The Job I love how dynamic the smartphone industry is and that there's something new to learn every single day - be it with respect to business or product innovation or the waves of changes in retail and e-commerce. It always keeps you on your toes. I am definitely a bit of a geek at […]

Iberdrola SA, Spain’s largest electricity company, agreed to buy UIL Holdings Corp. in a deal valued at about $3 billion in cash and shares to create a U.S. utility with about 3.1 million customers.

AlgaEnergy SA, part-owned by Spain’s Iberdrola SA and Repsol SA, is in talks with potential partners to set up a plant in Mexico to supply the American markets with biomass made from algae.

ABSTRACT

Synthesis and cleavage of the cell wall polymer peptidoglycan (PG) are carefully orchestrated processes and are essential for the growth and survival of bacteria. Yet, the function and importance of many enzymes that act on PG in Mycobacterium tuberculosis remain to be elucidated. We demonstrate that the activity of the N-acetylmuramyl-l-alanine amidase Ami1 is dispensable for cell division in M. tuberculosis in vitro yet contributes to the bacterium’s ability to persist during chronic infection in mice. Furthermore, the d,l-endopeptidase RipA, a predicted essential enzyme, is dispensable for the viability of M. tuberculosis but required for efficient cell division in vitro and in vivo. Depletion of RipA sensitizes M. tuberculosis to rifampin and to cell envelope-targeting antibiotics. Ami1 helps sustain residual cell division in cells lacking RipA, but the partial redundancy provided by Ami1 is not sufficient during infection, as depletion of RipA prevents M. tuberculosis from replicating in macrophages and leads to dramatic killing of the bacteria in mice. Notably, RipA is essential for persistence of M. tuberculosis in mice, suggesting that cell division is required during chronic mouse infection. Despite the multiplicity of enzymes acting on PG with redundant functions, we have identified two PG hydrolases that are important for M. tuberculosis to replicate and persist in the host.

IMPORTANCE Tuberculosis (TB) is a major global heath burden, with 1.6 million people succumbing to the disease every year. The search for new drugs to improve the current chemotherapeutic regimen is crucial to reducing this global health burden. The cell wall polymer peptidoglycan (PG) has emerged as a very successful drug target in bacterial pathogens, as many currently used antibiotics target the synthesis of this macromolecule. However, the multitude of genes encoding PG-synthesizing and PG-modifying enzymes with apparent redundant functions has hindered the identification of novel drug targets in PG synthesis in Mycobacterium tuberculosis. Here, we demonstrate that two PG-cleaving enzymes are important for virulence of M. tuberculosis. In particular, the d,l-endopeptidase RipA represents a potentially attractive drug target, as its depletion results in the clearance of M. tuberculosis from the host and renders the bacteria hypersusceptible to rifampin, a frontline TB drug, and to several cell wall-targeting antibiotics.

ABSTRACT

The Escherichia coli microcin C (McC) and related compounds are potent Trojan horse peptide-nucleotide antibiotics. The peptide part facilitates transport into sensitive cells. Inside the cell, the peptide part is degraded by nonspecific peptidases releasing an aspartamide-adenylate containing a phosphoramide bond. This nonhydrolyzable compound inhibits aspartyl-tRNA synthetase. In addition to the efficient export of McC outside the producing cells, special mechanisms have evolved to avoid self-toxicity caused by the degradation of the peptide part inside the producers. Here, we report that histidine-triad (HIT) hydrolases encoded in biosynthetic clusters of some McC homologs or by standalone genes confer resistance to McC-like compounds by hydrolyzing the phosphoramide bond in toxic aspartamide-adenosine, rendering them inactive.

IMPORTANCE Uncovering the mechanisms of resistance is a required step for countering the looming antibiotic resistance crisis. In this communication, we show how universally conserved histidine-triad hydrolases provide resistance to microcin C, a potent inhibitor of bacterial protein synthesis.

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.

Dalton Buysse, Anna-Katharina Pfitzner, Matt West, Aurelien Roux, and Greg Odorizzi

The ESCRT-III protein complex executes reverse-topology membrane scission. The scission mechanism is unclear but is linked to remodeling of ESCRT-III complexes at the membrane surface. At endosomes, ESCRT-III mediates the budding of intralumenal vesicles (ILVs). In Saccharomyces cerevisiae, ESCRT-III activity at endosomes is regulated through an unknown mechanism by Doa4, an ubiquitin hydrolase that deubiquitylates transmembrane proteins sorted into ILVs. We report that the non-catalytic N-terminus of Doa4 binds Snf7, the predominant ESCRT-III subunit. Through this interaction, Doa4 overexpression alters Snf7 assembly status and inhibits ILV membrane scission. In vitro, the Doa4 N-terminus inhibits association of Snf7 with Vps2, which functions with Vps24 to arrest Snf7 polymerization and remodel Snf7 polymer structure. In vivo, Doa4 overexpression inhibits Snf7 interaction with Vps2 and also with the ATPase Vps4, which is recruited by Vps2 and Vps24 to remodel ESCRT-III complexes by catalyzing subunit turnover. Our data suggest a mechanism by which the deubiquitylation machinery regulates ILV biogenesis by interfering with ESCRT-III remodeling.

Diadenosine tetraphosphate (Ap₄A) is a dinucleotide found in both prokaryotes and eukaryotes. In bacteria, its cellular levels increase following exposure to various stress signals and stimuli, and its accumulation is generally correlated with increased sensitivity to a stressor(s), decreased pathogenicity, and enhanced antibiotic susceptibility. Ap₄A is produced as a by-product of tRNA aminoacylation, and is cleaved to ADP molecules by hydrolases of the ApaH and Nudix families and/or by specific phosphorylases. Here, considering evidence that the recombinant protein YqeK from Staphylococcus aureus copurified with ADP, and aided by thermal shift and kinetic analyses, we identified the YqeK family of proteins (COG1713) as an unprecedented class of symmetrically cleaving Ap₄A hydrolases. We validated the functional assignment by confirming the ability of YqeK to affect in vivo levels of Ap₄A in B. subtilis. YqeK shows a catalytic efficiency toward Ap₄A similar to that of the symmetrically cleaving Ap₄A hydrolases of the known ApaH family, although it displays a distinct fold that is typical of proteins of the HD domain superfamily harboring a diiron cluster. Analysis of the available 3D structures of three members of the YqeK family provided hints to the mode of substrate binding. Phylogenetic analysis revealed the occurrence of YqeK proteins in a consistent group of Gram-positive bacteria that lack ApaH enzymes. Comparative genomics highlighted that yqeK and apaH genes share a similar genomic context, where they are frequently found in operons involved in integrated responses to stress signals.

IMPORTANCE Elevation of Ap₄A level in bacteria is associated with increased sensitivity to heat and oxidative stress, reduced antibiotic tolerance, and decreased pathogenicity. ApaH is the major Ap₄A hydrolase in gamma- and betaproteobacteria and has been recently proposed as a novel target to weaken the bacterial resistance to antibiotics. Here, we identified the orphan YqeK protein family (COG1713) as a highly efficient Ap₄A hydrolase family, with members distributed in a consistent group of bacterial species that lack the ApaH enzyme. Among them are the pathogens Staphylococcus aureus, Streptococcus pneumoniae, and Mycoplasma pneumoniae. By identifying the player contributing to Ap₄A homeostasis in these bacteria, we disclose a novel target to develop innovative antibacterial strategies.

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Barcelona's women have been crowned champions of Spain's Liga Iberdrola after the season was concluded due to the coronavirus pandemic on Friday.

German drugmaker Fresenius Kabi has made major investments in its U.S. manufacturing operations in recent years with some mixed quality results along the way. Now, one of the drugmaker's products faces a recall for more manufacturing woes.

The Antitrust Division closed its investigations into Google Inc.’s acquisition of Motorola Mobility Holdings Inc., the acquisitions by Apple Inc., Microsoft Corp. and Research in Motion Ltd. (RIM) of certain Nortel Networks Corporation patents, and the acquisition by Apple of certain Novell Inc. patents.

Roland Kaufmann, CEO of Axius Inc., pleaded guilty today in Brooklyn for conspiring to bribe stock brokers.

Roland Kaufmann, CEO of Axius, Inc., was sentenced today to serve 16 months in prison for his role in a conspiracy to bribe purported stock brokers and manipulate the stock of a company he controlled.

Check out the companies making headlines after the bell.

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Ignacio Galán says energy distributor’s listing highlights president’s market-friendly policies

Motorola disappointed consumers last month when it delayed the release of its Razr, but the firm has officially announced pre-sales start Jan. 26th with purchases beginning Feb. 6th.

Motorola is telling customers who preorder the device right now that they won't receive the phone until around February 18th, which is more than 10 days after its official launch.

The German film maker, 63, known for Godzilla and The Day After Tomorrow, says he should have stopped making the 2016 movie when Will Smith dropped out midway through filming.

The Motorola Razr foldable phone is expected to be launched in India on May 8.The flagship foldable phone will be available exclusively from Flipkart.Lenovo-owned smartphone maker Motorola had launched its flagship foldable phone, the Motorola Razr in India in March this year and the device has now been listed with May 8 as the tentative release date on Flipkart. The smartphone was originally scheduled to be launched in the country on April 2. However, the launch was postponed to May 6 due to the Coronavirus pandemic and the ongoing nationwide lockdown. While the device has been listed on Flipkart, the smartphone maker has not announced when the device will go on sale. The smartphone is priced at ₹1,24,999 for the single 6GB RAM + 128GB storage variant. As part of an introductory offer, Citibank

NATHAN SALT IN PARIS: With 246 million subscribers, the pressure is on to keep quality high in their coverage with Roland Garros always at risk of no play with the roof yet to arrive.

Jo Konta's French Open semi-final has been relegated to the third arena at Roland Garros on Friday and brought forward to the morning due to a very poor weather forecast.

The King of Clay is back in familiar settings as Rafael Nadal bids to win an unprecedented 12th French Open title on Sunday afternoon.

जानें कितना खास होगा मोटोरोला का आने वाला फोन, जिसके साथ पेन भी दिया जाएगा...

दमदार बैटरी के अलावा मोटोरोला के इस फोन में कैमरा भी ज़बरदस्त है. इसमें 48 मेगापिक्सल का तीन कैमरा और सेल्फी के लिए 28 मेगापिक्सल का कैमरा है...

मोटोरोला के इस फोन में धांसू कैमरा और दमदार बैटरी समेत कई खूबियां मौजूद हैं...

मोटोरोला का इतना महंगा फोन आखिर किन फीचर्स से लैस है, आइए जानें फोन की हर डिटेल...

जियो की नई सर्विस से मोटो रेज़र यूज़र बिना किसी फिज़िकल सिम कार्ड के जियो नेटवर्क पर कॉल रिसीव, डेटा का इस्तेमाल और ऐप्लिकेशंस चला पाएंगे.

FC Barcelona Femeni topped the table by nine points ahead of Atletico Madrid and with the Liga Iberdola season unable to be completed, the Catalans have been awarded the title.

Cham : Springer, [2019]

Online Resource

Barker Library - TA357.5.M84 B68 2014

Roland Berger Strategy Consultants

Online Resource

Online Resource

Goodman, Catherine Cavallaro, author

Anglin, Roland, 1959-

DaWaK (Conference) (16th : 2014 : Munich, Germany),

Motorola is back in the flagship game with premium Edge series.

Want to know how a real pro steals our nation's seat of power? Roland Emmerich, allow us to introduce you to General Zod.

Mike Seymour sits down with "Independence Day: Resurgence" director Roland Emmerich and discusses the astonishing visual effects used in his newest picture, as well as the revolutionary new N-Cam system.

A team within Motorola has been working on a crazy plan: to let users decide how their smartphone should look, and how it should work. The result is called the Moto Z, and it’s about to hit stores.

Kjellander, Roland, author

Baulieu, Laurent, author