Legion Of The Damned

Fr. Gregory tackles the difficult subject of depression and other mental health issues.

A leading manufacturer of premium hinges and door hardware, SOSS primarily sells its solutions in North American non-residential markets. 

Everything online in the industry, from white papers to webinars    

Zentra’s integrated solutions (combining software, hardware and related services) — initially offered in the United States — will secure properties while enabling hassle-free access.

Allegion’s Pure Access Cloud software provides a complete access control platform allowing for full installation, administration and management of its access control hardware.

The U.S. needs stronger policies and guidance to combat Legionnaires’ disease, a form of pneumonia caused by inhaling air contaminated with Legionella bacteria from water systems, says a new report from the National Academies of Sciences, Engineering, and Medicine.

Scalding remains a hidden danger lurking in homes across the United States, particularly impacting the vulnerable. The plumber can avoid the unintended consequences of simply lowering water temperatures.

Plumbing & Mechanical and PM Engineer Chief Editor Nicole Krawcke sits down with Legionella expert Dr. Janet Stout, PhD, to discuss best practice strategies in the plumbing industry for implementing risk assessments and Water Management Programs.

The code-writing organizations are currently finalizing the 2021 edition of the Plumbing Code, which may be adopted in your state or local jurisdiction by 2023. That is how far in advance hot subjects that are being discussed now wait before becoming law.

The West Virginia Supreme Court upheld an award of benefits for a janitor who contracted Legionnaires’ disease. Case: Scottish Rite Bodies of Charleston v. Weese, No. 22-0427, 06/10/2024, published. Facts: Thomas W. Weese worked…

https://www.lenovo.com/au/en/p/laptops/legion-laptops/legion…

Seems like a good deal on a good spec laptop. Might consider this myself, hoping there is CB coming in the next few days.

GSA is testing the water systems at 1,400 federal facilities to create a baseline and remediate any findings of Legionella and other problems.

The post Legionella bacteria in your office’s water? Don’t be alarmed first appeared on Federal News Network.

Even as they fundraise for other community organizations, some legions across Canada are having trouble keeping their own lights on amid rising inflation and maintenance costs.

This will be the first Remembrance Day celebrated at the new Royal Canadian Legion in Sault Ste. Marie. Branch 25 recently opened a new complex in the northern Ontario city, complete with a 108-unit apartment tower.

Read the in depth Review of Lenovo Legion Pro 5i 13th Gen Core i7-13700HX Laptops. Know detailed info about Lenovo Legion Pro 5i 13th Gen Core i7-13700HX configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

Read the in depth Review of Lenovo Legion Slim 5 Laptops. Know detailed info about Lenovo Legion Slim 5 configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

The American Legion Celebrates Signing of Veterans Caregivers and Families Relief Act

The latest version of the gaming laptop adds new functionalities to up the ante

Lenovo’s newly launched laptops are equipped with 12th generation Intel Core processor

The U.S. needs stronger policies and guidance to combat Legionnaires’ disease, a form of pneumonia caused by inhaling air contaminated with Legionella bacteria from water systems, says a new report from the National Academies of Sciences, Engineering, and Medicine.

Only Standalone Legionella Company to Present at Industry Show

The Hearoes Tour travels the nation to raise AWARENESS, increase ACCESS and encourage ACTION around hearing loss, the number one service-related injury affecting veterans

Fund raising by fire security company helps charities.

(United States Supreme Court) - Held that a Maryland public monument in the shape of a 32-foot tall Latin cross did not violate the Establishment Clause. A humanist group and others argued that the memorial to soldiers who died in World War I must be removed because of the crucifix shape. The U.S. Supreme Court disagreed. Justice Alito announced the judgment of the Court; however, only certain portions of his opinion received support from a majority of the justices.

A local 501st Legion member discusses his introduction to the Star Wars universe, what it takes to be a trooping member of the worldwide organization.

The transfer of a phosphate from ATP to a protein substrate, a modification known as protein phosphorylation, is catalyzed by protein kinases. Protein kinases play a crucial role in virtually every cellular activity. Recent studies of atypical protein kinases have highlighted the structural similarity of the kinase superfamily despite notable differences in primary amino acid sequence. Here, using a bioinformatics screen, we searched for putative protein kinases in the intracellular bacterial pathogen Legionella pneumophila and identified the type 4 secretion system effector Lpg2603 as a remote member of the protein kinase superfamily. Employing an array of biochemical and structural biology approaches, including in vitro kinase assays and isothermal titration calorimetry, we show that Lpg2603 is an active protein kinase with several atypical structural features. Importantly, we found that the eukaryote-specific host signaling molecule inositol hexakisphosphate (IP6) is required for Lpg2603 kinase activity. Crystal structures of Lpg2603 in the apo-form and when bound to IP6 revealed an active-site rearrangement that allows for ATP binding and catalysis. Our results on the structure and activity of Lpg2603 reveal a unique mode of regulation of a protein kinase, provide the first example of a bacterial kinase that requires IP6 for its activation, and may aid future work on the function of this effector during Legionella pathogenesis.

The transfer of a phosphate from ATP to a protein substrate, a modification known as protein phosphorylation, is catalyzed by protein kinases. Protein kinases play a crucial role in virtually every cellular activity. Recent studies of atypical protein kinases have highlighted the structural similarity of the kinase superfamily despite notable differences in primary amino acid sequence. Here, using a bioinformatics screen, we searched for putative protein kinases in the intracellular bacterial pathogen Legionella pneumophila and identified the type 4 secretion system effector Lpg2603 as a remote member of the protein kinase superfamily. Employing an array of biochemical and structural biology approaches, including in vitro kinase assays and isothermal titration calorimetry, we show that Lpg2603 is an active protein kinase with several atypical structural features. Importantly, we found that the eukaryote-specific host signaling molecule inositol hexakisphosphate (IP6) is required for Lpg2603 kinase activity. Crystal structures of Lpg2603 in the apo-form and when bound to IP6 revealed an active-site rearrangement that allows for ATP binding and catalysis. Our results on the structure and activity of Lpg2603 reveal a unique mode of regulation of a protein kinase, provide the first example of a bacterial kinase that requires IP6 for its activation, and may aid future work on the function of this effector during Legionella pathogenesis.

The transfer of a phosphate from ATP to a protein substrate, a modification known as protein phosphorylation, is catalyzed by protein kinases. Protein kinases play a crucial role in virtually every cellular activity. Recent studies of atypical protein kinases have highlighted the structural similarity of the kinase superfamily despite notable differences in primary amino acid sequence. Here, using a bioinformatics screen, we searched for putative protein kinases in the intracellular bacterial pathogen Legionella pneumophila and identified the type 4 secretion system effector Lpg2603 as a remote member of the protein kinase superfamily. Employing an array of biochemical and structural biology approaches, including in vitro kinase assays and isothermal titration calorimetry, we show that Lpg2603 is an active protein kinase with several atypical structural features. Importantly, we found that the eukaryote-specific host signaling molecule inositol hexakisphosphate (IP6) is required for Lpg2603 kinase activity. Crystal structures of Lpg2603 in the apo-form and when bound to IP6 revealed an active-site rearrangement that allows for ATP binding and catalysis. Our results on the structure and activity of Lpg2603 reveal a unique mode of regulation of a protein kinase, provide the first example of a bacterial kinase that requires IP6 for its activation, and may aid future work on the function of this effector during Legionella pathogenesis.

Michigan officials are ordering a Flint hospital to take steps to reduce the risk of exposure to Legionella bacteria and Legionnaires' disease at the facility.

ABSTRACT

Legionella pneumophila is an important cause of pneumonia. It invades alveolar macrophages and manipulates the immune response by interfering with signaling pathways and gene transcription to support its own replication. MicroRNAs (miRNAs) are critical posttranscriptional regulators of gene expression and are involved in defense against bacterial infections. Several pathogens have been shown to exploit the host miRNA machinery to their advantage. We therefore hypothesize that macrophage miRNAs exert positive or negative control over Legionella intracellular replication. We found significant regulation of 85 miRNAs in human macrophages upon L. pneumophila infection. Chromatin immunoprecipitation and sequencing revealed concordant changes of histone acetylation at the putative promoters. Interestingly, a trio of miRNAs (miR-125b, miR-221, and miR-579) was found to significantly affect intracellular L. pneumophila replication in a cooperative manner. Using proteome-analysis, we pinpointed this effect to a concerted downregulation of galectin-8 (LGALS8), DExD/H-box helicase 58 (DDX58), tumor protein P53 (TP53), and then MX dynamin-like GTPase 1 (MX1) by the three miRNAs. In summary, our results demonstrate a new miRNA-controlled immune network restricting Legionella replication in human macrophages.

IMPORTANCE Cases of Legionella pneumophila pneumonia occur worldwide, with potentially fatal outcome. When causing human disease, Legionella injects a plethora of virulence factors to reprogram macrophages to circumvent immune defense and create a replication niche. By analyzing Legionella-induced changes in miRNA expression and genomewide chromatin modifications in primary human macrophages, we identified a cell-autonomous immune network restricting Legionella growth. This network comprises three miRNAs governing expression of the cytosolic RNA receptor DDX58/RIG-I, the tumor suppressor TP53, the antibacterial effector LGALS8, and MX1, which has been described as an antiviral factor. Our findings for the first time link TP53, LGALS8, DDX58, and MX1 in one miRNA-regulated network and integrate them into a functional node in the defense against L. pneumophila.

ABSTRACT

Legionella pneumophila governs its interactions with host cells by secreting >300 different "effector" proteins. Some of these effectors contain eukaryotic domains such as the RCC1 (regulator of chromosome condensation 1) repeats promoting the activation of the small GTPase Ran. In this report, we reveal a conserved pattern of L. pneumophila RCC1 repeat genes, which are distributed in two main clusters of strains. Accordingly, strain Philadelphia-1 contains two RCC1 genes implicated in bacterial virulence, legG1 (Legionella eukaryotic gene 1), and ppgA, while strain Paris contains only one, pieG. The RCC1 repeat effectors localize to different cellular compartments and bind distinct components of the Ran GTPase cycle, including Ran modulators and the small GTPase itself, and yet they all promote the activation of Ran. The pieG gene spans the corresponding open reading frames of legG1 and a separate adjacent upstream gene, lpg1975. legG1 and lpg1975 are fused upon addition of a single nucleotide to encode a protein that adopts the binding specificity of PieG. Thus, a point mutation in pieG splits the gene, altering the effector target. These results indicate that divergent evolution of RCC1 repeat effectors defines the Ran GTPase cycle targets and that modulation of different components of the cycle might fine-tune Ran activation during Legionella infection.

IMPORTANCE Legionella pneumophila is a ubiquitous environmental bacterium which, upon inhalation, causes a life-threatening pneumonia termed Legionnaires’ disease. The opportunistic pathogen grows in amoebae and macrophages by employing a "type IV" secretion system, which secretes more than 300 different "effector" proteins into the host cell, where they subvert pivotal processes. The function of many of these effector proteins is unknown, and their evolution has not been studied. L. pneumophila RCC1 repeat effectors target the small GTPase Ran, a molecular switch implicated in different cellular processes such as nucleocytoplasmic transport and microtubule cytoskeleton dynamics. We provide evidence that one or more RCC1 repeat genes are distributed in two main clusters of L. pneumophila strains and have divergently evolved to target different components of the Ran GTPase activation cycle at different subcellular sites. Thus, L. pneumophila employs a sophisticated strategy to subvert host cell Ran GTPase during infection.

Legionella pneumophila, the etiological agent of Legionnaires’ disease, employs an arsenal of hundreds of Dot/Icm-translocated effector proteins to facilitate replication within eukaryotic phagocytes. Several effectors, called metaeffectors, function to regulate the activity of other Dot/Icm-translocated effectors during infection. The metaeffector Lpg2505 is essential for L. pneumophila intracellular replication only when its cognate effector, SidI, is present. SidI is a cytotoxic effector that interacts with the host translation factor eEF1A and potently inhibits eukaryotic protein translation by an unknown mechanism. Here, we evaluated the impact of Lpg2505 on SidI-mediated phenotypes and investigated the mechanism of SidI function. We determined that Lpg2505 binds with nanomolar affinity to SidI and suppresses SidI-mediated inhibition of protein translation. SidI binding to eEF1A and Lpg2505 is not mutually exclusive, and the proteins bind distinct regions of SidI. We also discovered that SidI possesses GDP-dependent glycosyl hydrolase activity and that this activity is regulated by Lpg2505. We have therefore renamed Lpg2505 MesI (metaeffector of SidI). This work reveals novel enzymatic activity for SidI and provides insight into how intracellular replication of L. pneumophila is regulated by a metaeffector.

Omadacycline is an aminomethylcycline antibiotic with in vitro activity against pathogens causing community-acquired bacterial pneumonia (CABP). This study investigated the activity of omadacycline against Legionella pneumophila strains isolated between 1995 and 2014 from nosocomial or community-acquired respiratory infections. Omadacycline exhibited extracellular activity similar to comparator antibiotics; intracellular penetrance was found by day 3 of omadacycline exposure. These results support the utility of omadacycline as an effective antibiotic for the treatment of CABP caused by L. pneumophila.

And more blaming the millennials, robots and boomers and kitchens are exhuasting.

A French Foreign Legion soldier was killed in combat in Mali, the Élysée presidential palace announced in a press release on Monday.

Amanda Holden has released the glittering official music video for her chart-topping charity hit Somewhere Over The Rainbow.

Britain's oldest poppy seller Walter Randall has died at the age of 104 after spending nearly 55 years selling poppies for the Royal British Legion. He was known as Wally in Leighton Buzzard.

The 38-year-old singer launched 12 one-of-a-kind products on her website, ranging from sweatshirts to wrapping paper and tree-trimming goodies.

A outdoor hot tub near a hotel in the Palmanova area of Majorca has been blamed for an outbreak of Legionnaires' disease that left one man dead and affected 19 other Brits.

Allegion India

Hurley, Kameron, author