The Amateur Traveler talks to Madeline Jhawar from Italy Beyond the Obvious about life as a tour guide for an adventure travel company. Madeline was previously on the Amateur Traveler talking about Travel to Sicily. Madeline talks about her misconceptions about what being a tour guide would be like and the reality of keeping a group of people happy (and not lost). She guided hiking and biking tours primarily in Italy. What skills do you need to be a successful tour guide? It might not be what you think.

The Amateur Traveler talks to Eric Schwartzman (author, educator and podcaster) about his hometown of Los Angeles. Over a two part series of episodes Eric will give us sample itineraries for 4 days in the Los Angeles area. Be forewarned that no theme parks will be involved in Eric's tour but instead an insider's look at LA. So pack up your swim suit, a sport coat and nice shoes and get in your car to explore LA. Along the way Eric points out the cafes, coffee shops, restaurants, hotels and movie locations that he thinks you should know about.

Day 1: Eric starts us at the beach at Santa Monica. We visit the Santa Monica Pier, the rides and the aquarium and then head to Venice with its pier, canals, and famous muscle beach.

Day 2: We follow Eric to Beverly Hills and Westwood. We look over the valley from the Getty Center above the valley. We visit Century City which is now the home for high rises but one was where John Wayne shot westerns. We go shopping on world famous Rodeo Drive.

The Amateur Traveler talks to Eric Schwartzman (author, educator and podcaster) about his hometown of Los Angeles. In this second part of a two part series of episodes Eric will give us the last two days of his sample itineraries for 4 days in the Los Angeles area. In this insider’s look at LA Eric points out the cafes, coffee shops, restaurants, hotels and movie locations that he thinks you should know about.

Day 3: Hollywood – Sunset Strip, Grauman’s Chinese Theater, Roosevelt, L.A.’s best chili dog, Academy Awards theater, Sunset Grill, Hollywood Cemetary and more.

Day 4: Downtown – Chinatown for dim sum, Olvera St. for Mole, Union Station for breathtaking Mission Architecture, Santee Alley and Los Angeles St. for discount children’s formal wear, Disney Hall for magnificent modern architecture and Our Lady of Angels Catholic Church.

The Amateur Traveler talks to Bethany of the Nevada Tourism Bureau about Lake Tahoe. Lake Tahoe is a high elevation alpine lake on the border of California and Nevada. It is surrounded by 18 ski areas so it is a popular winter destination. In the winter it is also a great place for back country hiking, cross country skiing, snowshoeing, and snowmobiling. In the Summer, Tahoe is a popular area for hiking, fishing and outdoor activities. But, there is another side to Tahoe which is the casinos, restaurants, and entertainment of Nevada's South Tahoe.

The Amateur Traveler talks to Carrie from cruisebuzz.net about a popular vacation spot just off the coast of California, Catalina Island. 

Hear about travel to Lassen National Park in northern California as the Amateur Traveler talks to Dick Jordan about this spectacular if less visited destination. Lassen is in northeastern California. It is just as easy to get to from San Francisco as Yosemite National Park but with fewer tourists and one more volcano. The park centers around the dormant volcano Mt. Lassen and features other geothermal active areas.

Hear about travel to Santa Barbara, California as the Amateur Traveler talks to Heather Simon from wellplannedtravel.net about the "American Riviera".

Hear about travel to San Diego as the Amateur Traveler talks to Mike from MikesRoadTrip.com about this beautiful city in Southern California.

Hear about travel to California's premier wine region of Napa and Sonoma as the Amateur Traveler talks again to free lance journalist Jill Robinson about this area with more than just wine... but a lot of that

Hear about travel to San Francisco, California as the Amateur Traveler talks to Jill Robinson and Kimberley Levato authors of 100 Things to Do in San Francisco Before You Die.

los ángeles,hollywood,california,southern california,travel

Hear about the best of California's state parks as the Amateur Traveler talks to Jeff Ohlfs who has been to all the parks in the state park system.

An evangelical church network in California will ignore Democratic Gov. Gavin Newsom’s executive prohibitions this month, opening sanctuary doors for communal worship despite the ongoing coronavirus pandemic. According to Fox News, California Church United, representing roughly 3,000 churches and 2.5 million congregants statewide, announced Thursday that it will return to conducting in-person services by Pentecost…

The post Huge Group of California Churches Announces Plan To Defy Governor Newsom’s Order appeared first on The Western Journal.

A year after the Obama administration changed its policy on which undocumented immigrants it would target for deportation, it's not clear who is being sent back.

Americans have been receiving contradictory information about the coronavirus pandemic, so much so that it's become a joke. One example is face masks: In March, the World Health Organization advised people to not wear masks if they aren't sick or caretakers of the sick. 

But given that some coronavirus patients are asymptomatic, opinions of masks from top officials have shifted. The CDC and the media now advise you to wear a damn mask. And a new study may provide more evidence that masks can help beat the outbreak.

According to this study, if 80 percent of Americans wore masks, coronavirus infections would plummet, Vanity Fair reports. The title of the study makes the researchers' view clear: Universal Masking is Urgent in the COVID-19 Pandemic. Read more...

The internet is a scary enough place as it is, and now with the added misinformation and panic surrounding the coronavirus pandemic, it's even scarier. Thanks to the United Nations and dozens of artists, however, the internet just got a little more beautiful. 

In late March, the UN put a call out to artists to help combat the spread of COVID-19. They sought creatives to create content around six areas of WHO and UN priority actions: personal hygiene, social distancing, knowing the symptoms, spreading kindness, myth-busting, and doing more/donating. Tens of thousands of artists answered the call in two weeks, and now the COVID-19 Response Creative Content Hub is available for browsing.  Read more...

With all the stress in the world — you know, a deadly, terrifying global pandemic — Spotify dropped a new service: a daily, personalized aimed at wellness. Fittingly, it's called Daily Wellness and I gave it a try. 

OK, first, let me drop my biases: I can be a cynical person and I'm pretty high energy — like hyper hyper — which has made meditation difficult for me. I can get both mentally and physically uncomfortable while trying anything resembling meditation or therapy or sincere reflection.

That being said, amid the pandemic — and battling some, let's say, serious anxiety — I've been taking active steps to try to improve my mental health. Therapy, meditation, exercise, whatever else, it all seemed like a good idea to help me get through the day. 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

Who is Patrick Mason? I just ran across a few short horror films he wrote and directed, and they're truly scary. Like edge-of-your-seat gasp-out-loud scary. Not only that, but they're beautifully made with good actors, especially Ayuda (see below). The three videos posted here are the ones I've seen so far, but there are more on his site, which I plan to watch tonight. Can't wait to see where this director takes us next.

Read the rest

The flood stricken Regional Municipality of Wood Buffalo says it is on track to lift its boil water advisory sooner than it was originally projected.

Sundowns coach Pitso Mosimane says the premature return of football, even behind closed doors, poses a number of potential problems.

Mother’s Day is just around the corner and finding the perfect gift for such a special occasion can be a really overwhelming task, particularly if you’re a last minute shopper. That’s why, to help you out, we’re sharing with you the best Mother’s Day gift ideas you can give to every supermom on your list. […]

The post DumbLittleMan’s Ultimate Gift Guide for Mother’s Day 2020 appeared first on Dumb Little Man.

Radoslaw Dobrolecki, US business development director at RTB House, discusses how artificial intelligence can help predict customer behavior at scale.

Omer Golan, founder and CEO of Outernets, discusses how artificial intelligence can improve the digital out-of-home industry.

Spotify will gain more than 10 million US listeners in 2020   February 25, 2020 (New York, NY) – Pandora is no longer the most popular music streaming service in the […]

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

The following article, ‘Schiff in Panic Mode’: Sources Say Russia Probe Transcripts Affirm Officials Found Nothing on Collusion, was first published on 100PercentFedUp.com.

Transcripts of House Intelligence Committee interviews have been cleared for release, and Adam Schiff is reportedly in panic mode. Unfortunately for Schiff, top law enforcement and intel officials said they saw no evidence of collusion between the Trump campaign and Russia in the transcripts. Republicans sought and got approval for the release of the transcripts […]

Continue reading: ‘Schiff in Panic Mode’: Sources Say Russia Probe Transcripts Affirm Officials Found Nothing on Collusion ...

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 ...

Research Event

Event participants

Michael Gasiorek, Professor of Economics, University of Sussex; Director, Interanalysis; Fellow, UK Trade Policy Observatory, University of Sussex
Julia Magntorn Garrett, Research Officer, UK Trade Policy Observatory, University of Sussex
Prof Jim Rollo, Deputy Director, UK Trade Policy Observatory, University of Sussex; Associate Fellow, Global Economy and Finance Department, Chatham House
Nicolo Tamberi, Research Officer in the Economics of Brexit, University of Sussex
L. Alan Winters, Professor of Economics, Director, UK Trade Policy Observatory, University of Sussex

Research Event

Event participants

Michael Gasiorek, Professor of Economics, UKTPO Fellow, University of Sussex; Director, Interanalysis
Julia Magntorn Garrett, Research Officer, UKTPO, University of Sussex
Allie Renison, Head of Europe and Trade Policy at the Institute of Directors
Maximiliano Mendez-Parra, Senior Research Fellow, Overseas Development Institute
Chair: Professor Jim Rollo, Associate Fellow, Global Economy and Finance Department, Chatham House; Deputy Director, UK Trade Policy Observatory

Bacterial type VII secretion systems secrete a wide range of extracellular proteins that play important roles in bacterial viability and in interactions of pathogenic mycobacteria with their hosts. Mycobacterial type VII secretion systems consist of five subtypes, ESX-1–5, and have four substrate classes, namely, Esx, PE, PPE, and Esp proteins. At least some of these substrates are secreted as heterodimers. Each ESX system mediates the secretion of a specific set of Esx, PE, and PPE proteins, raising the question of how these substrates are recognized in a system-specific fashion. For the PE/PPE heterodimers, it has been shown that they interact with their cognate EspG chaperone and that this chaperone determines the designated secretion pathway. However, both structural and pulldown analyses have suggested that EspG cannot interact with the Esx proteins. Therefore, the determining factor for system specificity of the Esx proteins remains unknown. Here, we investigated the secretion specificity of the ESX-1 substrate pair EsxB_1/EsxA_1 in Mycobacterium marinum. Although this substrate pair was hardly secreted when homologously expressed, it was secreted when co-expressed together with the PE35/PPE68_1 pair, indicating that this pair could stimulate secretion of the EsxB_1/EsxA_1 pair. Surprisingly, co-expression of EsxB_1/EsxA_1 with a modified PE35/PPE68_1 version that carried the EspG5 chaperone-binding domain, previously shown to redirect this substrate pair to the ESX-5 system, also resulted in redirection and co-secretion of the Esx pair via ESX-5. Our results suggest a secretion model in which PE35/PPE68_1 determines the system-specific secretion of EsxB_1/EsxA_1.

Cone photoreceptors in the retina enable vision over a wide range of light intensities. However, the processes enabling cone vision in bright light (i.e. photopic vision) are not adequately understood. Chromophore regeneration of cone photopigments may require the retinal pigment epithelium (RPE) and/or retinal Müller glia. In the RPE, isomerization of all-trans-retinyl esters to 11-cis-retinol is mediated by the retinoid isomerohydrolase Rpe65. A putative alternative retinoid isomerase, dihydroceramide desaturase-1 (DES1), is expressed in RPE and Müller cells. The retinol-isomerase activities of Rpe65 and Des1 are inhibited by emixustat and fenretinide, respectively. Here, we tested the effects of these visual cycle inhibitors on immediate, early, and late phases of cone photopic vision. In zebrafish larvae raised under cyclic light conditions, fenretinide impaired late cone photopic vision, while the emixustat-treated zebrafish unexpectedly had normal vision. In contrast, emixustat-treated larvae raised under extensive dark-adaptation displayed significantly attenuated immediate photopic vision concomitant with significantly reduced 11-cis-retinaldehyde (11cRAL). Following 30 min of light, early photopic vision was recovered, despite 11cRAL levels remaining significantly reduced. Defects in immediate cone photopic vision were rescued in emixustat- or fenretinide-treated larvae following exogenous 9-cis-retinaldehyde supplementation. Genetic knockout of Des1 (degs1) or retinaldehyde-binding protein 1b (rlbp1b) did not eliminate photopic vision in zebrafish. Our findings define molecular and temporal requirements of the nonphotopic or photopic visual cycles for mediating vision in bright light.

Research Event

Event participants

Ahmed Tabaqchali, Chief Investment Officer, Asia Frontier Capital Iraq Fund; Adjunct Assistant Professor, American University of Iraq Sulaimani
Moderator: Renad Mansour, Senior Research Fellow, Middle East and North Africa Programme, Chatham House

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.

Bacterial type VII secretion systems secrete a wide range of extracellular proteins that play important roles in bacterial viability and in interactions of pathogenic mycobacteria with their hosts. Mycobacterial type VII secretion systems consist of five subtypes, ESX-1–5, and have four substrate classes, namely, Esx, PE, PPE, and Esp proteins. At least some of these substrates are secreted as heterodimers. Each ESX system mediates the secretion of a specific set of Esx, PE, and PPE proteins, raising the question of how these substrates are recognized in a system-specific fashion. For the PE/PPE heterodimers, it has been shown that they interact with their cognate EspG chaperone and that this chaperone determines the designated secretion pathway. However, both structural and pulldown analyses have suggested that EspG cannot interact with the Esx proteins. Therefore, the determining factor for system specificity of the Esx proteins remains unknown. Here, we investigated the secretion specificity of the ESX-1 substrate pair EsxB_1/EsxA_1 in Mycobacterium marinum. Although this substrate pair was hardly secreted when homologously expressed, it was secreted when co-expressed together with the PE35/PPE68_1 pair, indicating that this pair could stimulate secretion of the EsxB_1/EsxA_1 pair. Surprisingly, co-expression of EsxB_1/EsxA_1 with a modified PE35/PPE68_1 version that carried the EspG5 chaperone-binding domain, previously shown to redirect this substrate pair to the ESX-5 system, also resulted in redirection and co-secretion of the Esx pair via ESX-5. Our results suggest a secretion model in which PE35/PPE68_1 determines the system-specific secretion of EsxB_1/EsxA_1.

Nucleoside analogues are a valuable experimental tool. Incorporation of these molecules into newly synthesized DNA (i.e. pulse-labeling) is used to monitor cell proliferation or to isolate nascent DNA. Some of the most common nucleoside analogues used for pulse-labeling of DNA in cells are the deoxypyrimidine analogues 5-ethynyl-2'-deoxyuridine (EdU) and 5-ethynyl-2'-deoxycytidine (EdC). Click chemistry enables conjugation of an azide molecule tagged with a fluorescent dye or biotin to the alkyne of the analog, which can then be used to detect incorporation of EdU and EdC into DNA. The use of EdC is often recommended because of the potential cytotoxicity associated with EdU during longer incubations. Here, by comparing the relative incorporation efficiencies of EdU and EdC during short 30-min pulses, we demonstrate significantly lower incorporation of EdC than of EdU in noninfected human fibroblast cells or in cells infected with either human cytomegalovirus or Kaposi's sarcoma-associated herpesvirus. Interestingly, cells infected with herpes simplex virus type-1 (HSV-1) incorporated EdC and EdU at similar levels during short pulses. Of note, exogenous expression of HSV-1 thymidine kinase increased the incorporation efficiency of EdC. These results highlight the limitations when using substituted pyrimidine analogues in pulse-labeling and suggest that EdU is the preferable nucleoside analogue for short pulse-labeling experiments, resulting in increased recovery and sensitivity for downstream applications. This is an important discovery that may help to better characterize the biochemical properties of different nucleoside analogues with a given kinase, ultimately leading to significant differences in labeling efficiency of nascent DNA.

US Secretary of State John Kerry and Iranian Minister of Foreign Affairs Dr Mohammad Javad Zarif have been voted as the winners of this year’s Chatham House Prize.

27 August 2015

3 February 2016

Drawing on the findings of a recent workshop exploring a potential conflict between China and Japan over disputed islands, this paper suggests there are significant differences between how the United States and Europe prioritize their interests in the Asia-Pacific.

18 May 2016

Based on an exercise which modelled violations of the Iran nuclear deal, this paper finds that the deal's framework enabled the transatlantic partners to remain united but domestic factors in the US and Europe could, in future, make this increasingly hard.

5 August 2016

Based on a workshop which played out a scenario of rising tensions between Turkey and Russia, this paper finds that the situation would have to escalate dramatically to threaten transatlantic unity.

Invitation Only Research Event

Event participants

Megan Greene, Managing Director and Chief Economist, Manulife Asset Management 

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.

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.

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.