Conozca todo sobre la Esclerosis Lateral Amiotrófica.

 La Federación Internacional de Asociaciones e Instituciones Bibliotecarias anunció el 21 de agosto la entrega del galardón al centro cultural español. Fran Cobo, su gestor cultural, habló sobre el premio.

La Biblioteca Gabo de Barcelona fue galardonada como la Mejor Biblioteca Pública del Mundo en 2023. Neus Castellano, su directora, comparte detalles exclusivos sobre este importante galardón.

Something Corporate played to a sold out crowd at the Concord Music Hall in Chicago on September 21st. The show was part of the Riot Fest after shows

To quote Riot Fest, "Don't cry because it's over, cry because it happened. See you next year!"

The Boogaloo Bois member fired shots at a police station.

He is being replaced by rookie Mac Jones.

Our Republican leaders don’t believe they have the authority, they don’t believe they’re legitimate, they don’t see the threat. They don’t want to see the threat because they know they can’t face the mob. They know they’re too weak. And so they offer trinkets and hope the mob will go away, but it won’t. Mobs can’t be sated. We thought Republicans understood that. That’s why we supported them. But this crisis has revealed the truth. Now we know who they are. It could not be clearer and now it’s time to find new leaders. Continue reading →

WARNING: Volume. RIP headphone users.

The threat actors behind the AndroxGh0st malware are now exploiting a broader set of security flaws impacting various internet-facing applications, while also deploying the Mozi botnet malware. "This botnet utilizes remote code execution and credential-stealing methods to maintain persistent access, leveraging unpatched vulnerabilities to infiltrate critical infrastructures," CloudSEK said in a

Several Capitol riot defendants have asked for hearings to be delayed in anticipation of pardons.

I have a close circle of clued-on/tech savvy friends whose views I take seriously. For the last few weeks, one of these friends has been sending me emails extolling the merits of something called IOTA – which calls itself as the next generation Blockchain.  At first, I thought of IOTA as yet another cryptocurrency. A [...]

Did you know that the Marines just celebrated their 249th birthday? This is one helluva tribute.

The post VETERAN’S DAY: You’re Gonna Love What One Patriotic Coffee Company Did For The Marines! appeared first on Clash Daily.

An important mechanism of resistance to β-lactam antibiotics is via their β-lactamase–catalyzed hydrolysis. Recent work has shown that, in addition to the established hydrolysis products, the reaction of the class D nucleophilic serine β-lactamases (SBLs) with carbapenems also produces β-lactones. We report studies on the factors determining β-lactone formation by class D SBLs. We show that variations in hydrophobic residues at the active site of class D SBLs (i.e. Trp105, Val120, and Leu158, using OXA-48 numbering) impact on the relative levels of β-lactones and hydrolysis products formed. Some variants, i.e. the OXA-48 V120L and OXA-23 V128L variants, catalyze increased β-lactone formation compared with the WT enzymes. The results of kinetic and product studies reveal that variations of residues other than those directly involved in catalysis, including those arising from clinically observed mutations, can alter the reaction outcome of class D SBL catalysis. NMR studies show that some class D SBL variants catalyze formation of β-lactones from all clinically relevant carbapenems regardless of the presence or absence of a 1β-methyl substituent. Analysis of reported crystal structures for carbapenem-derived acyl-enzyme complexes reveals preferred conformations for hydrolysis and β-lactone formation. The observation of increased β-lactone formation by class D SBL variants, including the clinically observed carbapenemase OXA-48 V120L, supports the proposal that class D SBL-catalyzed rearrangement of β-lactams to β-lactones is important as a resistance mechanism.

Gijs den Besten
Sep 1, 2013; 54:2325-2340
Reviews

Jason M. Ridlon
Feb 1, 2006; 47:241-259
Reviews

Erythromycin-resistance methyltransferases are SAM dependent Rossmann fold methyltransferases that convert A2058 of 23S rRNA to m6 2A2058. This modification sterically blocks binding of several classes of antibiotics to 23S rRNA, resulting in a multidrug-resistant phenotype in bacteria expressing the enzyme. ErmC is an erythromycin resistance methyltransferase found in many Gram-positive pathogens, whereas ErmE is found in the soil bacterium that biosynthesizes erythromycin. Whether ErmC and ErmE, which possess only 24% sequence identity, use similar structural elements for rRNA substrate recognition and positioning is not known. To investigate this question, we used structural data from related proteins to guide site-saturation mutagenesis of key residues and characterized selected variants by antibiotic susceptibility testing, single turnover kinetics, and RNA affinity–binding assays. We demonstrate that residues in α4, α5, and the α5-α6 linker are essential for methyltransferase function, including an aromatic residue on α4 that likely forms stacking interactions with the substrate adenosine and basic residues in α5 and the α5-α6 linker that likely mediate conformational rearrangements in the protein and cognate rRNA upon interaction. The functional studies led us to a new structural model for the ErmC or ErmE-rRNA complex.

Investigations of bacterial resistance strategies can aid in the development of new antimicrobial drugs as a countermeasure to the increasing worldwide prevalence of bacterial antibiotic resistance. One such strategy involves the TipA class of transcription factors, which constitute minimal autoregulated multidrug resistance (MDR) systems against diverse antibiotics. However, we have insufficient information regarding how antibiotic binding induces transcriptional activation to design molecules that could interfere with this process. To learn more, we determined the crystal structure of SkgA from Caulobacter crescentus as a representative TipA protein. We identified an unexpected spatial orientation and location of the antibiotic-binding TipAS effector domain in the apo state. We observed that the α6–α7 region of the TipAS domain, which is canonically responsible for forming the lid of antibiotic-binding cleft to tightly enclose the bound antibiotic, is involved in the dimeric interface and stabilized via interaction with the DNA-binding domain in the apo state. Further structural and biochemical analyses demonstrated that the unliganded TipAS domain sterically hinders promoter DNA binding but undergoes a remarkable conformational shift upon antibiotic binding to release this autoinhibition via a switch of its α6–α7 region. Hence, the promoters for MDR genes including tipA and RNA polymerases become available for transcription, enabling efficient antibiotic resistance. These insights into the molecular mechanism of activation of TipA proteins advance our understanding of TipA proteins, as well as bacterial MDR systems, and may provide important clues to block bacterial resistance.

Pectins are a major dietary nutrient source for the human gut microbiota. The prominent gut microbe Bacteroides thetaiotaomicron was recently shown to encode the founding member (BT1017) of a new family of pectin methylesterases essential for the metabolism of the complex pectin rhamnogalacturonan-II (RG-II). However, biochemical and structural knowledge of this family is lacking. Here, we showed that BT1017 is critical for the metabolism of an RG-II–derived oligosaccharide ΔBT1017oligoB generated by a BT1017 deletion mutant (ΔBT1017) during growth on carbohydrate extract from apple juice. Structural analyses of ΔBT1017oligoB using a combination of enzymatic, mass spectrometric, and NMR approaches revealed that it is a bimethylated nonaoligosaccharide (GlcA-β1,4-(2-O-Me-Xyl-α1,3)-Fuc-α1,4-(GalA-β1,3)-Rha-α1,3-Api-β1,2-(Araf-α1,3)-(GalA-α1,4)-GalA) containing components of the RG-II backbone and its side chains. We showed that the catalytic module of BT1017 adopts an α/β-hydrolase fold, consisting of a central twisted 10-stranded β-sheet sandwiched by several α-helices. This constitutes a new fold for pectin methylesterases, which are predominantly right-handed β-helical proteins. Bioinformatic analyses revealed that the family is dominated by sequences from prominent genera of the human gut microbiota, including Bacteroides and Prevotella. Our re-sults not only highlight the critical role played by this family of enzymes in pectin metabolism but also provide new insights into the molecular basis of the adaptation of B. thetaiotaomicron to the human gut.

David Durán
Nov 19, 2020; 0:RA120.002276v1-mcp.RA120.002276
Research

The Rhizobium-legume symbiosis is a beneficial interaction in which the bacterium converts atmospheric nitrogen into ammonia and delivers it to the plant in exchange for carbon compounds. This symbiosis implies the adaptation of bacteria to live inside host plant cells. In this work we apply RP-LC-MS/MS and  iTRAQ techniques to study the proteomic profile of endosymbiotic cells (bacteroids) induced by Rhizobium leguminosarum bv viciae strain UPM791 in legume nodules. Nitrogenase subunits, tricarboxylic acid cycle enzymes, and stress response proteins are amongst the most abundant from over one thousand rhizobial proteins identified in pea (Pisum sativum) bacteroids. Comparative analysis of bacteroids induced in pea and in lentil (Lens culinaris)nodules revealed the existence of a significant host-specific differential response affecting dozens of bacterial proteins, including stress-related proteins, transcriptional regulators, and proteins involved in the carbon and nitrogen metabolisms. A mutant affected in one of these proteins, homologous to a GntR-like transcriptional regulator, showed a symbiotic performance significantly  impaired in symbiosis with pea, but not with lentil plants. Analysis of the proteomes of bacteroids isolated from both hosts also revealed the presence of different sets of plant-derived nodule-specific cysteine rich (NCR) peptides, indicating that the endosymbiotic bacteria find a host-specific cocktail of chemical stressors inside the nodule. By studying variations of the bacterial response to different plant cell environments we will be able to identify specific limitations imposed by the host that might give us clues for the improvement of rhizobial performance.

Words offer a unique opportunity to separate the processing mechanisms of object subcomponents from those of the whole object, because the phonological or semantic information provided by the word subcomponents (i.e., sublexical information) can conflict with that provided by the whole word (i.e., lexical information). Previous studies have revealed some of the specific brain regions and temporal information involved in sublexical information processing. However, a comprehensive spatiotemporal neural network for sublexical processing remains to be fully elucidated due to the low temporal or spatial resolutions of previous neuroimaging studies. In this study, we recorded stereoelectroencephalography signals with high spatial and temporal resolutions from a large sample of 39 epilepsy patients (both sexes) during a Chinese character oral reading task. We explored the activated brain regions and their connectivity related to three sublexical effects: phonological regularity (whether the whole character's pronunciation aligns with its phonetic radical), phonological consistency (whether characters with the same phonetic radical share the same pronunciation), and semantic transparency (whether the whole character's meaning aligns with its semantic radical). The results revealed that sublexical effects existed in the inferior frontal gyrus, precentral and postcentral gyri, temporal lobe, and middle occipital gyrus. Additionally, connectivity from the middle occipital gyrus to the postcentral gyrus and from postcentral gyrus to the fusiform gyrus was associated with the sublexical effects. These findings provide valuable insights into the spatiotemporal dynamics of sublexical processing and object recognition in the brain.

February’s international symposium, entitled “The role of agricultural biotechnologies in sustainable food systems and nutrition”, will explore how the application of science and technology, and particularly agricultural biotechnologies, can benefit [...]

A new paper analyzes three decades of fatalities around the world and predicts how "superbugs" will affect human health in the future

Bobby Smyrniotis, shut out in five previous nominations, finally has a Coach of the Year Award to go with his four Canadian Premier League titles.

Monarch250 to bring affordable cancer treatment option to more cancer centers

Following the recent protests and riots, OM Panama's Mission Extreme group helps clean the Volcán police station.

Four of Fotress's properties were affected by floods. But the company said only minor flood damage and no significant structural damage has been identified so far.

The history of the Revolutionary War is full of heroes, men like George Washington, Marquis de Lafayette, and Nathanial Greene. Although many have been immortalized in song and verse, others have fallen into obscurity. Allen McLane is one such hero, serving as a soldier, a spy, a statesman, and more. This book, written as a […]

By a joint resolution approved by Congress on 12/18/2001, (Public Law 107-89) September 11th of each year has been designated as “Patriot Day”. This law also directs flags be lowered to half-staff on September 11th. In concurrence with this joint resolution, Governor Carney has ordered the U. S. and Delaware flags be flown at half-staff […]

By a joint resolution approved by Congress on 12/18/2001, (Public Law 107-89) September 11th of each year has been designated as “Patriot Day.” This law also directs flags be lowered to half-staff on September 11th. In concurrence with this joint resolution, Governor Carney has ordered the U. S. and Delaware flags be flown at half-staff […]

If you're not taking note of the Internet of Things, it's here, and it's making a difference, to industries and to marketers

Attorney General Kathy Jennings today announced that a coalition of 50 Attorneys General has reached a settlement with Marriott International, Inc. as the result of a multi-year data breach of one of its guest reservation databases. Under the settlement, Marriott has agreed to strengthen its data security practices using a dynamic risk-based approach, provide certain […]

IFTTT (If This Than That), a web-based software that automates and connects over 600 online services/software raised a $24M Series C led by Salesforce. Other investors include IBM and the Chamberlain Group and Fenox Venture Capital.

The latest round brings IFTTT’s funding to $63M and it will use the funding proceeds to provide integration for enterprise and IoT services and hiring. In IFTTT’s platform, applets are code/script users need to deploy to integrate two or more services (such Google Drive’s integration with Twitter/Facebook).

Investment in IFTTT reveals that Salesforce is consolidating its presence in enterprise IoT space. It also acquired Mulesoft, an integration platform that rivals Microsoft’s BizTalk.

IBM’s investment in IFTTT is also noteworthy as the former is pushing its IBM Watson IoT platform. The following statement also shows its keen interest in IFTTT.

Other recent investments in IoT companies include $30M Series B of Armis and Myriota's $15M for its IoT satellite-based connectivity platform.

For latest IoT funding and product news, please visit our IoT news section.

AstraZeneca will set up a R&D centre and an AI innovation centre in Shanghai, as well as create a $1bn fund that would invest in healthcare start-ups.

Scientific innovation, a conducive regulatory climate and increased globalisation of drug markets are driving an investment boom in biotechnology, with small companies and emerging markets shaking up the sector.

Global FDI in the biotechnology sector has witnessed year-on-year increase since 2015.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

By staying silent, these bystanders betray themselves, their communities, and democratic ideals—abandoning Amsterdam’s Israeli and Jewish guests.