Realtors® Applaud Administration’s Calls to End...

Tesla CEO Elon Musk said Saturday the company will file a lawsuit against Alameda County and threatened to move its headquarters and future programs to Texas or Nevada immediately, escalating a fight between the company and health officials over whether its factory in Fremont can reopen. Tesla had planned to bring back about 30% of […]

Paper is an essential commodity for office operations. Most conventional offices rely on paper for completing the simplest tasks. Even after digitization, the dream of a completely paperless office is far from reality. Humans are used to a standard form of note-taking and documentation. Here is how to achieve paperless operations and document automation with […]

The post Achieving Paperless Operations and Document Automation with AI and ML appeared first on ReadWrite.

velocityconf: @rkustner Congrats, thank you, and good luck!

velocityconf: Call for speakers and registration is open for @webperfdays in Silicon Valley http://t.co/cJKBmynkjI June 22, Google HQ (cc @sfwebperf)

velocityconf: RT @allspaw: Operations and System Safety - always a student http://t.co/1VYBEZYrK8 #devops #velocityconf

Harry and Meghan are celebrating 365 days around the sun with Archie!

South Africa's net death rate has decreased amid the Covid-19 pandemic over the past five weeks, despite the 186 deaths thus far, Health Minister Zweli Mkhize says.

Cosatu in the Western Cape says that it is deeply concerned over the "alarming rate on increase" in Covid-19 infections in the province.

You’ve probably attended a webinar or two (or more), but are you using them effectively as part of your overall content plan? In this blog post, we teach you the basics of hosting a webinar and how to use them effectively as you build out your content strategy and grow your business.

You’ve probably attended a webinar or two (or more), but are you using them effectively as part of your overall content plan? In this blog post, we teach you the basics of hosting a webinar and how to use them effectively as you build out your content strategy and grow your business.

Borrowing costs have stayed at or near record lows for five consecutive weeks.

Disneyland (Strategy)

Hear about travel to the Democratic Republic of the Congo (DRC) as the Amateur Traveler talks to Chris and Sasha Rosencranz about their recent trip to this African country. The DRC is located along the south bank of the Congo River. This large country used to be the Belgian Congo. Chris was previously on the Amateur Traveler talking about the Republic of the Congo as well.

Hear about travel to United Arab Emirates as the Amateur Traveler talks to travel writer Zora O'Neill about her recent trip to these small states on the Persian / Arabian Gulf.

Hear about travel to some of the WWII sites in Western Europe  as the Amateur Traveler talks to Gary Arndt from everything-everywhere.com about the Liberation Route.

Hear about travel to the United Arab Emirates (UAE) as the Amateur Traveler talks to Keri Hedrick from ourglobetrotters.com and familytravel-middleeast.com about her adopted country.

Hear about travel to Virunga National Park as the Amateur Traveler talks to Niall from Ireland about his visit to this stunning national park in the Democratic Republic of the Congo.

During times of panic and suffering, it is important to take a step back and remember that “God is always in control.” One NFL star known for proudly displaying his faith made that message quite clear during an episode of the Fox Nation show “Bible Study: Messages of Hope” which debuted this week. Demario Davis,…

The post ‘Man of God’ NFL Star Points Out Things To Be Grateful for During the Pandemic: ‘There’s So Much’ appeared first on The Western Journal.

As confetti floated through the air, a baby boy and his family celebrated his final chemotherapy treatment in time to go home before his first birthday. According to KSAZ, young Aaron has been battling a rare form of cancer called acute megakaryoblastic leukemia since he was four months old. Aaron was a patient at Duke…

The post 10-Month-Old Gets Heartwarming Celebration from Hospital Staff After Finishing Chemotherapy appeared first on The Western Journal.

“Outbreaks have sparked riots and propelled public-health innovations, prefigured revolutions and redrawn maps.” – The New Yorker, April 2020 “Nothing will be the same.”  That’s the overwhelming takeaway I’ve heard from dozens of conversations I’ve had with C-suite leaders, physicians, policy experts and media professionals these past few weeks.  When it comes to the business … Continue reading "An Open Letter To American Corporations: It’s Good Business (and Smart Marketing) To Support Quality Journalism"

The U.S. has deported an average of 403,500 people each year during the Obama administration. What else do the numbers say about the nation's immigration system?

Unless the Supreme Court acts fast, the window might be closed for President Obama on immigration reform.

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Wellness is a buzzy word lately. Over the past few years, we’ve seen a surge in all things health, wellness, and spirituality. Juice bars are popping up, boutique studios are becoming more accessible, and essential oils are chilling us out. Self-care is becoming more of the norm too, but amidst all this hype, it can be challenging to find the right routine that promotes good exercise, sleep, vitals, and mindset.  Read more...

In a world focused on buzzword-driven models and algorithms, you’d be forgiven for forgetting about the unreasonable importance of data preparation and quality: your models are only as good as the data you feed them. This is the garbage in, garbage out principle: flawed data going in leads to flawed results, algorithms, and business decisions. […]

Nicholas Love's Penguin Classics cover generator lets you upload an image and set type in humorous imitation of the label. It can also do the similar but inverted Oxford World Classics look. But sadly not the classic classics look.

Many excellent designs in this twitter thread; embedded here is my contribution. Read the rest

Police in Haiti are investigating allegations that the president of the national football federation raped teenage girls.

Six-time world champion Lewis Hamilton has said he feels "fresher than ever" following an unexpected break from Formula One.

The genial young administrator with a burgeoning reputation chuckles when it's pointed out to him that he can't seem to shake off 'working' for some of South Africa's biggest businessmen.

The naked mole rat (Heterocephalus glaber) is a rodent, known for its burrowing and is indigenous to East Africa. The mole rat possesses a number of characteristics which allow it to survive in underground and harsh environments.

The average naked mole rat is between 3 to 4 inches (8 to 10 centimeters) in length and weighs between 1.1 and 1.2 ounces (30 to 35 grams). They have small eyes, poor sight, and have legs that are quite short and thin. They are also able to move backward and forward at the same quick pace and have large teeth that allow them to dip. The term "naked" comes from the fact that they have very little hair and gray-pink skin.

The species is highly adapted to situations in which oxygen is limited within tunnels of their habitat. The lungs are small and their blood is greatly able to bond oxygen. They have very low metabolic and respiration rates. During periods of drought and hunger, the metabolic can decrease further to about 25% of its normal level.

The naked mole rat lives predominantly in the dry tropical grasslands in East Africa with large concentrations being concentrated in Somalia, Kenya, and southern Ethiopia. Groups of around 80 individual mole rats (although it can be as few as 20 and as many as 200) live within a complex burrowing system within the African desert. These tunnel systems can be quite long, between two to three miles in length.

There is a complex hierarchical structure where one queen and between 1 and 3 males reproduce, the other naked mole rats are workers and sterile. Dimorphism exists between the males, two forms of workers (tunnel digging/gathering and soldiers), and the breeding males. The breeding males and the queen can keep up their relationship for several years. The queens can live for a period of between 13 and 18 years and are quite hostile towards other females. Upon the death of the queen, another female will become queen in her place.

The naked mole rat mostly eats large tubers that they find underground during their mining exhibitions. However, they are also known for eating their own fecal matter. One tuber, depending upon its size, can feed a colony for several months or years as they only eat the inside of the tuber. They leave the outer parts so that the tuber is able to regenerate.

Naked mole rats are currently not a threatened species. Although their living conditions are tough, they are a widespread species.

Naked mole rats help in cancer research, because they never get cancer (read here).

We’ve been teaching people how to do remote work well for the better part of two decades. We wrote a whole book about the topic in 2013, called REMOTE: Office Not Required. Basecamp has been a remote company since day one, and our software is sold as an all-in-one toolkit for remote work. Yeah, we’re… keep reading

Part of the Going for gold promo for the BBC UK Homepage

The following article, MSNBC’s Brian Williams Chuckles With Dem Strategist as He Gloats, Mocks Trump About Tragic Downturn in Economy: “They were going to lose before this hit. They’re just going to lose worse now”, was first published on 100PercentFedUp.com.

James Carville spoke out before the coronavirus crisis to say that there is no way  Joe Biden has a chance at beating President Trump in the 2020 election. Well, He’s singing a different tune now at the expense of Americans suffering through this horrible pandemic and economic crisis. James Carvill is a Democratic strategist who […]

Continue reading: MSNBC’s Brian Williams Chuckles With Dem Strategist as He Gloats, Mocks Trump About Tragic Downturn in Economy: “They were going to lose before this hit. They’re just going to lose worse now” ...

The following article, Mother of the Year, Michelle Obama Explains How Having Kids Was A “Concession”… Had To Give Up Her “Aspirations and Dreams” [VIDEO], was first published on 100PercentFedUp.com.

While campaigning for her community organizer turned presidential candidate husband, Barack, Michelle Obama told a crowd of his supporters in Milwaukee, Wisconsin that for the first time in her life, she was proud to be an American. Four years later, Michelle Obama was a keynote speaker at the DNC convention, where she told Democrats how […]

Continue reading: Mother of the Year, Michelle Obama Explains How Having Kids Was A “Concession”… Had To Give Up Her “Aspirations and Dreams” [VIDEO] ...

The following article, Video: Dallas Salon Owner Shelley Luther Gets Surprise Visit from Sen Ted Cruz for a Celebratory Haircut, was first published on 100PercentFedUp.com.

When Dallas, Texas salon owner Shelley Luther opened her salon in defiance of the lockdown order in Texas, she was visited numerous times by the local police and then sentenced to 7 days in jail with a fine of $7,000. After public outrage at her punishment, the Texas Supreme Court stepped in to demand her […]

Continue reading: Video: Dallas Salon Owner Shelley Luther Gets Surprise Visit from Sen Ted Cruz for a Celebratory Haircut ...

The following article, Obama Private Call Released: Implores Political Operatives to Help Protect Him…”We gotta make this happen”, was first published on 100PercentFedUp.com.

Michael Isikoff at Yahoo News on Friday night released audio of a call from former President Barack Obama to political operatives and the media to help protect “the rule of law” by protecting him. Obama desperately wants the Deep State and media to protect him by helping elect Joe Biden: “The fact that there is […]

Continue reading: Obama Private Call Released: Implores Political Operatives to Help Protect Him…”We gotta make this happen” ...

Mother's Day is Sunday, but with COVID-19, it's forcing many to change their plans.

Manitoba’s unemployment rate nearly doubled between March and April, according to the monthly report from Statistics Canada released Friday morning.

Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral insulin resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis and has been linked to type 2 diabetes. Although many studies have attempted to link ER stress and T2DM, the specific effects of ER stress on beta-cell function remain incompletely understood. To determine the interrelationship between ER stress and beta-cell function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with the ER stress–inducer tunicamycin (TM). TM induced ER stress as expected, as evidenced by activation of the unfolded protein response. Beta cells treated with TM also exhibited concomitant alterations in their electrical activity and cytosolic free Ca2+ oscillations. As ER stress is known to reduce ER Ca2+ levels, we tested the hypothesis that the observed increase in Ca2+ oscillations occurred because of reduced ER Ca2+ levels and, in turn, increased store-operated Ca2+ entry. TM-induced cytosolic Ca2+ and membrane electrical oscillations were acutely inhibited by YM58483, which blocks store-operated Ca2+ channels. Significantly, TM-treated cells secreted increased insulin under conditions normally associated with only minimal release, e.g. 5 mm glucose, and YM58483 blocked this secretion. Taken together, these results support a critical role for ER Ca2+ depletion–activated Ca2+ current in mediating Ca2+-induced insulin secretion in response to ER stress.

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.

Tau is a microtubule-associated protein that plays a major role in Alzheimer's disease (AD) and other tauopathies. Recent reports indicate that, in the presence of crowding agents, tau can undergo liquid–liquid phase separation (LLPS), forming highly dynamic liquid droplets. Here, using recombinantly expressed proteins, turbidimetry, fluorescence microscopy imaging, and fluorescence recovery after photobleaching (FRAP) assays, we show that the divalent transition metal zinc strongly promotes this process, shifting the equilibrium phase boundary to lower protein or crowding agent concentrations. We observed no tau LLPS-promoting effect for any other divalent transition metal ions tested, including Mn2+, Fe2+, Co2+, Ni2+, and Cu2+. We also demonstrate that multiple zinc-binding sites on tau are involved in the LLPS-promoting effect and provide insights into the mechanism of this process. Zinc concentration is highly elevated in AD brains, and this metal ion is believed to be an important player in the pathogenesis of this disease. Thus, the present findings bring a new dimension to understanding the relationship between zinc homeostasis and the pathogenic process in AD and related neurodegenerative disorders.

6 January 2020

21 January 2020

Discussions of North African integration have evoked ideas of a shared identity and a common destiny in the region. However, recent attempts to build regional blocs in North Africa have been unsuccessful. This paper examines the benefits of a ‘synergistic’ approach to North African cooperation. 

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.

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.

Sulfur is essential for biological processes such as amino acid biogenesis, iron–sulfur cluster formation, and redox homeostasis. To acquire sulfur-containing compounds from the environment, bacteria have evolved high-affinity uptake systems, predominant among which is the ABC transporter family. Theses membrane-embedded enzymes use the energy of ATP hydrolysis for transmembrane transport of a wide range of biomolecules against concentration gradients. Three distinct bacterial ABC import systems of sulfur-containing compounds have been identified, but the molecular details of their transport mechanism remain poorly characterized. Here we provide results from a biochemical analysis of the purified Escherichia coli YecSC-FliY cysteine/cystine import system. We found that the substrate-binding protein FliY binds l-cystine, l-cysteine, and d-cysteine with micromolar affinities. However, binding of the l- and d-enantiomers induced different conformational changes of FliY, where the l- enantiomer–substrate-binding protein complex interacted more efficiently with the YecSC transporter. YecSC had low basal ATPase activity that was moderately stimulated by apo FliY, more strongly by d-cysteine–bound FliY, and maximally by l-cysteine– or l-cystine–bound FliY. However, at high FliY concentrations, YecSC reached maximal ATPase rates independent of the presence or nature of the substrate. These results suggest that FliY exists in a conformational equilibrium between an open, unliganded form that does not bind to the YecSC transporter and closed, unliganded and closed, liganded forms that bind this transporter with variable affinities but equally stimulate its ATPase activity. These findings differ from previous observations for similar ABC transporters, highlighting the extent of mechanistic diversity in this large protein family.

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.

Support from the Bill & Melinda Gates Foundation has enabled Chatham House to develop a global health security track at the Munich Security Conference (MSC).