119,026 research outputs found
Proinflammatory and Amyloidogenic S100A9 Induced by Traumatic Brain Injury in Mouse Model
Traumatic brain injury (TBI) represents a significant risk factor for development of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. The S100A9-driven amyloid-neuroinflammatory cascade occurring during primary and secondary TBI events can serve as a mechanistic link between TBI and Alzheimer’s as demonstrated recently in the human brain tissues. Here by using immunohistochemistry in the controlled cortical impact TBI mouse model we have found pro-inflammatory S100A9 in the brain tissues of all mice on the first and third post-TBI days, while 70% of mice did not show any S100A9 presence on seventh post-TBI day similar to controls. This indicates that defensive mechanisms effectively cleared S100A9 in these mouse brain tissues during post-TBI recovery. By using sequential immunohistochemistry we have shown that S100A9 was produced by both neuronal and microglial cells. However, Aβ peptide deposits characteristic for Alzheimer’s disease were not detected in any post-TBI animals. On the first and third post-TBI days S100A9 was found to aggregate intracellularly into amyloid oligomers, similar to what was previously observed in human TBI tissues. Complementary, by using Rayleigh scatting, intrinsic fluorescence and atomic force microscopy we demonstrated that in vitro S100A9 self-assembles into amyloid oligomers within minutes. Its amyloid aggregation is highly dependent on changes of environmental conditions such as variation of calcium levels, pH, temperature and reduction/oxidation, which might be relevant to perturbation of cellular and tissues homeostasis under TBI. Present results demonstrate that S100A9 induction mechanisms in TBI are similar in mice and humans, emphasizing that S100A9 is an important marker of brain injury and therefore can be a potential therapeutic target
Amyloid formation by the pro-inflammatory S100A8/A9 proteins in the ageing prostate.
BACKGROUND: The conversion of soluble peptides and proteins into polymeric amyloid structures is a hallmark of many age-related degenerative disorders, including Alzheimer's disease, type II diabetes and a variety of systemic amyloidoses. We report here that amyloid formation is linked to another major age-related phenomenon--prostate tissue remodelling in middle-aged and elderly men. METHODOLOGY/PRINCIPAL FINDINGS: By using multidisciplinary analysis of corpora amylacea inclusions in prostate glands of patients diagnosed with prostate cancer we have revealed that their major components are the amyloid forms of S100A8 and S100A9 proteins associated with numerous inflammatory conditions and types of cancer. In prostate protease rich environment the amyloids are stabilized by dystrophic calcification and lateral thickening. We have demonstrated that material closely resembling CA can be produced from S100A8/A9 in vitro under native and acidic conditions and shows the characters of amyloids. This process is facilitated by calcium or zinc, both of which are abundant in ex vivo inclusions. These observations were supported by computational analysis of the S100A8/A9 calcium-dependent aggregation propensity profiles. We found DNA and proteins from Escherichia coli in CA bodies, suggesting that their formation is likely to be associated with bacterial infection. CA inclusions were also accompanied by the activation of macrophages and by an increase in the concentration of S100A8/A9 in the surrounding tissues, indicating inflammatory reactions. CONCLUSIONS/SIGNIFICANCE: These findings, taken together, suggest a link between bacterial infection, inflammation and amyloid deposition of pro-inflammatory proteins S100A8/A9 in the prostate gland, such that a self-perpetuating cycle can be triggered and may increase the risk of malignancy in the ageing prostate. The results provide strong support for the prediction that the generic ability of polypeptide chains to convert into amyloids could lead to their involvement in an increasing number of otherwise apparently unrelated diseases, particularly those associated with ageing.Original Publication:Kiran Yanamandra, Oleg Alexeyev, Vladimir Zamotin, Vaibhav Srivastava, Andrei Shchukarev, Ann-Christin Brorsson, Gian Gaetano Tartaglia, Thomas Vogl, Rakez Kayed, Gunnar Wingsle, Jan Olsson, Christopher M Dobson, Anders Bergh, Fredrik Elgh and Ludmilla A Morozova-Roche, Amyloid formation by the pro-inflammatory S100A8/A9 proteins in the ageing prostate., 2009, PloS one, (4), 5, e5562.http://dx.doi.org/10.1371/journal.pone.000556
Concanavalin A fibrils formation from Coagulation of Long-lived" Crinkled" Intermediates
QTrim : a novel tool for the quality trimming of sequence reads generated using the Roche/454 sequencing platform
Background
Many high throughput sequencing (HTS) approaches, such as the Roche/454 platform, produce sequences in which the quality of the sequence (as measured by a Phred-like quality scores) decreases linearly across a sequence read. Undertaking quality trimming of this data is essential to enable confidence in the results of subsequent downstream analysis. Here, we have developed a novel, highly sensitive and accurate approach (QTrim) for the quality trimming of sequence reads generated using the Roche/454 sequencing platform (or any platform with long reads that outputs Phred-like quality scores).
Results
The performance of QTrim was evaluated against all other available quality trimming approaches on both poor and high quality 454 sequence data. In all cases, QTrim appears to perform equally as well as the best other approach (PRINSEQ) with these two methods significantly outperforming all other methods. Further analysis of the trimmed data revealed that the novel trimming approach implemented in QTrim ensures that the prevalence of low quality bases in the resulting trimmed data is substantially lower than PRINSEQ or any of the other approaches tested.
Conclusions
QTrim is a novel, highly sensitive and accurate algorithm for the quality trimming of Roche/454 sequence reads. It is implemented both as an executable program that can be integrated with standalone sequence analysis pipelines and as a web-based application to enable individuals with little or no bioinformatics experience to quality trim their sequence data
approximatelyT. Conover and S. L. Crawford in horse and carriage on 5th Avenue between Cherry and Columbia Streets, approximately 1889
Caption on mount: La Roche & Co., Photo. 606 Second Street, Seattle, Wash.
Handwritten on verso: Mr. C.T. Conover (left) owner 5260 17th Ave. N.E., Mr. S.L. (Samuel Leroy) Crawford. Taken on 5th Ave. between Cherry and Columbia.
PH Coll 503.4To order a reproduction, inquire about permissions, or for information about prices see:
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E. K. Breško-Breškovskaja na gastroljach v SŠA, oktjabr’ 1904 - mart 1905 g. Die russische sozialrevolutionäre Befreiungsbewegung, transnationale Öffentlichkeit und US-Dollars
Häfner L. E. K. Breško-Breškovskaja na gastroljach v SŠA, oktjabr’ 1904 - mart 1905 g. Die russische sozialrevolutionäre Befreiungsbewegung, transnationale Öffentlichkeit und US-Dollars. In: Morozova AJ, Suslov AJ, eds. Žit’ istoriej i dumat’ o buduščem: Sbornik statej i materialov k 60-letiju doktora istoričeskich nauk K. N. Morozova. Moskau: bez izdatel'stva; 2021: 235-245
On the mass radiated by coalescing black hole binaries
We derive an analytic phenomenological expression that predicts the final mass of the black hole (BH) remnant resulting from the merger of a generic binary system of BHs on quasi-circular orbits. Besides recovering the correct test-particle limit for extreme mass-ratio binaries, our formula reproduces well the results of all the numerical-relativity simulations published so far, both when applied at separations of a few gravitational radii and when applied at separations of tens of thousands of gravitational radii. These validations make our formula a useful tool in a variety of contexts ranging from gravitational-wave (GW) physics to cosmology. As representative examples, we first illustrate how it can be used to decrease the phase error of the effective-one-body waveforms during the ringdown phase. Second, we show that, when combined with the recently computed self-force correction to the binding energy of nonspinning BH binaries, it provides an estimate of the energy emitted during the merger and ringdown. Finally, we use it to calculate the energy radiated in GWs by massive BH binaries as a function of redshift, using different models for the seeds of the BH population
A. Doyon, L. Liaigre, Jacques Vaucanson, Mécanicien de génie, (Préface de Bertrand Gille), 1969
Roche Daniel. A. Doyon, L. Liaigre, Jacques Vaucanson, Mécanicien de génie, (Préface de Bertrand Gille), 1969. In: Dix-huitième Siècle, n°3, 1971. pp. 413-414
Supporting Data for Salt-Dependent Structure in Methylcellulose Fibrillar Gels
Data files used to generate all figures in the manuscript "Salt-Dependent Structure in Methylcellulose Fibrillar Gels" and its supplementary information.The collection of this data was supported primarily by the National Science Foundation through University of Minnesota MRSEC under award number DMR-1420013 and DMR-2011401.Liberman, Lucy; Schmidt, Peter W; Coughlin, McKenzie L; Matatyaho Ya'akobi, Asia; Davidovich, Irina; Edmund, Jerrick; Ertem, Sedef P; Morozova, Svetlana; Talmon, Yeshayahu; Bates, Frank S; Lodge, Timothy P. (2022). Supporting Data for Salt-Dependent Structure in Methylcellulose Fibrillar Gels. Retrieved from the University Digital Conservancy, https://doi.org/10.13020/dc5t-te76
Ford Foundation Building
General side view, from southwest, depicting full view of the south façade; The Ford Foundation building is a radical departure from the usual kind of New York office tower. Roche, who was the principal designer of this building, aimed at producing an environment for the prestigious Ford Foundation in which the individual worker or visitor could identify 'with the aims and intentions of the group.' The result is, as far as I know, unique in modern building: within the confines of a twelve-storey block, a vertical conservatory shaft rises to full height and windows open on to this planted space from all floors. The two uppermost floors contain the executive offices and dining areas which, instead of being planned on an L shape, close the square of the building. p. 286 Source: Sharp, Dennis; Twentieth century architecture : a visual history, London: Lund Humphries, 1991 (0853315981) (accessed 10/9/2007
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