scholarly journals Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in Drosophila melanogaster by phosphorylating acinus at serine437

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Nilay Nandi ◽  
Lauren K Tyra ◽  
Drew Stenesen ◽  
Helmut Krämer
Keyword(s):  
Drosophila Melanogaster ◽  
Nuclear Protein ◽  
Protective Role ◽  
Alpha Synuclein ◽  
Wild Type ◽  
Gain Of Function ◽  
Mitotic Kinase

Cdk5 is a post-mitotic kinase with complex roles in maintaining neuronal health. The various mechanisms by which Cdk5 inhibits and promotes neurodegeneration are still poorly understood. Here, we show that in Drosophila melanogaster Cdk5 regulates basal autophagy, a key mechanism suppressing neurodegeneration. In a targeted screen, Cdk5 genetically interacted with Acinus (Acn), a primarily nuclear protein, which promotes starvation-independent, basal autophagy. Loss of Cdk5, or its required cofactor p35, reduces S437-Acn phosphorylation, whereas Cdk5 gain-of-function increases pS437-Acn levels. The phospho-mimetic S437D mutation stabilizes Acn and promotes basal autophagy. In p35 mutants, basal autophagy and lifespan are reduced, but restored to near wild-type levels in the presence of stabilized AcnS437D. Expression of aggregation-prone polyQ-containing proteins or the Amyloid-β42 peptide, but not alpha-Synuclein, enhances Cdk5-dependent phosphorylation of S437-Acn. Our data indicate that Cdk5 is required to maintain the protective role of basal autophagy in the initial responses to a subset of neurodegenerative challenges.

The development of the sensory neuron pattern in the antennal disc of wild-type and mutant (lz3, ssa) Drosophila melanogaster

Development ◽  
1991 ◽  
Vol 112 (4) ◽  
pp. 1063-1075
Author(s):  
M.C. Lienhard ◽  
R.F. Stocker
Keyword(s):  
Drosophila Melanogaster ◽  
Sensory Neuron ◽  
Antennal Segment ◽  
Wild Type ◽  
Homeotic Mutant ◽  
In The Wild ◽  
The Brain ◽  
Antennal Disc ◽  
Antennal Nerve

The development of the sensory neuron pattern in the antennal disc of Drosophila melanogaster was studied with a neuron-specific monoclonal antibody (22C10). In the wild type, the earliest neurons become visible 3 h after pupariation, much later than in other imaginal discs. They lie in the center of the disc and correspond to the neurons of the adult aristal sensillum. Their axons join the larval antennal nerve and seem to establish the first connection towards the brain. Later on, three clusters of neurons appear in the periphery of the disc. Two of them most likely give rise to the Johnston's organ in the second antennal segment. Neurons of the olfactory third antennal segment are formed only after eversion of the antennal disc (clusters t1-t3). The adult pattern of antennal neurons is established at about 27% of metamorphosis. In the mutant lozenge3 (lz3), which lacks basiconic antennal sensilla, cluster t3 fails to develop. This indicates that, in the wild type, a homogeneous group of basiconic sensilla is formed by cluster t3. The possible role of the lozenge gene in sensillar determination is discussed. The homeotic mutant spineless-aristapedia (ssa) transforms the arista into a leg-like tarsus. Unlike leg discs, neurons are missing in the larval antennal disc of ssa. However, the first neurons differentiate earlier than in normal antennal discs. Despite these changes, the pattern of afferents in the ectopic tarsus appears leg specific, whereas in the non-transformed antennal segments a normal antennal pattern is formed. This suggests that neither larval leg neurons nor early aristal neurons are essential for the outgrowth of subsequent afferents.

scholarly journals Susceptibility to Entamoeba histolytica intestinal infection is related to reduction in natural killer T-lymphocytes in C57BL/6 mice

2012 ◽  
Vol 4 (1) ◽  
pp. 27 ◽  
Author(s):  
Fabrício M.S. Oliveira ◽  
Bernardo C. Horta ◽  
Luana O. Prata ◽  
Andrezza F. Santiago ◽  
Andréa C. Alves ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Natural Killer ◽  
Entamoeba Histolytica ◽  
Protective Role ◽  
Amoebic Liver Abscess ◽  
Wild Type ◽  
Quantitative Analyses ◽  
Cd1 Mice ◽  
Natural Killer T

<em>Entamoeba histolytica</em> is a protozoan that causes amoebiasis. Recent studies demonstrated that natural killer T lymphocytes (NKT) are critical for preventing the development of amoebic liver abscess. In spite of that, there are only a handful of studies in the area. Herein, we explored the role of NKT cells in <em>E. histolytica </em>infection using C57BL/6 wild-type and CD1-/- mice. Animals were inoculated with <em>E. histolytica</em> and sacrificed 48 hours later to collect caecum samples that were used for quantitative analyses of lesions, trophozoites, NK1.1+ T lymphocytes and expression of the mucus protein MUC-2 by immunohistochemistry technique. Quantitative analyses confirmed that the frequency of NK1.1+ T cells was significantly lower in samples from C57BL/6 CD1-/- mice as compared to their wild type (WT) counterparts. The extension of necrotic mucosa was larger and the number of trophozoites higher in Entamoeba (Eh)-infected CD1-/- mice when compared with Eh-infected WT mice. In mice from both groups, noninfected (CTRL) and Eh-infected CD1-/-, there was a reduction in the thickness of the caecal mucosa and in the MUC-2-stained area in comparison with CTRL- and Eh-WT mice. Our results showed that NKT lymphocytes contribute to resistance against <em>Entamoeba histolytica</em> infection and to the control of inflammation in the colitis induced by infection. The presence of a normal epithelial layer containing appropriate levels of mucus had also a protective role against infection.

scholarly journals Chemoreceptivity of Drosophila melanogaster

1946 ◽  
Vol 133 (870) ◽  
pp. 1-19 ◽  
Keyword(s):  
Drosophila Melanogaster ◽  
Olfactory Response ◽  
Sensory Function ◽  
Main Role ◽  
Wild Type ◽  
Long Distance ◽  
Pit Organ ◽  
Chemical Stimuli ◽  
Thermal Stimuli

The occurrence of mutants of Drosophila melanogaster distinguished by the absence or structural modification of the antennae provides a means of assessing the role of the antennae with respect to the reception of various classes of stimuli. Antennaless ( A 0 ) phenotypes of antennaless stock fail to respond to those chemical stimuli which lead the fly to its food. Their temperature reactions are normal, and their humidity responses are opposite to those of somatically wild-type flies of the same stock or of wild-type controls. Aristapedia ( ss a ), which have leg-like antennae equipped with surface pegs and cones of supposed sensory function present in the normal antenna but absent in the normal leg, respond to chemical stimuli and humidity differences. As compared with that of normal flies, the olfactory response of aristapedia ( ss a ) is somewhat less intense, the humidity reaction being somewhat stronger. These mutants do not give the characteristic responses evoked by thermal stimuli both in normal flies and antennaless phenotypes. The outstanding histological differences between the structure of the antenna of aristapedia and that of wild-type flies is the absence of the pit organ. It thus seems that the pit organ is not essential to the olfactory response and plays no essential part in the humidity response. Since antennaless ( A 0 ) responds normally to thermal stimuli, none of the putative sense organs of the antennae are essential to the recognition of temperature differences, and since aristapedia ( ss a ) responds more weakly to chemical stimuli than do normal flies, the pit organs may well be long-distance chemoreceptors. What is more certain is that either the peg-like organs or the cones on the surface of the distal joint of the antennae or both are chemoreceptors. The same remark is equally applicable to the perception of humidity differences. Experiments here recorded do not justify the identification of the function of one or other type of sensilla with one or the other type of receptivity. While it is unjustifiable to exclude the possibility that short-distance chemical stimuli play a part in the attraction of flies of opposite sex, it appears that the main role of chemoreceptivity in relation to the mating behaviour of D. melanogaster is to ensure the aggregation of flies of both sexes in situations where food is available and sexual congress can be evoked by other forms of stimulation.

scholarly journals Hepatic progenitor cells promote the repair of schistosomiasis liver injury by inhibiting IL-33 secretion in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Beibei Zhang ◽  
Xiaoying Wu ◽  
Jing Li ◽  
An Ning ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Progenitor Cells ◽  
Normal Liver ◽  
Protective Role ◽  
Dependent Manner ◽  
Hepatic Progenitor Cells ◽  
Wild Type ◽  
Mice Model

Abstract Background Hepatic schistosomiasis, a chronic liver injury induced by long-term Schistosoma japonicum (S. japonicum) infection, is characterized by egg granulomas and fibrotic pathology. Hepatic progenitor cells (HPCs), which are nearly absent or quiescent in normal liver, play vital roles in chronic and severe liver injury. But their role in the progression of liver injury during infection remains unknown. Methods In this study, the hepatic egg granulomas, fibrosis and proliferation of HPCs were analyzed in the mice model of S. japonicum infection at different infectious stages. For validating the role of HPCs in hepatic injury, tumor necrosis factor-like-weak inducer of apoptosis (TWEAK) and TWEAK blocking antibody were used to manipulate the proliferation of HPCs in wild-type and IL-33−/− mice infected with S. japonicum. Results We found that the proliferation of HPCs was accompanied by inflammatory granulomas and fibrosis formation. HPCs expansion promoted liver regeneration and inhibited inflammatory egg granulomas, as well as the deposition of fibrotic collagen. Interestingly, the expression of IL-33 was negatively associated with HPCs’ expansion. There were no obvious differences of liver injury caused by infection between wild-type and IL-33−/− mice with HPCs’ expansion. However, liver injury was more attenuated in IL-33−/− mice than wild-type mice when the proliferation of HPCs was inhibited by anti-TWEAK. Conclusions Our data uncovered a protective role of HPCs in hepatic schistosomiasis in an IL-33-dependent manner, which might provide a promising progenitor cell therapy for hepatic schistosomiasis.

scholarly journals THE ROLE OF TRANSCRIPTION FACTORS DFOXO, DSIR2 AND HSP70 IN LIFESPAN ALTERATION OF DROSOPHILA MELANOGASTER IN DIFFERENT LIGHT CONDITIONS

2010 ◽  
Vol 8 (3) ◽  
pp. 67-80 ◽  
Author(s):  
Aleksey A Moskalev ◽  
Olga A Malysheva
Keyword(s):  
Drosophila Melanogaster ◽  
Transcription Factors ◽  
Stress Response ◽  
Life Span ◽  
Light Regime ◽  
Light Conditions ◽  
Wild Type ◽  
Stress Response Genes ◽  
Significant Difference

It was investigated the role of stress-response genes (dFOXO, dSir2, Hsp70) in regulation of life span of Drosophila in response to light regime alteration. It was revealed the FOXO-dependant mechanism of lifespan increasing at darkness conditions. The distance of lifespan of FOXO homozygous mutants at different light conditions were absent 3 times from 4 times. It was shown, that homozygotes with deletion of dSir2 have more significant difference between lifespan at standard light and darkness conditions with comparing to wild type and heterozygous strain. The same tendency was also detected the in the strains with Hsp70 deletions. It was produced the evidences of two mechanisms of light regime influence on lifespan: metabolism intensification at light conditions and neuroendocrine-determinated lifespan increasing at darkness conditions.

FGF21 prevents low protein diet-induced renal inflammation in aged mice

2021 ◽  
Author(s):  
Han Fang ◽  
Sujoy Ghosh ◽  
Landon Sims ◽  
Kirsten P. Stone ◽  
Cristal M Hill ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Renal Damage ◽  
Protective Role ◽  
Wild Type ◽  
Kidney Weight ◽  
Albumin Creatinine Ratio ◽  
Low Protein ◽  
The Impact ◽  
Protein Diets

Low protein diets extend lifespan through a comprehensive improvement in metabolic health across multiple tissues and organs. Many of these metabolic responses to protein restriction are secondary to transcriptional activation and release of FGF21 from the liver. However, the effects of a low protein (LP) diet on the kidney in the context of aging has not been examined. Therefore, the goal of the current study was to investigate the impact of chronic consumption of a LP diet on the kidney in aging mice lacking FGF21. Wild type (WT, C57BL/6J) and FGF21 KO mice were fed a normal protein (NP, 20% casein) or a LP (5% casein) diet ad libitum from 3 to19 months of age. The LP diet led to a decrease in kidney weight and urinary albumin/creatinine ratio in both WT and FGF21 KO mice. Although the LP diet produced only mild fibrosis and infiltration of leukocytes in WT kidneys, the effects were significantly exacerbated by the absence of FGF21. Accordingly, transcriptomic analysis showed that inflammation-related pathways were significantly enriched and upregulated in response to LP diet in FGF21 KO but not WT mice. Collectively, these data demonstrate that the LP diet negatively affected the kidney during aging, but in the absence of FGF21, the LP diet-induced renal damage and inflammation were significantly worse, indicating a protective role of FGF21 in the kidney.

scholarly journals Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sangsu Bang ◽  
Christopher R. Donnelly ◽  
Xin Luo ◽  
Maria Toro-Moreno ◽  
Xueshu Tao ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Bacterial Infections ◽  
Protective Role ◽  
Host Cells ◽  
Biological Functions ◽  
Wild Type ◽  
Neuroprotectin D1 ◽  
Protective Actions ◽  
Protection Against Infection

AbstractGPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia following challenge by lipopolysaccharide (LPS), Listeria bacteria, and the mouse malaria parasite Plasmodium berghei. Sepsis induced by LPS and Listeria in wild-type mice is protected by artesunate (ARU) and neuroprotectin D1 (NPD1), but the protective actions of these agents are lost in Gpr37−/− mice. Notably, we found that ARU binds to GPR37 in macrophages and promotes phagocytosis and clearance of pathogens. Moreover, ablation of macrophages potentiated infection, sepsis, and their sequelae, whereas adoptive transfer of NPD1- or ARU-primed macrophages reduced infection, sepsis, and pain-like behaviors. Our findings reveal physiological actions of ARU in host cells by activating macrophages and suggest that GPR37 agonists may help to treat sepsis, bacterial infections, and malaria.

CD177+ neutrophils as functionally activated neutrophils negatively regulate IBD

Gut ◽  
2017 ◽  
Vol 67 (6) ◽  
pp. 1052-1063 ◽  
Author(s):  
Guangxi Zhou ◽  
Lin Yu ◽  
Leilei Fang ◽  
Wenjing Yang ◽  
Tianming Yu ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Peripheral Blood ◽  
Transforming Growth Factor ◽  
Intestinal Barrier ◽  
Transforming Growth Factor Β ◽  
Interferon Γ ◽  
Protective Role ◽  
Neutrophil Extracellular Trap ◽  
Wild Type

BackgroundNeutrophils are accumulated in inflamed mucosa of IBD and play an important role in the pathogenesis. CD177 is expressed in neutrophils specifically and upregulated during inflammation. However, the role of CD177+ neutrophils in pathogenesis of IBD remains elusive.Materials and methodsExpression of CD177 was analysed in peripheral blood and intestinal mucosa from patients with IBD using quantitative RT-PCR, flow cytometry and immunohistochemistry. CD177+ and CD177− neutrophils were isolated to determine gene differences by RNA sequencing. Colitis was established in CD177−/− and wild-type mice in response to dextran sulfate sodium (DSS) insults to determine the role of CD177+ neutrophils in IBD.ResultsCD177+ neutrophils were markedly increased in peripheral blood and inflamed mucosa from patients with active IBD compared with healthy controls. RNA sequencing revealed that differential gene expression between CD177+ and CD177− neutrophils from patients with IBD was associated with response to bacterial defence, hydrogen peroxide and reactive oxygen species (ROS). CD177+ neutrophils produced lower levels of proinflammatory cytokines (ie, interferon-γ, interleukin (IL)-6, IL-17A), but higher levels of IL-22 and transforming growth factor-β, and exhibited increased bactericidal activities (ie, ROS, antimicrobial peptides, neutrophil extracellular trap) compared with CD177− subset. CD177−/− mice developed more severe colitis on DSS insults compared with wild-type mice. Moreover, CD177 deficiency led to compromised intestinal barrier and impaired antibacterial immunity through decreased production of IL-22 by CD177− neutrophils.ConclusionsCD177+ neutrophils represent functionally activated population and play a protective role in IBD through increased bactericidal activity and IL-22 production. Targeting CD177+ neutrophils may be beneficial for treatment of IBD.

scholarly journals Protective Role of Spore Structural Components in Determining Bacillus subtilis Spore Resistance to Simulated Mars Surface Conditions

2012 ◽  
Vol 78 (24) ◽  
pp. 8849-8853 ◽  
Author(s):  
Ralf Moeller ◽  
Andrew C. Schuerger ◽  
Günther Reitz ◽  
Wayne L. Nicholson
Keyword(s):  
Bacillus Subtilis ◽  
Dipicolinic Acid ◽  
Protective Role ◽  
Structural Components ◽  
Wild Type ◽  
Content Type ◽  
Surface Conditions ◽  
Bacillus Subtilis Spore ◽  
Spore Resistance

ABSTRACTSpores of wild-type and mutantBacillus subtilisstrains lacking various structural components were exposed to simulated Martian atmospheric and UV irradiation conditions. Spore survival and mutagenesis were strongly dependent on the functionality of all of the structural components, with small acid-soluble spore proteins, coat layers, and dipicolinic acid as key protectants.

Sign in / Sign up

Export Citation Format

Share Document