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Boris Palmer: FDP macht umstrittenem Grünen-Politiker Aufnahmeangebot

Nach seinen provokanten Aussagen zur Corona-Pandemie diskutieren die Grünen über einen Parteiausschluss von Tübingens Oberbürgermeister Boris Palmer. Nun macht ihm die FDP Avancen.




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Small tribes seal borders, push testing to keep out virus




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Tribune Editorial: We are all guinea pigs now




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Brooklyn man triumphs in lengthy Airbnb battle with city as judge orders city to ‘leave the poor guy alone’

A disabled Brooklynite who ran afoul of Department of Buildings officials by renting out his home to Airbnb users triumphed last week when a Manhattan judge ordered the city to repay his $4,375 fine and cover any additional costs and payouts in his battle with the de Blasio administration. The decision ended a legal battle pitting Stanley “Skip” Karol against the city that began with an anonymous phone call back in July 2018.




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French World War II patriot Cécile Rol-Tanguy dead at 101

French Resistance leader Cecile Rol-Tanguy has died at the age of 101.




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French World War II patriot Cécile Rol-Tanguy dead at 101

French Resistance leader Cecile Rol-Tanguy has died at the age of 101.




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Brooklyn man triumphs in lengthy Airbnb battle with city as judge orders city to ‘leave the poor guy alone’

A disabled Brooklynite who ran afoul of Department of Buildings officials by renting out his home to Airbnb users triumphed last week when a Manhattan judge ordered the city to repay his $4,375 fine and cover any additional costs and payouts in his battle with the de Blasio administration. The decision ended a legal battle pitting Stanley “Skip” Karol against the city that began with an anonymous phone call back in July 2018.




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Summer 2020: quarantine move will trigger 'bank holiday traffic every day' as prices soar above £2k for a week at Center Parcs

Exclusive: 'As well as staggered working hours we need to stagger holidays,' says AA president Edmund King




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Virus corona: Hơn bốn triệu người nhiễm Covid-19 trên toàn thế giới

Các chuyên gia cảnh báo số lượng nhiễm trùng thực sự có thể cao hơn do tỷ lệ xét nghiệm thấp ở nhiều quốc gia.




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Lions' triumph over All Blacks marked another historic day for rugby union



VICTORY for the Lions yesterday morning courtesy of a stirring late comeback against the All Blacks was magnificent sporting theatre and the perfect result to set up a series decider next weekend.




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Musk threatens to exit California over virus restrictions

Tesla CEO Elon Musk threatened Saturday to pull the company's factory and headquarters out of California in an escalating spat with local officials who have stopped the company from reopening its electric vehicle factory.




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Purdue football offseason notes | More trick plays in 2018?

Tracking the Boilermakers throughout the offseason

       




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Pasquale Amore, who died of COVID-19, was the gregarious patriarch of a large family

Pasquale "Patrick" Amore, 88, had an infectious laugh and a zest for life. He died of COVID-19 at the age of 88.

       




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6 Tips and Tricks for Hiking the Inca Trail

My flight was booked! My dream of hiking the Inca Trail, and walking through the sun gate to Machu Picchu was finally becoming a reality. But then, the reality hit me. I have never done an overnight hike before! What do I pack? How do I get into shape? Is it safe? Do I go alone or with a group? As excited as I was, I realized I had a lot of planning ahead of me, but every moment of preparation (and sometimes extreme anxiety) was all worth it. Here are a few tips and tricks that helped me not only survive the Inca Trail, but have the trip of a lifetime!

  1. Find an Incredible Tour Group

Before booking my trip, I was not sure how I felt about going with a tour group. I was worried that traveling with a group of strangers would take away from the trip. However, after plenty of research, I decided to go with Active Adventures on the Ultimate Peru Adventure.

Our trip leader was not only full of helpful and interesting information, but became a friend who gave local tips, and made me feel comfortable and safe. I became close friends with my small tour group of 10 people, and still keep in touch with them. Picking a quality tour group like Active Adventures not only helped take the stress out of travelling logistics, but is truly what made my trip an enjoyable experience. (And for all the foodies out there, our Inca Trail chefs were incredible).

  1. Get Fit

On the Inca Trail we had people of all ages, sizes, and fitness levels. However, I highly recommend preparing your body a little, and familiarizing yourself with how your body reacts to high altitude. But, don’t worry, you don’t need to an extreme amount of training. To prepare, I went on one to two hikes a week, and did plenty of dog walking. My hikes on average ranged from 3 to 7 miles.

However, as fit as you are, everybody reacts differently to altitude. Try finding a hike in your area that has somewhat of a higher altitude. I only had the opportunity to do one higher altitude hike. It was not as high as the Inca Trail, but it still gave me an idea of how my body feels in high altitude. But don’t stress out too much! Your tour leader has helped many people hike the Inca Trail, and will be there to help you if you start to feel sick, or simply need a little extra motivation.

  1. Technology Tools

I am a firm believer in digital detoxing when traveling, but when hiking in the wilderness, it is comforting to know that I have helpful resources at my fingertips if I ever need it. When hiking or traveling, there are always a few resources and apps I like to have on my phone or iTouch to stay safe.

As a traveler, we are more vulnerable to security threats or identity theft on public computers and Wi-Fi. I choose to use a VPN when traveling for Wi-Fi security in hotels, to avoid computer viruses, and to gain access to content that is geo-blocked. For my Inca Trail trek I downloaded the MotionX GPS app. The app supports GPS navigation without the need for cell service. Thankfully our guides kept us on track, but it was comforting knowing that if anything happened, I could use my phone as a backup for navigation help.

  1. Make a Visit to Your Doctor

When traveling anywhere, it is important to check in with your doctor. Different regions of the world may require various vaccinations, or medication. Before visiting your doctor, it is also helpful to do a little bit of your own research as to what medications or vaccinations are needed for travel. Your doctor may be familiar with vaccinations needed for Peru, but you are the only person who knows what your trip will consist of. Be sure to mention to your doctor if you are going to the Peruvian Amazon, or high altitude.

For the Inca Trail I recommend packing the following medications:

-Altitude sickness medication (Acetazolamide)

                       -Imodium

                       -Antibiotics (Ciprofloxacin)

                       -Bug spray (not technically a medication, but important to bring as well)

                       -Ibuprofen (always good to have)

This list is most likely what your doctor will recommend as well, but be sure to do your own research as well. You may need malaria pills or certain vaccinations depending on where else your trip is going, or personal previous medical history.

  1. Pack Light

The hardest part of my trip (aside from trekking up the stairs of the Inca Trail) was packing! There are several limitations on how much you pack on the Inca Trail in order to maintain that porters are being treated fairly and respectfully. Each porter is limited to carrying 20kg. This includes all blankets, clothes, and the porter’s personal belongings. Talk to your Active Adventure tour guide before leaving on your trip to find out up to date information on how much you are able to pack, and information on sleeping bags and pads.

Aside from packing light, there are of course certain items you will want to pack, depending on the time of year your trek is. I used Her Packing List, along with the information provided by Active Adventures to help me in packing everything I need.

  1. Have the Time of Your Life

Last, but not least, be ready to have incredible experiences and memories that will last a life time. When I first booked my trip to Peru and the Inca Trail I had certain expectations and ideas of what the trip would be like. I was looking forward to seeing Machu Picchu, but what I found was that the most memorable and exciting parts of my trip were not necessarily seeing the big tourist spots like Machu Picchu, but the journey getting there, and the unexpected surprises that came along the way. Peru and its people exceeded all expectations, and opened my mind in ways I did not know were possible.

Hi, my name is Jess Signet. My parents were travelers since before I was born. Even in the womb, I was able to travel all over the place! Boy, did things NOT change as I grew older!
Knowing there’s more to the world than the bubble I live in made me want to travel even further. Traveling is my drug and I’m addicted. (Please, no intervention!)

 



  • Hiking and Trekking
  • Tips and Things To Know

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Quebec regions fear Montrealers could spread COVID-19 as restrictions lift

Residents of Quebec’s regions want Montrealers to stay away, considering the city has the highest concentration of COVID-19 infections in Canada.




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London, Rome, Paris Top TripAdvisor's Most-Reviewed Cities List

Filed under: , , , ,

Alamy
The litany of year-end travel-related lists continues. Today, it's TripAdvisor, which unveiled its most reviewed cities. Leading the way: London, Rome and Paris, according to the Telegraph. The top U.S city was New York, which ranked fourth overall -- a stunning blow for American exceptionalism.

Continue reading London, Rome, Paris Top TripAdvisor's Most-Reviewed Cities List

London, Rome, Paris Top TripAdvisor's Most-Reviewed Cities List originally appeared on Gadling on Tue, 17 Dec 2013 14:11:00 EST. Please see our terms for use of feeds.

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Tribute will help you create a heartfelt video montage and it won’t take you hours to do it

It seemed like such a great idea at the time. You wanted to put together a video for a loved one, including all their family and friends singing their praises, making their life look as epic as a Hollywood production.

Oh, it was a Hollywood production, all right. Contributors showed up late and sent weird file formats, editing took forever, the music wasn’t right...and on it went. Before you know it, a simple tribute video you thought might take an hour or two consumed multiple nights and had you cursing the day you ever thought of the idea.

Video montages take work. But by enlisting Tribute to help you assemble your message of love, It’s all a lot more manageable.

In fact, the Tribute process is so easy that you probably won’t have to do more than a few minutes of work to produce a high-quality tribute video that brings tears of joy. No, seriously...Tribute swears 80 percent of their videos elicit actual tears of joy. Of course, there’s no way of knowing their metrics for judging the results of their 500,000 Tribute videos so far...but if they’re close, your odds for an emotional testament to your subject are pretty darn high.

With Tribute, you just enter the emails for all the people you’d like to contribute to the video. Tribute emails your participants, explains the project, and guides your subjects through how to shoot and submit their segment for the finished video.

Once all your videos are in, Tribute will compile all your clips into a touching, polished montage. Read the rest




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Rep. Ilhan Omar Asks For Contributions To Her Campaign To Help MN Food Bank…Food Bank Director Says Omar Has Nothing To Do With Project: “I have no idea where this money is going”

The following article, Rep. Ilhan Omar Asks For Contributions To Her Campaign To Help MN Food Bank…Food Bank Director Says Omar Has Nothing To Do With Project: “I have no idea where this money is going”, was first published on 100PercentFedUp.com.

Ilhan Omar is a lot of things. First, and foremost, she’s deceitful. David Steinberg of PJ Media was one of the first investigative journalists to break the story about the anti-Semitic, freshman lawmaker’s marriage to her immigrant brother while she was still married to her first husband, who she has since divorced after having an […]

Continue reading: Rep. Ilhan Omar Asks For Contributions To Her Campaign To Help MN Food Bank…Food Bank Director Says Omar Has Nothing To Do With Project: “I have no idea where this money is going” ...




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The Bo Xilai Trial and Chinese Politics

26 August 2013

Dr Tim Summers

Senior Consulting Fellow, Asia-Pacific Programme (based in Hong Kong)

Scandal and speculation surrounding the demise of Politburo member Bo Xilai raised questions about the stability and cohesiveness of China's political elite. However as his trial comes to an end the main political challenge is not at the elite level, but in the Communist party's ability to gain legitimacy among the wider public. 

The trial of Bo Xilai for bribery, embezzlement and abuse of power has generated a number of surprises. To start with, there has been more transparency than most observers had expected, with the court issuing transcripts at regular intervals. Plus, the court used Chinese social media to post images of the proceedings.

This level of transparency is unusual in Chinese trials. However, we should be cautious about seeing this as a precedent for the future development of judicial practice. Bo's case is rather special, both because of the senior positions he held and because of the level of speculation around the case – and Bo's fate – ever since the drama began last February when Wang Lijun, Bo's former police chief in Chongqing, fled to the US Consulate-General in Chengdu. 

Wang, who is already serving a prison sentence after being convicted of abuse of power and other offences, gave testimony at Bo's trial. The exchanges between Bo and Wang will be picked over further, with their salacious details of the arguments that apparently ensued in January 2012 when Wang told Bo that Bo's wife was suspected of murdering British businessman Neil Heywood, in Chongqing the previous November. 

It is highly likely that Bo will be found guilty. Nonetheless, the trial gave Bo the opportunity to put across his views in court. He surprised observers on the first day by retracting confessions he made during the pre-trial investigation process. It is not clear whether this was expected by the prosecutors in advance of the trial, but it contributed to the trial lasting for five days – much longer than expected. 

Result already decided

Most media coverage and comment has focused on the details of the various events, which came out in court. However the political implications lie elsewhere. 

The trial should not be seen in isolation but as the culmination of a process which began in the days after Wang's attempted defection was brought to light. The party's subsequent handling of Bo Xilai proceeded in cautious stages: first the removal from his post as Party Secretary in Chongqing in March last year, then his 'suspension' from the Politburo and Party Central Committee a month later while an investigation was carried out by the party. Only in September 2012 was Bo expelled from the Communist Party and the file handed over to state authorities for prosecution.

This train of events serves as a reminder of the context in which China's judicial system operates. Whatever the transparency of proceedings in court, or the professionalism of judges and lawyers, the party's 'leadership' of judicial work means that politically important cases are often subject to direction from the party apparatus. 

Popular, not elite, politics is at stake

The Bo case has often been presented as a story of turbulence and factional infighting at the top of the party. But in November 2012 the party delivered a clear leadership transition at the top of both party and military from Hu Jintao to Xi Jinping, with the government handover in March this year. With the new team firmly in place, the transparency accorded to Bo's trial demonstrates confidence among the leadership, not division. 

Political challenges lie not at the top of the party, but in the ability of the party leadership to achieve legitimacy among the wider public. The revelations in the Bo case, from last spring and up to and including the trial, have increased levels of public cynicism about the behaviour of senior officials. Posts on China's social media will provide glimpses of the wider response to the trial; popular opinion is likely to be divided – as it was when Bo was still a serving official, and has remained since his removal from office. 

Given that the party seeks to present itself as being 'responsive' to public concerns, the main political implications of the trial will be seen in the impact it has on the leadership's credibility, not in elite politics. It is that imperative, not judicial reform, which explains what we have been allowed to see of the trial. 

To comment on this article, please contact Chatham House Feedback




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Fasthosts ECommerce anyone tried it?




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South Dakota Governor demands Sioux tribes 'immediately' remove COVID-19 checkpoints because they interfere with traffic

South Dakota Governor Kristi Noem sent letters to two Sioux tribes demanding they remove COVID-19 checkpoints because they interfere with traffic.





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The federal government finally announced initial plans to distribute Gilead's coronavirus drug remdesivir after days of confusion

The government said it's distributing the promising coronavirus drug, remdesivir, to some hard-hit states. Eventually, all 50 states should get it.





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Tripoli airport shelling hits fuel tanks, passenger plane-ministry

Shelling of Tripoli's Mitiga airport early on Saturday, part of an intensified barrage of artillery fire on the capital in recent days, hit fuel tanks and damaged passenger planes, the Transport Ministry said in a statement. Mitiga is the last functioning airport in the Libyan capital, though civilian flights stopped in March because of repeated shelling even before the country imposed a lockdown over the coronavirus pandemic. Brega Petroleum Marketing Company, part of the National Oil Corporation, said its jet fuel tanks at Mitiga caught fire after coming under attack and firemen were working to control the blaze.





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New study examines lifting of pub and nightclub restrictions

(University of Stirling) A new University of Stirling study is seeking to understand how the easing of COVID-19 pandemic restrictions on licensed premises can be effectively managed to protect emergency services.




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Cell-specific expression of the transcriptional regulator RHAMM provides a timing mechanism that controls appropriate wound re-epithelialization [Glycobiology and Extracellular Matrices]

Prevention of aberrant cutaneous wound repair and appropriate regeneration of an intact and functional integument require the coordinated timing of fibroblast and keratinocyte migration. Here, we identified a mechanism whereby opposing cell-specific motogenic functions of a multifunctional intracellular and extracellular protein, the receptor for hyaluronan-mediated motility (RHAMM), coordinates fibroblast and keratinocyte migration speed and ensures appropriate timing of excisional wound closure. We found that, unlike in WT mice, in Rhamm-null mice, keratinocyte migration initiates prematurely in the excisional wounds, resulting in wounds that have re-surfaced before the formation of normal granulation tissue, leading to a defective epidermal architecture. We also noted aberrant keratinocyte and fibroblast migration in the Rhamm-null mice, indicating that RHAMM suppresses keratinocyte motility but increases fibroblast motility. This cell context–dependent effect resulted from cell-specific regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation and expression of a RHAMM target gene encoding matrix metalloprotease 9 (MMP-9). In fibroblasts, RHAMM promoted ERK1/2 activation and MMP-9 expression, whereas in keratinocytes, RHAMM suppressed these activities. In keratinocytes, loss of RHAMM function or expression promoted epidermal growth factor receptor–regulated MMP-9 expression via ERK1/2, which resulted in cleavage of the ectodomain of the RHAMM partner protein CD44 and thereby increased keratinocyte motility. These results identify RHAMM as a key factor that integrates the timing of wound repair by controlling cell migration.




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Inter-{alpha}-inhibitor heavy chain-1 has an integrin-like 3D structure mediating immune regulatory activities and matrix stabilization during ovulation [Glycobiology and Extracellular Matrices]

Inter-α-inhibitor is a proteoglycan essential for mammalian reproduction and also plays a less well-characterized role in inflammation. It comprises two homologous “heavy chains” (HC1 and HC2) covalently attached to chondroitin sulfate on the bikunin core protein. Before ovulation, HCs are transferred onto the polysaccharide hyaluronan (HA) to form covalent HC·HA complexes, thereby stabilizing an extracellular matrix around the oocyte required for fertilization. Additionally, such complexes form during inflammatory processes and mediate leukocyte adhesion in the synovial fluids of arthritis patients and protect against sepsis. Here using X-ray crystallography, we show that human HC1 has a structure similar to integrin β-chains, with a von Willebrand factor A domain containing a functional metal ion-dependent adhesion site (MIDAS) and an associated hybrid domain. A comparison of the WT protein and a variant with an impaired MIDAS (but otherwise structurally identical) by small-angle X-ray scattering and analytical ultracentrifugation revealed that HC1 self-associates in a cation-dependent manner, providing a mechanism for HC·HA cross-linking and matrix stabilization. Surprisingly, unlike integrins, HC1 interacted with RGD-containing ligands, such as fibronectin, vitronectin, and the latency-associated peptides of transforming growth factor β, in a MIDAS/cation-independent manner. However, HC1 utilizes its MIDAS motif to bind to and inhibit the cleavage of complement C3, and small-angle X-ray scattering–based modeling indicates that this occurs through the inhibition of the alternative pathway C3 convertase. These findings provide detailed structural and functional insights into HC1 as a regulator of innate immunity and further elucidate the role of HC·HA complexes in inflammation and ovulation.




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Glucocerebrosidases catalyze a transgalactosylation reaction that yields a newly-identified brain sterol metabolite, galactosylated cholesterol [Glycobiology and Extracellular Matrices]

β-Glucocerebrosidase (GBA) hydrolyzes glucosylceramide (GlcCer) to generate ceramide. Previously, we demonstrated that lysosomal GBA1 and nonlysosomal GBA2 possess not only GlcCer hydrolase activity, but also transglucosylation activity to transfer the glucose residue from GlcCer to cholesterol to form β-cholesterylglucoside (β-GlcChol) in vitro. β-GlcChol is a member of sterylglycosides present in diverse species. How GBA1 and GBA2 mediate β-GlcChol metabolism in the brain is unknown. Here, we purified and characterized sterylglycosides from rodent and fish brains. Although glucose is thought to be the sole carbohydrate component of sterylglycosides in vertebrates, structural analysis of rat brain sterylglycosides revealed the presence of galactosylated cholesterol (β-GalChol), in addition to β-GlcChol. Analyses of brain tissues from GBA2-deficient mice and GBA1- and/or GBA2-deficient Japanese rice fish (Oryzias latipes) revealed that GBA1 and GBA2 are responsible for β-GlcChol degradation and formation, respectively, and that both GBA1 and GBA2 are responsible for β-GalChol formation. Liquid chromatography–tandem MS revealed that β-GlcChol and β-GalChol are present throughout development from embryo to adult in the mouse brain. We found that β-GalChol expression depends on galactosylceramide (GalCer), and developmental onset of β-GalChol biosynthesis appeared to be during myelination. We also found that β-GlcChol and β-GalChol are secreted from neurons and glial cells in association with exosomes. In vitro enzyme assays confirmed that GBA1 and GBA2 have transgalactosylation activity to transfer the galactose residue from GalCer to cholesterol to form β-GalChol. This is the first report of the existence of β-GalChol in vertebrates and how β-GlcChol and β-GalChol are formed in the brain.




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Glycation-mediated inter-protein cross-linking is promoted by chaperone-client complexes of {alpha}-crystallin: Implications for lens aging and presbyopia [Glycobiology and Extracellular Matrices]

Lens proteins become increasingly cross-linked through nondisulfide linkages during aging and cataract formation. One mechanism that has been implicated in this cross-linking is glycation through formation of advanced glycation end products (AGEs). Here, we found an age-associated increase in stiffness in human lenses that was directly correlated with levels of protein–cross-linking AGEs. α-Crystallin in the lens binds to other proteins and prevents their denaturation and aggregation through its chaperone-like activity. Using a FRET-based assay, we examined the stability of the αA-crystallin–γD-crystallin complex for up to 12 days and observed that this complex is stable in PBS and upon incubation with human lens–epithelial cell lysate or lens homogenate. Addition of 2 mm ATP to the lysate or homogenate did not decrease the stability of the complex. We also generated complexes of human αA-crystallin or αB-crystallin with alcohol dehydrogenase or citrate synthase by applying thermal stress. Upon glycation under physiological conditions, the chaperone–client complexes underwent greater extents of cross-linking than did uncomplexed protein mixtures. LC-MS/MS analyses revealed that the levels of cross-linking AGEs were significantly higher in the glycated chaperone–client complexes than in glycated but uncomplexed protein mixtures. Mouse lenses subjected to thermal stress followed by glycation lost resilience more extensively than lenses subjected to thermal stress or glycation alone, and this loss was accompanied by higher protein cross-linking and higher cross-linking AGE levels. These results uncover a protein cross-linking mechanism in the lens and suggest that AGE-mediated cross-linking of α-crystallin–client complexes could contribute to lens aging and presbyopia.




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Processivity of dextransucrases synthesizing very-high-molar-mass dextran is mediated by sugar-binding pockets in domain V [Glycobiology and Extracellular Matrices]

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.




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The Escherichia coli cellulose synthase subunit G (BcsG) is a Zn2+-dependent phosphoethanolamine transferase [Glycobiology and Extracellular Matrices]

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.




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Catabolic degradation of endothelial VEGFA via autophagy [Glycobiology and Extracellular Matrices]

Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion of autophagy-related 5 (ATG5), results in accumulation of intracellular VEGFA, indicating that VEGFA is a basal autophagic substrate. Mechanistically, decorin increased the VEGFA clearance rate by augmenting autophagic flux, a process that required RAB24 member RAS oncogene family (RAB24), a small GTPase that facilitates the disposal of autophagic compartments. We validated these findings by demonstrating the physiological relevance of this process in vivo. Mice starved for 48 h exhibited a sharp decrease in overall cardiac and aortic VEGFA that could be blocked by systemic chloroquine treatment. Thus, our findings reveal a unified mechanism for the metabolic control of endothelial VEGFA for autophagic clearance in response to decorin and canonical pro-autophagic stimuli. We posit that the VEGFR2/AMPK/PEG3 axis integrates the anti-angiogenic and pro-autophagic bioactivities of decorin as the molecular basis for tumorigenic suppression. These results support future therapeutic use of decorin as a next-generation protein therapy to combat cancer.




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Endorepellin evokes an angiostatic stress signaling cascade in endothelial cells [Glycobiology and Extracellular Matrices]

Endorepellin, the C-terminal fragment of the heparan sulfate proteoglycan perlecan, influences various signaling pathways in endothelial cells by binding to VEGFR2. In this study, we discovered that soluble endorepellin activates the canonical stress signaling pathway consisting of PERK, eIF2α, ATF4, and GADD45α. Specifically, endorepellin evoked transient activation of VEGFR2, which, in turn, phosphorylated PERK at Thr980. Subsequently, PERK phosphorylated eIF2α at Ser51, upregulating its downstream effector proteins ATF4 and GADD45α. RNAi-mediated knockdown of PERK or eIF2α abrogated the endorepellin-mediated up-regulation of GADD45α, the ultimate effector protein of this stress signaling cascade. To functionally validate these findings, we utilized an ex vivo model of angiogenesis. Exposure of the aortic rings embedded in 3D fibrillar collagen to recombinant endorepellin for 2–4 h activated PERK and induced GADD45α vis à vis vehicle-treated counterparts. Similar effects were obtained with the established cellular stress inducer tunicamycin. Notably, chronic exposure of aortic rings to endorepellin for 7–9 days markedly suppressed vessel sprouting, an angiostatic effect that was rescued by blocking PERK kinase activity. Our findings unravel a mechanism by which an extracellular matrix protein evokes stress signaling in endothelial cells, which leads to angiostasis.




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Eight Policies to Boost the Economic Contribution of Employment-Based Immigration

Drawing on experiences from Asia, Europe, North America, and the Pacific region, this report presents eight strategies that represent best practices developed by immigrant-receiving countries to increase the economic contributions of immigration.




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Tribute to a modern languages pioneer

On this Teachers’ Day, I fondly remember Fraulein Daphne Adams, my first German teacher who influenced my love for languages and who transitioned recently in Jamaica. Miss Adams was first and foremost an excellent, no-nonsense teacher of modern...




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Trinidad to start reopening Tuesday, but borders to remain closed until June

(CMC): Trinidad and Tobago says its borders are to remain closed until June, even as it embarks on softening restrictions to re energise the economy, which had been halted by COVID-19.   Prime Minister Dr Keith Rowley said the...




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Outpouring of tributes for Roger Chang at thanksgiving service

The words humble and affectionate were among the many adjectives that reverberated during the virtual thanksgiving service for 62-year-old Roger Chang, as family friends paid tribute to the late businessman.  Chang, who went missing on...




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Developing a Road Map for Engaging Diasporas in Development: A Handbook for Policymakers and Practitioners in Home and Host Countries

This practical handbook highlights policies and programs that can magnify the resources, both human and financial, that emigrants and their descendants contribute to development. It gives concrete examples of policies and programs that have been effective, and pulls out both useful lessons and common challenges associated with the topics at hand.




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Immigrants: Contributors to the Economy or Competitors for American Jobs?

Briefing and discussion of the release of the latest paper by MPI's Labor Markets Initiative: The Impact of Immigrants in Recession and Economic Expansion.




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Immigrants: Contributors to the Economy or Competitors for American Jobs?

Briefing and discussion of the release of the latest paper by MPI's Labor Markets Initiative. Speakers are report author Giovanni Peri, UC Davis Professor of Economics; Ross Eisenbrey, Vice President, Economic Policy Institute; and Demetrios G. Papademetriou, MPI President.




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Bumblebee’s electric field sensor identified

Mechanosensory hairs covering bumblebees’ bodies detect the small electrical fields emitted by flowers

Bumblebees use the fine hairs covering their bodies to detect electrical fields produced by the flowers they feed on and pollinate, according to a new study by researchers at the University of Bristol. The findings, just published in Proceedings of the National Academy of Sciences, may help to solve the mystery of how insects and other terrestrial creatures detect and respond to electric fields.

It’s well known that bumblebees use their sense of smell, as well as visual cues such as the colour, shape, and patterning of flowers, to find nectar, and in 2013, biologist Daniel Robert and his colleagues reported the surprising finding that they can also detect floral electric fields.

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