Remembering Rosemary Hollis (1952-2020) News Release sysadmin 12 June 2020

Professor Rosemary Hollis, a highly respected authority on the Middle East, died suddenly last week. Rosy is remembered with great respect and affection, as a colleague and a friend.

Evolving evidence suggests that nicotine may contribute to impaired asthma control by stimulating expression of nerve growth factor (NGF), a neurotrophin associated with airway remodeling and airway hyperresponsiveness. We explored the hypothesis that nicotine increases NGF by reducing lung fibroblast (LF) microRNA-98 (miR-98) and PPARγ levels, thus promoting airway remodeling. Levels of NGF, miR-98, PPARγ, fibronectin 1 (FN1), endothelin-1 (EDN1, herein referred to as ET-1), and collagen (COL1A1 and COL3A1) were measured in human LFs isolated from smoking donors, in mouse primary LFs exposed to nicotine (50 μg/ml), and in whole lung homogenates from mice chronically exposed to nicotine (100 μg/ml) in the drinking water. In selected studies, these pathways were manipulated in LFs with miR-98 inhibitor (anti-miR-98), miR-98 overexpression (miR-98 mimic), or the PPARγ agonist rosiglitazone. Compared with unexposed controls, nicotine increased NGF, FN1, ET-1, COL1A1, and COL3A1 expression in human and mouse LFs and mouse lung homogenates. In contrast, nicotine reduced miR-98 levels in LFs in vitro and in lung homogenates in vivo. Treatment with anti-miR-98 alone was sufficient to recapitulate increases in NGF, FN1, and ET-1, whereas treatment with a miR-98 mimic significantly suppressed luciferase expression in cells transfected with a luciferase reporter linked to the putative seed sequence in the NGF 3'UTR and also abrogated nicotine-induced increases in NGF, FN1, and ET-1 in LFs. Similarly, rosiglitazone increased miR-98 and reversed nicotine-induced increases in NGF, FN1, and ET-1. Taken together, these findings demonstrate that nicotine-induced increases in NGF and other markers of airway remodeling are negatively regulated by miR-98.

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.

A. I. Aptekarev and M. L. Yattselev
Trans. Moscow Math. Soc. 83 (), 251-268.
Abstract, references and article information

Simone Cecchini and Rudolf Zeidler
Trans. Amer. Math. Soc. 377 (), 5271-5288.
Abstract, references and article information

Denise Uwamariya and Xiangfeng Yang
Theor. Probability and Math. Statist. 111 (), 167-179.
Abstract, references and article information

Lutz Mattner
Theor. Probability and Math. Statist. 111 (), 45-122.
Abstract, references and article information

Bo Shan Deval, Xabier García-Martínez and Tim Van der Linden
Proc. Amer. Math. Soc. 152 (), 5039-5053.
Abstract, references and article information

Yu. L. Ershov
St. Petersburg Math. J. 35 (), 461-465.
Abstract, references and article information

Hideaki Kuge
Dec 1, 2020; 61:1747-1763
Research Articles

In SAS Life Science Analytics Framework 4.6, group membership removal fails with an exception if a user is set as assignee, a candidate, or a notification recipient in a user task for a Process Flow . The Process

The plasma membrane of neurons consists of distinct domains, each of which carries specialized functions and a characteristic set of membrane proteins. While this compartmentalized membrane organization is essential for neuronal functions, it remains controversial how neurons establish these domains on the laterally fluid membrane. Here, using immunostaining, lipid-MS analysis and gene ablation with the CRISPR/Cas9 system, we report that the pancreatic lipase-related protein 2 (PLRP2), a phospholipase A1 (PLA1), is a key organizer of membrane protein localization at the neurite tips of PC12 cells. PLRP2 produced local distribution of 1-oleoyl-2-palmitoyl-PC at these sites through acyl-chain remodeling of membrane phospholipids. The resulting lipid domain assembled the syntaxin 4 (Stx4) protein within itself by selectively interacting with the transmembrane domain of Stx4. The localized Stx4, in turn, facilitated the fusion of transport vesicles that contained the dopamine transporter with the domain of the plasma membrane, which led to the localized distribution of the transporter to that domain. These results revealed the pivotal roles of PLA1, specifically PLRP2, in the formation of functional domains in the plasma membrane of neurons. In addition, our results suggest a mode of membrane organization in which the local acyl-chain remodeling of membrane phospholipids controls the selective localization of membrane proteins by regulating both lipid-protein interactions and the fusion of transport vesicles to the lipid domain.

En France, environ 2 à 4 % de la population, souvent des femmes, est touchée par la fibromyalgie. Mais en réalité, qu’est-ce que la fibromyalgie ? Quelles sont les astuces naturelles permettant de soulager les patients qui présentent des symptômes de cette maladie ? Quels sont les symptômes de la fibromyalgie ? La fibromyalgie, ou syndrome fibromyalgique, […]

L’article Quelques remèdes de grand-mère pour soulager les symptômes de la fibromyalgie est apparu en premier sur Ortho Doc France.

As the capability of mass spectrometry-based proteomics has matured, tens of thousands of peptides can be measured simultaneously, which has the benefit of offering a systems view of protein expression. However, a major challenge is that with an increase in throughput, protein quantification estimation from the native measured peptides has become a computational task. A limitation to existing computationally-driven protein quantification methods is that most ignore protein variation, such as alternate splicing of the RNA transcript and post-translational modifications or other possible proteoforms, which will affect a significant fraction of the proteome. The consequence of this assumption is that statistical inference at the protein level, and consequently downstream analyses, such as network and pathway modeling, have only limited power for biomarker discovery. Here, we describe a Bayesian model (BP-Quant) that uses statistically derived peptides signatures to identify peptides that are outside the dominant pattern, or the existence of multiple over-expressed patterns to improve relative protein abundance estimates. It is a research-driven approach that utilizes the objectives of the experiment, defined in the context of a standard statistical hypothesis, to identify a set of peptides exhibiting similar statistical behavior relating to a protein. This approach infers that changes in relative protein abundance can be used as a surrogate for changes in function, without necessarily taking into account the effect of differential post-translational modifications, processing, or splicing in altering protein function. We verify the approach using a dilution study from mouse plasma samples and demonstrate that BP-Quant achieves similar accuracy as the current state-of-the-art methods at proteoform identification with significantly better specificity. BP-Quant is available as a MatLab ® and R packages at https://github.com/PNNL-Comp-Mass-Spec/BP-Quant.

Gender-smart Procurement: Policies for Driving Change Research paper sysadmin 14 December 2017

Governments should use public procurement policy as a strategic lever to accelerate gender-inclusive economic growth through the application of state spending power.

• Governments need to rethink public procurement policy. They need to use it as a strategic lever to accelerate gender-inclusive economic growth through the application of state spending power, while maintaining rigorous governance standards. Reform of public procurement to make it more gender-inclusive could create a ‘diversity dividend’ through increased job creation and economic growth. Gender-smart procurement policies could also mitigate economic and business risk by rendering supply chains more diverse.
• In 2014, G20 members agreed to reduce the gender gap in the labour market by 25 per cent by 2025. Procurement policy is one of the most powerful tools governments have to achieve this goal. All G20 members, regardless of the differences in their legal frameworks, can implement measures that will increase the ability of women to benefit from procurement policy.
• Public procurement accounts for around one-fifth of global gross domestic product (GDP). It is estimated that women entrepreneurs supply only 1 per cent of this market. Women’s businesses face considerable barriers to accessing procurement tenders and winning procurement contracts. The inadequate design of many procurement processes prevents more inclusive gender outcomes for citizens. Governments should redefine procurement policies to make explicit the requirement that increasing women’s workforce participation, through greater use of female suppliers, is a key objective when selecting bids for procurement contracts.
• Through the use of policy and spending levers, governments can play four primary roles in encouraging procurement from enterprises owned by women, or from businesses committed to promoting female labour participation. These roles are:
  - To direct reforms of government procurement – reviewing procurement policies and practices to ensure sustainable and inclusive procurement;
  - To reduce barriers to women’s participation in the economy – creating the support mechanisms to ensure an environment in which businesses owned by women can flourish;
  - To help scale up gender-smart procurement in the private sector – expanding government’s role in encouraging private companies to spend more of their procurement budgets with women’s businesses; and
  - To encourage increased transparency on the issues – creating and sharing procurement databases and lessons learned, especially at the regional level.
• Companies can also benefit from having more diverse supply chains and volunteering for accreditation schemes. They can start conversations with government about national regulation that encourages diversity in procurement, leading by example.
• The G20 should set measurable and time-bound targets in the area of gender-smart procurement, to build on the momentum of UN reforms and incorporate good practice in supply chain management.

DNA polymerase from bacteriophage T7 undergoes large, substrate-induced conformational changes that are thought to account for high replication fidelity, but prior studies were adversely affected by mutations required to construct a Cys-lite variant needed for site-specific fluorescence labeling. Here we have optimized the direct incorporation of a fluorescent un-natural amino acid, (7-hydroxy-4-coumarin-yl)-ethylglycine, using orthogonal amber suppression machinery in Escherichia coli. MS methods verify that the unnatural amino acid is only incorporated at one position with minimal background. We show that the single fluorophore provides a signal to detect nucleotide-induced conformational changes through equilibrium and stopped-flow kinetic measurements of correct nucleotide binding and incorporation. Pre-steady-state chemical quench methods show that the kinetics and fidelity of DNA replication catalyzed by the labeled enzyme are largely unaffected by the unnatural amino acid. These advances enable rigorous analysis to establish the kinetic and mechanistic basis for high-fidelity DNA replication.

The Supreme Court appeared skeptical that companies should be required to include past events in their risk disclosure statements during oral arguments for Facebook Inc. vs. Amalgamated Bank on Wednesday.

The U.S. Food and Drug Administration has determined commonly used oral phenylephrine is "not effective" and has proposed its removal from over-the-counter nasal decongestants.

An additional five rhesus macaque monkeys that escaped from a South Carolina research facility last week have been recovered, meaning about a dozen of the rhesus macaque primates remain at large.

Premier League reference David Coote is suspended indefinitely after videos surfaced that appeared to show him criticizing former Liverpool coach Jurgen Klopp, officials announced Monday.

The U.S. Navy began its deep-sea search this week for the remains of an MH-60S Sea Hawk helicopter and the remains of five sailors who died after the aircraft crashed into waters off the San Diego coast on Aug. 31.

Four U.S. Marines remain hospitalized after an attack near Hamid Karzai International Airport in Kabul, Afghanistan, last month as service members were evacuating foreign nationals and refugees.

Consumers thinking of dining out for their next meal may want to consider one instruction for the server -- hold the salt.

The U.S. Food and Drug Administration has determined commonly used oral phenylephrine is "not effective" and has proposed its removal from over-the-counter nasal decongestants.

An additional five rhesus macaque monkeys that escaped from a South Carolina research facility last week have been recovered, meaning about a dozen of the rhesus macaque primates remain at large.

The fate of fictional Montana Gov. John Dutton -- played by Kevin Costner -- has finally been disclosed in the Season 5B premiere of "Yellowstone" that aired on Paramount Sunday night.

The fourth film in the "Bridget Jones" British rom-com series is set to premiere in the United States on Peacock Feb. 13.

Congress is voting on a bill Tuesday that will empower the executive branch to remove the tax-exempt status from any nonprofit it deems to be supporting terrorists.

On Nov. 13, 1956, the U.S. Supreme Court upheld the federal district court's ruling in Browder v. Gayle (1956) that segregation on interstate buses was unconstitutional.

AI is shaping every aspect of our lives — but only a handful of tech giants have a say in what this technology can do. So what's going on with world governments? Bilawal Sidhu, host of "The TED AI Show," sits down with geopolitical expert Ian Bremmer to unpack the UN's just-released plan for "Governing AI for Humanity," a report that focuses on the urgent need to guide AI towards helping everyone thrive, rather than just the powerful few. Together, they explore the complexities of AI's rapid growth on a worldwide scale and take a clear-eyed look at the pivotal decisions facing us in the very near future.

The result of the 2024 US presidential election will be critical for Americans and the world. In a fascinating conversation, geopolitical expert Ian Bremmer digs into proposed policies from Kamala Harris and Donald Trump and explores how they think about everything from foreign policy to immigration and the economy. Discover unexpected similarities and crucial differences between the candidates — and get ready for what's to come. (This live conversation, recorded October 10, 2024, was hosted by TED’s Helen Walters. Visit ted.com/membership to support TED today and join more exclusive events like this one.)

In this in-depth discussion on the implications of Donald Trump’s re-election as US president, geopolitical expert Ian Bremmer explores the key issues that shaped the result — as well as the coming shifts in US foreign policy, from the Russia-Ukraine conflict to the US-China relationship and the Middle East. Learn more about the economic pressures, complex global dynamics and central personalities (including Elon Musk) that will define a second Trump presidency. (This live conversation, recorded on November 7, 2024, was hosted by TED’s Helen Walters.)

Montana's highest court has struck down a tuition tax-credit program which, as enacted by that state's legislature, allowed tuition scholarships to benefit students at private religious schools as well as secular schools.

Groups on all sides of the debate over private school choice agree that a U.S. Supreme Court ruling will be tremendously consequential. But it may take some time for the ripple effects to spread.

The U.S. Supreme Court agreed to review a decision by Montana's highest court that struck down a tuition tax-credit program allowing tuition scholarships to benefit students at private religious schools.

The justices ruled 5-4 that a Montana state constitutional provision barring aid to religion discriminated against religious schools and families seeking to benefit from a tax credit for donations for scholarships.

The 5-4 decision involving a dispute in Montana appears to cast doubt on as many as 30 state constitutions that bar aid to religious schools.

Amy Coney Barrett succeeds the late Justice Ruth Bader Ginsburg in time to hear arguments in two cases being watched in the education community.

Chief technology officers are facing an unprecedented test of digital preparedness due to the coronavirus pandemic, struggling with shortfalls of available learning devices and huge Wi-Fi access challenges.

An Ohio appellate court struck down a district's policy allowing staff members to carry concealed weapons in school with 24 hours of "active shooter/killer training."

Several states already offer a state-sanctioned LMS option to their schools, with some encouraging results in their efforts to cut costs and improve technical capabilities.