulator of CFS stability, dampens the activation of the mitochondrial stress response and prevents mitochondrial dysfunction. Genetic or pharmacological activation of mitochondrial stress signaling induces CFS gene expression and concomitant relocalization to CFSs of FANCD2. FANCD2 attenuates CFS gene transcription and pr…
IFNL3/4 genotype is associated with altered immune cell populations in peripheral blood in chronic hepatitis C infection
2016
Single-nucleotide polymorphisms near the interferon lambda 3 (IFNL3) gene predict outcomes to infection and anti-viral treatment in hepatitis C virus (HCV) infection. To identify IFNL3 genotype effects on peripheral blood, we collected phenotype data on 400 patients with genotype 1 chronic hepatitis C (CHC). The IFNL3 responder genotype predicted significantly lower white blood cells (WBCs), as well as lower absolute numbers of monocytes, neutrophils and lymphocytes for both rs8099917 and rs12979860. We sought to define the WBC subsets driving this association using flow cytometry of 67 untreated CHC individuals. Genotype-associated differences were seen in the ratio of CD4CD45RO+ to CD4CD4…