A lone developer from the company that provided aerodynamic analysis for the cars in the PlayStation game Gran Turismo has applied the tooling to demonstrate the spread of germs with and without wearing a mask

Katherine S. O’Neal
Nov 1, 2016; 29:249-252
Pharmacy and Therapeutics

The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces a dextran of the highest molar mass reported to date (∼109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very-high-molar-mass polymer. In domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of glycoside hydrolase 70 (GH70) glucansucrases that are known to be involved in glucan binding. We investigated their role in polymer synthesis through several approaches, including monitoring of dextran synthesis, affinity assays, sugar binding pocket deletions, site-directed mutagenesis, and construction of chimeric enzymes. Substitution of only two stacking aromatic residues in two consecutive sugar-binding pockets (variant DSR-OKΔ1-Y1162A-F1228A) induced quasi-complete loss of very-high-molar-mass dextran synthesis, resulting in production of only 10–13 kg/mol polymers. Moreover, the double mutation completely switched the semiprocessive mode of DSR-OKΔ1 toward a distributive one, highlighting the strong influence of these pockets on enzyme processivity. Finally, the position of each pocket relative to the active site also appeared to be important for polymer elongation. We propose that sugar-binding pockets spatially closer to the catalytic domain play a major role in the control of processivity. A deep structural characterization, if possible with large-molar-mass sugar ligands, would allow confirming this hypothesis.

VOLUME 289 (2014) PAGES 30635–30644This article has been withdrawn by Guangnan Chen, Dongkyoo Park, Francis A. Cucinotta, David S. Yu, Xingming Deng, William S. Dynan, Paul W. Doetsch, and Ya Wang. Hongyan Wang, Xiang Wang, Xiangming Zhang, and Xiaobing Tang could not be reached. The last two lanes of the actin immunoblot in Fig. 1A were reused in the last two lanes of the actin immunoblot in Fig. 1C. In Fig. 2A, the γ-H2AX and the merge with DAPI images for no IR treatment do not match. In Fig. 3A, lanes 3 and 4 of the γ-H2AX immunoblot were reused in lanes 7 and 8, and lanes 5 and 6 of the H2A immunoblot were reused in lanes 7 and 8. In Fig. 3B, lanes 5 and 6 of the H2A immunoblot were reused in lanes 7 and 8. In Fig. 3C, lanes 5 and 6 of the γ-H2AX immunoblot were reused in lanes 7 and 8. Additionally, lanes 1 and 2 of the H2A immunoblot were reused in lanes 3 and 4. In Fig. 3D, lanes 1 and 2 of the Mre11 immunoblot from lysates were reused in lanes 4 and 5. In the γ-H2AX immunoblot, lane 3 was reused in lane 7, and lane 4 was reused in lanes 6 and 8. Also in the H2A immunoblot, lanes 1 and 2 were reused in lanes 3 and 4. In Fig. 4B, lanes 2 and 6 of the Mre11 immunoblot from Ogg1−/− cells are the same. In the Ape1...

(University of Sydney) In a study published today in Current Biology, researchers from University of Sydney have identified the single gene that determines how Cape honey bees reproduce without ever having sex. One gene, GB45239 on chromosome 11, is responsible for virgin births.

Xien Yu Chua
Apr 1, 2020; 19:730-743
Technological Innovation and Resources

Lindsay K Pino
Apr 20, 2020; 0:P119.001913v1-mcp.P119.001913
Perspective

2 July 2019

Research Event

Event participants

Professor Tony Chafer, University of Portsmouth
Professor Gordon Cumming, Cardiff University
Dr Roel van der Velde, Cardiff University
Ahmed Soliman, Research Fellow, Horn of Africa, Chatham House
Dr Elisa Lopez Lucia, Université Libre de Bruxelles; University of Portsmouth
Chair: Janet Adama Mohammed, West Africa Programme Director, Conciliation Resources

Invitation Only Research Event

Event participants

Miklos Gosztonyi, Conflict Analyst, South Sudan, Norwegian Refugee Council
Matthew F. Pritchard, Research and Policy Specialist, McGill University
Joshua Craze, Writer and Researcher
Teohna Williams, CEO, Business Plan for Peace

Recurrent urinary tract infections (UTIs) pose a significant burden on the health care system. Underlying mechanisms predisposing children to UTIs and associated changes in the urinary proteome are not well understood. We aimed to investigate the urinary proteome of a subset of children who have vesicoureteral reflux (VUR) and recurrent UTIs because of their risk of developing infection-related renal damage. Improving diagnostic modalities to identify UTI risk factors would significantly alter the clinical management of children with VUR. We profiled the urinary proteomes of 22 VUR patients with low grade VUR (1–3 out of 5), a history of recurrent UTIs, and renal scarring, comparing them to those obtained from 22 age-matched controls. Urinary proteins were analyzed by mass spectrometry followed by protein quantitation based on spectral counting. Of the 2,551 proteins identified across both cohorts, 964 were robustly quantified, as defined by meeting criteria with spectral count (SC) ≥2 in at least 7 patients in either VUR or control cohort. Eighty proteins had differential expression between the two cohorts, with 44 proteins significantly up-regulated and 36 downregulated (q <0.075, FC ≥1.2). Urinary proteins involved in inflammation, acute phase response (APR), modulation of extracellular matrix (ECM), and carbohydrate metabolism were altered among the study cohort.

Dynamic tyrosine phosphorylation is fundamental to a myriad of cellular processes. However, the inherently low abundance of tyrosine phosphorylation in the proteome and the inefficient enrichment of phosphotyrosine(pTyr)-containing peptides has led to poor pTyr peptide identification and quantitation, critically hindering researchers' ability to elucidate signaling pathways regulated by tyrosine phosphorylation in systems where cellular material is limited. The most popular approaches to wide-scale characterization of the tyrosine phosphoproteome use pTyr enrichment with pan-specific, anti-pTyr antibodies from a large amount of starting material. Methods that decrease the amount of starting material and increase the characterization depth of the tyrosine phosphoproteome while maintaining quantitative accuracy and precision would enable the discovery of tyrosine phosphorylation networks in rarer cell populations. To achieve these goals, the BOOST (Broad-spectrum Optimization Of Selective Triggering) method leveraging the multiplexing capability of tandem mass tags (TMT) and the use of pervanadate (PV) boost channels (cells treated with the broad-spectrum tyrosine phosphatase inhibitor PV) selectively increased the relative abundance of pTyr-containing peptides. After PV boost channels facilitated selective fragmentation of pTyr-containing peptides, TMT reporter ions delivered accurate quantitation of each peptide for the experimental samples while the quantitation from PV boost channels was ignored. This method yielded up to 6.3-fold boost in pTyr quantification depth of statistically significant data derived from contrived ratios, compared with TMT without PV boost channels or intensity-based label-free (LF) quantitation while maintaining quantitative accuracy and precision, allowing quantitation of over 2300 unique pTyr peptides from only 1 mg of T cell receptor-stimulated Jurkat T cells. The BOOST strategy can potentially be applied in analyses of other post-translational modifications where treatments that broadly elevate the levels of those modifications across the proteome are available.

Kristian K Kristensen
Apr 23, 2020; 0:jlr.ILR120000780v1-jlr.ILR120000780
Images in Lipid Research

Teng-Fei Yuan
Apr 1, 2020; 61:580-586
Methods

A double Google header as Henry Burrell leads Scott Carey and Sean Bradley down the tech rabbit hole. Alphabet's most famous outlet has redesigned Gmail for desktop, but what does that mean for businesses and consumers. Will anyone notice?

Then what is Chat? Not Google Chat or Android Chat, mind - just Chat. Will the Google-led initiative really transform text messaging on Android or is it doomed to forever to be a fragmented mess?

Sean then talks us through the latest AMD processors to challenge Intel. Intel hasn't had the best of year's after Apple announced it is going solo. Is there a change afoot?

See acast.com/privacy for privacy and opt-out information.

Data independent acquisition (DIA) is an attractive alternative to standard shotgun proteomics methods for quantitative experiments. However, most DIA methods require collecting exhaustive, sample-specific spectrum libraries with data dependent acquisition (DDA) to detect and quantify peptides. In addition to working with non-human samples, studies of splice junctions, sequence variants, or simply working with small sample yields can make developing DDA-based spectrum libraries impractical. Here we illustrate how to acquire, queue, and validate DIA data without spectrum libraries, and provide a workflow to efficiently generate DIA-only chromatogram libraries using gas-phase fractionation (GPF). We present best-practice methods for collecting DIA data using Orbitrap-based instruments, and develop an understanding for why DIA using an Orbitrap mass spectrometer should be approached differently than when using time-of-flight instruments. Finally, we discuss several methods for analyzing DIA data without libraries.

Analyzing global steroid metabolism in humans can shed light on the etiologies of steroid-related diseases. However, existing methods require large amounts of serum and lack the evaluation of accuracy. Here, we developed an LC/MS/MS method for the simultaneous quantification of 12 steroid hormones: testosterone, pregnenolone, progesterone, androstenedione, corticosterone, 11-deoxycortisol, cortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, estriol, and estradiol. Steroids and spiked internal standards in 100 μl serum were extracted by protein precipitation and liquid-liquid extraction. The organic phase was dried by evaporation, and isonicotinoyl chloride was added for steroid derivatization, followed by evaporation under nitrogen and redissolution in 50% methanol. Chromatographic separation was performed on a reverse-phase PFP column, and analytes were detected on a triple quadrupole mass spectrometer with ESI. The lower limits of quantification ranged from 0.005 ng/ml for estradiol to 1 ng/ml for cortisol. Apparent recoveries of steroids at high, medium, and low concentrations in quality control samples were between 86.4% and 115.0%. There were limited biases (–10.7% to 10.5%) between the measured values and the authentic values, indicating that the method has excellent reliability. An analysis of the steroid metabolome in pregnant women highlighted the applicability of the method in clinical serum samples. We conclude that the LC/MS/MS method reported here enables steroid metabolome analysis with high accuracy and reduced serum consumption, indicating that it may be a useful tool in both clinical and scientific laboratory research.

The signing of veteran outfielder Michael Brantley by the Astros came a week after the Winter Meetings and only a few days before Christmas, meaning it didn't exactly garner much attention on national, or even local, news cycles. For the Astros, Brantley was exactly the player they needed at exactly the right price -- two years and $32 million -- and the kind of addition that should fire up the fanbase.

With the emergence of sofobuvir, a new direct acting antiviral, treatment for Hepatitis C infection is currently undergoing it's greatest change since the discovery of the virus 25 years ago. However Gilead, who manufacture the treatment, are under fire for the cost of the druge - around $90 000 for a course of treatment. Victor Roy, doctoral...

Thailand has become a key destination for migrant workers, primarily from Myanmar, Cambodia, and Laos. Many lack authorization, however, and as their numbers have grown, so has the government's intent in regulating their movement—sometimes provoking unintended results. This article explores recent patterns in labor migration to Thailand and examines the likely impacts of a 2017 decree criminalizing illegal employment.

Amid aging populations and the growth of chronic diseases, the demand for skilled health-care professionals is on the rise in the United States, Canada, and Mexico. This report explores the policy implications, benefits, and challenges of harmonizing nursing qualifications in the region, suggesting that a more collaborative approach could result in greater supply and quality of nurses.

Gina Agiostratidou
Dec 1, 2017; 40:1622-1630
Continuous Glucose Monitoring and Risk of Hypoglycemia

As the COVID-19 pandemic begins to take root in Africa, experts say that digitizing financial services could help keep the continent safe

The American Dental Association has released interim guidance for dentists on how to minimize the risk of COVID-19 transmission before, during and after treating dental emergencies.

The ADA announced April 6 the recipients of its third annual 10 Under 10 Awards, which recognizes 10 new dentists who demonstrate excellence early in their careers.

A panel of ADA experts answered members’ questions in a video released April 8 regarding the Association’s interim guidance for minimizing the risk of COVID-19 transmission while performing emergency and urgent dental care.

With the growing urbanization and consolidation of Nicaraguan immigrants in sectors such as construction and domestic service, Costa Rica has shifted its focus from immigration enforcement to integration. Tension has emerged between the government and private sector as a new mechanism for regularizing unauthorized immigrant workers has failed to gain traction.

I was recently asked if I thought the pandemic is a national trauma. The answer is a simple “Yes.” By the standards of the DSM-5 (Diagnostic and Statistical Manual), the...

For the study, 10 couples spent 45 minutes inside a brain scanner together in close physical contact.

→ Support PsyBlog for just $5 per month. Enables access to articles marked (M) and removes ads.

→ Explore PsyBlog's ebooks, all written by Dr Jeremy Dean:

• Accept Yourself: How to feel a profound sense of warmth and self-compassion
• The Anxiety Plan: 42 Strategies For Worry, Phobias, OCD and Panic
• Spark: 17 Steps That Will Boost Your Motivation For Anything
• Activate: How To Find Joy Again By Changing What You Do

In 1996, Agnes Binagwaho returned home to Rwanda in the aftermath of its genocide. She considered leaving amid the overwhelming devastation, but women in her community motivated her to stay and help rebuild -- and she's glad she did. In an inspiring talk, Binagwaho reflects on her work as Rwanda's former Minister of Health and discusses her new women's education initiative for the country, which strives to create one of the greatest levels of gender equality worldwide.

STANDARD ERRORS VS STANDARD DEVIATIONS Click to enlarge There’s an ancient haiku that goes: People confuse a well-estimated mean with a certain outcome Ok, that’s not true. But Jake Hofman, Dan Goldstein, and Jessica Hullman have a new paper (recently accepted at CHI 2020) about this. They bet you’ll think the results of their paper […]

The post How visualizing inferential uncertainty can mislead readers about treatment effects in scientific results appeared first on Decision Science News.

The momentum to raise teacher salaries in several states has ground to a halt amid fears of coronavirus’ massive economic blow.

From Trash to Treasure is an intensely honest account of a life powerfully redeemed and is a demonstration of the goodness of God. Lee Habbershaw's journey to recovery from sexual abuse moved me to tears - sometimes in compassion, but often in joy. The book is rich with the landmark of life events and Biblical truths which, layer by layer, led Lee into the powerful teaching and counselling ministry she operates in today. This book could change your life (page 7)

Dementia -- Treatment.

Stuttgart : F. Enke, 1883.

Sean L. Simpson, F. DuBois Bowman, Paul J. Laurienti

Source: Statist. Surv., Volume 7, 1--36.

Abstract:
Complex functional brain network analyses have exploded over the last decade, gaining traction due to their profound clinical implications. The application of network science (an interdisciplinary offshoot of graph theory) has facilitated these analyses and enabled examining the brain as an integrated system that produces complex behaviors. While the field of statistics has been integral in advancing activation analyses and some connectivity analyses in functional neuroimaging research, it has yet to play a commensurate role in complex network analyses. Fusing novel statistical methods with network-based functional neuroimage analysis will engender powerful analytical tools that will aid in our understanding of normal brain function as well as alterations due to various brain disorders. Here we survey widely used statistical and network science tools for analyzing fMRI network data and discuss the challenges faced in filling some of the remaining methodological gaps. When applied and interpreted correctly, the fusion of network scientific and statistical methods has a chance to revolutionize the understanding of brain function.

Gaoxiang Jia, Xinlei Wang, Qiwei Li, Wei Lu, Ximing Tang, Ignacio Wistuba, Yang Xie.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1617--1647.

Abstract:
Formalin-fixed paraffin-embedded (FFPE) samples have great potential for biomarker discovery, retrospective studies and diagnosis or prognosis of diseases. Their application, however, is hindered by the unsatisfactory performance of traditional gene expression profiling techniques on damaged RNAs. NanoString nCounter platform is well suited for profiling of FFPE samples and measures gene expression with high sensitivity which may greatly facilitate realization of scientific and clinical values of FFPE samples. However, methodological development for normalization, a critical step when analyzing this type of data, is far behind. Existing methods designed for the platform use information from different types of internal controls separately and rely on an overly-simplified assumption that expression of housekeeping genes is constant across samples for global scaling. Thus, these methods are not optimized for the nCounter system, not mentioning that they were not developed for FFPE samples. We construct an integrated system of random-coefficient hierarchical regression models to capture main patterns and characteristics observed from NanoString data of FFPE samples and develop a Bayesian approach to estimate parameters and normalize gene expression across samples. Our method, labeled RCRnorm, incorporates information from all aspects of the experimental design and simultaneously removes biases from various sources. It eliminates the unrealistic assumption on housekeeping genes and offers great interpretability. Furthermore, it is applicable to freshly frozen or like samples that can be generally viewed as a reduced case of FFPE samples. Simulation and applications showed the superior performance of RCRnorm.

Lekha Patel, Nils Gustafsson, Yu Lin, Raimund Ober, Ricardo Henriques, Edward Cohen.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1397--1429.

Abstract:
Fluorescing molecules (fluorophores) that stochastically switch between photon-emitting and dark states underpin some of the most celebrated advancements in super-resolution microscopy. While this stochastic behavior has been heavily exploited, full characterization of the underlying models can potentially drive forward further imaging methodologies. Under the assumption that fluorophores move between fluorescing and dark states as continuous time Markov processes, the goal is to use a sequence of images to select a model and estimate the transition rates. We use a hidden Markov model to relate the observed discrete time signal to the hidden continuous time process. With imaging involving several repeat exposures of the fluorophore, we show the observed signal depends on both the current and past states of the hidden process, producing emission probabilities that depend on the transition rate parameters to be estimated. To tackle this unusual coupling of the transition and emission probabilities, we conceive transmission (transition-emission) matrices that capture all dependencies of the model. We provide a scheme of computing these matrices and adapt the forward-backward algorithm to compute a likelihood which is readily optimized to provide rate estimates. When confronted with several model proposals, combining this procedure with the Bayesian Information Criterion provides accurate model selection.

Germans -- South Australia.

The rainbow sports bra and leggings set from Splits59 is a must-have for anyone craving a pop of color in their workout wardrobe.

M Steriade
Aug 1, 1993; 13:3252-3265
Articles

But the scientists still aren’t sure what the birds are saying

It all began when three frustrated women sought the no-bounce zone

Buenos Aires, Argentina :: Maintenance crew share Christ's love with local welders helping repair Logos Hope.