Lipid rafts, solid regions of the plasma membrane enriched in cholesterol and glycosphingolipids, are essential parts of a cell. Functionally, lipid rafts present a platform that facilitates interaction of cells with the outside world. However, the unique properties of lipid rafts required to fulfill this function at the same time make them susceptible to exploitation by pathogens. Many steps of pathogen interaction with host cells, and sometimes all steps within the entire lifecycle of various pathogens, rely on host lipid rafts. Such steps as binding of pathogens to the host cells, invasion of intracellular parasites into the cell, the intracellular dwelling of parasites, microbial assembly and exit from the host cell, and microbe transfer from one cell to another all involve lipid rafts. Interaction also includes modification of lipid rafts in host cells, inflicted by pathogens from both inside and outside the cell, through contact or remotely, to advance pathogen replication, to utilize cellular resources, and/or to mitigate immune response. Here, we provide a systematic overview of how and why pathogens interact with and exploit host lipid rafts, as well as the consequences of this interaction for the host, locally and systemically, and for the microbe. We also raise the possibility of modulation of lipid rafts as a therapeutic approach against a variety of infectious agents.

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Cytochrome c oxidase (CcO) reduces O2 to water, coupled with a proton-pumping process. The structure of the O2-reduction site of CcO contains two reducing equivalents, Fea32+ and CuB1+, and suggests that a peroxide-bound state (Fea33+–O−–O−–CuB2+) rather than an O2-bound state (Fea32+–O2) is the initial catalytic intermediate. Unexpectedly, however, resonance Raman spectroscopy results have shown that the initial intermediate is Fea32+–O2, whereas Fea33+–O−–O−–CuB2+ is undetectable. Based on X-ray structures of static noncatalytic CcO forms and mutation analyses for bovine CcO, a proton-pumping mechanism has been proposed. It involves a proton-conducting pathway (the H-pathway) comprising a tandem hydrogen-bond network and a water channel located between the N- and P-side surfaces. However, a system for unidirectional proton-transport has not been experimentally identified. Here, an essentially identical X-ray structure for the two catalytic intermediates (P and F) of bovine CcO was determined at 1.8 Å resolution. A 1.70 Å Fe–O distance of the ferryl center could best be described as Fea34+ = O2−, not as Fea34+–OH−. The distance suggests an ∼800-cm−1 Raman stretching band. We found an interstitial water molecule that could trigger a rapid proton-coupled electron transfer from tyrosine-OH to the slowly forming Fea33+–O−–O−–CuB2+ state, preventing its detection, consistent with the unexpected Raman results. The H-pathway structures of both intermediates indicated that during proton-pumping from the hydrogen-bond network to the P-side, a transmembrane helix closes the water channel connecting the N-side with the hydrogen-bond network, facilitating unidirectional proton-pumping during the P-to-F transition.

pncRNA-D is an irradiation-induced 602-nt long noncoding RNA transcribed from the promoter region of the cyclin D1 (CCND1) gene. CCND1 expression is predicted to be inhibited through an interplay between pncRNA-D and RNA-binding protein TLS/FUS. Because the pncRNA-D–TLS interaction is essential for pncRNA-D–stimulated CCND1 inhibition, here we studied the possible role of RNA modification in this interaction in HeLa cells. We found that osmotic stress induces pncRNA-D by recruiting RNA polymerase II to its promoter. pncRNA-D was highly m6A-methylated in control cells, but osmotic stress reduced the methylation and also arginine methylation of TLS in the nucleus. Knockdown of the m6A modification enzyme methyltransferase-like 3 (METTL3) prolonged the half-life of pncRNA-D, and among the known m6A recognition proteins, YTH domain-containing 1 (YTHDC1) was responsible for binding m6A of pncRNA-D. Knockdown of METTL3 or YTHDC1 also enhanced the interaction of pncRNA-D with TLS, and results from RNA pulldown assays implicated YTHDC1 in the inhibitory effect on the TLS–pncRNA-D interaction. CRISPR/Cas9-mediated deletion of candidate m6A site decreased the m6A level in pncRNA-D and altered its interaction with the RNA-binding proteins. Of note, a reduction in the m6A modification arrested the cell cycle at the G0/G1 phase, and pncRNA-D knockdown partially reversed this arrest. Moreover, pncRNA-D induction in HeLa cells significantly suppressed cell growth. Collectively, these findings suggest that m6A modification of the long noncoding RNA pncRNA-D plays a role in the regulation of CCND1 gene expression and cell cycle progression.

tRNAs universally carry a CCA nucleotide triplet at their 3'-ends. In eukaryotes, the CCA is added post-transcriptionally by the CCA-adding enzyme (CAE). The mitochondrion of the parasitic protozoan Trypanosoma brucei lacks tRNA genes and therefore imports all of its tRNAs from the cytosol. This has generated interest in the tRNA modifications and their distribution in this organism, including how CCA is added to tRNAs. Here, using a BLAST search for genes encoding putative CAE proteins in T. brucei, we identified a single ORF, Tb927.9.8780, as a potential candidate. Knockdown of this putative protein, termed TbCAE, resulted in the accumulation of truncated tRNAs, abolished translation, and inhibited both total and mitochondrial CCA-adding activities, indicating that TbCAE is located both in the cytosol and mitochondrion. However, mitochondrially localized tRNAs were much less affected by the TbCAE ablation than the other tRNAs. Complementation assays revealed that the N-terminal 10 amino acids of TbCAE are dispensable for its activity and mitochondrial localization and that deletion of 10 further amino acids abolishes both. A growth arrest caused by the TbCAE knockdown was rescued by the expression of the cytosolic isoform of yeast CAE, even though it was not imported into mitochondria. This finding indicated that the yeast enzyme complements the essential function of TbCAE by adding CCA to the primary tRNA transcripts. Of note, ablation of the mitochondrial TbCAE activity, which likely has a repair function, only marginally affected growth.

The arrangement of functionally-related genes in operons is a fundamental element of how genetic information is organized in prokaryotes. This organization ensures coordinated gene expression by co-transcription. Often, however, alternative genetic responses to specific stress conditions demand the discoordination of operon expression. During cold temperature stress, accumulation of the gene encoding the sole Asp–Glu–Ala–Asp (DEAD)-box RNA helicase in Synechocystis sp. PCC 6803, crhR (slr0083), increases 15-fold. Here, we show that crhR is expressed from a dicistronic operon with the methylthiotransferase rimO/miaB (slr0082) gene, followed by rapid processing of the operon transcript into two monocistronic mRNAs. This cleavage event is required for and results in destabilization of the rimO transcript. Results from secondary structure modeling and analysis of RNase E cleavage of the rimO–crhR transcript in vitro suggested that CrhR plays a role in enhancing the rate of the processing in an auto-regulatory manner. Moreover, two putative small RNAs are generated from additional processing, degradation, or both of the rimO transcript. These results suggest a role for the bacterial RNA helicase CrhR in RNase E-dependent mRNA processing in Synechocystis and expand the known range of organisms possessing small RNAs derived from processing of mRNA transcripts.

V. V. Vlasov and N. A. Rautian
Trans. Moscow Math. Soc. 80 (2020), 169-188.
Abstract, references and article information

K. A. Mirzoev and T. A. Safonova
Trans. Moscow Math. Soc. 80 (2020), 133-151.
Abstract, references and article information

Trans. Moscow Math. Soc. 80 (2020), 113-122.
Abstract, references and article information

S. A. Nazarov
Trans. Moscow Math. Soc. 80 (2020), 1-51.
Abstract, references and article information

O que é Candidíase? Candidíase, é uma infecção sistêmica causada pelo fungos da Candida albicans. A Candida albicans é um tipo de fungo (levedura) que vive em harmonia no organismo,…

The post Candidíase – Conheça as causas, sintomas e tratamentos appeared first on Saúde Próspera.

A. Knightly and C. Li
Memoirs of the AMS 224 (2012).
Abstract, references and article information

Publication Date: Apr 10 2020 The SEC will withdraw the existing approval order and the fund will become subject to the requirements of Rule 6c-11 and Nasdaq Rule 5704....

Publication Date: Apr 10 2020 Yes. According to the SEC, once an ETF becomes eligible to operate under Rule 6c-11 and elects to list on Nasdaq under Nasdaq Rule 5704, the existing order related to that fund (and all other funds under that exemptive order) will be rescinded. Once a fund is listed under Nasdaq Rule 5704, it will not be able to relist under Nasdaq Rule 5705(b) (Index Fund Shares) or Nasdaq Rule 5735 (Managed Fund Shares) unless a new exemptive relief order is obtained from the SEC....

Publication Date: Apr 10 2020 Funds listed under Nasdaq Rule 5704 are required to submit an annual certification regarding the funds compliance with Rule 6c-11 during the most recent fiscal year. The certification is required within 30 calendar days of a fund’s fiscal year end. The certification can be found here....

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1 November 2019

The 'Security and Prosperity in Asia' conference looked at the impact of international law in the Asia-Pacific with a focus on regional economic and security issues such as the South China Sea disputes.

Invitation Only Research Event

6 November 2019 , Volume 95, Number 6

Members Event

Event participants

Dr Mukulika Banerjee, Associate Professor; Director, South Asia Centre, LSE

Kapil Komireddi, Author, Malevolent Republic: A Short History of the New India

Deepa Kumar, Lead India Analyst, Country Risk, IHS Markit

Chair: Dr Gareth Price, Senior Research Fellow, Asia-Pacific Programme, Chatham House

8 January 2020 , Volume 96, Number 1

8 January 2020 , Volume 96, Number 1

8 January 2020 , Volume 96, Number 1

8 January 2020 , Volume 96, Number 1

8 January 2020 , Volume 96, Number 1

8 January 2020 , Volume 96, Number 1

6 November 2019 , Volume 96, Number 1

The first issue of International Affairs in 2020 explores the geopolitics of the 'Indo-Pacific' region.

Research Event

Corporate Members Event

Event participants

Dr Yu Jie, Senior Research Fellow on China, Asia-Pacific Programme, Chatham House
David Lubin, Associate Fellow, Global Economy and Finance Programme, Chatham House; Managing Director and Head of Emerging Markets Economics, Citi
Jinny Yan, Managing Director and Chief China Economist, ICBC Standard
Chair: Creon Butler, Director, Global Economy and Finance Programme, Chatham House

Research Event

Event participants

K. Anis Ahmed, Publisher, Dhaka Tribune and Bangla Tribune; Author of Good Night, Mr. Kissinger, Co-director, Dhaka Literary Festival
Meenakshi Ganguly, South Asia Director, Human Rights Watch
Chair: Ed Cumming, Writer, The Independent

24 March 2020

China’s Belt and Road Initiative (BRI) is having profound impacts on recipient countries. This paper examines the benefits and costs of the BRI and its projects to Sri Lanka and the lessons that may improve future BRI projects in Sri Lanka and elsewhere.

Invitation Only Research Event

Event participants

Dr Kurt Campbell, Chairman, CEO and Co-Founder, The Asia Group; Assistant Secretary of State for East Asian and Pacific Affairs, 2009-13
Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme, Chatham House

9 April 2020

Research Event

Event participants

Yu Jie, Senior Research Fellow on China, Asia-Pacific Programme, Chatham House
Kerry Brown, Associate Fellow, Asia-Pacific Programme, Chatham House; Professor of Chinese Studies and Director of Lau China Institute, King’s College London

Origami paper-folding may not seem like a subject for mathematical investigation or one with sophisticated applications, yet anyone who has tried to fold a road map or wrap a present knows that origami is no trivial matter. Mathematicians, computer scientists, and engineers have recently discovered that this centuries-old subject can be used to solve many modern problems.The methods of origami are now used to fold objects such as automobile air bags and huge space telescopes efficiently, and may be related to how proteins fold. Manufacturers often want to make a product out of a single piece of material. The manufacturing problem then becomes one of deciding whether a shape can be folded and if so, is there an efficient way to find a good fold? Thus, many origami research problems have to do with algorithm complexity and optimization theory. A testament to the diversity of origami, as well as the power of mathematics, is its applicability to problems at the molecular level, in manufacturing, and in outer space. For More Information: http://db.uwaterloo.ca/~eddemain/papers/MapFolding/

Experts are adept at answering questions in their fields, but even the most knowledgeable authority can.t be expected to keep up with all the data generated today. Computers can handle data, but until now, they were inept at understanding questions posed in conversational language. Watson, the IBM computer that won the Jeopardy! Challenge, is an example of a computer that can answer questions using informal, nuanced, even pun-filled, phrases. Graph theory, formal logic, and statistics help create the algorithms used for answering questions in a timely manner.not at all elementary. Watson.s creators are working to create technology that can do much more than win a TV game show. Programmers are aiming for systems that will soon respond quickly with expert answers to real-world problems.from the fairly straightforward, such as providing technical support, to the more complex, such as responding to queries from doctors in search of the correct medical diagnosis. Most of the research involves computer science, but mathematics will help to expand applications to other industries and to scale down the size and cost of the hardware that makes up these modern question-answering systems. For More Information: Final Jeopardy: Man vs. Machine and the Quest to Know Everything, Stephen Baker, 2011.

Once a problem only in the developed world, obesity is now a worldwide epidemic. The overwhelming cause of the epidemic is a dramatic increase in the food supply and in food consumption not a surprise. Yet there are still many mysteries about weight change that can.t be answered either inside the lab, because of the impracticality of keeping people isolated for long periods of time, or outside, because of the unreliability of dietary diaries. Mathematical models based on differential equations can help overcome this roadblock and allow detailed analysis of the relationship between food intake, metabolism, and weight change. The models. predictions fit existing data and explain such things as why it is hard to keep weight off and why obese people are more susceptible to further weight gain. Researchers are also investigating why dieters often plateau after a few months and slowly regain weight. A possible explanation is that metabolism slows to match the drop in food consumed, but models representing food intake and energy expenditure as a dynamical system show that such a weight plateau doesn.t take effect until much later. The likely culprit is a combination of slower metabolism and a lack of adherence to the diet. Most people are in approximate steady state, so that long-term changes are necessary to gain or lose weight. The good news is that each (enduring) drop of 10 calories a day translates into one pound of weight loss over three years, with about half the loss occurring in the first year. For More Information: Quantification of the effect of energy imbalance on bodyweight, Hall et al. Lancet, Vol. 378 (2011), pp. 826-837.

There.s more mathematics involved in juggling than just trying to make sure that the number of balls (or chainsaws) that hits the ground stays at zero. Subjects such as combinatorics and abstract algebra help jugglers answer important questions, such as whether a particular juggling pattern can actually be juggled. For example, can balls be juggled so that the time period that each ball stays aloft alternates between five counts and one? The answer is Yes. Math also tells you that the number of balls needed for such a juggling pattern is the average of the counts, in this case three. Once a pattern is shown to be juggleable and the number of balls needed is known, equations of motion determine the speed with which each ball must be thrown and the maximum height it will attain. Obviously the harder a juggler throws, the faster and higher an object will go. Unfortunately hang time increases proportionally to the square root of the height, so the difficulty of keeping many objects in the air increases very quickly. Both math and juggling have been around for millennia yet questions still remain in both subjects. As two juggling mathematicians wrote, .A juggler, like a mathematician, is never finished: there is always another great unsolved problem.

There.s more mathematics involved in juggling than just trying to make sure that the number of balls (or chainsaws) that hits the ground stays at zero. Subjects such as combinatorics and abstract algebra help jugglers answer important questions, such as whether a particular juggling pattern can actually be juggled. For example, can balls be juggled so that the time period that each ball stays aloft alternates between five counts and one? The answer is Yes. Math also tells you that the number of balls needed for such a juggling pattern is the average of the counts, in this case three. Once a pattern is shown to be juggleable and the number of balls needed is known, equations of motion determine the speed with which each ball must be thrown and the maximum height it will attain. Obviously the harder a juggler throws, the faster and higher an object will go. Unfortunately hang time increases proportionally to the square root of the height, so the difficulty of keeping many objects in the air increases very quickly. Both math and juggling have been around for millennia yet questions still remain in both subjects. As two juggling mathematicians wrote, .A juggler, like a mathematician, is never finished: there is always another great unsolved problem.