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1.
Sci Total Environ ; 752: 142223, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33207502

RESUMO

Microplastics pollution poses a new threat to the environment of intertidal zone. The sea forest, mangrove, has been polluted by a large number of plastic debris worldwide. To fill the gaps in knowledge of mangrove rhizosphere microbes connected with the 'plasticsphere', a semi-controlled in situ exposure experiment for nine different types of microplastics were conducted in mangrove ecosystem. A sign of biodegrading was observed on polyethylene, polyamide 6 and polyvinyl chloride microplastics surface after 3 months exposure. We discovered that the metabolic activities of the dominant bacteria on certain microplastics were related to the specific groups on polymers molecule. The selective colonization may be driven by the chemotaxis of bacteria. Specially, microplastics biofilms of polyethylene, polyamide 6, polyvinyl chloride and expanded polystyrene possess distinctive dominant bacteria assemblages which have great significance in ecosystem processes involving carbon cycle or sulfur cycle. Community of mangrove soil microorganism and microplastic biofilm varies as the seasons changes. As a new niche, microplastics has higher inclusivity to bacteria than surrounding soil. Additionally, pathogens for human beings (Vibrio parahaemolyticus and Escherichia-Shigella) were detected both in microplastics and soil. We stress that the interaction between microplastics and rhizosphere microorganisms may affect the growth and health of mangrove plants. Besides, we point out that mangrove rhizosphere microorganism can be an ideal candidate for plastics-degradation.


Assuntos
Plásticos , Poluentes Químicos da Água , Quimiotaxia , Ecossistema , Monitoramento Ambiental , Microplásticos , Rizosfera , Poluentes Químicos da Água/análise
2.
Nat Commun ; 11(1): 5778, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33188196

RESUMO

Breakdown of vascular barriers is a major complication of inflammatory diseases. Anucleate platelets form blood-clots during thrombosis, but also play a crucial role in inflammation. While spatio-temporal dynamics of clot formation are well characterized, the cell-biological mechanisms of platelet recruitment to inflammatory micro-environments remain incompletely understood. Here we identify Arp2/3-dependent lamellipodia formation as a prominent morphological feature of immune-responsive platelets. Platelets use lamellipodia to scan for fibrin(ogen) deposited on the inflamed vasculature and to directionally spread, to polarize and to govern haptotactic migration along gradients of the adhesive ligand. Platelet-specific abrogation of Arp2/3 interferes with haptotactic repositioning of platelets to microlesions, thus impairing vascular sealing and provoking inflammatory microbleeding. During infection, haptotaxis promotes capture of bacteria and prevents hematogenic dissemination, rendering platelets gate-keepers of the inflamed microvasculature. Consequently, these findings identify haptotaxis as a key effector function of immune-responsive platelets.


Assuntos
Plaquetas/patologia , Vasos Sanguíneos/patologia , Quimiotaxia , Inflamação/patologia , Pneumonia/sangue , Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Adulto , Animais , Movimento Celular , Microambiente Celular , Modelos Animais de Doenças , Fibrinogênio/metabolismo , Humanos , Lipopolissacarídeos , Lesão Pulmonar/microbiologia , Lesão Pulmonar/patologia , Staphylococcus aureus Resistente à Meticilina/fisiologia , Camundongos Endogâmicos C57BL , Microvasos/patologia , Pneumonia/microbiologia , Pseudópodes/metabolismo
3.
Nat Commun ; 11(1): 5763, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33188180

RESUMO

The prokaryotic chemotaxis system is arguably the best-understood signaling pathway in biology. In all previously described species, chemoreceptors organize into a hexagonal (P6 symmetry) extended array. Here, we report an alternative symmetry (P2) of the chemotaxis apparatus that emerges from a strict linear organization of the histidine kinase CheA in Treponema denticola cells, which possesses arrays with the highest native curvature investigated thus far. Using cryo-ET, we reveal that Td chemoreceptor arrays assume an unusual arrangement of the supra-molecular protein assembly that has likely evolved to accommodate the high membrane curvature. The arrays have several atypical features, such as an extended dimerization domain of CheA and a variant CheW-CheR-like fusion protein that is critical for maintaining an ordered chemosensory apparatus. Furthermore, the previously characterized Td oxygen sensor ODP influences CheA ordering. These results suggest a greater diversity of the chemotaxis signaling system than previously thought.


Assuntos
Membrana Celular/metabolismo , Células Quimiorreceptoras/citologia , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Membrana Celular/ultraestrutura , Células Quimiorreceptoras/metabolismo , Quimiotaxia , Sequência Conservada , Escherichia coli/citologia , Deleção de Genes , Histidina Quinase/metabolismo , Domínios Proteicos , Homologia de Sequência de Aminoácidos , Treponema/metabolismo
4.
Proc Natl Acad Sci U S A ; 117(45): 28412-28421, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33122439

RESUMO

Foraging is a vital behavioral task for living organisms. Behavioral strategies and abstract mathematical models thereof have been described in detail for various species. To explore the link between underlying neural circuits and computational principles, we present how a biologically detailed neural circuit model of the insect mushroom body implements sensory processing, learning, and motor control. We focus on cast and surge strategies employed by flying insects when foraging within turbulent odor plumes. Using a spike-based plasticity rule, the model rapidly learns to associate individual olfactory sensory cues paired with food in a classical conditioning paradigm. We show that, without retraining, the system dynamically recalls memories to detect relevant cues in complex sensory scenes. Accumulation of this sensory evidence on short time scales generates cast-and-surge motor commands. Our generic systems approach predicts that population sparseness facilitates learning, while temporal sparseness is required for dynamic memory recall and precise behavioral control. Our work successfully combines biological computational principles with spike-based machine learning. It shows how knowledge transfer from static to arbitrary complex dynamic conditions can be achieved by foraging insects and may serve as inspiration for agent-based machine learning.


Assuntos
Insetos/fisiologia , Modelos Neurológicos , Neurônios/fisiologia , Neurônios Receptores Olfatórios/fisiologia , Animais , Inteligência Artificial , Quimiotaxia , Biologia Computacional , Simulação por Computador , Condicionamento Clássico , Drosophila melanogaster/fisiologia , Aprendizado de Máquina , Memória/fisiologia , Corpos Pedunculados/fisiologia , Redes Neurais de Computação , Olfato
5.
PLoS One ; 15(10): e0240540, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33048984

RESUMO

BACKGROUND AND AIMS: Pathophysiological roles of monocytes in atrial fibrillation (AF), particularly for the progression of structural remodeling of the left atrium (LA), remain elusive. This study examined the association between the characteristics of circulating and local monocytes and extent of structural remodeling in LA, gauged by LA size, in AF patients. METHODS: First, 161 AF patients who were referred for catheter ablation were enrolled and divided into two groups according to the median of LA diameter (≤39 mm: normal LA group, >39 mm: enlarged LA group). As a control group, 22 patients underwent catheter ablation for paroxysmal supraventricular tachycardia (PSVT) without history of AF were analyzed. Blood samples were collected for flow cytometric analyses to evaluate monocyte subsets based on the levels of CD14 and CD16. Moreover, monocytes were isolated from blood to measure CC chemokine receptor 2 (CCR2) transcripts and protein levels, and migratory activity toward monocyte chemoattractant protein 1 (MCP-1). Second, to characterize the local monocytes in the atrial wall in AF, the resected left atrial appendages (LAA) in AF patients underwent cardiac surgery were histologically evaluated (n = 20). RESULTS: The proportions of monocyte subsets based on CD14 and CD16 expressions were not significantly different between the normal and enlarged LA group. Both transcripts and total protein levels of CCR2 in monocytes were higher in the enlarged LA group compared to those in the normal LA group. In the enlarged LA group, monocytes exhibited more enhanced migratory activity than the normal LA group. Moreover, we found a significantly higher number of CCR2-positive monocytes/macrophages in the LAA in the enlarged LA group. CONCLUSION: Enhanced migratory activity in circulating and local monocytes may play a pivotal role in the pathogenesis of progression in atrial remodeling in AF patients.


Assuntos
Fibrilação Atrial/fisiopatologia , Remodelamento Atrial/fisiologia , Quimiotaxia , Monócitos/fisiologia , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/cirurgia , Estudos de Casos e Controles , Ablação por Cateter , Progressão da Doença , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Taquicardia Ventricular/sangue , Taquicardia Ventricular/cirurgia
6.
PLoS One ; 15(10): e0240789, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33091017

RESUMO

In a recent study, using an in vitro model to study intravaginal nanoparticle exposure during yeast infections, we demonstrated that C. albicans exposure suppressed apoptotic gene expression and induced oxidative stress and pyroptosis in vaginal epithelial cells. The mucous-penetrating drug delivery nanoparticles made from poly-(D, L-lactic-co-glycolic acid)-(polyethylene glycol) induced cytotoxicity by activating apoptosis, endoplasmic reticulum (ER) stress, oxidative stress, and DNA damage repair responses alone and, in some cases with C. albicans. In the current study we evaluated the effects of fluorescently-labelled nanoparticles in CBA/J mice challenged intravaginally for two hours followed by intravaginal challenge with C. albicans for 18 hours. Nanoparticle treatment increased systemic translocation of C. albicans threefold in the heart. C. albicans also increased systemic distribution of the nanoparticles fivefold in the heart. Flow cytometric assays showed co-localization of the nanoparticles with epithelial cells, macrophages and dendritic cells. Nanoparticle-treated, C. albicans-infected mice exhibited induction of autophagy, ER stress, apoptosis, and inflammatory serum cytokines. C. albicans infection was associated with pyroptosis and suppressed expression of ER stress and apoptosis-related genes. Induction of apoptosis during nanoparticle treatment and in nanoparticle-treated-C. albicans infected mice was observed as DNA damage responses, mitochondrial depolarization and (Poly [ADP-Ribose] Polymerase) cleavage. C. albicans infection was associated with increased mRNA expression of anti-apoptotic genes. Both C. albicans infection and nanoparticle treatment showed enhanced chemoattraction of dendritic cells and polymorphonuclear cells to factors in vaginal washings in a chemotaxis assay. This study shows that both intravaginal treatment of mice with the nanoparticles and infection with C. albicans induce cytotoxic and inflammatory responses. C. albicans also suppressed cell apoptosis. These results clarify our understanding of how nanoparticles modulate host cellular responses during C. albicans infection and will be applicable for future research and development of intravaginal nanomedicines.


Assuntos
Candida albicans/fisiologia , Candidíase/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Inflamação/genética , Nanopartículas/química , Polietilenoglicóis/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Vagina/microbiologia , Animais , Apoptose , Candidíase/genética , Candidíase/microbiologia , Linhagem Celular , Quimiotaxia , Citocinas/metabolismo , Células Dendríticas/patologia , Modelos Animais de Doenças , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Camundongos Endogâmicos CBA , Neutrófilos/patologia , Especificidade de Órgãos , Estresse Fisiológico , Vagina/patologia , Leveduras
7.
Nature ; 586(7828): 299-304, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32999457

RESUMO

Blood vessels support tumours by providing nutrients and oxygen, while also acting as conduits for the dissemination of cancer1. Here we use mouse models of breast and lung cancer to investigate whether endothelial cells also have active 'instructive' roles in the dissemination of cancer. We purified genetically tagged endothelial ribosomes and their associated transcripts from highly and poorly metastatic tumours. Deep sequencing revealed that metastatic tumours induced expression of the axon-guidance gene Slit2 in endothelium, establishing differential expression between the endothelial (high Slit2 expression) and tumoural (low Slit2 expression) compartments. Endothelial-derived SLIT2 protein and its receptor ROBO1 promoted the migration of cancer cells towards endothelial cells and intravasation. Deleting endothelial Slit2 suppressed metastatic dissemination in mouse models of breast and lung cancer. Conversely, deletion of tumoural Slit2 enhanced metastatic progression. We identified double-stranded RNA derived from tumour cells as an upstream signal that induces expression of endothelial SLIT2 by acting on the RNA-sensing receptor TLR3. Accordingly, a set of endogenous retroviral element RNAs were upregulated in metastatic cells and detected extracellularly. Thus, cancer cells co-opt innate RNA sensing to induce a chemotactic signalling pathway in endothelium that drives intravasation and metastasis. These findings reveal that endothelial cells have a direct instructive role in driving metastatic dissemination, and demonstrate that a single gene (Slit2) can promote or suppress cancer progression depending on its cellular source.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Endotélio/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metástase Neoplásica , Proteínas do Tecido Nervoso/metabolismo , Receptor 3 Toll-Like/metabolismo , Animais , Quimiotaxia , Modelos Animais de Doenças , Progressão da Doença , Células Endoteliais/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Camundongos , Metástase Neoplásica/genética , Proteínas do Tecido Nervoso/genética , RNA de Cadeia Dupla , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Transdução de Sinais , Receptor 3 Toll-Like/deficiência , Receptor 3 Toll-Like/genética , Células Tumorais Cultivadas
8.
Proc Natl Acad Sci U S A ; 117(43): 26766-26772, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33051299

RESUMO

Archaea swim using the archaellum (archaeal flagellum), a reversible rotary motor consisting of a torque-generating motor and a helical filament, which acts as a propeller. Unlike the bacterial flagellar motor (BFM), ATP (adenosine-5'-triphosphate) hydrolysis probably drives both motor rotation and filamentous assembly in the archaellum. However, direct evidence is still lacking due to the lack of a versatile model system. Here, we present a membrane-permeabilized ghost system that enables the manipulation of intracellular contents, analogous to the triton model in eukaryotic flagella and gliding Mycoplasma We observed high nucleotide selectivity for ATP driving motor rotation, negative cooperativity in ATP hydrolysis, and the energetic requirement for at least 12 ATP molecules to be hydrolyzed per revolution of the motor. The response regulator CheY increased motor switching from counterclockwise (CCW) to clockwise (CW) rotation. Finally, we constructed the torque-speed curve at various [ATP]s and discuss rotary models in which the archaellum has characteristics of both the BFM and F1-ATPase. Because archaea share similar cell division and chemotaxis machinery with other domains of life, our ghost model will be an important tool for the exploration of the universality, diversity, and evolution of biomolecular machinery.


Assuntos
Membrana Celular , Quimiotaxia/fisiologia , Haloferax volcanii , Modelos Biológicos , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/metabolismo , Proteínas Arqueais/química , Proteínas Arqueais/metabolismo , Membrana Celular/química , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular , Flagelos/química , Flagelos/metabolismo , Haloferax volcanii/citologia , Haloferax volcanii/metabolismo , Cinética , Proteínas Quimiotáticas Aceptoras de Metil/química , Proteínas Quimiotáticas Aceptoras de Metil/metabolismo , Proteínas Motores Moleculares/química , Proteínas Motores Moleculares/metabolismo
9.
Exp Parasitol ; 219: 108009, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33007296

RESUMO

Cell-cell interaction and active migration (and invasion) of parasites into skin host-cell(s) are key steps for successful infection by Leishmania. Chemotaxis constitutes a primordial chapter of Leishmania-host cell interaction, potentially modulated by neuropeptides released into the skin due, for example, to the noxious stimuli represented by the insect bite. Herein we have evaluated in vitro the effect of sensory (Substance P, SP) and autonomic (Vasoactive Intestinal Peptide, VIP, and Neuropeptide Y, NPY) neuropeptides on parasite taxis, and investigated the potential modulatory effect of SP on Leishmania (Viannia) braziliensis-macrophage interaction. We demonstrated that VIP (10-10 M) and NPY (10-9 M) are chemorepellent to the parasites, while SP (10-8 M) produces a chemoattractant response. SP did not affect macrophage viability but seems to impair parasite-macrophage interaction as it decreased promastigote adherence to macrophages. As this effect is blocked by ([D-Pro 2, D-Trp7,9]-Substance P (10-6 M), the observed action may be mediated by neurokinin-1 (NK1) transmembrane receptors. VIP and NPY repellent chemotactic effect is impaired by their corresponding receptor antagonists. Additionally, they suggest that SP may be a key molecule to guide promastigote migration towards, and interaction, with dendritic cells and macrophage host cells.


Assuntos
Leishmania braziliensis/metabolismo , Neuropeptídeo Y/metabolismo , Substância P/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Quimiotaxia , Flagelos/ultraestrutura , Leishmania braziliensis/fisiologia , Leishmania braziliensis/ultraestrutura , Macrófagos , Camundongos
10.
Proc Natl Acad Sci U S A ; 117(41): 25553-25559, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-32999070

RESUMO

Neutrophils and dendritic cells when migrating in confined environments have been shown to actuate a directional choice toward paths of least hydraulic resistance (barotaxis), in some cases overriding chemotactic responses. Here, we investigate whether this barotactic response is conserved in the more primitive model organism Dictyostelium discoideum using a microfluidic chip design. This design allowed us to monitor the behavior of single cells via live imaging when confronted with bifurcating microchannels, presenting different combinations of hydraulic and chemical stimuli. Under the conditions employed we find no evidence in support of a barotactic response; the cells base their directional choices on the chemotactic cues. When the cells are confronted by a microchannel bifurcation, they often split their leading edge and start moving into both channels, before a decision is made to move into one and retract from the other channel. Analysis of this decision-making process has shown that cells in steeper nonhydrolyzable adenosine- 3', 5'- cyclic monophosphorothioate, Sp- isomer (cAMPS) gradients move faster and split more readily. Furthermore, there exists a highly significant strong correlation between the velocity of the pseudopod moving up the cAMPS gradient to the total velocity of the pseudopods moving up and down the gradient over a large range of velocities. This suggests a role for a critical cortical tension gradient in the directional decision-making process.


Assuntos
Movimento Celular/fisiologia , Tomada de Decisões/fisiologia , Dictyostelium/fisiologia , Modelos Biológicos , Resposta Táctica/fisiologia , Quimiotaxia/fisiologia , Desenho de Equipamento , Técnicas Analíticas Microfluídicas , Pressão , Análise de Célula Única
11.
Folia Biol (Praha) ; 66(3): 104-110, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33069189

RESUMO

Cancer development is a highly complicated process in which tumour growth depends on the development of its vascularization system. To support their own growth, tumour cells significantly modify their microenvironment. One of such modifications inflicted by tumours is stimulation of endothelial cell migration and proliferation. There is accumulating evidence that extracellular vesicles (EVs) secreted by tumour cells (tumour-derived EVs, TEVs) may be regarded as "messengers" with the potential for affecting the biological activities of target cells. Interaction of TEVs with different cell types occurs in an auto- and paracrine manner and may lead to changes in the function of the latter, e.g., promoting motility, proliferation, etc. This study analysed the proangiogenic activity of EVs derived from human pancreatic adenocarcinoma cell line (HPC-4, TEVHPC) in vitro and their effect in vivo on Matrigel matrix vascularization in severe combined immunodeficient (SCID) mice. TEVHPC enhanced proliferation of HPC-4 cells and induced their motility. Moreover, TEVHPC stimulated human umbilical vein endothelial cell (HUVEC) proliferation and migration in vitro. Additionally, TEVHPC influenced secretion of proangiogenic factors (IL-8, VEGF) by HUVEC cells and supported Matrigel matrix haemoglobinization in vivo. These data show that TEVs may support tumour propagation in an autocrine manner and may support vascularization of the tumour. The presented data are in line with the theory that tumour cells themselves are able to modulate the microenvironment via TEVs to maximize their growth potential.


Assuntos
Carcinoma Ductal Pancreático/patologia , Vesículas Extracelulares/patologia , Neoplasias Pancreáticas/patologia , Animais , Comunicação Autócrina , Divisão Celular , Linhagem Celular Tumoral , Quimiotaxia , Colágeno , Combinação de Medicamentos , Células Endoteliais da Veia Umbilical Humana , Humanos , Interleucina-8/genética , Interleucina-8/metabolismo , Laminina , Camundongos , Camundongos SCID , Transplante de Neoplasias , Neovascularização Patológica/etiologia , Proteoglicanas , RNA Mensageiro/biossíntese , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Nat Commun ; 11(1): 5076, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033264

RESUMO

Proper threat-reward decision-making is critical to animal survival. Emerging evidence indicates that the motor system may participate in decision-making but the neural circuit and molecular bases for these functions are little known. We found in C. elegans that GABAergic motor neurons (D-MNs) bias toward the reward behavior in threat-reward decision-making by retrogradely inhibiting a pair of premotor command interneurons, AVA, that control cholinergic motor neurons in the avoidance neural circuit. This function of D-MNs is mediated by a specific ionotropic GABA receptor (UNC-49) in AVA, and depends on electrical coupling between the two AVA interneurons. Our results suggest that AVA are hub neurons where sensory inputs from threat and reward sensory modalities and motor information from D-MNs are integrated. This study demonstrates at single-neuron resolution how motor neurons may help shape threat-reward choice behaviors through interacting with other neurons.


Assuntos
Caenorhabditis elegans/fisiologia , Neurônios GABAérgicos/metabolismo , Locomoção/fisiologia , Neurônios Motores/metabolismo , Animais , Aprendizagem da Esquiva , Viés , Proteínas de Caenorhabditis elegans/metabolismo , Quimiotaxia , Fenômenos Eletrofisiológicos , Junções Comunicantes/metabolismo , Glicerol/farmacologia , Interneurônios/metabolismo , Optogenética , Concentração Osmolar , Receptores Colinérgicos/metabolismo , Sinapses/metabolismo
13.
Anticancer Res ; 40(11): 6327-6335, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109570

RESUMO

BACKGROUND/AIM: Despite numerous studies, the etiology of chronic lymphocytic leukemia (CLL) remains unknown. A hypothesis of autoantigen stimulation in leukemic clone selection might explain 'stereotypy' of B-cell receptors. In healthy cells, cofilin-1 (CFL1) has multiple functions. Its role was described in several malignancies. The aim of this study was characterization of the role of CFL1 in CLL. Materialas and Methods: Cells from peripheral blood of 180 patients and 42 healthy volunteers (HVs) were isolated. Gene expression was assessed with reverse transcription polymerase chain reaction (RT-qPCR); western blot was performed for determination of protein level and activity. After silencing of CFL1 gene, cell ability for migration and chemotaxis was investigated with Transwell method. Post-silencing, apoptosis and cell cycle was determined by flow cytometry. RESULTS: In RT-qPCR, we observed significantly higher expression of CFL1. Higher activity of protein in CLL cells when compared to HVs was detected. Knock-down of CFL1 led to decreased chemotaxis and migration of CLL cells versus cells from HVs. Apoptosis was increased amongst cells with silenced CFL1 and correlated with higher proportion of cells in the G2/M phase. CONCLUSION: Significantly higher expression of CFL1 mRNA in CLL and higher protein activity might indicate high utilization of CFL1 in malignant cells, maintaining their viability, as its inhibition affected viability, cell-cycle progression and motility of leukemia cells.


Assuntos
Cofilina 1/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Transdução de Sinais , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Quimiotaxia/genética , Cofilina 1/genética , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Frações Subcelulares/metabolismo
14.
Nat Commun ; 11(1): 5370, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097708

RESUMO

The discovery of TREM2 as a myeloid-specific Alzheimer's disease (AD) risk gene has accelerated research into the role of microglia in AD. While TREM2 mouse models have provided critical insight, the normal and disease-associated functions of TREM2 in human microglia remain unclear. To examine this question, we profile microglia differentiated from isogenic, CRISPR-modified TREM2-knockout induced pluripotent stem cell (iPSC) lines. By combining transcriptomic and functional analyses with a chimeric AD mouse model, we find that TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis, culminating in an impaired response to beta-amyloid plaques in vivo. Single-cell sequencing of xenotransplanted human microglia further highlights a loss of disease-associated microglial (DAM) responses in human TREM2 knockout microglia that we validate by flow cytometry and immunohistochemistry. Taken together, these studies reveal both conserved and novel aspects of human TREM2 biology that likely play critical roles in the development and progression of AD.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Regulação da Expressão Gênica , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Microglia/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Morte Celular , Linhagem Celular , Quimiocina CXCL12/metabolismo , Quimiotaxia , Modelos Animais de Doenças , Feminino , Técnicas de Inativação de Genes , Predisposição Genética para Doença/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Camundongos Transgênicos , Fagocitose , Placa Amiloide/metabolismo , Receptores CXCR4/metabolismo , Transcriptoma
15.
Nat Commun ; 11(1): 5371, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097715

RESUMO

Autoinducer-2 (AI-2) is a quorum sensing signal that mediates communication within and between many bacterial species. However, its known receptors (LuxP and LsrB families) are not found in all the bacteria capable of responding to this signaling molecule. Here, we identify a third type of AI-2 receptor, consisting of a dCACHE domain. AI-2 binds to the dCACHE domain of chemoreceptors PctA and TlpQ of Pseudomonas aeruginosa, thus inducing chemotaxis and biofilm formation. Boron-free AI-2 is the preferred ligand for PctA and TlpQ. AI-2 also binds to the dCACHE domains of histidine kinase KinD from Bacillus subtilis and diguanylate cyclase rpHK1S-Z16 from Rhodopseudomonas palustris, enhancing their enzymatic activities. dCACHE domains (especially those belonging to a subfamily that includes the AI-2 receptors identified in the present work) are present in a large number of bacterial and archaeal proteins. Our results support the idea that AI-2 serves as a widely used signaling molecule in the coordination of cell behavior among prokaryotic species.


Assuntos
Quimiotaxia/fisiologia , Homosserina/análogos & derivados , Homosserina/metabolismo , Lactonas/metabolismo , Células Procarióticas/metabolismo , Proteínas Arqueais , Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Liases de Carbono-Enxofre/genética , Liases de Carbono-Enxofre/metabolismo , Proteínas de Transporte/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli , Homosserina/química , Homosserina/genética , Lactonas/química , Ligantes , Fósforo-Oxigênio Liases , Pseudomonas aeruginosa/metabolismo , Percepção de Quorum , Rodopseudomonas/metabolismo , Transdução de Sinais/fisiologia
16.
Nat Commun ; 11(1): 5264, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067433

RESUMO

Soil-inhabiting fungal pathogens use chemical signals released by roots to direct hyphal growth towards the host plant. Whether other soil microorganisms exploit this capacity for their own benefit is currently unknown. Here we show that the endophytic rhizobacterium Rahnella aquatilis locates hyphae of the root-infecting fungal pathogen Fusarium oxysporum through pH-mediated chemotaxis and uses them as highways to efficiently access and colonize plant roots. Secretion of gluconic acid (GlcA) by R. aquatilis in the rhizosphere leads to acidification and counteracts F. oxysporum-induced alkalinisation, a known virulence mechanism, thereby preventing fungal infection. Genetic abrogation or biochemical inhibition of GlcA-mediated acidification abolished biocontrol activity of R. aquatilis and restored fungal infection. These findings reveal a new way by which bacterial endophytes hijack hyphae of a fungal pathogen in the soil to gain preferential access to plant roots, thereby protecting the host from infection.


Assuntos
Endófitos/fisiologia , Fusarium/fisiologia , Rahnella/fisiologia , Quimiotaxia , Endófitos/genética , Fusarium/genética , Hifas , Lycopersicon esculentum/microbiologia , Doenças das Plantas/microbiologia , Raízes de Plantas/microbiologia , Plantas , Rahnella/genética
17.
J Insect Sci ; 20(5)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32869852

RESUMO

The azalea lace bug (Stephanitis pyrioides Scott) (Hemiptera: Tingidae) is an invasive pest of rhododendrons and azaleas (Ericaceae: Rhododendron), which feeds on the underside of leaves causing chlorosis, reduced photosynthesis, and even plant death. While insecticides can control this pest, growers, landscape managers, and homeowners have requested softer alternatives. Augmentative release of predatory green lacewing Chrysoperla sp. (Neuroptera: Chrysopidae) eggs and larvae has reduced S. pyrioides, but large-scale implementation may not be practical nor cost-effective. Attracting naturally occurring Chrysopidae with plant volatiles may be an economical and convenient option. In this study, we tested whether volatile blends 1) attracted Chrysoperla sp., and 2) controlled S. pyrioides populations on Rhododendron spp. in farm or urban landscapes. Experimental plots contained different multicomponent lures placed aboveground next to infested plants. Adult Chrysoperla sp., other natural enemies, and S. pyrioides from egg to adult stages were monitored in both farm and urban landscapes for two summers. Overall, two out of three volatile blends consistently attracted Chrysoperla sp. to sticky traps near baited plants. Methyl salicylate + acetic acid + 2-phenylethanol (methyl salicylate blend) and acetophenone + acetic acid + 2-phenylethanol (acetophenone blend) captured more adult Chrysoperla sp. than control traps in farm landscapes. However, only the acetophenone blend was associated with a slight reduction of S. pyrioides. Additional research is needed to determine whether the phenology of the first generation of both species are synchronized for effective season biological control in the Pacific Northwest.


Assuntos
Quimiotaxia , Hemípteros , Controle de Insetos/instrumentação , Insetos/fisiologia , Compostos Orgânicos Voláteis/administração & dosagem , Animais , Cidades , Fazendas , Ninfa , Oregon , Óvulo , Rhododendron/crescimento & desenvolvimento
18.
PLoS Biol ; 18(9): e3000828, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32936797

RESUMO

Many herbivorous insects are mono- or oligophagous, having evolved to select a limited range of host plants. They specifically identify host-plant leaves using their keen sense of taste. Plant secondary metabolites and sugars are thought to be key chemical cues that enable insects to identify host plants and evaluate their quality as food. However, the neuronal and behavioral mechanisms of host-plant recognition are poorly understood. Here, we report a two-factor host acceptance system in larvae of the silkworm Bombyx mori, a specialist on several mulberry species. The first step is controlled by a chemosensory organ, the maxillary palp (MP). During palpation at the leaf edge, the MP detects trace amounts of leaf-surface compounds, which enables host-plant recognition without biting. Chemosensory neurons in the MP are tuned with ultrahigh sensitivity (thresholds of attomolar to femtomolar) to chlorogenic acid (CGA), quercetin glycosides, and ß-sitosterol (ßsito). Only if these 3 compounds are detected does the larva make a test bite, which is evaluated in the second step. Low-sensitivity neurons in another chemosensory organ, the maxillary galea (MG), mainly detect sucrose in the leaf sap exuded by test biting, allowing larvae to accept the leaf and proceed to persistent biting (feeding). The two-factor host acceptance system reported here may commonly underlie stereotyped feeding behavior in many phytophagous insects and determine their feeding habits.


Assuntos
Bombyx/fisiologia , Comportamento de Escolha , Dieta , Comportamento Alimentar/fisiologia , Larva/fisiologia , Papilas Gustativas/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Comportamento Animal/fisiologia , Bombyx/anatomia & histologia , Bombyx/crescimento & desenvolvimento , Células Quimiorreceptoras/fisiologia , Quimiotaxia/fisiologia , Sinais (Psicologia) , Comportamento Exploratório/fisiologia , Interações Hospedeiro-Parasita/fisiologia , Larva/anatomia & histologia , Larva/citologia , Morus/química , Folhas de Planta/química , Paladar/fisiologia , Papilas Gustativas/anatomia & histologia
19.
Sci Rep ; 10(1): 15887, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985511

RESUMO

Most motile bacteria are propelled by rigid, helical, flagellar filaments and display distinct swimming patterns to explore their favorable environments. Escherichia coli cells have a reversible rotary motor at the base of each filament. They exhibit a run-tumble swimming pattern, driven by switching of the rotational direction, which causes polymorphic flagellar transformation. Here we report a novel swimming mode in E. coli ATCC10798, which is one of the original K-12 clones. High-speed tracking of single ATCC10798 cells showed forward and backward swimming with an average turning angle of 150°. The flagellar helicity remained right-handed with a 1.3 µm pitch and 0.14 µm helix radius, which is consistent with the feature of a curly type, regardless of motor switching; the flagella of ATCC10798 did not show polymorphic transformation. The torque and rotational switching of the motor was almost identical to the E. coli W3110 strain, which is a derivative of K-12 and a wild-type for chemotaxis. The single point mutation of N87K in FliC, one of the filament subunits, is critical to the change in flagellar morphology and swimming pattern, and lack of flagellar polymorphism. E. coli cells expressing FliC(N87K) sensed ascending a chemotactic gradient in liquid but did not spread on a semi-solid surface. Based on these results, we concluded that a flagellar polymorphism is essential for spreading in structured environments.


Assuntos
Quimiotaxia/fisiologia , Escherichia coli K12/fisiologia , Flagelos/fisiologia , Modelos Biológicos , Mutação
20.
Nat Commun ; 11(1): 4453, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901025

RESUMO

Archaea have evolved to survive in some of the most extreme environments on earth. Life in extreme, nutrient-poor conditions gives the opportunity to probe fundamental energy limitations on movement and response to stimuli, two essential markers of living systems. Here we use three-dimensional holographic microscopy and computer simulations to reveal that halophilic archaea achieve chemotaxis with power requirements one hundred-fold lower than common eubacterial model systems. Their swimming direction is stabilised by their flagella (archaella), enhancing directional persistence in a manner similar to that displayed by eubacteria, albeit with a different motility apparatus. Our experiments and simulations reveal that the cells are capable of slow but deterministic chemotaxis up a chemical gradient, in a biased random walk at the thermodynamic limit.


Assuntos
Archaea/fisiologia , Quimiotaxia/fisiologia , Modelos Biológicos , Simulação por Computador , Extremófilos/fisiologia , Haloarcula/fisiologia , Haloferax/fisiologia , Holografia , Imageamento Tridimensional , Microscopia de Vídeo , Movimento/fisiologia , Nutrientes/fisiologia
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