-
Frontiers in Molecular Neuroscience 2024Aging is defined as a progressive decline of cognitive and physiological functions over lifetime. Since the definition of the nine hallmarks of aging in 2013 by... (Review)
Review
Aging is defined as a progressive decline of cognitive and physiological functions over lifetime. Since the definition of the nine hallmarks of aging in 2013 by López-Otin, numerous studies have attempted to identify the main regulators and contributors in the aging process. One interesting group of proteins whose participation has been implicated in several aging hallmarks are the nuclear DBF2-related (NDR) family of serine-threonine AGC kinases. They are one of the core components of the Hippo signaling pathway and include NDR1, NDR2, LATS1 and LATS2 in mammals, along with its highly conserved metazoan orthologs; Trc in , SAX-1 in , CBK1, DBF20 in and orb6 in . These kinases have been independently linked to the regulation of widely diverse cellular processes disrupted during aging such as the cell cycle progression, transcription, intercellular communication, nutrient homeostasis, autophagy, apoptosis, and stem cell differentiation. However, a comprehensive overview of the state-of-the-art knowledge regarding the post-translational modifications of and by NDR kinases in aging has not been conducted. In this review, we summarize the current understanding of the NDR family of kinases, focusing on their relevance to various aging hallmarks, and emphasize the growing body of evidence that suggests NDR kinases are essential regulators of aging across species.
PubMed: 38803357
DOI: 10.3389/fnmol.2024.1371086 -
Narra J Apr 2024It is widely acknowledged that smoking exacerbates the severity of infectious diseases. A presumed mechanism involves the damage inflicted by tobacco smoke on the organs...
It is widely acknowledged that smoking exacerbates the severity of infectious diseases. A presumed mechanism involves the damage inflicted by tobacco smoke on the organs of host organisms. In this study, an alternative hypothesis was explored: smoking enhances the virulence of bacteria. This possibility was investigated using as the model bacteria and as the host organism. Our inquiry focused on the potential gene expression changes in subsequent to exposure to tobacco smoke extracts. Analysis of the transcription promoter activity of genes encoding proteins within the two-component system, a regulatory machinery governing gene expression, revealed the suppression of thirteen out of 23 promoters in response to tobacco smoke extracts. Subsequently, was infected with exposed to tobacco smoke extracts or left untreated. Interestingly, there were no significant differences observed in the survival periods of following infection with , whether treated or untreated with tobacco smoke extracts. Contrary to the initial hypothesis, the findings suggest that while tobacco smoke extracts alter gene expression in , these changes do not appear to impact bacterial virulence. Although this study has illuminated the influence of tobacco smoke extracts on the gene expression of , further analyses are necessary to elucidate the implications of these changes. Nevertheless, the results imply that smoking affects not only host organisms but may also exert influence on invading bacteria.
Topics: Escherichia coli; Animals; Virulence; Nicotiana; Drosophila; Gene Expression Regulation, Bacterial; Smoke; Virulence Factors
PubMed: 38798851
DOI: 10.52225/narra.v4i1.754 -
BioRxiv : the Preprint Server For... May 2024RNA editing is a post-transcriptional source of protein diversity and occurs across the animal kingdom. Given the complete profile of mRNA targets and their editing rate...
RNA editing is a post-transcriptional source of protein diversity and occurs across the animal kingdom. Given the complete profile of mRNA targets and their editing rate in individual cells is unclear, we analyzed single cell RNA transcriptomes from larval tonic and phasic glutamatergic motoneuron subtypes to determine the most highly edited targets and identify cell-type specific editing. From ∼15,000 genes encoded in the genome, 316 high confidence A-to-I canonical RNA edit sites were identified, with 102 causing missense amino acid changes in proteins regulating membrane excitability, synaptic transmission, and cellular function. Some sites showed 100% editing in single neurons as observed with mRNAs encoding mammalian AMPA receptors. However, most sites were edited at lower levels and generated variable expression of edited and unedited mRNAs within individual neurons. Together, these data provide insights into how the RNA editing landscape alters protein function to modulate the properties of two well-characterized neuronal populations in .
PubMed: 38798345
DOI: 10.1101/2024.05.17.594696 -
Nature Communications May 2024As daughter centrioles assemble during G2, they recruit conserved Ana3/RTTN followed by its partner Rcd4/PPP1R35. Together, this contributes to the subsequent...
As daughter centrioles assemble during G2, they recruit conserved Ana3/RTTN followed by its partner Rcd4/PPP1R35. Together, this contributes to the subsequent recruitment of Ana1/CEP295, required for the centriole's conversion to a centrosome. Here, we show that Rcd4/PPP1R35 is also required to maintain 9-fold centriole symmetry in the Drosophila male germline; its absence causes microtubule triplets to disperse into a reduced number of doublet or singlet microtubules. rcd4-null mutant spermatocytes display skinny centrioles that elongate normally and localize centriolar components correctly. Mutant spermatocytes also have centrioles of normal girth that splay at their proximal ends when induced to elongate by Ana1 overexpression. Skinny and splayed spermatid centrioles can still recruit a proximal centriole-like (PCL) structure marking a capability to initiate features of centriole duplication in developing sperm. Thus, stable 9-fold symmetry of microtubule triplets is not essential for centriole growth, correct longitudinal association of centriole components, and aspects of centriole duplication.
Topics: Centrioles; Animals; Male; Drosophila Proteins; Spermatocytes; Microtubules; Drosophila melanogaster; Spermatids; Cell Cycle Proteins; Microtubule-Associated Proteins; Mutation; Drosophila
PubMed: 38796459
DOI: 10.1038/s41467-024-48831-y -
Plants (Basel, Switzerland) May 2024The γ-aminobutyric acid (GABA) receptors play pivotal roles in the transmission of neuronal information in the nervous system of insects, which has led these proteins...
The γ-aminobutyric acid (GABA) receptors play pivotal roles in the transmission of neuronal information in the nervous system of insects, which has led these proteins to be targeted by synthetic and natural products. Here, we assessed the insecticidal potential of the essential oil of (Gardner) Sch. Bip., a neotropical Asteraceae plant used in traditional medicine, for controlling (Matsumura) adults by feeding exposure. By using in silico approaches, we disentangle the contribution of GABA receptors and other potential neuronal targets (e.g., acetylcholinesterase, glutathione-S-transferases) in insects that may explain the essential oil differential activities against and two essential pollinator bees ( Linnaeus and Friese). Neral (26.7%) and geranial (33.9%) were the main essential oil components which killed with an estimated median lethal concentration (LC) of 2.25 µL/mL. Both pollinator forager bee species, which would likely contact this compound in the field, were more tolerant to the essential oil and did not have their diet consumptions affected by the essential oil. Based on the molecular predictions for the three potential targets and the essential oil main components, a higher affinity of interaction with the GABA receptors of (geranial -6.2 kcal/mol; neral -5.8 kcal/mol) in relation to (geranial -5.2 kcal/mol; neral -4.9 kcal/mol) would contribute to explaining the difference in toxicities observed in the bioassays. Collectively, our findings indicated the involvement of GABA receptors in the potential of essential oil as an alternative tool for controlling .
PubMed: 38794461
DOI: 10.3390/plants13101392 -
Molecules (Basel, Switzerland) May 2024A previous study reported that the ethanolic extract of the edible fern, (Retz.) Sw. (DE), obtained from a non-optimized extraction condition exhibited anti-Alzheimer's...
A previous study reported that the ethanolic extract of the edible fern, (Retz.) Sw. (DE), obtained from a non-optimized extraction condition exhibited anti-Alzheimer's disease (AD) properties through the inhibition of a rate-limiting enzyme in amyloid peptide formation, β-secretase-1 (BACE-1). Nevertheless, a non-optimized or suboptimal extraction may lead to several issues, such as a reduction in extraction efficiency and increased time and plant materials. In this study, extraction of the DE was optimized to obtain appropriate BACE-1 inhibition using a Box-Behnken design (BBD) and response surface methodology (RSM). Data revealed that the optimal extraction condition was 70% (/) aqueous ethanol, 50 min extraction time, 30 °C extraction temperature, and 1:30 g/mL solid/liquid ratio, giving BACE-1 inhibition at 56.33%. In addition, the extract also exhibited significant antioxidant activities compared to the non-optimized extraction. Metabolomic phytochemical profiles and targeted phytochemical analyses showed that kaempferol, quercetin, and their derivatives as well as rosmarinic acid were abundant in the extract. The optimized DE extract also acted synergistically with donepezil, an AD drug suppressing BACE-1 activities. Data received from -expressing human amyloid precursor proteins (APPs) and BACE-1, representing the amyloid hypothesis, showed that the optimized DE extract penetrated the fly brains, suppressed BACE-1 activities, and improved locomotor functions. The extract quenched the expression of glutathione S transferase D1 (GSTD1), inositol-requiring enzyme (IRE-1), and molecular chaperone-binding immunoglobulin (Bip), while donepezil suppressed these genes and other genes involved in antioxidant and endoplasmic reticulum (ER) stress response, including superoxide dismutase type 1 (SOD1), activating transcription factor 6 (ATF-6), and protein kinase R-like endoplasmic reticulum kinase (PERK). To sum up, the optimized extraction condition reduced extraction time while resulting in higher phytochemicals, antioxidants, and BACE-1 inhibitors.
Topics: Antioxidants; Alzheimer Disease; Plant Extracts; Phytochemicals; Amyloid Precursor Protein Secretases; Animals; Ferns; Humans; Aspartic Acid Endopeptidases
PubMed: 38792065
DOI: 10.3390/molecules29102204 -
International Journal of Molecular... May 2024In holometabolous insects, such as and , prothoracicotropic hormone (PTTH) is well established to be critical in controlling developmental transitions and metamorphosis...
In holometabolous insects, such as and , prothoracicotropic hormone (PTTH) is well established to be critical in controlling developmental transitions and metamorphosis by stimulating the biosynthesis of ecdysone in the prothoracic glands (PGs). However, the physiological role of PTTH and the receptor Torso in hemimetabolous insects remains largely unexplored. In this study, homozygous PTTH- and Torso-null mutants of the brown planthopper (BPH), , were successfully generated by employing clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR-Cas9). Further characterization showed that both and mutants exhibited prolonged nymphal duration and increased final adult size. Enzyme-linked immunosorbent assay (ELISA) revealed that and mutants exhibited a significant reduction in 20-hydroxyecdysone (20E) in fifth-instar nymphs at 48 h post-ecdysis compared to controls. Furthermore, our results indicated that both and mutants had shortened lifespan, reduced female fecundity, and reduced egg hatching rates in adults. These findings suggest a conserved role for the PTTH-Torso signaling system in the regulation of developmental transitions by stimulating ecdysone biosynthesis in hemimetabolous insects.
Topics: Animals; Hemiptera; Ecdysone; Signal Transduction; Reproduction; Insect Hormones; Homeostasis; Body Size; Insect Proteins; Female; Gene Expression Regulation, Developmental; Male; Metamorphosis, Biological
PubMed: 38791179
DOI: 10.3390/ijms25105138 -
International Journal of Molecular... May 2024The additional sex combs-like (ASXL) family, a mammalian homolog of the () of , has been implicated in transcriptional regulation via chromatin modifications. Abnormal... (Review)
Review
The additional sex combs-like (ASXL) family, a mammalian homolog of the () of , has been implicated in transcriptional regulation via chromatin modifications. Abnormal expression of ASXL family genes leads to myelodysplastic syndromes and various types of leukemia. De novo mutation of these genes also causes developmental disorders. Genes in this family and their neighbor genes are evolutionary conserved in humans and mice. This review provides a comprehensive summary of epigenetic regulations associated with ASXL family genes. Their expression is commonly regulated by DNA methylation at CpG islands preceding transcription starting sites. Their proteins primarily engage in histone tail modifications through interactions with chromatin regulators (PRC2, TrxG, PR-DUB, SRC1, HP1α, and BET proteins) and with transcription factors, including nuclear hormone receptors (RAR, PPAR, ER, and LXR). Histone modifications associated with these factors include histone H3K9 acetylation and methylation, H3K4 methylation, H3K27 methylation, and H2AK119 deubiquitination. Recently, non-coding RNAs have been identified following mutations in the ASXL1 or ASXL3 gene, along with circular ASXLs and microRNAs that regulate ASXL1 expression. The diverse epigenetic regulations linked to ASXL family genes collectively contribute to tumor suppression and developmental processes. Our understanding of ASXL-regulated epigenetics may provide insights into the development of therapeutic epigenetic drugs.
Topics: Humans; Epigenesis, Genetic; Animals; DNA Methylation; Repressor Proteins; Histones; Mutation
PubMed: 38791157
DOI: 10.3390/ijms25105119 -
Genes May 2024Innate immune response is the first line of host defense against pathogenic microorganisms, and its excessive or insufficient activation is detrimental to the organism....
Innate immune response is the first line of host defense against pathogenic microorganisms, and its excessive or insufficient activation is detrimental to the organism. Many individual microRNAs (miRNAs) have emerged as crucial post-transcriptional regulators of immune homeostasis in . However, the synergistical regulation of miRNAs located within a cluster on the Imd-immune pathway remains obscured. In our study, a genetic screening with 52 transgenic UAS-miRNAs was performed to identify ten miRNAs or miRNA clusters, including the miR310~313 cluster, which may function on Imd-dependent immune responses. The miRNA RT-qPCR analysis showed that the expression of miR-310~313 cluster members exhibited an increase at 6-12 h post infection. Furthermore, the overexpression of the miR-310~313 cluster impaired the survival. And the overexpression of miR-310/311/312 reduced expression, an indication of Imd pathway induced by Gram-negative bacteria. Conversely, the knockdown of miR-310/311/312 led to increases in expression. The Luciferase reporter expression assays and RT-qPCR analysis confirmed that miR-310~313 cluster members directly co-targeted and inhibited transcription. These findings reveal that the members of the miR-310~313 cluster synergistically inhibit Imd-dependent immune responses by co-targeting the Imd gene in .
Topics: Animals; MicroRNAs; Drosophila Proteins; Drosophila melanogaster; Immunity, Innate; Multigene Family; Gram-Negative Bacterial Infections; Signal Transduction; Gene Expression Regulation; Genetic Testing; Escherichia coli
PubMed: 38790230
DOI: 10.3390/genes15050601 -
Genes Apr 2024Hairless (H) encodes the major antagonist in the Notch signaling pathway, which governs cellular differentiation of various tissues in . By binding to the Notch signal...
Hairless (H) encodes the major antagonist in the Notch signaling pathway, which governs cellular differentiation of various tissues in . By binding to the Notch signal transducer Suppressor of Hairless (Su(H)), H assembles repressor complexes onto Notch target genes. Using genome engineering, three new alleles, , and were generated and a phenotypic series was established by several parameters, reflecting the residual H-Su(H) binding capacity. Occasionally, homozygous flies develop to adulthood. They were compared with the likewise semi-viable allele affecting H-Su(H) nuclear entry. The homozygotes were short-lived, sterile and flightless, yet showed largely normal expression of several mitochondrial genes. Typical for mutants, both and homozygous alleles displayed strong defects in wing venation and mechano-sensory bristle development. Strikingly, however, displayed only a loss of bristles, whereas bristle organs of flies showed a complete shaft-to-socket transformation. Apparently, the impact of is restricted to lateral inhibition, whereas that of also affects the respective cell type specification. Notably, reduction in gene dosage only suppressed the bristle phenotype, but amplified that of . We interpret these differences as to the role of H regarding Su(H) stability and availability.
Topics: Animals; Drosophila Proteins; Alleles; Drosophila melanogaster; Wings, Animal; Transcription Factors; Gene Expression Regulation, Developmental; Repressor Proteins; Receptors, Notch; Signal Transduction
PubMed: 38790181
DOI: 10.3390/genes15050552