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How many hair follicles are innervated by one afferent axon? A confocal microscopic analysis of palisade endings in the auricular skin of thy1-YFP transgenic mouse

SUZUKI, Maasa; EBARA, Satomi; KOIKE, Taro; TONOMURA, Sotatsu; KUMAMOTO, Kenzo
Fonte: The Japan Academy Publicador: The Japan Academy
Tipo: Artigo de Revista Científica
Publicado em 11/12/2012 EN
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Hairs are known as a sensory apparatus for touch. Their follicles are innervated predominantly by palisade endings composed of longitudinal and circumferential lanceolate endings. However, little is known as to how their original primary neurons make up a part of the ending. In this study, innervation of the palisade endings was investigated in the auricular skin of thy1-YFP transgenic mouse. Major observations were 1) Only a small portion of PGP9.5-immunopositive axons showed YFP-positivity, 2) All of thy1-YFP-positive sensory axons were thick and myelinated, 3) Individual thy1-YFP-positive trunk axons innervated 4–54 hair follicles, 4) Most palisade endings had a gap of lanceolate ending arrangement, 5) PGP9.5-immunopositive 10–32 longitudinal lanceolate endings were closely arranged. Only a part of them were thy1-YFP-positive axons that originated from 1–3 afferents, and 6) Single nerve bundles of the dermal nerve network included both bidirectional afferents. Palisade endings innervated by multiple sensory neurons might be highly sensitive to hair movement.

The Anticancer Activity Compared Between Triptorelin and a New Gonadotropin Releasing Hormone Analogue

Saleh-Abady, Mohammad Mirzaei; Alizadeh, Abdolali; Shamsipour, Fereshteh; Naderi-Manesh, Hossein
Fonte: Avicenna Research Institute Publicador: Avicenna Research Institute
Tipo: Artigo de Revista Científica
Publicado em //2009 EN
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Gonadotropin releasing hormone (GnRH) plays a key role in reproduction. This decapeptide is synthesized and released by hypothalamus and induces the pituitary gonadotrop cells to release pituitary gonadotropin hormones. In some extrapituitary compartments GnRH and its receptor act as part of the autocrine regulatory system of cell proliferation. The anticancer activity of GnRH and its analogues has been observed by many researchers. In this study the anticancer activity of a new analogue of GnRH and triptorelin was investigated by cell proliferation assay. Results indicate that proliferation of human breast and ovarian cancer cell lines are dose-dependently inhibited. The inhibitory efficiency of the new analogue is proved to be higher than the original triptorelin. In addition to its antimitogenic activity, evidence was found for the involvement of the apoptotic mechanism in the action of the new analogue and triptorelin. In conclusion, the new analogue can be considered as a good pharmaceutical candidate.

Nonsense and Sense Suppression Abilities of Original and Derivative Methanosarcina mazei Pyrrolysyl-tRNA Synthetase-tRNAPyl Pairs in the Escherichia coli BL21(DE3) Cell Strain

Odoi, Keturah A.; Huang, Ying; Rezenom, Yohannes H.; Liu, Wenshe R.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 08/03/2013 EN
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Systematic studies of nonsense and sense suppression of the original and three derivative Methanosarcina mazei PylRS-tRNAPyl pairs and cross recognition between nonsense codons and various tRNAPyl anticodons in the Escherichia coli BL21(DE3) cell strain are reported. is orthogonal in E. coli and able to induce strong amber suppression when it is co-expressed with pyrrolysyl-tRNA synthetase (PylRS) and charged with a PylRS substrate, Nε-tert-butoxycarbonyl-l-lysine (BocK). Similar to, is also orthogonal in E. coli and can be coupled with PylRS to genetically incorporate BocK at an ochre mutation site. Although is expected to recognize a UAG codon based on the wobble hypothesis, the PylRS- pair does not give rise to amber suppression that surpasses the basal amber suppression level in E. coli. E. coli itself displays a relatively high opal suppression level and tryptophan (Trp) is incorporated at an opal mutation site. Although the PylRS- pair can be used to encode BocK at an opal codon, the pair fails to suppress the incorporation of Trp at the same site. fails to deliver BocK at an AGG codon when co-expressed with PylRS in E. coli.

The new modern era of yeast genomics: community sequencing and the resulting annotation of multiple Saccharomyces cerevisiae strains at the Saccharomyces Genome Database

Engel, Stacia R.; Cherry, J. Michael
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Publicado em 13/03/2013 EN
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The first completed eukaryotic genome sequence was that of the yeast Saccharomyces cerevisiae, and the Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/) is the original model organism database. SGD remains the authoritative community resource for the S. cerevisiae reference genome sequence and its annotation, and continues to provide comprehensive biological information correlated with S. cerevisiae genes and their products. A diverse set of yeast strains have been sequenced to explore commercial and laboratory applications, and a brief history of those strains is provided. The publication of these new genomes has motivated the creation of new tools, and SGD will annotate and provide comparative analyses of these sequences, correlating changes with variations in strain phenotypes and protein function. We are entering a new era at SGD, as we incorporate these new sequences and make them accessible to the scientific community, all in an effort to continue in our mission of educating researchers and facilitating discovery.

Comparison of protein patterns between Plasmodium falciparum mutant clone T9/94-M1-1(b3) induced by pyrimethamine and the original parent clone T9/94

Rungsihirunrat, Kanchana; Chaijaroenkul, Wanna; Siripoon, Napaporn; Seugorn, Aree; Thaithong, Sodsri; Na-Bangchang, Kesara
Fonte: Asian Pacific Tropical Medicine Press Publicador: Asian Pacific Tropical Medicine Press
Tipo: Artigo de Revista Científica
Publicado em /01/2012 EN
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Scoliosis correction with shape-memory metal: results of an experimental study

Wever, D.; Elstrodt, J.; Veldhuizen, A.; v Horn, J.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
EN
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The biocompatibility and functionality of a new scoliosis correction device, based on the properties of the shape-memory metal nickel-titanium alloy, were studied. With this device, the shape recovery forces of a shape-memory metal rod are used to achieve a gradual three-dimensional scoliosis correction. In the experimental study the action of the new device was inverted: the device was used to induce a scoliotic curve instead of correcting one. Surgical procedures were performed in six pigs. An originally curved squared rod, in the cold condition, was straightened and fixed to the spine with pedicle screws. Peroperatively, the memory effect of the rod was activated by heating the rod to 50°C by a low-voltage, high-frequency current. After 3 and after 6 months the animals were sacrificed. The first radiographs, obtained immediately after surgery, showed in all animals an induced curve of about 40° Cobb angle – the original curve of the rod. This curve remained constant during the follow-up. The postoperative serum nickel measurements were around the detection limit, and were not significantly higher compared to the preoperative nickel concentration. Macroscopic inspection after 3 and 6 months showed that the device was almost overgrown with newly formed bone. Corrosion and fretting processes were not observed. Histologic examination of the sections of the surrounding tissues and sections of the lung...

Cotrel-Dubousset instrumentation for the treatment of severe scoliosis

De Giorgi, G.; Stella, G.; Becchetti, S.; Martucci, G.; Miscioscia, D.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
Publicado em /02/1999 EN
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In a multicentric study, 36 cases (40 curves) of severe scoliosis were analysed; 19 were idiopathic and 17 neurological, Cobb angles ranged from 70° to 145°, all had undergone three-rod Cotrel-Dubousset (CD) instrumentation. The correction on the frontal plane achieved more than 50% of the preoperative angle (53.9% for idiopathic curves and 55.6% for neurological ones). On the sagittal plane the pathological shape of the spine was reduced and distinctly ameliorated. In ten patients, the authors successfully applied a technique, alternative to the original one, which was based on the use of two or three screws in the lumbar area, one supplementary pedicle transverse claw on the cranial area and two rods connected by a domino, instead of a single rod (the longer one applied on the concave side). The main complications were: one case of infection, three of vascular compression of the duodenum, one of crank-shaft phenomenon and one laminar hook displacement. The excellent result achieved in both, idiopathic and neurological severe and stiff scoliosis shows the efficacy, reliability and versatility of CD three-rod instrumentation.

Reducing the cervical flexion tear-drop fracture with a posterior approach and plating technique: an original method

Signoret, F.; Jacquot, F. P.; Feron, J.-M.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
Publicado em /04/1999 EN
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Flexion tear-drop fractures (FTDF) in the cervical spine constitute a highly unstable condition with a high incidence of neurological complications due to posterior displacement of the fractured vertebra in the spinal canal. The widely accepted surgical management for this condition includes complete excision and grafting of the vertebral body through an anterior approach. Thorough radiological and CT analysis of FTDF shows that the vertebral body is often separated into two parts by a sagittal plane fracture, but remains continuous through the pedicle and anterior arch of the vertebral foramen with the lateral mass and the articular processes. We therefore hypothesized that reduction would be possible by acting on the articular process through a posterior approach with a particular plating technique. Eight patients with FTDF were operated on with the technique we describe. Three had complete tetraplegia, four had incomplete tetraplegia and one was normal. A preoperative CT scan was made in all patients. Local kyphosis, posterior displacement of the vertebral body, and general lordosis in the cervical spine were recorded. In all cases, a satisfactory reduction was achieved on the postoperative radiographs and at the mean follow-up of 18.6 ± 12.1 months...

Surgical treatment of nonunited fractures of the odontoid process, with special reference to occipitocervical fusion for unreducible atlantoaxial subluxation or instability

Dai, L. Y.; Yuan, W.; Ni, B.; Liu, H. K.; Jia, L. S.; Zhao, D. L.; Xu, Y. K.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
Publicado em /04/2000 EN
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Fifty-seven consecutive patients treated surgically for nonunited fractures of the odontoid process were reviewed. All patients presented late, exhibiting neurological deficits subsequent to nonunion. Delay in presentation was between ¶6 and 120 months (mean 32 months) after the original injury, due to missed diagnosis or inappropriate management. Seven patients who were reduced in traction underwent a Gallie atlantoaxial fusion. In the remaining 50 patients who were unreducible, an occipitocervical arthrodesis was performed. They were followed up for a minimum of 2 years, except one who died from postoperative respiratory failure. All patients obtained a solid bony union, including two in whom nonunion occurred following atlantoaxial fusion, and occipitocervical fusion was added as a rescue. Thirty-eight patients achieved excellent neurological recovery, nine still had some disability, five retained their neurological deficits and two reported a deterioration. In two patients, a recurrence in a traumatic episode was experienced long after a resolution. Our findings demonstrate that occipitocervical arthrodesis is preferable for unreducible subluxation or instability of atlantoaxial articulation in nonunion of odontoid fractures.

Can a short spinal cord produce scoliosis?

Porter, Richard W.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
EN
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Some patients with scoliosis have a relatively short vertebral canal. This poses the question of whether a short spinal cord may sometimes cause scoliosis. The present paper presents two observations that may support this concept. It presents a scoliosis model demonstrating what effect a short, unforgiving spinal cord might have on the spinal column. The model uses two flexible parallel tubes with the facility to tighten one. It demonstrates that a short, unforgiving spinal cord could produce the abnormal rotatory anatomy observed at the apex in scoliosis, with first lordosis, then lateral deviation and finally a rotation of the vertebral column, with the rotation occurring between the canal and the vertebral body, around the axis of the cord. The anatomy of the apical vertebra is described from two museum specimens, a computed tomography (CT) myelogram and seven magnetic resonance imaging (MRI) studies. The study confirms that the vertebral canal and the intervertebral foraminae retain their original orientation. The spinal cord is eccentric in the canal towards the concavity of the curve; the major component of rotation occurs anterior to the vertebral canal and the axis of this rotation seems to be at the site of the spinal cord. These observations do not establish that a short spinal cord will result in scoliosis...

CT study of craniovertebral rotation in whiplash injury

Patijn, J.; Wilmink, J.; ter Linden, F. H. J.; Kingma, H.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
EN
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The present study investigates the diagnostic value of rotatory computed tomography (CT) examinations in normal subjects and patients with whiplash associated disorders (WAD), with the aim of reproducing earlier findings of rotatory CT studies. Forty-seven WAD patients with persistent complaints after a rear-end collision (non-cranial contact acceleration/deceleration trauma) were enrolled in this study. To guarantee a maximally homogeneous study population, only WAD patients with a marked passive cervical retroflexion restriction were included. Transversal CT slices in left and right rotation were made for all cervical levels (the skull included). CT slices in neutral position were used to reconstruct partially depicted vertebrae. Absolute rotatory values were estimated according the method of Penning and Dvorak. For all levels the relative rotatory (RR) value was calculated by dividing absolute rotation values of a particular cervical level by the corresponding total cervical rotation. The measuring error was estimated by comparing the findings of two separately performed measuring procedures. Two age groups of WAD patients were formed. A younger group was matched for age with 26 normal healthy volunteers (the original data of an earlier study). The use of neutral CT slices for reconstruction of a partially depicted cervical vertebra resulted in a measurement error of 1.9° at the level of C0/C1 (occiput/atlas) and 3.5° at C1/C2. Suspected hypermobility as defined by Dvorak was rare in our WAD patients (6.4% C0/C1 and 10.6% C1/C2). RR values at C0/C1 were significantly larger in 79% of the WAD patients. Discriminant analysis of the RR values showed 80% correctly classified WAD patients. Only 11.5% of the normal subjects were classified as false-positive. Since no hypermobility was found at C1/C2...

DARPin-targeting of Measles Virus: Unique Bispecificity, Effective Oncolysis, and Enhanced Safety

Friedrich, Katrin; Hanauer, Jan RH; Prüfer, Steffen; Münch, Robert C; Völker, Iris; Filippis, Christodoulos; Jost, Christian; Hanschmann, Kay-Martin; Cattaneo, Roberto; Peng, Kah-Whye; Plückthun, Andreas; Buchholz, Christian J; Cichutek, Klaus; Mühle
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
EN
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Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancers. Many naturally occurring viruses have a preferential, although nonexclusive, tropism for tumors and tumor cells. In addition, specific targeting of cancer cells can be achieved at the virus entry level. We optimized retargeting of cell entry by elongating the measles virus attachment protein with designed ankyrin repeat proteins (DARPins), while simultaneously ablating entry through the natural receptors. DARPin-targeted viruses were strongly attenuated in off-target tissue, thereby enhancing safety, but completely eliminated tumor xenografts. Taking advantage of the unique properties of DARPins of being fused without generating folding problems, we generated a virus simultaneous targeting two different tumor markers. The bispecific virus retained the original oncolytic efficacy, while providing proof of concept for a strategy to counteract issues of resistance development. Thus, DARPin-targeting opens new prospects for the development of personalized, targeted therapeutics.

Cortical tibial osteoperiosteal flap technique to achieve bony bridge in transtibial amputation: experience in nine adult patients

Mongon, Mauricio Leal; Piva, Felipe Alberto; Mistro Neto, Sylvio; Carvalho, Jose Andre; Belangero, William Dias; Livani, Bruno
Fonte: Springer Milan Publicador: Springer Milan
Tipo: Artigo de Revista Científica
EN
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Amputation, especially of the lower limbs, is a surgical procedure that gives excellent results when conducted under the appropriate conditions. In 1949 Ertl developed a technique for transtibial osteomyoplastic amputation which restored the intraosseous pressure through canal obliteration and expanded the area of terminal support through a bony bridge between the fibula and distal tibia. The aim of this study was to investigate the effectiveness of a modification of the original Ertl’s technique in which a cortical osteoperiosteal flap created from the tibia is used to form a bony bridge during transtibial amputation in adults. Nine patients underwent leg amputations with the cortical tibial osteoperiosteal flap technique for reconstruction of the stump. The average duration of follow-up was 30.8 (range, 18–41) months. The post-surgery examination included a clinical examination and radiography. A 6-min walk test (Enright in Respir Care 48(8):783–785, 2003) was performed in the 32nd week after amputation. At 24th week post-surgery, all patients had stumps that were painless and able to bear full weight through the end. The creation of a cortical osteoperiosteal flap from the tibia to the fibula during transtibial amputation is a safe and effective technique that provides a strong and painless terminal weight-bearing stump. This constitutes a useful option for young patients...

BDNF overexpression in mouse hippocampal astrocytes promotes local neurogenesis and elicits anxiolytic-like activities

Quesseveur, G; David, D J; Gaillard, M C; Pla, P; Wu, M V; Nguyen, H T; Nicolas, V; Auregan, G; David, I; Dranovsky, A; Hantraye, P; Hen, R; Gardier, A M; Déglon, N; Guiard, B P
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
EN
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The therapeutic activity of selective serotonin (5-HT) reuptake inhibitors (SSRIs) relies on long-term adaptation at pre- and post-synaptic levels. The sustained administration of SSRIs increases the serotonergic neurotransmission in response to a functional desensitization of the inhibitory 5-HT1A autoreceptor in the dorsal raphe. At nerve terminal such as the hippocampus, the enhancement of 5-HT availability increases brain-derived neurotrophic factor (BDNF) synthesis and signaling, a major event in the stimulation of adult neurogenesis. In physiological conditions, BDNF would be expressed at functionally relevant levels in neurons. However, the recent observation that SSRIs upregulate BDNF mRNA in primary cultures of astrocytes strongly suggest that the therapeutic activity of antidepressant drugs might result from an increase in BDNF synthesis in this cell type. In this study, by overexpressing BDNF in astrocytes, we balanced the ratio between astrocytic and neuronal BDNF raising the possibility that such manipulation could positively reverberate on anxiolytic-/antidepressant-like activities in transfected mice. Our results indicate that BDNF overexpression in hippocampal astrocytes produced anxiolytic-/antidepressant-like activity in the novelty suppressed feeding in relation with the stimulation of hippocampal neurogenesis whereas it did not potentiate the effects of the SSRI fluoxetine on these parameters. Moreover...

Memory of Conditioned Taste Aversion Is Erased by Inhibition of PI3K in the Insular Cortex

Slouzkey, Ilana; Rosenblum, Kobi; Maroun, Mouna
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
EN
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The conditioned taste aversion (CTA) paradigm, in which association between a novel taste and visceral malaise is formed, gives a unique experimental setting to examine the mechanisms underlying memory acquisition and extinction processes. AKT is a main kinase of the phosphoinositide 3-kinase cascade (PI3K) and has been implicated in long-term memory. We have recently reported that blockade of PI3K in the basolateral amygdala (BLA) before retrieval of fear memory was associated with long-term reduction in fear responses, suggesting a possible role of PI3K inhibition in fear erasure. In this study, we aimed to elucidate whether PI3K has a similar role in the insular cortex (IC), which has a crucial role in CTA acquisition, consolidation, maintenance, and extinction. To that end, we (1) monitored AKT phosphorylation in the IC following CTA acquisition and extinction and (2) inhibited PI3K by local microinjection of the PI3K inhibitor LY294002 at different stages of CTA acquisition and extinction. Our results show that while AKT phosphorylation is increased following CTA learning, it is decreased following CTA extinction. Inhibition of AKT phosphorylation in the IC before or after the first CTA retrieval test resulted in reduction in the aversion index. This reduction in aversion is due to the erasure of the original CTA trace memory...

Smooth muscles and stem cells of embryonic guts express KIT, PDGFRRA, CD34 and many other stem cell antigens: suggestion that GIST arise from smooth muscles and gut stem cells

Terada, Tadashi
Fonte: e-Century Publishing Corporation Publicador: e-Century Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em 15/05/2013 EN
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Gastrointestinal stromal tumor (GIST) is believed to original from interstitial cells of (ICC) present in Auerbach’s nerve plexus. GIST frequently shows gain-of-function mutations of KIT and PDGFRA. In practical pathology, GIST is diagnosed by positive immunostaining or KIT and/or CD34. The author herein demonstrates that human embryonic gastrointestinal tract smooth muscles (HEGITSM) and human embryonic stem gastrointestinal cells (HEGISC) consistently express KIT, CD34, NCAM, PDGFRA and other stem cell (SC) antigens NSE, synaptophysin, chromogranin, bcl-2, ErbB, and MET throughout the embryonic development of 7-40 gestational week (GW). CK14 was negative. The author examines 42 cases (7-40 GW) of embryonic GI tract (EGI). The HEGISM, HEGIST, and gall bladder smooth muscles (SM) were consistently positive for KIT, CD34, NCAM, PDGFRA, synaptophysin, chromogranin, NSE, bcl-2, ErbB2, and MET in foregut, stomach, GB, midgut, and hindgut throughout the fetal life (7-40 GW). The stem cells (SC) were seen to create the SM, nerves, ICC, and other all structures of GI tract. In adult gastrointestinal walls (n=30), KIT, CD34, PDGFRA, and S100 proteins were expressed in Auerbach’s nerve plexus and ICC. The bronchial and vascular SM of embryos did not express these molecules. In GIST...

UMD-MLH1/MSH2/MSH6 databases: description and analysis of genetic variations in French Lynch syndrome families

Grandval, Philippe; Fabre, Aurélie J.; Gaildrat, Pascaline; Baert-Desurmont, Stéphanie; Buisine, Marie-Pierre; Ferrari, Anthony; Wang, Qing; Béroud, Christophe; Olschwang, Sylviane
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Publicado em 31/05/2013 EN
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Lynch syndrome is an autosomal dominant disease caused by germ line heterozygous mutations mainly involving the MSH2, MLH1 and MSH6 genes that belong to the DNA MisMatch Repair (MMR) genes family. The French network counting the 16 licensed laboratories involved in Lynch syndrome genetic testing developed three locus-specific databases with the UMD® software (www.umd.be/MLH1/, www.umd.be/MSH2/ and www.umd.be/MSH6/) that presently contain a total of 7047 sequence variations including 707 distinct variations of a priori unknown functional significance (VUS) that were identified through complete mutation screening or targeted predictive testing. Mutation carriers are at high risk for developing early-onset colorectal and endometrial adenocarcinomas. Consensus clinical guidelines have been proposed, allowing the efficient detection of curable lesions. The major challenge of genetic testing is to reliably classify the genomic variations in those patients who seek genetic counseling. Combining the interactive tools of the software, the relevant published data and mainly original information produced by the French MisMatch Repair network, the UMD-MLH1/MSH2/MSH6 databases provide interpretation data for the 707 VUS that were classified according to the IARC 5-Class system. These public databases are regularly updated to improve the classification of all registered VUS...

Estimation of plasma lipids and its significance on histopathological grades in oral cancer: Prognostic significance an original research

Sherubin, Eugenia J; Kannan, Karthiga S; Kumar, Dhineksh N; Joseph, Isaac
Fonte: Medknow Publications & Media Pvt Ltd Publicador: Medknow Publications & Media Pvt Ltd
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
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Phylogenetic beta diversity in bacterial assemblages across ecosystems: deterministic versus stochastic processes

Wang, Jianjun; Shen, Ji; Wu, Yucheng; Tu, Chen; Soininen, Janne; Stegen, James C; He, Jizheng; Liu, Xingqi; Zhang, Lu; Zhang, Enlou
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
EN
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Increasing evidence has emerged for non-random spatial distributions of microbes, but knowledge of the processes that cause variation in microbial assemblage among ecosystems is lacking. For instance, some studies showed that deterministic processes such as habitat specialization are important, while other studies hold that bacterial communities are assembled by stochastic forces. Here we examine the relative influence of deterministic and stochastic processes for bacterial communities from subsurface environments, stream biofilm, lake water, lake sediment and soil using pyrosequencing of the 16S ribosomal RNA gene. We show that there is a general pattern in phylogenetic signal in species ecological niches across recent evolutionary time for all studied habitats, enabling us to infer the influences of community assembly processes from patterns of phylogenetic turnover in community composition. The phylogenetic dissimilarities among-habitat types were significantly higher than within them, and the communities were clustered according to their original habitat types. For communities within-habitat types, the highest phylogenetic turnover rate through space was observed in subsurface environments, followed by stream biofilm on mountainsides...

Lentiviral Delivery of the Human Wild-type Tau Protein Mediates a Slow and Progressive Neurodegenerative Tau Pathology in the Rat Brain

Caillierez, Raphaëlle; Bégard, Séverine; Lécolle, Katia; Deramecourt, Vincent; Zommer, Nadège; Dujardin, Simon; Loyens, Anne; Dufour, Noëlle; Aurégan, Gwennaëlle; Winderickx, Joris; Hantraye, Philippe; Déglon, Nicole; Buée, Luc; Colin, Morvane
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
EN
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Most models for tauopathy use a mutated form of the Tau gene, MAPT, that is found in frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) and that leads to rapid neurofibrillary degeneration (NFD). Use of a wild-type (WT) form of human Tau protein to model the aggregation and associated neurodegenerative processes of Tau in the mouse brain has thus far been unsuccessful. In the present study, we generated an original “sporadic tauopathy-like” model in the rat hippocampus, encoding six Tau isoforms as found in humans, using lentiviral vectors (LVs) for the delivery of a human WT Tau. The overexpression of human WT Tau in pyramidal neurons resulted in NFD, the morphological characteristics and kinetics of which reflected the slow and sporadic neurodegenerative processes observed in sporadic tauopathies, unlike the rapid neurodegenerative processes leading to cell death and ghost tangles triggered by the FTDP-17 mutant Tau P301L. This new model highlights differences in the molecular and cellular mechanisms underlying the pathological processes induced by WT and mutant Tau and suggests that preference should be given to animal models using WT Tau in the quest to understand sporadic tauopathies.