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151.
152.
Deanna M Church Valerie A Schneider Karyn Meltz Steinberg Michael C Schatz Aaron R Quinlan Chen-Shan Chin Paul A Kitts Bronwen Aken Gabor T Marth Michael M Hoffman Javier Herrero M Lisandra Zepeda Mendoza Richard Durbin Paul Flicek 《Genome biology》2015,16(1)
The human genome reference assembly is crucial for aligning and analyzing sequence data, and for genome annotation, among other roles. However, the models and analysis assumptions that underlie the current assembly need revising to fully represent human sequence diversity. Improved analysis tools and updated data reporting formats are also required. 相似文献
153.
Intraspecific variability in root colonization, extraradical growth pattern, and survival after cold storage of Lactarius deliciosus isolates was determined in pure culture conditions using Pinus pinaster as a host plant. The ectomycorrhizal ability of L. deliciosus at 30, 45, and 60 days from inoculation was highly variable among isolates and was negatively correlated to the age of the
culture (time elapsed from isolation). The formation of rhizomorphs was related to colonization ability, but no relationship
was found between colonization and formation of extraradical mycelium. The final colonization achieved at 60 days from inoculation
was not related to the tree species under which the sporocarps were collected. However, isolates from sporocarps collected
under P. pinaster colonized more rapidly the seedlings than those collected under other pine species. The climatic range of the sporocarps
from which the isolates were obtained (maritime vs. continental) was not related to the formation of mycorrhizas at 60 days
from inoculation. However, isolates from sporocarps collected from a maritime climate area colonized more rapidly the P. pinaster seedlings than those collected from a continental zone. Tolerance to cold water storage of L. deliciosus was also isolate dependent. Growth revival in agar was obtained from most of the isolates after 28 months of cold storage
at 4°C, but only 10 out of 29 isolates showed unaffected growth. The ITS rDNA alignment of all the L. deliciosus isolates showed a low variability with identities over 99%. Most of the variation was detected in the ITS1 region and consisted
in single nucleotide changes and/or punctual indel mutations. The number of base differences per sequence from averaging over
all sequence pairs was 1.329, which is in the low range when compared with other ectomycorrhizal species. No ITS pattern due
to geographical origin of the isolates could be discerned. 相似文献
154.
Role of astrocytes in neurovascular coupling 总被引:1,自引:0,他引:1
Neural activity is intimately tied to blood flow in the brain. This coupling is specific enough in space and time that modern imaging methods use local hemodynamics as a measure of brain activity. In this review, we discuss recent evidence indicating that neuronal activity is coupled to local blood flow changes through an intermediary, the astrocyte. We highlight unresolved issues regarding the role of astrocytes and propose ways to address them using novel techniques. Our focus is on cellular level analysis in?vivo, but we also relate mechanistic insights gained from ex?vivo experiments to native tissue. We also review some strategies to harness advances in optical and genetic methods to study neurovascular coupling in the intact brain. 相似文献
155.
Wang GZ Haile PA Daniel T Belot B Viet AQ Goodman KB Sha D Dowdell SE Varga N Hong X Chakravorty S Webb C Cornejo C Olzinski A Bernard R Evans C Emmons A Briand J Chung CW Quek R Lee D Gough PJ Sehon CA 《Bioorganic & medicinal chemistry letters》2011,21(24):7291-7294
A series of biarylsulfonamides was identified as hCCR2 receptor antagonist but suffered from high plasma protein binding resulting in a >100 fold shift in activity in a functional GTPγS assay run in tandem in the presence and absence of human serum albumin. Introduction of an aryl amide with ethylenediamine linker led to compounds with reduced shifts and improved activity in whole blood. 相似文献
156.
Schmolke M Manicassamy B Pena L Sutton T Hai R Varga ZT Hale BG Steel J Pérez DR García-Sastre A 《PLoS pathogens》2011,7(8):e1002186
Highly pathogenic avian influenza A viruses (HPAIV) of the H5N1 subtype occasionally transmit from birds to humans and can cause severe systemic infections in both hosts. PB1-F2 is an alternative translation product of the viral PB1 segment that was initially characterized as a pro-apoptotic mitochondrial viral pathogenicity factor. A full-length PB1-F2 has been present in all human influenza pandemic virus isolates of the 20(th) century, but appears to be lost evolutionarily over time as the new virus establishes itself and circulates in the human host. In contrast, the open reading frame (ORF) for PB1-F2 is exceptionally well-conserved in avian influenza virus isolates. Here we perform a comparative study to show for the first time that PB1-F2 is a pathogenicity determinant for HPAIV (A/Viet Nam/1203/2004, VN1203 (H5N1)) in both mammals and birds. In a mammalian host, the rare N66S polymorphism in PB1-F2 that was previously described to be associated with high lethality of the 1918 influenza A virus showed increased replication and virulence of a recombinant VN1203 H5N1 virus, while deletion of the entire PB1-F2 ORF had negligible effects. Interestingly, the N66S substituted virus efficiently invades the CNS and replicates in the brain of Mx+/+ mice. In ducks deletion of PB1-F2 clearly resulted in delayed onset of clinical symptoms and systemic spreading of virus, while variations at position 66 played only a minor role in pathogenesis. These data implicate PB1-F2 as an important pathogenicity factor in ducks independent of sequence variations at position 66. Our data could explain why PB1-F2 is conserved in avian influenza virus isolates and only impacts pathogenicity in mammals when containing certain amino acid motifs such as the rare N66S polymorphism. 相似文献
157.
Makarava N Kovacs GG Savtchenko R Alexeeva I Budka H Rohwer RG Baskakov IV 《PLoS pathogens》2011,7(12):e1002419
The transmissible agent of prion disease consists of a prion protein in its abnormal, β-sheet rich state (PrP(Sc)), which is capable of replicating itself according to the template-assisted mechanism. This mechanism postulates that the folding pattern of a newly recruited polypeptide chain accurately reproduces that of a PrP(Sc) template. Here we report that authentic PrP(Sc) and transmissible prion disease can be generated de novo in wild type animals by recombinant PrP (rPrP) amyloid fibrils, which are structurally different from PrP(Sc) and lack any detectable PrP(Sc) particles. When induced by rPrP fibrils, a long silent stage that involved two serial passages preceded development of the clinical disease. Once emerged, the prion disease was characterized by unique clinical, neuropathological, and biochemical features. The long silent stage to the disease was accompanied by significant transformation in neuropathological properties and biochemical features of the proteinase K-resistant PrP material (PrPres) before authentic PrP(Sc) evolved. The current work illustrates that transmissible prion diseases can be induced by PrP structures different from that of authentic PrP(Sc) and suggests that a new mechanism different from the classical templating exists. This new mechanism designated as "deformed templating" postulates that a change in the PrP folding pattern from the one present in rPrP fibrils to an alternative specific for PrP(Sc) can occur. The current work provides important new insight into the mechanisms underlying genesis of the transmissible protein states and has numerous implications for understanding the etiology of neurodegenerative diseases. 相似文献
158.
Judit Kocsis Tamás Mészáros Balázs Madaras Éva Katalin Tóth Szilárd Kamondi Péter Gál Lilian Varga Zoltán Prohászka George Füst 《Cell stress & chaperones》2011,16(1):49-55
Recently, we reported that high soluble Hsp70 (sHsp70) level was a significant predictor of mortality during an almost 3-year-long
follow-up period in patients with colorectal cancer. This association was the strongest in the group of <70-year-old female
patients as well as in those who were in a less advanced stage of the disease at baseline. According to these observations,
measurement of the serum level of sHsp70 is a useful, stage-independent prognostic marker in colorectal cancer, especially
in patients without distant metastasis. Since many literature data indicated that measurement of C-reactive protein (CRP)
and other acute phase proteins (APPs) may also be suitable for predicting the mortality of patients with colorectal cancer,
it seemed reasonable to study whether the effect of sHsp70 and other APPs are related or independent. In order to answer this
question, we measured the concentrations of CRP as well as of other complement-related APPs (C1 inhibitor, C3, and C9) along
with that of the MASP-2 complement component in the sera of 175 patients with colorectal cancer and known levels of sHsp70,
which have been used in our previous study. High (above median) levels of CRP, C1 esterase inhibitor (C1-INH), and sHsp70
were found to be independently associated with poor patient survival, whereas no such association was observed with the other
proteins tested. According to the adjusted Cox proportional hazards analysis, the additive effect of high sHsp70, CRP, and
C1-INH levels on the survival of patients exceeded that of high sHsp70 alone, with a hazard ratio (HR) of 2.83 (1.13–70.9).
In some subgroups of patients, such as in females [HR 4.80 (1.07–21.60)] or in ≤70-year-old patients [HR 11.53 (2.78–47.70)],
even greater differences were obtained. These findings indicate that the clinical mortality–prediction value of combined measurements
of sHsp70, CRP, and C1-INH with inexpensive methods can be very high, especially in specific subgroups of patients with colorectal
cancer. 相似文献
159.
160.
Taube C Tertilt C Gyülveszi G Dehzad N Kreymborg K Schneeweiss K Michel E Reuter S Renauld JC Arnold-Schild D Schild H Buhl R Becher B 《PloS one》2011,6(7):e21799
Interleukin (IL)-22 is an effector cytokine, which acts primarily on epithelial cells in the skin, gut, liver and lung. Both pro- and anti-inflammatory properties have been reported for IL-22 depending on the tissue and disease model. In a murine model of allergic airway inflammation, we found that IL-22 is predominantly produced by innate lymphoid cells in the inflamed lungs, rather than TH cells. To determine the impact of IL-22 on airway inflammation, we used allergen-sensitized IL-22-deficient mice and found that they suffer from significantly higher airway hyperreactivity upon airway challenge. IL-22-deficiency led to increased eosinophil infiltration lymphocyte invasion and production of CCL17 (TARC), IL-5 and IL-13 in the lung. Mice treated with IL-22 before antigen challenge displayed reduced expression of CCL17 and IL-13 and significant amelioration of airway constriction and inflammation. We conclude that innate IL-22 limits airway inflammation, tissue damage and clinical decline in allergic lung disease. 相似文献