Using a simple, environment friendly proteome extraction (TOP), we were able to optimize the analysis of clinical samples. Using our TOP method we analyzed a clinical cohort of microsatellite stable (MSS) and unstable (MSI-H) colorectal carcinoma (CRC). We identified a tumor cell specific, STAT1-centered, immune signature expressed by the MSI-H tumor cells. We then showed that long, but not short, exposure to Interferon- induces a similar signature in vitro. We identified 10 different temporal protein expression patterns, classifying the Interferon- protein temporal regulation in CRC. Our data sheds light on the changes that tumor cells undergo under long-term immunological pressure in vivo, the importance of STAT proteins in specific biological scenarios. The data generated could help find novel clinical biomarkers and therapeutic approaches.

The absence of the dystrophin protein in Duchenne muscular dystrophy (DMD) results in myofiber fragility and a plethora of downstream secondary pathologies. Although a variety of experimental therapies are in development, achieving effective treatments for DMD remains exceptionally challenging, not least because the pathological consequences of dystrophin loss are incompletely understood. Here we have performed proteome profiling in tibialis anterior muscles from two murine DMD models (mdx and mdx52) at three ages (8, 16, and 80 weeks of age), all n = 3. High-resolution isoelectric focusing liquid chromatography-tandem MS (HiRIEF-LC–MS/MS) was used to quantify the expression of 4974 proteins across all 27 samples. The two dystrophic models were found to be highly similar, whereas multiple proteins were differentially expressed relative to WT (C57BL/6) controls at each age. Furthermore, 1795 proteins were differentially expressed when samples were pooled across ages and dystrophic strains. These included numerous proteins associated with the extracellular matrix and muscle function that have not been reported previously. Pathway analysis revealed multiple perturbed pathways and predicted upstream regulators, which together are indicative of cross-talk between inflammatory, metabolic, and muscle growth pathways (e.g. TNF, INF, NF-B, SIRT1, AMPK, PGC-1α, PPARs, ILK, and AKT/PI3K). Upregulation of CAV3, MVP and PAK1 protein expression was validated in dystrophic muscle by Western blot. Furthermore, MVP was upregulated during, but not required for, the differentiation of C2C12 myoblasts suggesting that this protein may affect muscle regeneration. This study provides novel insights into mutation-independent proteomic signatures characteristic of the dystrophic phenotype and its progression with aging.

Colorectal cancer (CRC) arises as the consequence of progressive changes from normal epithelial cells through polyp to tumor, and thus is an useful model for studying metabolic shift. In the present study, we studied the metabolomic profiles using high analyte specific gas chromatography/mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) to attain a systems-level view of the shift in metabolism in cells progressing along the path to CRC. Colonic tissues including tumor, polyps and adjacent matched normal mucosa from 26 patients with sporadic CRC from freshly isolated resections were used for this study. The metabolic profiles were obtained using GC/MS and LC/MS/MS. Our data suggest there was a distinct profile change of a wide range of metabolites from mucosa to tumor tissues. Various amino acids and lipids in the polyps and tumors were elevated, suggesting higher energy needs for increased cellular proliferation. In contrast, significant depletion of glucose and inositol in polyps revealed that glycolysis may be critical in early tumorigenesis. In addition, the accumulation of hypoxanthine and xanthine, and the decrease of uric acid concentration, suggest that the purine biosynthesis pathway could have been substituted by the salvage pathway in CRC. Further, there was a step-wise reduction of deoxycholic acid concentration from mucosa to tumors. It appears that to gain a growth advantage, cancer cells may adopt alternate metabolic pathways in tumorigenesis and this flexibility allows them to adapt and thrive in harsh environment.

The choice for adjuvant chemotherapy in stage II colorectal cancer (CRC) is controversial as many patients are cured by surgery alone and it is difficult to identify patients with high-risk of recurrence of the disease. There is a need for better stratification of this group of patients. Mass spectrometry imaging could identify patients at risk. We report here the N-glycosylation signatures of the different cell populations in a group of stage II CRC tissue samples. The cancer cells, compared to normal epithelial cells, have increased levels of sialylation and high-mannose glycans, as well as decreased levels of fucosylation and highly branched N-glycans. When looking at the interface between cancer and its microenvironment, it seems that the cancer N-glycosylation signature spreads into the surrounding stroma at the invasive front of the tumor. This finding was more outspoken in patients with a worse outcome within this sample group.

We have previously shown that multimers of plasma pentraxin-3 (PTX3) were predictive of survival in patients with sepsis. To characterize the release kinetics and cellular source of plasma protein changes in sepsis, serial samples were obtained from healthy volunteers (n=10, 3 time-points) injected with low-dose endotoxin (LPS) and analyzed using data-independent acquisition (DIA) MS. The human plasma proteome response was compared to an LPS-induced endotoxemia model in mice. Proteomic analysis of human plasma revealed a rapid neutrophil degranulation signature, followed by a rise in acute phase proteins. Changes in circulating PTX3 correlated with increases in neutrophil-derived proteins following LPS injection. Time course analysis of the plasma proteome in mice showed a time-dependent increase in multimeric PTX3, alongside increases in neutrophil-derived myeloperoxidase (MPO) upon LPS treatment. The mechanisms of oxidation-induced multimerisation of PTX3 were explored in two genetic mouse models: MPO global knock-out mice and LysM CreNox2KO mice, in which NADPH oxidase 2 (Nox2) is only deficient in myeloid cells. Nox2 is the enzyme responsible for the oxidative burst in neutrophils. Increases in plasma multimeric PTX3 were not significantly different between wildtype and MPO or LysM CreNox2KO knock-out mice. Thus, PTX3 may already be stored and released in a multimeric form. Through in vivo neutrophil depletion and multiplexed vascular proteomics, PTX3 multimer deposition within the aorta was confirmed to be neutrophil-dependent. Proteomic analysis of aortas from LPS-injected mice returned PTX3 as the most upregulated protein, where multimeric PTX3 was deposited as early as 2 h post-LPS along with other neutrophil-derived proteins. In conclusion, the rise in multimeric PTX3 upon LPS injection correlates with neutrophil-related protein changes in plasma and in aortas. MPO and myeloid Nox2 are not required for the multimerisation of PTX3; instead, neutrophil extravasation is responsible for the LPS-induced deposition of multimeric PTX3 in the aorta.

Idaho officials asked a U.S. Supreme Court justice to block an injunction that allows a group backing an education ballot initiative to collect electronic signatures because of COVID-19.

The U.S. Supreme Court blocked an injunction that had allowed a group backing an Idaho education spending measure to collect electronic signatures because of the coronavirus pandemic.

Idaho officials asked a U.S. Supreme Court justice to block an injunction that allows a group backing an education ballot initiative to collect electronic signatures because of COVID-19.

Legislation passed by the State Senate on Tuesday is one step away from ensuring Delawareans are protected from unfair business practices by a statute as protective as the law in nearly every other state. House Bill 91, sponsored by Rep. David Bentz, D-Newark, and Sen. Trey Paradee, D-Dover, amends Delaware’s Consumer Fraud Act to explicitly add unfair practices to the list of prohibited practices. […]

Read the in depth Review of Kindle Paperwhite Signature Edition Tablets. Know detailed info about Kindle Paperwhite Signature Edition configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

Veterans are at an increased risk for prostate cancer, a disease with extraordinary clinical and molecular heterogeneity, compared with the general population. However, little is known about the underlying molecular heterogeneity within the veteran population and its impact on patient management and treatment. Using clinical and targeted tumor sequencing data from the National Veterans Affairs health system, we conducted a retrospective cohort study on 45 patients with advanced prostate cancer in the Veterans Precision Oncology Data Commons (VPODC), most of whom were metastatic castration-resistant. We characterized the mutational burden in this cohort and conducted unsupervised clustering analysis to stratify patients by molecular alterations. Veterans with prostate cancer exhibited a mutational landscape broadly similar to prior studies, including KMT2A and NOTCH1 mutations associated with neuroendocrine prostate cancer phenotype, previously reported to be enriched in veterans. We also identified several potential novel mutations in PTEN, MSH6, VHL, SMO, and ABL1. Hierarchical clustering analysis revealed two subgroups containing therapeutically targetable molecular features with novel mutational signatures distinct from those reported in the Catalogue of Somatic Mutations in Cancer database. The clustering approach presented in this study can potentially be used to clinically stratify patients based on their distinct mutational profiles and identify actionable somatic mutations for precision oncology.

Using a gene signature technique to customize chemotherapy for patients with early triple negative breast cancer may be a promising strategy to increase disease-free survival.

Coimbatore’s legendary Annapoorna Hotel can teach marketers a lesson or two

Priced at ₹78.90 lakh, ex-showroom, the tech-laden car is powered by a 2-litre diesel engine

The real estate developer is targeting collections of ₹3800 crore in the current fiscal year

Aniket Mahato, one of prominent faces of the doctors’ movement who fell ill during the hunger strike, has sought Chief Minister Mamata Banerjee’s intervention to resolve the crisis

Anomalous Payloadbased Worm Detection and Signature Generation.

The present work reports on the charge and spin density modelling of YTiO3 in its ferromagnetic state (TC = 27 K). Accurate polarized neutron diffraction and high-resolution X-ray diffraction (XRD) experiments were carried out on a single crystal at the ORPHÉE reactor (LLB) and SPRING8 synchrotron source. The experimental data are modelled by the spin resolved pseudo-atomic multipolar model (Deutsch et al., 2012). The refinement strategy is discussed and the result of this electron density modelling is compared with that from XRD measured at 100 K and with density functional theory calculations. The results show that the spin and charge densities around the Ti atom have lobes directed away from the O atoms, confirming the filling of the t2g orbitals of the Ti atom. The dxy orbital is less populated than dxz and dyz, which is a sign of a partial lift of degeneracy of the t2g orbitals. This study confirms the orbital ordering at low temperature (20 K), which is already present in the paramagnetic state above the ferromagnetic transition (100 K).

In recent research on Santa Rosa Island off the coast of Southern California, isotope readings of carbon and nitrogen found in the bones of Chumash Indians and domestic dogs excavated from archaeological sites show that both humans and dogs have nearly identical signatures of stable isotopes.

The post Ancient bond between humans and dogs revealed in isotopic signatures of their bones appeared first on Smithsonian Insider.

With a non-stop babble of hums, grunts and shrill squeals as they argue over fish and defend their territories, the Amazon’s giant otters are one […]

The post With voices joined in chorus, giant otter families create a distinct sound signature appeared first on Smithsonian Insider.

A recent study demonstrates, for the first time, a method for tracking nitrogen oxide (NOx) emissions and applies it specifically to soils. The ‘chemical fingerprinting’ method allows soil NOx to be distinguished from other sources of NOx, such as vehicles and power plants. It, therefore, paves the way for a more precise understanding of agriculture’s contribution particularly to air pollution, climate change, ecosystems and environmental damage.

The Silicon Valley tech startup and the lodging platform partner to help make vacationing in a stranger's condo a more energy-efficient affair.

New Episodes of Be Something Wonderful Radio With Tom Kearin Coming in Early 2018

eSign Genie customers now have access to expanded functionality through new integrations with the Zapier platform and the Windows Printer driver

The official Ford Licensee and one of the leading manufacturers and fragrance distributors on the global market - Palm Beach Beaute Inc. announces the launch of the new Men's Ford Mustang Fragrance.

DWF Short Hair Stylist Cares for Clients Inside and Out

It's Turtle Splash time again in Melbourne, Florida, to raise funds and awareness for individuals with disabilities.

G2Crowd's Winter 2019 Report recognizes InsureSign as the No. 1 ranked e-signature software for usability, results and customer support

The easy-to-use e-signature software is named the industry leader for usability and customer support in G2Crowd's Spring 2019 Report

eSign Genie Rolls Out Integration with G Suite for its Digital Signature Software

eSign Genie Rolls Out WordPress Plugin for its Digital Signature Software

The U.S. General Services Administration has issued an order to accept e-signatures for surety bonds to allow infrastructure projects to move forward.

Visual localization is a useful alternative to standard localization techniques. It works by utilizing cameras. In a typical scenario, features are extracted from captured images and compared with geo-referenced databases. Location information is then inferred from the matching results. Conventional schemes mainly use low-level visual features. These approaches offer good accuracy but suffer from scalability issues. In order to assist localization in large urban areas, this work explores a different path by utilizing high-level semantic information. It is found that object information in a street view can facilitate localization. A novel descriptor scheme called "semantic signature" is proposed to summarize this information. A semantic signature consists of type and angle information of visible objects at a spatial location. Several metrics and protocols are proposed for signature comparison and retrieval. They illustrate different trade-offs between accuracy and complexity. Extensive simulation results confirm the potential of the proposed scheme in large-scale applications. This paper is an extended version of a conference paper in CBMI'18. A more efficient retrieval protocol is presented with additional experiment results.

By a genome-wide gene analysis of expression profiles of known or putative gene sequences in peripheral blood and biopsy samples, the present inventors have identified a consensus set of gene expression-based molecular biomarkers for distinguishing liver transplantation patients who have Acute Rejection (AR), Hepatitis C Virus Recurrence (HCV-R), both AR/HCV-R, or Acute Dysfunction No Rejection (ADNR). These molecular biomarkers are useful for diagnosis, prognosis and monitoring of liver transplantation patients.

A method of detecting an electric arc in an electrical system from a signal originating from at least one sensor detecting acoustic waves in the system, including: a) calculating by means of a processing device, over a sliding window of signal samples, at least one statistical parameter selected from the skewness and the kurtosis of the signal; b) detecting a possible occurrence of an event by taking into account said at least one statistical parameter; and c) performing a frequency analysis of the signal enabling to identify an electric arc when an event is detected at step b).

Top-end property specialists launch in West Midlands and Warwickshire.

You can have signatures on/off on a per message base as well .. like it's off in this one ... I think ... it tries to do smart stuff with that ... showing a sig on all old posts unless it was deactivated for it on the per message base .. when the s ...

A Denver judge ordered that U.S. Senate candidate Michelle Ferrigno Warren must be placed on the June 30 primary ballot, despite falling well short of the Colorado Secretary of State's usual signature requirement.

The Los Angeles Times' accomplishments in 2016 included winning its 44th Pulitzer Prize, and attaining record growth in digital readership and subscriptions.

Zellweger, who won at the Golden Globes, Screen Actors Guild Awards and British Academy Film Awards this year, has stuck to a flattering sartorial script.

An Ontario judge has dispensed with the need for a signature on a probation order due to the risks of COVID-19.

We here at Patriot Depot have mastered the art of creating the perfect cup o' joe: no cream, no sugar, and one Donald. (You can alter the first two according to taste.)

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Whatever meager gains Trump’s trade deals represent hardly look worth the pain we endured getting here.