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.

En fonction de leurs causes, les douleurs du côté droit peuvent se manifester de différentes manières. Les symptômes de ces douleurs peuvent également varier d’une personne à une autre. Certaines personnes décrivent les douleurs du côté comme des sensations de crampes, de brûlures ou de piqûres. D’autres en revanche parlent de douleurs sourdes ou lancinantes qui irradient […]

L’article Douleurs côté droit sous les côtes : comment les soulager naturellement est apparu en premier sur Ortho Doc France.

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.

In a universe not unlike ours, a tech-environmentalist group claims to have created an AI that is the direct “voice of the earth,” a computer connected via electrodes to the mycelium network under an ancient forest named S.A.N (Sentient Advocate of Nature). The film imagines what nature thinks of human impact on the planet, as a renowned reporter conducts a world-first interview with S.A.N.

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.

Sometimes, in fact, nature is stranger than fiction

More on biomimicry: http://j.mp/RI3OOB Scientists believe the iridescent wings of the morphos butterfly could be used in technology to benefit humans.

An increasing number of people in France espouse a clothing-free lifestyle

Quebec provincial police have confirmed that the body found in a Montreal nature park on Oct. 30 was that of kidnapping victim and cryptocurrency influencer Kevin Mirshahi.

Roughly 30 percent of Catalonia is protected land making it a stunning place to hit the trails

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 science major in the Penn State Eberly College of Science has been renamed integrative science as part of a modern refresh to reflect its interdisciplinary nature.

Outdoor exploration allows children to have fun while making sense of the world around them and developing their critical-thinking skills.

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. […]

It is definitely in the fitness of things that the Supreme Court in a most learned, laudable, landmark, logical and latest judgment titled Ramji Lal Bairwa & Anr vs State of Rajasthan & Ors in Criminal Appeal No. 3403 of 2023 (@ SLP (Crl.) No. 12912 of 2022) and cited in Neutral Citation No.: 2024 I

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.

Susana Muhamad is Minister of Environment and Sustainable Development of Colombia and President of the 2024 UN Biodiversity Conference, and Kaveh Zahedi is Director of FAO Office of Climate Change, Biodiversity and Environment

Extreme heat is an invisible but increasingly tangible climate risk. It varies by time and place and has wide-reaching but unequal impacts, particularly to women and vulnerable people. As global temperatures rise, extreme heat events (heat waves) are becoming more frequent and severe.

This brochure outlines how nature is being rapidly degraded and shows how ADB-designed nature-based solutions (NBS) can help protect vulnerable communities and ecosystems to make countries in Asia and the Pacific more climate resilient.

Lush and vibrant cinematography plus a "cast" of real animals make Heart of an Oak an enthralling celebration of the natural world

High-speed camera recordings show that springtails spin at up to 368 rotations per second when they jump away from danger

Musing on John Lewis-Stempel's latest book, England: A natural history, James McConnachie marks the flowering of other, more diverse voices in nature writing

Shortlisted for the Close-up Photographer of the Year contest, these images zoom in on animals in all their glory

Simple words like "force" and "particle" can mislead us as to what reality is actually like. Physicist Matt Strassler unpacks how to see things more clearly

Claudia de Rham has spent much of her life dedicated to unravelling the true nature of gravity, thinking deeply about gravitons, the hypothetical carrier of this enigmatic force

Simple words like "force" and "particle" can mislead us as to what reality is actually like. Physicist Matt Strassler unpacks how to see things more clearly

Although the COP16 summit in Colombia ended with some important agreements, countries still aren’t moving fast enough to stem biodiversity loss

Shortlisted for the Close-up Photographer of the Year contest, these images zoom in on animals in all their glory

Title: Getting Kids Out in Nature Boosts Lung Health, Study Finds
Category: Health News
Created: 7/27/2022 12:00:00 AM
Last Editorial Review: 7/27/2022 12:00:00 AM

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.

Aug 15, 2023

As a Predoctoral Research Fellow at the Belfer Center’s Environment and Natural Resources Program and Science, Technology, and Public Policy Program, Lydia Zemke has spent the last two years studying climate finance in developing countries. As she rounds out her time at the Belfer Center, Zemke she reflects on her research interests, her experience conducting fieldwork in Kenya and Costa Rica, and her advice for other early-career researchers. 

Alam-Pedja looduskaitseala, Alam-Pedja Nature Reserve, Estonia.

While trying to generate XML in java utility in ITR 3, I am getting an error of "Please specify the nature". Please help in solving it. While clicking on error it redirect to schedule BP. I have already selected code under the nature of business. Pls Help

Once again, we take a look at the traditional "if (boolean) return true; else return false;" pattern. But today's, from RJ, offers us a bonus twist.

public override bool IsValid
{
   get
   {
      if (!base.IsValid)
         return false;

      return true;
   }
}

As promised, this is a useless conditional. return base.IsValid would do the job just as well. Except, that's the twist, isn't it. base is our superclass. We're overriding a method on our superclass to… just do what the base method does.

This entire function could just be deleted. No one would notice. And yet, it hasn't been. Everyone agrees that it should be, yet it hasn't been. No one's doing it. It just sits there, like a pimple, begging to be popped.

Although the COP16 summit in Colombia ended with some important agreements, countries still aren’t moving fast enough to stem biodiversity loss

Thanks to Sivakumar ji for the ID

Left me pondering

Nelliyampathy Forest, Kerala, Oct., 2024

The flowers of the snakeweed plant are popular with many butterflies, including the

please id this insect. it was as small as a grain

Rusty marsh dart (Ceriagrion olivaceum) (Female here) is a species of damselfly found in south and southeast Asia. Two subspecies are mentioned. Ceriagrion olivaceum olivaceum and Ceriagrion olivaceum aurantiacum.C. o. olivaceum is widespread in India and Southeast Asia and probably the one here C. o. aurantiacum is only known from southwest India. It is a medium-sized damselfly with olivaceous brown capped greenish eyes. Its thorax is olive green, paler on the sides. Female is similar to the male. Male @ http://www.indianaturewatch.net/displayimage.php?id=663008