Joachim Kock and David I. Spivak
Proc. Amer. Math. Soc. 148 (2020), 2317-2329.
Abstract, references and article information

Extracytoplasmic sugar decoration of glycopolymer components of the bacterial cell wall contributes to their structural diversity. Typically, the molecular mechanism that underpins such a decoration process involves a three-component glycosylation system (TGS) represented by an undecaprenyl-phosphate (Und-P) sugar-activating glycosyltransferase (Und-P GT), a flippase, and a polytopic glycosyltransferase (PolM GT) dedicated to attaching sugar residues to a specific glycopolymer. Here, using bioinformatic analyses, CRISPR-assisted recombineering, structural analysis of cell wall–associated polysaccharides (CWPS) through MALDI-TOF MS and methylation analysis, we report on three such systems in the bacterium Lactococcus lactis. On the basis of sequence similarities, we first identified three gene pairs, csdAB, csdCD, and csdEF, each encoding an Und-P GT and a PolM GT, as potential TGS component candidates. Our experimental results show that csdAB and csdCD are involved in Glc side-chain addition on the CWPS components rhamnan and polysaccharide pellicle (PSP), respectively, whereas csdEF plays a role in galactosylation of lipoteichoic acid (LTA). We also identified a potential flippase encoded in the L. lactis genome (llnz_02975, cflA) and confirmed that it participates in the glycosylation of the three cell wall glycopolymers rhamnan, PSP, and LTA, thus indicating that its function is shared by the three TGSs. Finally, we observed that glucosylation of both rhamnan and PSP can increase resistance to bacteriophage predation and that LTA galactosylation alters L. lactis resistance to bacteriocin.

Bokai Song
Apr 28, 2020; 0:RA120.001981v1-mcp.RA120.001981
Research

Invitation Only Research Event

Event participants

Professor Philippe Sands QC, Professor of Law, UCL 
Richard Burt, Managing Partner, McLarty Associates
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme; Dean, Queen Elizabeth II Academy, Chatham House

The cyclic GMP-AMP synthase (cGAS) protein is a pattern-recognition receptor of the mammalian innate immune system that is recognized as a main cytosolic sensor of pathogenic or damaged DNA. cGAS DNA binding initiates catalytic production of the second messenger, cyclic GMP-AMP, which activates the STING-TBK1-IRF3 signaling axis to induce cytokine expression. Post-translational modification (PTM) has started to be recognized as a critical component of cGAS regulation, yet the extent of these modifications remains unclear. Here, we report the identification and functional analysis of cGAS phosphorylations and acetylations in several cell types under basal and immune-stimulated conditions. cGAS was enriched by immunoaffinity purification from human primary fibroblasts prior to and after infection with herpes simplex virus type 1 (HSV-1), as well as from immune-stimulated STING-HEK293T cells. Six phosphorylations and eight acetylations were detected, of which eight PTMs were not previously documented. PTMs were validated by parallel reaction monitoring (PRM) mass spectrometry in fibroblasts, HEK293T cells, and THP-1 macrophage-like cells. Primary sequence and structural analysis of cGAS highlighted a subset of PTM sites with elevated surface accessibility and high evolutionary sequence conservation. To assess the functional relevance of each PTM, we generated a series of single-point cGAS mutations. Stable cell lines were constructed to express cGAS with amino acid substitutions that prevented phosphorylation (Ser-to-Ala) and acetylation (Lys-to-Arg) or that mimicked the modification state (Ser-to-Asp and Lys-to-Gln). cGAS-dependent apoptotic and immune signaling activities were then assessed for each mutation. Our results show that acetyl-mimic mutations at Lys384 and Lys414 inhibit the ability of cGAS to induce apoptosis. In contrast, the Lys198 acetyl-mimic mutation increased cGAS-dependent interferon signaling when compared to the unmodified charge-mimic. Moreover, targeted PRM quantification showed that Lys198 acetylation is decreased upon infections with two herpesviruses—HSV-1 and human cytomegalovirus (HCMV), highlighting this residue as a regulatory point during virus infection.

Invitation Only Research Event

Event participants

Professor Philippe Sands QC, Professor of Law, UCL 
Richard Burt, Managing Partner, McLarty Associates
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme; Dean, Queen Elizabeth II Academy, Chatham House

Invitation Only Research Event

Event participants

Professor Philippe Sands QC, Professor of Law, UCL 
Richard Burt, Managing Partner, McLarty Associates
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme; Dean, Queen Elizabeth II Academy, Chatham House

Ruth L. Coleman
May 1, 2007; 30:1292-1293
BR Cardiovascular and Metabolic Risk

If Democrats Hillary Clinton and Barack Obama ever took a break from fundraising to bone up on psychology, they might realize the need to talk up . . . John Edwards.

It appears that United Airlines has stopped using a classic decoy pricing approach for in-flight wifi options.

The post Decoy Pricing: Did United Airlines Fire Their Behavioral Economist? appeared first on Neuromarketing.

Paris : G. Steinheil, 1892.

Patrick L. Combettes, Christian L. Müller.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 207--238.

Abstract:
We introduce a flexible optimization model for maximum likelihood-type estimation (M-estimation) that encompasses and generalizes a large class of existing statistical models, including Huber’s concomitant M-estimator, Owen’s Huber/Berhu concomitant estimator, the scaled lasso, support vector machine regression, and penalized estimation with structured sparsity. The model, termed perspective M-estimation, leverages the observation that convex M-estimators with concomitant scale as well as various regularizers are instances of perspective functions, a construction that extends a convex function to a jointly convex one in terms of an additional scale variable. These nonsmooth functions are shown to be amenable to proximal analysis, which leads to principled and provably convergent optimization algorithms via proximal splitting. We derive novel proximity operators for several perspective functions of interest via a geometrical approach based on duality. We then devise a new proximal splitting algorithm to solve the proposed M-estimation problem and establish the convergence of both the scale and regression iterates it produces to a solution. Numerical experiments on synthetic and real-world data illustrate the broad applicability of the proposed framework.

Tensor Train decomposition is used across many branches of machine learning. We present T3F—a library for Tensor Train decomposition based on TensorFlow. T3F supports GPU execution, batch processing, automatic differentiation, and versatile functionality for the Riemannian optimization framework, which takes into account the underlying manifold structure to construct efficient optimization methods. The library makes it easier to implement machine learning papers that rely on the Tensor Train decomposition. T3F includes documentation, examples and 94% test coverage.

Piotr Kokoszka, Neda Mohammadi Jouzdani.

Source: Bernoulli, Volume 26, Number 3, 2383--2399.

Abstract:
This paper is concerned with frequency domain theory for functional time series, which are temporally dependent sequences of functions in a Hilbert space. We consider a variance decomposition, which is more suitable for such a data structure than the variance decomposition based on the Karhunen–Loéve expansion. The decomposition we study uses eigenvalues of spectral density operators, which are functional analogs of the spectral density of a stationary scalar time series. We propose estimators of the variance components and derive convergence rates for their mean square error as well as their asymptotic normality. The latter is derived from a frequency domain invariance principle for the estimators of the spectral density operators. This principle is established for a broad class of linear time series models. It is a main contribution of the paper.

Akio Fujiwara, Koichi Yamagata.

Source: Bernoulli, Volume 26, Number 3, 2105--2142.

Abstract:
We herein develop a theory of contiguity in the quantum domain based upon a novel quantum analogue of the Lebesgue decomposition. The theory thus formulated is pertinent to the weak quantum local asymptotic normality introduced in the previous paper [Yamagata, Fujiwara, and Gill, Ann. Statist. 41 (2013) 2197–2217], yielding substantial enlargement of the scope of quantum statistics.

A new analysis of ancient ostrich eggs at the British Museum underscores the interconnectedness of the ancient world

The current deconfinement plan in the Montreal area could lead to a rapid increase in deaths in the city, according to findings by Quebec's public health institute. 

Decorate a guitar, skateboard, or bike to help veterans, foster children  AZFamily

The Migration Policy Institute published the first in a series of reports that aim to educate parents, policymakers, and the public about how to find and use data to examine whether schools are adequately serving their English-language-learner students.

Burundi is back in the spotlight of the world’s media and the agenda of the United Nations Security Council. As recently as two years ago, the country was considered a success story in peacebuilding circles, but now the news is firmly of a negative variety. The UN is trying to prevent a new civil war in a region still haunted by the Rwandan genocide. How did success so quickly turn to failure?

A new protocol using aerosolized hydrogen peroxide to decontaminate N95 respirators could allow them to be safely reused in hospital settings. The protocol, optimized by a team of Penn State researchers, inactivates viruses without deforming or damaging the respirator and could help hospitals overcome the current respirator shortage due to the COVID-19 pandemic.

Theme for the 2019 display is “Here We Go a Caroling.”

We have recently ridden the new 2020 TVS Apache RTR 200 4V on a racetrack and came back impressed. Here is why!

Mumbai Police drew inspiration from a topic that has been trending all over social media - the name of Elon Musk's newborn baby boy - to devise a brainteaser with an important message.

117 bytes small Linux/x86 encoding of random bytes + XOR/SUB/NOT/ROR and also decodes ROL/NOT/ADD/XOR execve(/bin/sh) shellcode.

A VAX decoy script to grab some accunts.

Wireless Decoder is an application that demonstrates how to recover wireless passwords on Vista/Win7/Win8. Comes with source and the binary.

...

Since the controversial removal of Dr Aniekeme Uwah as the Akwa Ibom State Epidemiologist, several lies have continuously been peddled by media hirelings of 'powers that be' to smear the character of the renowned and celebrated medical expert. Ordinarily , one would not bother about their mischief; but in an article titled " COVID-19 testing and controversies in Akwa Ibom" published in some national dailies and online platforms  by Usman Yusuf ( obviously a fake name), the hireling struggled albeit unsuccessfully to paint a picture of Dr Aniekeme Uwah being removed for unethical practices.

As the Akwa Ibom NMA PRO stated on a Live radio interview, after the infamous redeployment, the reason for Dr Aniekeme Uwah's removal as state Epidemiologist was his refusal to carry out the Commissioner for health's bidding of testing  only 10 persons instead of 31 who had met the case definition .

To cover up the overwhelming public backlash that greeted the politicization of Dr Uwah's removal, aides and hirelings of 'powers that be' have tried justifying the removal of the epidemiologist by first claiming he "banged the phone on the Governor " to later changing the story, that the cerebral Doctor is responsible for the number of positive COVID-19 cases in the state amongst other fables. 

This only proves the truism , that " to cover up one lie, many other lies will have to be told..." and desperately so if I may add.

 Some of the despicable falsehood peddled against  Dr Aniekeme Uwah include falsifying NCDC results.This assertion betrays the writer's ignorance of the procedures for sample collection and test results. 

As the State Epidemiologist, it should be noted that Dr Uwah worked with an incident Management Committee (IMC) which included doctors and other Supervisory agencies like NCDC and the World Health Organization(WHO).

It is under the watchful eyes of these disciplined medical professionals, that samples which meet case definition are gotten and sent to laboratories in Edo State or Ebonyi State with adequate security escort. The results are instantly communicated  by the Laboratory to the NCDC headquarters and the state is copied.

One wonders how Dr Aniekeme Uwah had the powers to change negative results in these laboratories to positive and subsequently force or bribe 12 persons (as at when he was epidemiologist) who were predominantly medics to move into the Isolation Center for treatment. This thinking is not only absurd, but smirks of conspiracy by the writer and cohorts. 

Moreover, four new positive cases have been confirmed after he was redeployed as state Epidemiologist, did he still influence those results?

In another online defamatory write up by yet another faceless hireling Bassey Wils, it was alleged that the former Epidemiologist was angered that his proposal for purchase of laboratory equipment was rejected.

This is obviously far from the truth. The writer is obviously unaware of the workings of Government and the procedures for procurement in a ministry that has a Commissioner.   Even if the Epidemiologist would have recommended that the state had its own laboratory to stop incessant travels to other states for tests confirmations, it would best remain only a novel suggestion as the implementation of such ideas rest between the Commissioner for health and agencies of Government responsible for such procurement . 

The said fake Bassey Wils also blamed the former Epidemiologist for the embarrassment the state suffered during it's infamous imbrioglio with NCDC over the 5 index cases..This is a case of selective amnesia suffered by Blackmailer hiding under the moniker of Bassey Wils. For the avoidance of doubt, It was the Commissioner for Health who held a world press conference to disagree with the results of the 5 index cases and NCDC procedures not Dr Aniekeme Uwah. This further goes to buttress the allegations against " Powers" over their intentions to suppress testing to avoid a record of high positive results by the state as stated by the NMA PRO on radio. 

Further more, the fake Bassey Wills claimed Dr Aniekeme Uwah  went against NCDC guidelines which stated that only 10 samples should be sent in a day.  

For avoidance of doubt, it must be stated unequivocally that such guidelines does not exist.

On April 27, 2020 Dr Sani Aliyu, National Coordinator presidential task force ( PTF) on COVID-19 said on National TV and i quote " I will like to emphasize that there is no limit to testing when it comes to COVID-19. Covid numbers is not an issue of competition between states. There is no shame if a state comes up with positive numbers. In other to deal with an epidemic, we need to have transparency in numbers and that transparency is linked to the number of tests. If you do not know the extent of the problem, you will not be able to deal with it. I am appealing to state governments to please continue helping the state emergency operating centers and state ministry of health to make sure that everybody that needs to be tested has the opportunity to get the test done " . 

One would expect that after such affirmative words by the PTF on no ceilings for tests , Fake Bassey Wils and his gang of liars will bury their heads in shame. 

It shouldn't be taken for granted that the suspected case confirmed positive from the 31 would have been missed if Dr Aniekeme Uwah had carried out the Commissioner 's directive to take only 10samples.  This most likely would have led to more spread of the pandemic in the state if that suspected case was not tested or would have made the health of the patient worse if not timely diagnosed. 

Apart from this,  a large number of Doctors who were exposed to COVID-19 had been out of work for up to a month on self isolation because they had not been tested, thus leading to loss of man hours and critical essential services, and inadvertently leading to denial of life - saving services by these experts to those who needed their expertise. 

The fact that Dr Aniekeme Uwah insisted on these Doctors getting tested as part of the 31 , helped seventeen out of the eighteen of them whose results came out negative return to work at the University of Uyo teaching Hospital almost immediately. 

Dr Aniekeme Uwah should be commended for such clinical dexterity.  This tests are conducted free of charge by NCDC, so why the fuss of testing a large number? Why the insistence of testing a smaller number when everyone that met case definition at the time could be tested at once to save time and ensure clinical efficacy? 

The state loses nothing by testing more as tests are free of charge. Instead, the more agressive it gets with testing, the clearer the picture of viral penetration. That is pure Epidemiology! 

In the words of Dr Emmanuel John, the NMA PRO on radio, " testing is a clinical decision. And no doctor should have recourse to a political mastermind before taking such decisions"

Another allegation by Bassey Wils bothering a late surgeon need not be dignified for the respect of the dead and family. But it must be noted that the allegations remain false and spurious, tailored only the damage reputation of Dr Aniekeme Uwah. fortunately for every discerning mind, Bassey Wil's campaign of calumny has largely been mischievous, comic at it's best and utterly balderdash.

Fake Bassey Wil's nonsensical allegation of having evidence of text messages between Dr Aniekeme Uwah and "middle men" is not only absurd and baseless but further attempts to 'give a dog a bad name in order to hang it'. Such text messages remain only in the conjecture of his imagination. If there is any iota of truth, I challenge fake Bassey Wils to produce such evidences in court or forever bury his head in the pit of hell.

Lastly Fake Bassey Wils, a leader of the blackmail syndicate alleged that Dr Aniekeme Uwah put the state in bad light during a National Survey that ranked the state as leading in the number of persons living with HIV/AIDs in the country.  He doesn't realize that his particular allegation, provides more evidence as to the unquenching thirst for suppressing data and statistics by those in authority.

The fact remains that after the result of the HIV/AIDs National and Impact survey was published in Abuja by Federal Ministry Of Health, Dr Aniekeme Uwah moved by passion and love for his people, sensitized the public on the dangers of HIV/ AIDs and how infection can be reduced.

 He admonished on Abstainance, faithfulness to sexual partners, usage condoms and usage of anti-retroviral drugs to suppress the viral load  thereby hindering further transmission. 

In saner climes, Such patriotic zeal, would  been encouraged ; as truly there is need for sensitization of the masses whose majority especially in rural areas are still in illusion about HIV/AIDs.

 Instead of commending Dr Uwah for putting in time and personal resources to educate the masses, the "powers that be" sternly condemned Dr Aniekeme Uwah  for educating the masses about HIV/AIDs and claimed he put state in bad light. He was queried! What a sad irony!

One would ask, what is the gain of the state if it hides the figures of the HIV/AIDs prevalence from the masses? What is the intention of hiding the result of  the national survey? To record more infections due to ignorance of the populace? It has been a long walk to trampling on truth, honesty and dedication to duty.

In the court of public opinion, Dr Aniekeme Uwah has acquitted himself as a professional of unparalleled integrity.

A courageous medical doctor whose commitment to the service of humanity is common to none. 

Dr Uwah is loyal to the Hippocratic oath and will remain resolute in advocating for better health care delivery to the people.

 His award of Honor by the African Union for dedicating Six months of his life to Liberia in the fight of Ebola remains indelible.

He was also honoured as the most outstanding NMA state chairman by the National President and National Officers Committee of the NMA during his tenure as Chairman. 

His exploits as NMA Chairman include building the first Doctors Mess in Nigeria, The first NMA Clinic in Nigeria, Doctors Court as well as numerous free Surgical outreach accross the state. 

It is worthy of note that during his tenure as NMA Chairman, he pushed for the establishment of the State Primary Health Care Development Agency and State Insurance Scheme.

In the past two years, Dr Aniekeme Uwah was the chairman Planning Committee of National Physicians Week in Rivers State and Ondo State as well as the chairman Planning committee of the National Executive Council meeting of the Association in Akwa Ibom State. This is a testament to his Sterling leadership qualities which has earned him the trust of his colleagues Nationwide. 

As State Epidemiologist,  Dr Aniekeme Uwah's achievements are enormous but to mention

1. Partnering with WHO to donate motorcycles to all the 31 Disease Surveillance Officers (DSNOs) in the 31 LGAs in the state to enhance their mobility.

2. Training of the 31DSNOs and other Health workers on frontline field epidemiology in partnership with AFENET.

3. Donation of Lap top computers and android phones to all the 31DSNOs to enhance their disease surveillance activities etc

Recently , Dr Aniekeme Uwah was appointed Secretary of the Common Wealth Medical Association's Committee on Covid-19 response. The Common Wealth Comprises of 54 countries accross all continents. Only Men of proven track record get such International appointments. 

These and more are some of Dr Aniekeme Uwah's legacies that his blackmailers cannot wish away.

No greater testimonial would Dr Uwah wish  for in times like this, than that of The DG of NCDC,  Dr Chikwe Ihekweazu who while responding to the redeployment saga on national TV said "The state Epidemiologist, Dr Aniekeme Uwah is a great colleague who did his work creditably. He is one of my great colleagues .. we worked on Ebola outbreak together. I wish him well in his new assignment".

I understand that Dr Uwah's traducers and their media hirelings are intimidated by his towering profile. I would rather implore them to work hard on improving their miserable lives rather than constantly attempt to defame and disparage a man whose track record is way beyond their reach. It will remain a mere waste of time! 

It is worthy of note, that Dr Aniekeme Uwah's removal as state Epidemiologist to suppress Covid 19 test results has already made him a hero, a professional of no mean repute in the court of public opinion and no volume of blackmail can change that narrative!

- Asteroid Bassey writes in from Uyo.

[Observer] President Yoweri Kaguta Museveni has cautioned the general public to always wear masks whenever they are out of their homes. The president said wearing mask will help combat the spread of the Coronavirus (COVID-19) and its infection to other people.

Calls for Australian businesses to diversify away from China as their main trading partner are nothing more than a “zombie economic idea” that is being used as a political tool to expedite the decoupling of the two countries, according to a report by the Australia-China Relations Institute at the University of Technology Sydney.The debate about Australia’s over-dependence on China for its livelihood has ramped up recently, triggered by the interruption of supply chains during China’s…

Title: Quick Decompression Aids Spinal Injury Recovery
Category: Health News
Created: 4/29/2008 2:00:00 AM
Last Editorial Review: 4/29/2008 12:00:00 AM

ABSTRACT

All enterococci produce a complex polysaccharide called the enterococcal polysaccharide antigen (EPA). This polymer is required for normal cell growth and division and for resistance to cephalosporins and plays a critical role in host-pathogen interaction. The EPA contributes to host colonization and is essential for virulence, conferring resistance to phagocytosis during the infection. Recent studies revealed that the "decorations" of the EPA polymer, encoded by genetic loci that are variable between isolates, underpin the biological activity of this surface polysaccharide. In this work, we investigated the structure of the EPA polymer produced by the high-risk enterococcal clonal complex Enterococcus faecalis V583. We analyzed purified EPA from the wild-type strain and a mutant lacking decorations and elucidated the structure of the EPA backbone and decorations. We showed that the rhamnan backbone of EPA is composed of a hexasaccharide repeat unit of C2- and C3-linked rhamnan chains, partially substituted in the C3 position by α-glucose (α-Glc) and in the C2 position by β-N-acetylglucosamine (β-GlcNAc). The so-called "EPA decorations" consist of phosphopolysaccharide chains corresponding to teichoic acids covalently bound to the rhamnan backbone. The elucidation of the complete EPA structure allowed us to propose a biosynthetic pathway, a first essential step toward the design of antimicrobials targeting the synthesis of this virulence factor.

IMPORTANCE Enterococci are opportunistic pathogens responsible for hospital- and community-acquired infections. All enterococci produce a surface polysaccharide called EPA (enterococcal polysaccharide antigen) required for biofilm formation, antibiotic resistance, and pathogenesis. Despite the critical role of EPA in cell growth and division and as a major virulence factor, no information is available on its structure. Here, we report the complete structure of the EPA polymer produced by the model strain E. faecalis V583. We describe the structure of the EPA backbone, made of a rhamnan hexasaccharide substituted by Glc and GlcNAc residues, and show that teichoic acids are covalently bound to this rhamnan chain, forming the so-called "EPA decorations" essential for host colonization and pathogenesis. This report represents a key step in efforts to identify the structural properties of EPA that are essential for its biological activity and to identify novel targets to develop preventive and therapeutic approaches against enterococci.

Summary:

In this issue of Cancer Discovery, Li and colleagues provide a blueprint for the identification and functional validation of cancer-associated mutations in noncoding regions of the genome. Integration of whole-genome sequencing and high-throughput epigenome editing screens is starting to reveal the extent to which noncoding genetic lesions contribute to cancer.

See related article by Li et al., p. 724.

To mark Friday's 75th anniversary of the end of World War II in Europe, the British government revealed the final Nazi message intercepted and decoded by U.K. codebreakers as Allied forces were advancing through Germany.

The Nintendo game has been hugely popular during lockdown

In the era of COVID-19, surgical masks are a necessity for all healthcare workers and an effective way to curtail the spread of the virus within the general public. Since surgical masks are still in relatively short supply, companies and researchers have been working on ways to make available masks last longer. Cleanbox Technology, based […]

The European Medicines Agency’s Committee for Medicinal Products for Human Use has given its recommendation for the approval of Kalydeco for the treatment of children and adolescents with cystic fibrosis in a new indication, Vertex has revealed.

RBI's COVID-19 Regulatory Package: From Repo Rate & CRR Cuts to 3-months moratorium on term loans, RBI Governor Shaktikanta Das announced several measures while addressing the media after the release of Seventh Bi-monthly Monetary Policy Statement 2019-20.

A linguist explains how limited our thinking about extraterrestrials can be