velocityconf: RT @OReillyAnimals Advice, please! Elephant Listening Project asks for ideas/solutions/help with 3 practical problems http://t.co/Y90YP3maoz

Ciara offers pregnancy advice to expecting moms during the Covid-19 pandemic

An alleged robber, who was wounded while his two suspected accomplices were killed in a shootout with police, has been arrested.

Stay up to date with the latest news, views and analysis as the number of coronavirus cases in SA increases.

The author made sense in both the argument put forth as well as in accurately describing the actual policing festive season operations on the ground in the bustling and busy city centre of Durban.

Nowadays many shoppers don’t even remember how they learned about an eCommerce brand in the first place. If you ask them, the most popular answer is “I found it somewhere on the Internet”. Commercial information is all over the place, so nobody cares about the “channel” they use to find it anymore.

Nowadays many shoppers don’t even remember how they learned about an eCommerce brand in the first place. If you ask them, the most popular answer is “I found it somewhere on the Internet”. Commercial information is all over the place, so nobody cares about the “channel” they use to find it anymore.

From smartphone-operated elevators to contactless coffee machines, businesses are trying to eliminate major touchpoints to help deter coronavirus spread in the workplace.

The French Riviera (Nice, Cannes, Antibes) and Monaco

The Amateur Traveler talks to Ira Bernstein about why he continues to go back to Venice and the Veneto (the Italian state where Venice is) annually. Learn about other parts of Venice besides the tourist filled Saint Mark's square. We talk about the Gheto in the Cannaregio sestieri. We talk about how to get around, where you can stay for less money and why you might want to stay outside of Venice. We talk about the glass blowers of Morano and the lace makers of Borano. Then we get outside of Venice to Padua, Verona, and Bassano del Grappa. We will stand in Galileo's lectern at the university of Padua (where they paid him his weight in gold to come teach). And we will visit the (fake) balcony of Juliet in Padua where we will rub a statue of Juliet for luck.

The Amateur Traveler talks to Janice Waugh from Solo Traveler about solo travel as a woman, particularly solo international travel. Janice did not set out to be a solo traveler but after the death of her husband she gained her courage to travel again.

Hear about travel to the Westfjords of Iceland as the Amateur Traveler talks to Katie Hammel of Vaitor.com about her trip to this remote region of the island.

The water level is rising in Venice, while the buildings are sinking. An ambitious plan is underway to save the ancient city from an untimely demise.

It’s not good for people to be alone. Quarantining has been difficult for many people who have gotten used to socializing daily, and because of that, some have found ways to follow the rules but feel a little less isolated. Some neighborhoods have decided to be social while maintaining the suggested distance apart, whether that’s…

The post ‘The Voice’ Contestant Alexa Cappelli Treats Neighbors to Weekly Performance in Her Cul-de-Sac appeared first on The Western Journal.

Eleven members of the Secret Service have tested positive for COVID-19, according a new report. Yahoo News reported Friday it has seen Department of Homeland Security documents which show that 11 individuals currently have the virus and that 23 members of the Secret Service have recovered from the disease. Another 60 employees of the agency…

The post Report: Secret Service Discovers Nearly a Dozen Coronavirus Cases in Its Own Ranks appeared first on The Western Journal.

The Justice Department has intervened in troubled police departments for 20 years. Are reform efforts working?

TL;DR: A one-year subscription to Norton Secure VPN is on sale for £2.50 per month, saving you 50% on list price.

It feels like the world of VPNs is expanding, with more and more providers entering the market and increased demand from users. 

This market can be a daunting place, especially as you probably won't be familiar with most of the available providers. This doesn't mean you shouldn't consider these services, but we totally understand if you're reluctant to invest in an unknown provider.

Fortunately for those who would prefer to subscribe to an established provider, there are plenty of options from the leading names in securityNorton is one such brand, with a comprehensive VPN service on sale for just £2.50 per month. Read more...

Guy Fieri — one of the most popular celebrity chefs— has spent nearly 15 years starring in and hosting entertaining culinary shows. But one of Fieri's favorite things to watch on television isn't food-focused. It's the workplace comedy, The Office.

That's right, the Mayor of Flavortown is obsessed with the employees of Dunder Mifflin's Scranton branch. And much to his delight, he recently got to team up with one of the show's former stars, John Krasinski, to help lift spirits and raise money for restaurant workers in need.

Fieri guest starred on the potluck episode of Some Good News, in which Krasinski invited famous chefs to cook viewer-submitted recipes on video chat. Fieri made a "Dynamite," which has Big Sloppy Joe Energy. And then Krasnski surprised him by announcing a $3 million PepsiCo donation to his Restaurant Employee Relief Fund, which provides financial assistance to restaurant workers impacted coronavirus. Read more...

Yesterday saw the online premier of a mini-episode of a new animated comic series based on the classic Gilbert Shelton underground comic, the Fabulous Furry Freak Brothers. As a hippie wannabe teen in the 70s, this (and Zap! Comics) was everything to me.

In 1969, life in San Francisco consists of free love, communal living, and political protest. Freewheelin’ Franklin Freek (Harrelson), Fat Freddy Freekowtski (Goodman), Phineas T. Phreakers (Davidson) and their mischievous, foul-mouthed cat, Kitty (Haddish) spend their days dodging many things —- the draft, the narcs, and steady employment -– all while searching for an altered state of bliss.

But after partaking of a genetically-mutated strain of marijuana, the Freaks wake up 50 years later to discover a much different society. Quickly feeling like fish out of water in a high-tech world of fourth-wave feminism, extreme gentrification and intense political correctness, the Freaks learn how to navigate life in 2020 -— where, surprisingly, their precious cannabis is now legal.

OK, sounds good. But is it? If the reaction to the first mini-episode is any indication, maybe the Freaks should have remained in their drug-induced coma. As one Facbooker commented: "Get yourself a collected set of the original comic and skip this drivel!"

Read the rest

Prime Minister Justin Trudeau says Canada will not pay the full price for medical masks that do not live up to medical standards.

Most Realtors® Don’t Expect Steep Price Declines in...

People are always curious about work-from-home (WFH), remote working setups. So, I posted a Basecamp message asking our employees to share a photo of their home office, desk, table, whatever. Here’s what came in. First, the ask: And the answers, in the order they came in: Andy Didorosi, Marketing Justin White, Programmer Jonas Downey, Designer… keep reading

The DML News App offers the best in news reporting.

The post REPORT: Recent documents reveal number of Secret Service agents with COVID-19 appeared first on Dennis Michael Lynch.

An "appalling prank" in Innisfil sent South Simcoe Police officers on a mission to identify the culprits involved.

Police officers responding to a call about a man with a machete in Oppenheimer Park Friday afternoon found what they were looking for, and then some.

The incident happened in the West Point Grey neighbourhood around 3:30 p.m. on Wednesday, police said.

The following article, MI Barber Shop Owner Defies Gov. Whitmer Shutdown Order…Opens Business…Police Officer Walks In…Says, “I love you!”…Walks Out, was first published on 100PercentFedUp.com.

Last week, we reported about how Shelley Luther, owner of the Salon Á La Mode in North Dallas, Texas, who opened up her business in defiance of lockdown orders in the city. The salon owner said that she was ignoring a citation and a cease and desist order from the city to shut down. This one […]

Continue reading: MI Barber Shop Owner Defies Gov. Whitmer Shutdown Order…Opens Business…Police Officer Walks In…Says, “I love you!”…Walks Out ...

The following article, Breaking: Justice Department Dropping Michael Flynn Criminal Case, was first published on 100PercentFedUp.com.

Michael Flynn has finally been exonerated. The Associated Press is reporting exclusively that the Justice Department said it is dropping the criminal case against President Trump’s first national security adviser, Michael Flynn. In court documents being filed Thursday, the Justice Department said it is dropping the case “after a considered review of all the facts […]

Continue reading: Breaking: Justice Department Dropping Michael Flynn Criminal Case ...

The following article, BREAKING: Vice President Mike Pence’s Press Sec Katie Miller, Wife of President Trump’s Sr. Advisor, Stephen Miller, Tests Positive For COVID-19, was first published on 100PercentFedUp.com.

Only moments ago, White House Press Secretary Kayleigh McEnany confirmed that a member of Vice President Mike Pence’s team tested positive for coronavirus. Watch: White House Press Secretary Kayleigh McEnany confirms a member of Vice President Mike Pence's team tested positive for coronavirus pic.twitter.com/3VaUXbwMq7 — Bloomberg QuickTake (@QuickTake) May 8, 2020 Reuters White House Correspondent […]

Continue reading: BREAKING: Vice President Mike Pence’s Press Sec Katie Miller, Wife of President Trump’s Sr. Advisor, Stephen Miller, Tests Positive For COVID-19 ...

Essex County OPP have released a composite drawing of a suspect reported to be impersonating a police officer in Lakeshore.

Mutations in retinaldehyde-binding protein 1 (RLBP1), encoding the visual cycle protein cellular retinaldehyde-binding protein (CRALBP), cause an autosomal recessive form of retinal degeneration. By binding to 11-cis-retinoid, CRALBP augments the isomerase activity of retinoid isomerohydrolase RPE65 (RPE65) and facilitates 11-cis-retinol oxidation to 11-cis-retinal. CRALBP also maintains the 11-cis configuration and protects against unwanted retinaldehyde activity. Studying a sibling pair that is compound heterozygous for mutations in RLBP1/CRALBP, here we expand the phenotype of affected individuals, elucidate a previously unreported phenotype in RLBP1/CRALBP carriers, and demonstrate consistencies between the affected individuals and Rlbp1/Cralbp−/− mice. In the RLBP1/CRALBP-affected individuals, nonrecordable rod-specific electroretinogram traces were recovered after prolonged dark adaptation. In ultrawide-field fundus images, we observed radially arranged puncta typical of RLBP1/CRALBP-associated disease. Spectral domain-optical coherence tomography (SD-OCT) revealed hyperreflective aberrations within photoreceptor-associated bands. In short-wavelength fundus autofluorescence (SW-AF) images, speckled hyperautofluorescence and mottling indicated macular involvement. In both the affected individuals and their asymptomatic carrier parents, reduced SW-AF intensities, measured as quantitative fundus autofluorescence (qAF), indicated chronic impairment in 11-cis-retinal availability and provided information on mutation severity. Hypertransmission of the SD-OCT signal into the choroid together with decreased near-infrared autofluorescence (NIR-AF) provided evidence for retinal pigment epithelial cell (RPE) involvement. In Rlbp1/Cralbp−/− mice, reduced 11-cis-retinal levels, qAF and NIR-AF intensities, and photoreceptor loss were consistent with the clinical presentation of the affected siblings. These findings indicate that RLBP1 mutations are associated with progressive disease involving RPE atrophy and photoreceptor cell degeneration. In asymptomatic carriers, qAF disclosed previously undetected visual cycle deficiency.

Webinar Research Event

Event participants

Mohammed Masbah, Director, Moroccan Institute for Policy Analysis; Associate Fellow, MENA Programme, Chatham House
Moderator: Lina Khatib, Director, MENA Programme, Chatham House

28 April 2020

This paper aims to assist the region’s local authorities, and their key foreign backers, in understanding how transitional justice can provide alternative avenues for holding local ISIS members to account while contributing to the healing of communities.

Research Event

Haid Haid, Senior Consulting Fellow, Middle East and North Africa Programme, Chatham House
Sara Kayyali, Syria Researcher, Middle East and North Africa Division, Human Rights Watch
Moderator: Lina Khatib, Director, Middle East and North Africa Programme, Chatham House

Haploinsufficiency of Meis homeobox 2 (MEIS2), encoding a transcriptional regulator, is associated with human cleft palate, and Meis2 inactivation leads to abnormal palate development in mice, implicating MEIS2 functions in palate development. However, its functional mechanisms remain unknown. Here we observed widespread MEIS2 expression in the developing palate in mice. Wnt1Cre-mediated Meis2 inactivation in cranial neural crest cells led to a secondary palate cleft. Importantly, about half of the Wnt1Cre;Meis2f/f mice exhibited a submucous cleft, providing a model for studying palatal bone formation and patterning. Consistent with complete absence of palatal bones, the results from integrative analyses of MEIS2 by ChIP sequencing, RNA-Seq, and an assay for transposase-accessible chromatin sequencing identified key osteogenic genes regulated directly by MEIS2, indicating that it plays a fundamental role in palatal osteogenesis. De novo motif analysis uncovered that the MEIS2-bound regions are highly enriched in binding motifs for several key osteogenic transcription factors, particularly short stature homeobox 2 (SHOX2). Comparative ChIP sequencing analyses revealed genome-wide co-occupancy of MEIS2 and SHOX2 in addition to their colocalization in the developing palate and physical interaction, suggesting that SHOX2 and MEIS2 functionally interact. However, although SHOX2 was required for proper palatal bone formation and was a direct downstream target of MEIS2, Shox2 overexpression failed to rescue the palatal bone defects in a Meis2-mutant background. These results, together with the fact that Meis2 expression is associated with high osteogenic potential and required for chromatin accessibility of osteogenic genes, support a vital function of MEIS2 in setting up a ground state for palatal osteogenesis.

Bacterial products such as lipopolysaccharides (or endotoxin) cause systemic inflammation, resulting in a substantial global health burden. The onset, progression, and resolution of the inflammatory response to endotoxin are usually tightly controlled to avoid chronic inflammation. Members of the NF-κB family of transcription factors are key drivers of inflammation that activate sets of genes in response to inflammatory signals. Such responses are typically short-lived and can be suppressed by proteins that act post-translationally, such as the SOCS (suppressor of cytokine signaling) family. Less is known about direct transcriptional regulation of these responses, however. Here, using a combination of in vitro approaches and in vivo animal models, we show that endotoxin treatment induced expression of the well-characterized transcriptional repressor Krüppel-like factor 3 (KLF3), which, in turn, directly repressed the expression of the NF-κB family member RELA/p65. We also observed that KLF3-deficient mice were hypersensitive to endotoxin and exhibited elevated levels of circulating Ly6C+ monocytes and macrophage-derived inflammatory cytokines. These findings reveal that KLF3 is a fundamental suppressor that operates as a feedback inhibitor of RELA/p65 and may be important in facilitating the resolution of inflammation.

Heterotrimeric G proteins mediate a variety of signaling processes by coupling G protein–coupled receptors to intracellular effector molecules. In Drosophila, the Gαq gene encodes several Gαq splice variants, with the Gαq1 isoform protein playing a major role in fly phototransduction. However, Gαq1 null mutant flies still exhibit a residual light response, indicating that other Gαq splice variants or additional Gq α subunits are involved in phototransduction. Here, we isolated a mutant fly with no detectable light responses, decreased rhodopsin (Rh) levels, and rapid retinal degeneration. Using electrophysiological and genetic studies, biochemical assays, immunoblotting, real-time RT-PCR, and EM analysis, we found that mutations in the Gαq gene disrupt light responses and demonstrate that the Gαq3 isoform protein is responsible for the residual light response in Gαq1 null mutants. Moreover, we report that Gαq3 mediates rhodopsin synthesis. Depletion of all Gαq splice variants led to rapid light-dependent retinal degeneration, due to the formation stable Rh1-arrestin 2 (Arr2) complexes. Our findings clarify essential roles of several different Gαq splice variants in phototransduction and retinal integrity in Drosophila and reveal that Gαq3 functions in rhodopsin synthesis.

15 October 2019

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.

Bacterial biofilms are cellular communities that produce an adherent matrix. Exopolysaccharides are key structural components of this matrix and are required for the assembly and architecture of biofilms produced by a wide variety of microorganisms. The human bacterial pathogens Escherichia coli and Salmonella enterica produce a biofilm matrix composed primarily of the exopolysaccharide phosphoethanolamine (pEtN) cellulose. Once thought to be composed of only underivatized cellulose, the pEtN modification present in these matrices has been implicated in the overall architecture and integrity of the biofilm. However, an understanding of the mechanism underlying pEtN derivatization of the cellulose exopolysaccharide remains elusive. The bacterial cellulose synthase subunit G (BcsG) is a predicted inner membrane–localized metalloenzyme that has been proposed to catalyze the transfer of the pEtN group from membrane phospholipids to cellulose. Here we present evidence that the C-terminal domain of BcsG from E. coli (EcBcsGΔN) functions as a phosphoethanolamine transferase in vitro with substrate preference for cellulosic materials. Structural characterization of EcBcsGΔN revealed that it belongs to the alkaline phosphatase superfamily, contains a Zn2+ ion at its active center, and is structurally similar to characterized enzymes that confer colistin resistance in Gram-negative bacteria. Informed by our structural studies, we present a functional complementation experiment in E. coli AR3110, indicating that the activity of the BcsG C-terminal domain is essential for integrity of the pellicular biofilm. Furthermore, our results established a similar but distinct active-site architecture and catalytic mechanism shared between BcsG and the colistin resistance enzymes.

Research Event

Haid Haid, Senior Consulting Fellow, Middle East and North Africa Programme, Chatham House
Sara Kayyali, Syria Researcher, Middle East and North Africa Division, Human Rights Watch
Moderator: Lina Khatib, Director, Middle East and North Africa Programme, Chatham House

Margrit Schwarz
Sep 1, 1998; 39:1833-1843
Articles

RK Tangirala
Nov 1, 1995; 36:2320-2328
Articles

Saverio Cinti
Nov 1, 2005; 46:2347-2355
Research Articles

Heterotrimeric G proteins mediate a variety of signaling processes by coupling G protein–coupled receptors to intracellular effector molecules. In Drosophila, the Gαq gene encodes several Gαq splice variants, with the Gαq1 isoform protein playing a major role in fly phototransduction. However, Gαq1 null mutant flies still exhibit a residual light response, indicating that other Gαq splice variants or additional Gq α subunits are involved in phototransduction. Here, we isolated a mutant fly with no detectable light responses, decreased rhodopsin (Rh) levels, and rapid retinal degeneration. Using electrophysiological and genetic studies, biochemical assays, immunoblotting, real-time RT-PCR, and EM analysis, we found that mutations in the Gαq gene disrupt light responses and demonstrate that the Gαq3 isoform protein is responsible for the residual light response in Gαq1 null mutants. Moreover, we report that Gαq3 mediates rhodopsin synthesis. Depletion of all Gαq splice variants led to rapid light-dependent retinal degeneration, due to the formation stable Rh1-arrestin 2 (Arr2) complexes. Our findings clarify essential roles of several different Gαq splice variants in phototransduction and retinal integrity in Drosophila and reveal that Gαq3 functions in rhodopsin synthesis.

Motor protein-based active transport is essential for mRNA localization and local translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased yeast two–hybrid screen for interactions between murine RNA-binding proteins (RBPs) and motor proteins, here we identified protein interaction with APP tail-1 (PAT1) as a potential direct adapter between zipcode-binding protein 1 (ZBP1, a β-actin RBP) and the kinesin-I motor complex. The amino acid sequence of mouse PAT1 is similar to that of the kinesin light chain (KLC), and we found that PAT1 binds to KLC directly. Studying PAT1 in mouse primary hippocampal neuronal cultures from both sexes and using structured illumination microscopic imaging of these neurons, we observed that brain-derived neurotrophic factor (BDNF) enhances co-localization of dendritic ZBP1 and PAT1 within granules that also contain kinesin-I. PAT1 is essential for BDNF-stimulated neuronal growth cone development and dendritic protrusion formation, and we noted that ZBP1 and PAT1 co-locate along with β-actin mRNA in actively transported granules in living neurons. Acute disruption of the PAT1–ZBP1 interaction in neurons with PAT1 siRNA or a dominant-negative ZBP1 construct diminished localization of β-actin mRNA but not of Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) mRNA in dendrites. The aberrant β-actin mRNA localization resulted in abnormal dendritic protrusions and growth cone dynamics. These results suggest a critical role for PAT1 in BDNF-induced β-actin mRNA transport during postnatal development and reveal a new molecular mechanism for mRNA localization in vertebrates.

28 April 2020

This paper aims to assist the region’s local authorities, and their key foreign backers, in understanding how transitional justice can provide alternative avenues for holding local ISIS members to account while contributing to the healing of communities.