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401.
Julia Scharnert Lilo Greune Dagmar Zeuschner Marie-Luise Lubos M. Alexander Schmidt Christian Rüter 《Cellular and molecular life sciences : CMLS》2013,70(24):4809-4823
Extracellular Gram-negative pathogenic bacteria target essential cytoplasmic processes of eukaryotic cells by using effector protein delivery systems such as the type III secretion system (T3SS). These secretion systems directly inject effector proteins into the host cell cytoplasm. Among the T3SS-dependent Yop proteins of pathogenic Yersinia, the function of the effector protein YopM remains enigmatic. In a recent study, we demonstrated that recombinant YopM from Yersinia enterocolitica enters host cells autonomously without the presence of bacteria and thus identified YopM as a novel bacterial cell-penetrating protein. Following entry YopM down-regulates expression of pro-inflammatory cytokines such as tumor necrosis factor α. These properties earmark YopM for further development as a novel anti-inflammatory therapeutic. To elucidate the uptake and intracellular targeting mechanisms of this bacterial cell-penetrating protein, we analyzed possible routes of internalization employing ultra-cryo electron microscopy. Our results reveal that under physiological conditions, YopM enters cells predominantly by exploiting endocytic pathways. Interestingly, YopM was detected free in the cytosol and inside the nucleus. We could not observe any colocalization of YopM with secretory membranes, which excludes retrograde transport as the mechanism for cytosolic release. However, our findings indicate that direct membrane penetration and/or an endosomal escape of YopM contribute to the cytosolic and nuclear localization of the protein. Surprisingly, even when endocytosis is blocked, YopM was found to be associated with endosomes. This suggests an intracellular endosome-associated transport of YopM. 相似文献
402.
Cerf M Thiruvengadam N Mormann F Kraskov A Quiroga RQ Koch C Fried I 《Nature》2010,467(7319):1104-1108
Daily life continually confronts us with an exuberance of external, sensory stimuli competing with a rich stream of internal deliberations, plans and ruminations. The brain must select one or more of these for further processing. How this competition is resolved across multiple sensory and cognitive regions is not known; nor is it clear how internal thoughts and attention regulate this competition. Recording from single neurons in patients implanted with intracranial electrodes for clinical reasons, here we demonstrate that humans can regulate the activity of their neurons in the medial temporal lobe (MTL) to alter the outcome of the contest between external images and their internal representation. Subjects looked at a hybrid superposition of two images representing familiar individuals, landmarks, objects or animals and had to enhance one image at the expense of the other, competing one. Simultaneously, the spiking activity of their MTL neurons in different subregions and hemispheres was decoded in real time to control the content of the hybrid. Subjects reliably regulated, often on the first trial, the firing rate of their neurons, increasing the rate of some while simultaneously decreasing the rate of others. They did so by focusing onto one image, which gradually became clearer on the computer screen in front of their eyes, and thereby overriding sensory input. On the basis of the firing of these MTL neurons, the dynamics of the competition between visual images in the subject's mind was visualized on an external display. 相似文献
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404.
Viacheslav A. Trach Alexander A. Khaustov Evert E. Lindquist 《Journal of Natural History》2019,53(13-14):761-778
Adult females of a new species, Mucroseius insolitus sp. nov., are described from the metathoracic spiracular atria of the Black pine sawyer beetle Monochamus galloprovincialis (Coleoptera: Cerambycidae) from Asian Russia (Altai Republic and Tyumen Province). The new species differs from all congeners by the absence of the otherwise autapomorphic distal flangelike process (mucro) of the fixed chela. The genus Mucroseius is recorded for the first time in Russia, and its generic concept is reviewed.
urn:lsid:zoobank.org:act:AB3BDB6A-63C3-4970-A192-A3C539C48BA1 相似文献
405.
406.
407.
MB Gerstein A Kundaje M Hariharan SG Landt KK Yan C Cheng XJ Mu E Khurana J Rozowsky R Alexander R Min P Alves A Abyzov N Addleman N Bhardwaj AP Boyle P Cayting A Charos DZ Chen Y Cheng D Clarke C Eastman G Euskirchen S Frietze Y Fu J Gertz F Grubert A Harmanci P Jain M Kasowski P Lacroute J Leng J Lian H Monahan H O'Geen Z Ouyang EC Partridge D Patacsil F Pauli D Raha L Ramirez TE Reddy B Reed M Shi T Slifer J Wang L Wu X Yang KY Yip G Zilberman-Schapira S Batzoglou A Sidow PJ Farnham RM Myers 《Nature》2012,489(7414):91-100
408.
409.
Josefowicz SZ Niec RE Kim HY Treuting P Chinen T Zheng Y Umetsu DT Rudensky AY 《Nature》2012,482(7385):395-399
A balance between pro- and anti-inflammatory mechanisms at mucosal interfaces, which are sites of constitutive exposure to microbes and non-microbial foreign substances, allows for efficient protection against pathogens yet prevents adverse inflammatory responses associated with allergy, asthma and intestinal inflammation. Regulatory T (T(reg)) cells prevent systemic and tissue-specific autoimmunity and inflammatory lesions at mucosal interfaces. These cells are generated in the thymus (tT(reg) cells) and in the periphery (induced (i)T(reg) cells), and their dual origin implies a division of labour between tT(reg) and iT(reg) cells in immune homeostasis. Here we show that a highly selective blockage in differentiation of iT(reg) cells in mice did not lead to unprovoked multi-organ autoimmunity, exacerbation of induced tissue-specific autoimmune pathology, or increased pro-inflammatory responses of T helper 1 (T(H)1) and T(H)17 cells. However, mice deficient in iT(reg) cells spontaneously developed pronounced T(H)2-type pathologies at mucosal sites--in the gastrointestinal tract and lungs--with hallmarks of allergic inflammation and asthma. Furthermore, iT(reg)-cell deficiency altered gut microbial communities. These results suggest that whereas T(reg) cells generated in the thymus appear sufficient for control of systemic and tissue-specific autoimmunity, extrathymic differentiation of T(reg) cells affects commensal microbiota composition and serves a distinct, essential function in restraint of allergic-type inflammation at mucosal interfaces. 相似文献
410.
F Odoardi C Sie K Streyl VK Ulaganathan C Schläger D Lodygin K Heckelsmiller W Nietfeld J Ellwart WE Klinkert C Lottaz M Nosov V Brinkmann R Spang H Lehrach M Vingron H Wekerle C Flügel-Koch A Flügel 《Nature》2012,488(7413):675-679
The blood–brain barrier (BBB) and the environment of the central nervous system (CNS) guard the nervous tissue from peripheral immune cells. In the autoimmune disease multiple sclerosis, myelin-reactive T-cell blasts are thought to transgress the BBB and create a pro-inflammatory environment in the CNS, thereby making possible a second autoimmune attack that starts from the leptomeningeal vessels and progresses into the parenchyma. Using a Lewis rat model of experimental autoimmune encephalomyelitis, we show here that contrary to the expectations of this concept, T-cell blasts do not efficiently enter the CNS and are not required to prepare the BBB for immune-cell recruitment. Instead, intravenously transferred T-cell blasts gain the capacity to enter the CNS after residing transiently within the lung tissues. Inside the lung tissues, they move along and within the airways to bronchus-associated lymphoid tissues and lung-draining mediastinal lymph nodes before they enter the blood circulation from where they reach the CNS. Effector T cells transferred directly into the airways showed a similar migratory pattern and retained their full pathogenicity. On their way the T cells fundamentally reprogrammed their gene-expression profile, characterized by downregulation of their activation program and upregulation of cellular locomotion molecules together with chemokine and adhesion receptors. The adhesion receptors include ninjurin 1, which participates in T-cell intravascular crawling on cerebral blood vessels. We detected that the lung constitutes a niche not only for activated T cells but also for resting myelin-reactive memory T cells. After local stimulation in the lung, these cells strongly proliferate and, after assuming migratory properties, enter the CNS and induce paralytic disease. The lung could therefore contribute to the activation of potentially autoaggressive T cells and their transition to a migratory mode as a prerequisite to entering their target tissues and inducing autoimmune disease. 相似文献