By Matt Solomon Published: November 11th, 2024

If you've grown a garden for a while, you may have noticed that the last few years have been brutal due to climate change-related patterns. One month it's drought and the next it's flooding. What is the best watering system for your home garden and can it help you navigate the climate ups and downs? Here are some great options with the pros and cons so you can decide the right garden irrigation system for your micro climate.[...]

A teen in Canada may be the first person to catch an H5 bird flu virus within the country. Health officials are now working to confirm the diagnosis.

Budget season is upon us, and everyone in your organization is vying for their slice of the pie. Every year, every department has a pet project that they present as absolutely essential to profitability, business continuity, and quite possibly the future of humanity itself. And no doubt that some of these actually may be mission critical. But as cybersecurity professionals, we understand that

The Canadian government on Wednesday ordered ByteDance-owned TikTok to dissolve its operations in the country, citing national security risks, but stopped short of instituting a ban on the popular video-sharing platform. "The decision was based on the information and evidence collected over the course of the review and on the advice of Canada's security and intelligence community and other

An ongoing phishing campaign is employing copyright infringement-related themes to trick victims into downloading a newer version of the Rhadamanthys information stealer since July 2024. Cybersecurity firm Check Point is tracking the large-scale campaign under the name CopyRh(ight)adamantys. Targeted regions include the United States, Europe, East Asia, and South America. "The campaign

Come one, come all! nycdevops does its first virtual meetup! All are invited!

• Speaker: Adarsh Shah
• Topic: "Continuous Delivery for Machine Learning"
• Time: Thursday, September 17, 2020, 5-630 PM
• Link: https://www.meetup.com/nycdevops/events/272914068/

Hope to see you there!

"It’s wonderful to find somebody who can show us this positive side of ourselves," Yamada says of the idea behind her new film.

The trails through our public lands weren’t designed for wheelchairs, but new wheelchairs are designed for those trails. National Park Service accessibility specialist Quinn Brett wants parks to catch up with wheelchair technology, increasing access to American wilderness.

Các hình ảnh vệ tinh mới cho thấy đảo Tri Tôn thuộc quần đảo Hoàng Sa đang trở thành một trong những căn cứ do thám chính của Trung Quốc trên Biển Đông.

Việc Trung Quốc lắp đặt hệ thống radar SIAR trên đảo Tri Tôn thuộc quần đảo Hoàng Sa tạo ra nguy cơ lớn cho Việt Nam. Đây là một mắt xích quan trọng để hoàn thiện mạng lưới phát hiện và theo dõi của Trung Quốc trên toàn bộ Biển Đông.

Engenheiros ficaram chocados ao encontrar a mensagem bem no fundo da parede de um farol no sul da Escócia.

Discussão nas redes sociais está gerando pressões para mudança nas leis trabalhista; mas empresários são contra.

By Mariane Angela Democratic New York City Mayor Eric Adams’ office announced Thursday that New York City will stop providing food vouchers to migrants, CBS News New York reported. NYC will phase out out a program that gave prepaid debit cards to migrant families in city-funded hotels to purchase their own meals and essentials, according to […]

The post NYC Mayor Eric Adams Announces End To NYC Food Vouchers For Illegal Immigrants appeared first on Liberty Unyielding.

A court challenge means the government will look again at the cap on the Disabled Facilities Grant.

I haven’t written for Powdered Wig since October 2020. This once profitable site has now been destroyed by Big Tech, especially Fascistbook, Twitter, and Google. So, at 66 years old, I find myself making a living in the construction field […]

The post Is populism dead? Are We the People now forever under the thumb of unbridled global tyranny? Madame Defarge chimes in appeared first on Powdered Wig Society.

Scotland call up Stuart Armstrong for the games against Croatia and Poland as Che Adams and Lewis Morgan withdraw from the squad.

Before Ruben Amorim takes over as Manchester United manager, Match of the Day 2's Theo Walcott explains why some of United's attacking players will need to adapt their game under their new boss.

Members of Canada women's coaching staff "objected" to flying drones over training sessions before the scandal at Paris 2024.

Shopify's surge added fuel to Canada's strong market rally, helping its benchmark index cross 25,000 for the first time.

July was a big month for model releases: There are new large models from Mistral and Meta, smaller multilingual models from Mistral and DeepL, another Mistral model that specializes in code generation, and a small version of GPT-4o. The security world saw another software supply chain disaster when CrowdStrike released a bad software update that […]

This month, we’ll give AI a rest. Alex Russell has finished an excellent series of posts titled “Reckoning.” It’s a must-read for web developers. If you want to understand why our networks and laptops are much faster than they were 15 or 20 years ago, but the web is slower, it comes down to one […]

The model release train continues, with Mistral’s multimodal Pixtral 12B, OpenAI’s o1 models, and Roblox’s model for building 3D scenes. We also have another important AI-enabled programming tool: Cursor is an alternative to GitHub Copilot that’s getting rave reviews. Security will never cease to be a problem, but this month seems particularly problematic. The Mirai […]

October had many language model releases. The mid-size models, and even the small models, are catching up to frontier models like GPT-4.5o in performance. But the release that blew us all away wasn’t a language model: It was Claude’s computer use API. Computer use allows you to teach Claude how to use a computer: how […]

Climate Change and the Pacific: Impacts and Adaptation 27 November 2018 — 8:30AM TO 10:00AM Anonymous (not verified) 14 November 2018 Royal Academy of Arts

Cancer cachexia is characterized by reductions in peripheral lean muscle mass. Prior studies have primarily focused on increased protein breakdown as the driver of cancer-associated muscle wasting. Therapeutic interventions targeting catabolic pathways have, however, largely failed to preserve muscle mass in cachexia, suggesting that other mechanisms might be involved. In pursuit of novel pathways, we used untargeted metabolomics to search for metabolite signatures that may be linked with muscle atrophy. We injected 7-week–old C57/BL6 mice with LLC1 tumor cells or vehicle. After 21 days, tumor-bearing mice exhibited reduced body and muscle mass and impaired grip strength compared with controls, which was accompanied by lower synthesis rates of mixed muscle protein and the myofibrillar and sarcoplasmic muscle fractions. Reductions in protein synthesis were accompanied by mitochondrial enlargement and reduced coupling efficiency in tumor-bearing mice. To generate mechanistic insights into impaired protein synthesis, we performed untargeted metabolomic analyses of plasma and muscle and found increased concentrations of two methylarginines, asymmetric dimethylarginine (ADMA) and NG-monomethyl-l-arginine, in tumor-bearing mice compared with control mice. Compared with healthy controls, human cancer patients were also found to have higher levels of ADMA in the skeletal muscle. Treatment of C2C12 myotubes with ADMA impaired protein synthesis and reduced mitochondrial protein quality. These results suggest that increased levels of ADMA and mitochondrial changes may contribute to impaired muscle protein synthesis in cancer cachexia and could point to novel therapeutic targets by which to mitigate cancer cachexia.

Litong Nie
Dec 1, 2020; 19:2015-2029
Research

Protein biosynthesis is fundamental to cellular life and requires the efficient functioning of the translational machinery. At the center of this machinery is the ribosome, a ribonucleoprotein complex that depends heavily on Mg2+ for structure. Recent work has indicated that other metal cations can substitute for Mg2+, raising questions about the role different metals may play in the maintenance of the ribosome under oxidative stress conditions. Here, we assess ribosomal integrity following oxidative stress both in vitro and in cells to elucidate details of the interactions between Fe2+ and the ribosome and identify Mn2+ as a factor capable of attenuating oxidant-induced Fe2+-mediated degradation of rRNA. We report that Fe2+ promotes degradation of all rRNA species of the yeast ribosome and that it is bound directly to RNA molecules. Furthermore, we demonstrate that Mn2+ competes with Fe2+ for rRNA-binding sites and that protection of ribosomes from Fe2+-mediated rRNA hydrolysis correlates with the restoration of cell viability. Our data, therefore, suggest a relationship between these two transition metals in controlling ribosome stability under oxidative stress.

You encounter this issue when the table metadata matches the data source. In this scenario, no metadata update is required.

You might receive a Segmentation Violation when opening a database table in SAS. The SAS Log contains the error and traceback:

When you publish a model to SAS Metadata Repository by using SAS Model Manager, the publishing process fails and the following error is generated: "The model model-name has a function of ';Transformation';, which is not supported for

Insulin receptor substrate 2 (IRS2) is an essential adaptor that mediates signaling downstream of the insulin receptor and other receptor tyrosine kinases. Transduction through IRS2-dependent pathways is important for coordinating metabolic homeostasis, and dysregulation of IRS2 causes systemic insulin signaling defects. Despite the importance of maintaining proper IRS2 abundance, little is known about what factors mediate its protein stability. We conducted an unbiased proteomic screen to uncover novel substrates of the Anaphase Promoting Complex/Cyclosome (APC/C), a ubiquitin ligase that controls the abundance of key cell cycle regulators. We found that IRS2 levels are regulated by APC/C activity and that IRS2 is a direct APC/C target in G₁. Consistent with the APC/C's role in degrading cell cycle regulators, quantitative proteomic analysis of IRS2-null cells revealed a deficiency in proteins involved in cell cycle progression. We further show that cells lacking IRS2 display a weakened spindle assembly checkpoint in cells treated with microtubule inhibitors. Together, these findings reveal a new pathway for IRS2 turnover and indicate that IRS2 is a component of the cell cycle control system in addition to acting as an essential metabolic regulator.

Studies in the yeast Saccharomyces cerevisiae have helped define mechanisms underlying the activity of the ubiquitin–proteasome system (UPS), uncover the proteasome assembly pathway, and link the UPS to the maintenance of cellular homeostasis. However, the spectrum of UPS substrates is incompletely defined, even though multiple techniques—including MS—have been used. Therefore, we developed a substrate trapping proteomics workflow to identify previously unknown UPS substrates. We first generated a yeast strain with an epitope tagged proteasome subunit to which a proteasome inhibitor could be applied. Parallel experiments utilized inhibitor insensitive strains or strains lacking the tagged subunit. After affinity isolation, enriched proteins were resolved, in-gel digested, and analyzed by high resolution liquid chromatography-tandem MS. A total of 149 proteasome partners were identified, including all 33 proteasome subunits. When we next compared data between inhibitor sensitive and resistant cells, 27 proteasome partners were significantly enriched. Among these proteins were known UPS substrates and proteins that escort ubiquitinated substrates to the proteasome. We also detected Erg25 as a high-confidence partner. Erg25 is a methyl oxidase that converts dimethylzymosterol to zymosterol, a precursor of the plasma membrane sterol, ergosterol. Because Erg25 is a resident of the endoplasmic reticulum (ER) and had not previously been directly characterized as a UPS substrate, we asked whether Erg25 is a target of the ER associated degradation (ERAD) pathway, which most commonly mediates proteasome-dependent destruction of aberrant proteins. As anticipated, Erg25 was ubiquitinated and associated with stalled proteasomes. Further, Erg25 degradation depended on ERAD-associated ubiquitin ligases and was regulated by sterol synthesis. These data expand the cohort of lipid biosynthetic enzymes targeted for ERAD, highlight the role of the UPS in maintaining ER function, and provide a novel tool to uncover other UPS substrates via manipulations of our engineered strain.

Specific E3 ligases target tumor suppressors for degradation. Inhibition of such E3 ligases may be an important approach to cancer treatment. RNF146 is a RING domain and PARylation-dependent E3 ligase that functions as an activator of the β-catenin/Wnt and YAP/Hippo pathways by targeting the degradation of several tumor suppressors. Tankyrases 1 and 2 (TNKS1/2) are the only known poly-ADP-ribosyltransferases that require RNF146 to degrade their substrates. However, systematic identification of RNF146 substrates have not yet been performed. To uncover substrates of RNF146 that are targeted for degradation, we generated RNF146 knockout cells and TNKS1/2-double knockout cells and performed proteome profiling with label-free quantification as well as transcriptome analysis. We identified 160 potential substrates of RNF146, which included many known substrates of RNF146 and TNKS1/2 and 122 potential TNKS-independent substrates of RNF146. In addition, we validated OTU domain-containing protein 5 and Protein mono-ADP-ribosyltransferase PARP10 as TNKS1/2-independent substrates of RNF146 and SARDH as a novel substrate of TNKS1/2 and RNF146. Our study is the first proteome-wide analysis of potential RNF146 substrates. Together, these findings not only demonstrate that proteome profiling can be a useful general approach for the systemic identification of substrates of E3 ligases but also reveal new substrates of RNF146, which provides a resource for further functional studies.

Paramphistomosis, caused by the rumen fluke, Calicophoron daubneyi, is a parasitic infection of ruminant livestock which has seen a rapid rise in prevalence throughout Western Europe in recent years. Following ingestion of metacercariae (parasite cysts) by the mammalian host, newly-excysted juveniles (NEJs) emerge and invade the duodenal submucosa which causes significant pathology in heavy infections. The immature larvae then migrate upwards, along the gastrointestinal tract, and enter the rumen where they mature and begin to produce eggs. Despite their emergence, and sporadic outbreaks of acute disease, we know little about the molecular mechanisms used by C. daubneyi to establish infection, acquire nutrients and to avoid the host immune response. Here, transcriptome analysis of four intra-mammalian life-cycle stages, integrated with secretome analysis of the NEJ and adult parasites (responsible for acute and chronic disease respectively), revealed how the expression and secretion of selected families of virulence factors and immunomodulators are regulated in accordance with fluke development and migration. Our data show that whilst a family of cathepsins B with varying S2 sub-site residues (indicating distinct substrate specificities) are differentially secreted by NEJs and adult flukes, cathepsins L and F are secreted in low abundance by NEJs only. We found that C. daubneyi has an expanded family of aspartic peptidases, which is up-regulated in adult worms, although they are underrepresented in the secretome. The most abundant proteins in adult fluke secretions were helminth defence molecules (HDMs) that likely establish an immune environment permissive to fluke survival and/or neutralise pathogen-associated molecular patterns (PAMPs) such as bacterial lipopolysaccharide in the microbiome-rich rumen. The distinct collection of molecules secreted by C. daubneyi allowed the development of the first coproantigen-based ELISA for paramphistomosis which, importantly, did not recognise antigens from other helminths commonly found as co-infections with rumen fluke.

Business Development in Madagascar: How to Enable Entrepreneurialism 15 November 2017 — 12:00PM TO 1:00PM Anonymous (not verified) 9 November 2017 Chatham House, London

Canada ordered striking dock workers back to the ports of Vancouver, Prince Rupert and Montreal on Tuesday to clear out more than a week of container congestion bound for the United States and Canada.

Building an integrated workload-driven system with optimized performance is a resource-intensive and time-consuming effort. The QCT Platform on Demand (QCT POD) offers an on-premises HPC/AI converged system, featuring best-practice hardware […]

The post QCT POD- An Adaptive Converged Platform for HPC and AI appeared first on HPCwire.

Canada ordered striking dock workers back to the ports of Vancouver, Prince Rupert and Montreal on Tuesday to clear out more than a week of container congestion bound for the United States and Canada.

What will the world look like in 2030? International business consultant Nikolaus S. Lang predicts the evolution of a multipolar world, with multiple emerging coalitions of countries acting in new ways to achieve their economic, technological and military goals. He dives into what this will mean for the global economy, offering five tips for business leaders to prepare for the coming geopolitical landscape.

A six-time world yo-yo champion, Shu Takada is spinning his dreams into reality. Watch how he turns a humble pastime into a mesmerizing art form, blending yo-yo wizardry with dance and acrobatics.

The state requested a waiver from the federal requirement in January. Failure to meet the 95-percent requirement can lead to funding penalties for states.

In addition to a delay, Wisconsin had to eliminate certain questions from its Smarter Balanced exam, after opting not to use the adaptive testing feature of the test.

Student Achievement (NAEP 2003)

State of the States: Education highlights from latest governor's address before the legislature.