14,299 research outputs found
Proinflammatory and Amyloidogenic S100A9 Induced by Traumatic Brain Injury in Mouse Model
No full textTraumatic 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.
No full textBACKGROUND: 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
No full textQTrim : a novel tool for the quality trimming of sequence reads generated using the Roche/454 sequencing platform
No full textBackground
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
Handwritten note by Judge Michael J. Roche
No full textNote by United States District Judge Michael J. Roche: "Filed July 2, 1943 In the above-entitled cause it appearing upon the face of the petition that petitioner is not entitled to a writ of habeas corpus, and it further appearing that she has not exhausted her administrative remedies under the provisions of Executive Order No. 9102 (7 Fed. Reg. 2165) and the regulations promulgated thereunder, IT IS THEREFORE ordered that the petition for a write of habeas corpus be, and the same is, hereby denied, dated: July 2, 1943." Note is written on the back of a document titled "Statement of Oswald Garrison Villard on Chinese Exclusion before the H. R. Committee on Immigration and Naturalization on May 20, 1943."The ACLU-Northern California case file records contain legal documents and correspondence pertaining to the case Ex parte Mitsuye Endo (1944), in which the United States Supreme court unanimously ruled that the federal government could not indefinitely detain United States citizens who were loyal to the government. Files include documents related to the Gordon Hirabayashi Supreme Court case Hirabayashi v. United States
approximatelyT. Conover and S. L. Crawford in horse and carriage on 5th Avenue between Cherry and Columbia Streets, approximately 1889
No full textCaption 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.
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Vsevolod Garshin’s Dialogue with History: Notes on Vasily Surikov’s "Boyarynya Morozova"
No full textThe author of the article analyzes a review by the Russian writer and critic Vsevolod Garshin for his perception of Vasily Surikov’s painting Boyarynya Morozova. In the eyes of Garshin Morozova, an apologist of the Old Rite, is an irrational fanatic, sacrificing her life for mere phantoms. Garshin judges Morozova’s martyrdom in a very emotional and subjective way and does not understand the cultural and historic meaning of the act. The personal nature of Garshin’s dialogue with history is emphasized in the article
E. K. Breško-Breškovskaja na gastroljach v SŠA, oktjabr’ 1904 - mart 1905 g. Die russische sozialrevolutionäre Befreiungsbewegung, transnationale Öffentlichkeit und US-Dollars
No full textHäfner 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
No full textWe 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
Vsevolod Garshin’s Dialogue with History: Notes on Vasily Surikov’s "Boyarynya Morozova"
No full textThe author of the article analyzes a review by the Russian writer and critic Vsevolod Garshin
for his perception of Vasily Surikov’s painting "Boyarynya Morozova". In the eyes of Garshin Morozova,
an apologist of the Old Rite, is an irrational fanatic, sacrificing her life for mere phantoms.
Garshin judges Morozova’s martyrdom in a very emotional and subjective way and does not understand
the cultural and historic meaning of the act. The personal nature of Garshin’s dialogue with
history is emphasized in the article
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