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51.
52.
T Yvanka de Soysa Allison Ulrich Timo Friedrich Danielle Pite Shannon L Compton Deborah Ok Rebecca L Bernardos Gerald B Downes Shizuka Hsieh Rachael Stein M Caterina Lagdameo Katherine Halvorsen Lydia-Rose Kesich Michael JF Barresi 《BMC biology》2012,10(1):1-25
Background
During nerve growth, cytoplasmic vesicles add new membrane preferentially to the growth cone located at the distal tip of extending axons. Growth cone membrane is also retrieved locally, and asymmetric retrieval facilitates membrane remodeling during growth cone repulsion by a chemorepellent gradient. Moreover, growth inhibitory factors can stimulate bulk membrane retrieval and induce growth cone collapse. Despite these functional insights, the processes mediating local membrane remodeling during axon extension remain poorly defined.Results
To investigate the spatial and temporal dynamics of membrane retrieval in actively extending growth cones, we have used a transient labeling and optical recording method that can resolve single vesicle events. Live-cell confocal imaging revealed rapid membrane retrieval by distinct endocytic modes based on spatial distribution in Xenopus spinal neuron growth cones. These modes include endocytic "hot-spots" triggered at the base of filopodia, at the lateral margins of lamellipodia, and along dorsal ridges of the growth cone. Additionally, waves of endocytosis were induced when individual filopodia detached from the substrate and fused with the growth cone dorsal surface or with other filopodia. Vesicle formation at sites of membrane remodeling by self-contact required F-actin polymerization. Moreover, bulk membrane retrieval by macroendocytosis correlated positively with the substrate-dependent rate of axon extension and required the function of Rho-family GTPases.Conclusions
This study provides insight into the dynamic membrane remodeling processes essential for nerve growth by identifying several distinct modes of rapid membrane retrieval in the growth cone during axon extension. We found that endocytic membrane retrieval is intensified at specific subdomains and may drive the dynamic membrane ruffling and re-absorption of filopodia and lamellipodia in actively extending growth cones. The findings offer a platform for determining the molecular mechanisms of distinct endocytic processes that may remodel the surface distribution of receptors, ion channels and other membrane-associated proteins locally to drive growth cone extension and chemotactic guidance. 相似文献53.
Two polarized patterns (Th1 and Th2) of cytokines regulate inflammatory responses. Each cytokine pattern inhibits production of the opposing pattern. Lymphocytes from inflamed intestine due to Crohn's disease secrete a Th1 pattern of cytokines. Crohn's disease is most prevalent in highly industrialized countries with temperate climates. It occurs rarely in tropical third world countries with poor sanitation. We propose that exposure to an environmental agent predisposes individuals to Crohn's disease. Parasitic worms (helminths) are common in tropical climates and in populations subject to crowding and poor sanitation. Children are most subject to helminthic colonization. Many helminths live within or migrate through the human gut where they interact with the mucosal immune system. The host mounts a mucosal response that includes Th2 cytokine production limiting helminthic colonization. Helminths and their eggs probably are the most potent stimulators of mucosal Th2 responses. The Th2 response provoked by parasitic worms can modulate immune reactions to unrelated parasitic, bacterial, and viral infections. Many people in developed countries now live in increasingly hygienic environments, avoiding exposure to helminths. Perhaps failure to acquire these parasites and experience mucosal Th2 conditioning predisposes to Crohn's disease, which is an overly active Th1 inflammation. 相似文献
54.
Victoria?PetriEmail author G?Thomas?Hayman Marek?Tutaj Jennifer?R?Smith Stanley?JF?Laulederkind Shur-Jen?Wang Rajni?Nigam Jeff?De Pons Mary?Shimoyama Melinda?R?Dwinell Elizabeth?A?Worthey Howard?J?Jacob 《Human genomics》2014,8(1):17
Background
Biological systems are exquisitely poised to respond and adjust to challenges, including damage. However, sustained damage can overcome the ability of the system to adjust and result in a disease phenotype, its underpinnings many times elusive. Unraveling the molecular mechanisms of systems biology, of how and why it falters, is essential for delineating the details of the path(s) leading to the diseased state and for designing strategies to revert its progression. An important aspect of this process is not only to define the function of a gene but to identify the context within which gene functions act. It is within the network, or pathway context, that the function of a gene fulfills its ultimate biological role. Resolving the extent to which defective function(s) affect the proceedings of pathway(s) and how altered pathways merge into overpowering the system's defense machinery are key to understanding the molecular aspects of disease and envisioning ways to counteract it. A network-centric approach to diseases is increasingly being considered in current research. It also underlies the deployment of disease pathways at the Rat Genome Database Pathway Portal. The portal is presented with an emphasis on disease and altered pathways, associated drug pathways, pathway suites, and suite networks.Results
The Pathway Portal at the Rat Genome Database (RGD) provides an ever-increasing collection of interactive pathway diagrams and associated annotations for metabolic, signaling, regulatory, and drug pathways, including disease and altered pathways. A disease pathway is viewed from the perspective of networks whose alterations are manifested in the affected phenotype. The Pathway Ontology (PW), built and maintained at RGD, facilitates the annotations of genes, the deployment of pathway diagrams, and provides an overall navigational tool. Pathways that revolve around a common concept and are globally connected are presented within pathway suites; a suite network combines two or more pathway suites.Conclusions
The Pathway Portal is a rich resource that offers a range of pathway data and visualization, including disease pathways and related pathway suites. Viewing a disease pathway from the perspective of underlying altered pathways is an aid for dissecting the molecular mechanisms of disease.55.
Adhemar Longatto Filho Tiago Gil Oliveira Céline Pinheiro Marcos Brasilino de Carvalho Otávio Alberto Curioni Ana Maria da Cunha Mercante Fernando C Schmitt Gilka JF Gattás 《World journal of surgical oncology》2007,5(1):140
Background
Lymphatic vessels are major routes for metastasis in head and neck squamous cell carcinoma (HNSCC), but lymphatic endothelial cells (LECs) are difficult to recognize in tumor histological sections. D2-40 stains podoplanin, a molecule expressed in LECs, however, the potential prognostic usefulness of this molecule is not completely understood in HNSCC. We aimed to investigate the value of assessing peritumoral and intratumoral lymphatic vessel density (LVD) as prognostic marker for HNSCC.Methods
Thirty-one cases of HNSCC were stained for D2-40 and CD31. LVD and blood vessel density (BVD) were assessed by counting positive reactions in 10 hotspot areas at ×200 magnification.Results
D2-40 was specific for lymphatic vessels and did not stain blood vascular endothelial cells. LECs showed more tortuous and disorganized structure in intratumoral lymphatic vessels than in peritumoral ones. No statistical differences were observed between peritumoral-LVD and intratumoral-LVD or between peritumoral-BVD and intratumoral-BVD. Tumor D2-40 staining was positively associated with lymphatic vessel invasion (p = 0.011).Conclusion
LVD is a powerful marker for HNSCC prognosis. We found significant differences in peritumoral and intratumoral D2-40 immunoreactivity, which could have important implications in future therapeutic strategies and outcome evaluation.56.
Seth M Barribeau Ben M Sadd Louis du Plessis Mark JF Brown Severine D Buechel Kaat Cappelle James C Carolan Olivier Christiaens Thomas J Colgan Silvio Erler Jay Evans Sophie Helbing Elke Karaus H Michael G Lattorff Monika Marxer Ivan Meeus Kathrin N?pflin Jinzhi Niu Regula Schmid-Hempel Guy Smagghe Robert M Waterhouse Na Yu Evgeny M Zdobnov Paul Schmid-Hempel 《Genome biology》2015,16(1)
57.
S Larroudé N Massei P Reyes‐Marchant C Delattre JF Humbert 《Global Change Biology》2013,19(5):1620-1631
The impact of climate change and of other anthropogenic pressures on the structure and composition of phytoplankton communities of large European rivers remains poorly documented. Here we report the findings of a study of the changes in the phytoplankton community of the middle segment of the river Loire over the past 24 years. An attempt is made to distinguish between the impact of changes acting at the local scale and that of those acting more globally. A dramatic reduction in phytoplankton abundance was observed, particularly in the mid ‐1990s; this was concomitant with an increase in the relative proportion of cyanobacteria. At the same time, the phytoplankton community displayed increasing richness and diversity, and little change in its size structure. All these changes seem to be related to local changes, in particular to the reduction in phosphorus concentrations, as well as to changes in climate, throughout modifications in the river discharge and water temperature. Interestingly, herbicide contamination also appeared to be of particular importance in explaining the unexpected increase in the proportion of cyanobacteria in the phytoplankton community after the 1990s. These findings suggest that combinations of numerous anthropogenic pressures acting at different spatial and temporal scales have led to a mix of predictable and unpredictable changes occurring in the phytoplankton community of the river Loire, with probable consequences for the trophic networks in this river. 相似文献
58.
JP Valde LG Lawson A Lindberg JF Agger H Saloniemi O Østerås 《Acta veterinaria Scandinavica》2004,45(4):201-210
Data from the national dairy cow recording systems during 1997 were used to calculate lactation-specific cumulative risk of mastitis treatments and cumulative risk of removal from the herds in Denmark, Finland Norway and Sweden. Sweden had the lowest risk of recorded mastitis treatments during 305 days of lactation and Norway had the highest risk. The incidence risk of recorded mastitis treatments during 305 days of lactation in Denmark, Finland, Norway and Sweden was 0.177, 0.139, 0.215 and 0.127 for first parity cows and 0.228, 0.215, 0.358 and 0.204 for parities higher than three, respectively. The risk of a first parity cow being treated for mastitis was almost 3 times higher at calving in Norway than in Sweden. The period with the highest risk for mastitis treatments was from 2 days before calving until 14 days after calving and the highest risk for removal was from calving to 10 days after calving in all countries.The study clearly demonstrated differences in bovine mastitis treatment patterns among the Nordic countries. The most important findings were the differences in treatment risks during different lactations within each country, as well as differences in strategies with respect to the time during lactation mastitis was treated. 相似文献
59.
Vincens P; Buffat L; Andre C; Chevrolat JP; Boisvieux JF; Hazout S 《Bioinformatics (Oxford, England)》1998,14(8):715-725
MOTIVATION: Complete genomic sequences will become available in the future.
New methods to deal with very large sequences (sizes beyond 100 kb)
efficiently are required. One of the main aims of such work is to increase
our understanding of genome organization and evolution. This requires
studies of the locations of regions of similarity. RESULTS: We present here
a new tool, ASSIRC ('Accelerated Search for SImilarity Regions in
Chromosomes'), for finding regions of similarity in genomic sequences. The
method involves three steps: (i) identification of short exact chains of
fixed size, called 'seeds', common to both sequences, using hashing
functions; (ii) extension of these seeds into putative regions of
similarity by a 'random walk' procedure; (iii) final selection of regions
of similarity by assessing alignments of the putative sequences. We used
simulations to estimate the proportion of regions of similarity not
detected for particular region sizes, base identity proportions and seed
sizes. This approach can be tailored to the user's specifications. We
looked for regions of similarity between two yeast chromosomes (V and IX).
The efficiency of the approach was compared to those of conventional
programs BLAST and FASTA, by assessing CPU time required and the regions of
similarity found for the same data set. AVAILABILITY: Source programs are
freely available at the following address: ftp://ftp.biologie.ens.
fr/pub/molbio/assirc.tar.gz CONTACT: vincens@biologie.ens.fr,
hazout@urbb.jussieu.fr
相似文献
60.
The structure of pseudorabies virus (PRV) capsids isolated from the nucleus of infected cells and from PRV virions was determined by cryo-electron microscopy (cryo-EM) and compared to herpes simplex virus type 1 (HSV-1) capsids. PRV capsid structures closely resemble those of HSV-1, including distribution of the capsid vertex specific component (CVSC) of HSV-1, which is a heterodimer of the pUL17 and pUL25 proteins. Occupancy of CVSC on all PRV capsids is near 100%, compared to ~ 50% reported for HSV-1 C-capsids and 25% or less that we measure for HSV-1 A- and B-capsids. A PRV mutant lacking pUL25 does not produce C-capsids and lacks visible CVSC density in the cryo-EM-based reconstruction. A reconstruction of PRV capsids in which green fluorescent protein was fused within the N-terminus of pUL25 confirmed previous studies with a similar HSV-1 capsid mutant localizing pUL25 to the CVSC density region that is distal to the penton. However, comparison of the CVSC density in a 9-Å-resolution PRV C-capsid map with the available crystal structure of HSV-1 pUL25 failed to find a satisfactory fit, suggesting either a different fold for PRV pUL25 or a capsid-bound conformation for pUL25 that does not match the X-ray model determined from protein crystallized in solution. The PRV capsid imaged within virions closely resembles C-capsids with the addition of weak but significant density shrouding the pentons that we attribute to tegument proteins. Our results demonstrate significant structure conservation between the PRV and HSV capsids. 相似文献