L.A. tenants will soon have the right to sue landlords who violate restrictions the city has put in place during the coronavirus crisis.

California says bars that reopen without state permission could lose alcohol license

Afghanistan is investigating the alleged torture and drowning of migrants at the Iranian border.

The al-Hota gorge became "a place of horror" under the jihadist group, Human Rights Watch says.

Analysts say IS is exploiting the coronavirus pandemic, which is occupying authorities' attention.

President Trump believes the US is being unfairly treated by other countries when it comes to trade.

Formula 1 hopes to squeeze 16 races into a truncated season, but how could it all work?

The EEC is donating £1.8 million to help combat the famine in Ethiopia.

Migrants in Calais and the UK say the Covid-19 pandemic is deepening the struggles they face.

"Onward" and "Soul" deal with the eternal and the ethereal.

A record number of migrants crossed the English Channel on Friday.

Giants' offensive line is allowing an adjusted sack rate of over eight percent, the eighth-worst in the NFL.

The Democratic presidential candidate criticized the president for saying there were “people on both sides” of the exoneration of the men wrongly accused of raping a jogger.

Review of 'A Good Provider Is One Who Leaves: One Family and Migration in the 21st Century' by Jason DeParle

Gov. Greg Abbott’s decision plays into some unfortunate stereotypes.

“It’s just so unfair that American companies aren’t allowed to pay bribes to get business overseas.”

Young medical students and health-care workers simply want to keep contributing in the only home they know.

Reopening the country may be bad from a public health standpoint, but the president is pushing for it anyway.

The communications regulator is asking telecom companies to consider lowering the cost of data in a bid to ensure productivity during the period the coronavirus outbreak.

A lack of high demand spectrum has been a long-running complaint by SA telecoms groups, who say that it is needed to reduce data prices and increase speed.

The new Pinterest app on Shopify is now available in the U.S. and Canada.

Please visit Search Engine Land for the full article.

Here are the latest top Covid-19 stories from around the world.

In many areas of the country, landlords are prohibited from evicting tenants who are experiencing financial hardship due to the COVID-19 pandemic. Take these steps if you’re losing rental income.

From the virtual 2020 REALTORS® Legislative Meetings, April 27-May 15

Landlords who are missing thousands of dollars in rent or who find their properties damaged or strewn with garbage are concerned some tenants are taking advantage of the eviction ban put in place during the pandemic.

Restaurants have been struggling to stay afloat since the pandemic hit, but there has been a silver lining: relaxed liquor laws mean customers can get their booze delivered along with their meals.

Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton's tyrosine kinase (BTK), such as ibrutinib, is limited by primary or secondary resistance to this drug. Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK's catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-γ2 (PLCγ2). The PLCγ2 variants typically do not exhibit constitutive activity in cell-free systems, leading to the suggestion that in intact cells they are hypersensitive to Rac family small GTPases or to the upstream kinases spleen-associated tyrosine kinase (SYK) and Lck/Yes-related novel tyrosine kinase (LYN). The sensitivity of the PLCγ2 variants to BTK itself has remained unknown. Here, using genetically-modified DT40 B lymphocytes, along with various biochemical assays, including analysis of PLCγ2-mediated inositol phosphate formation, inositol phospholipid assessments, fluorescence recovery after photobleaching (FRAP) static laser microscopy, and determination of intracellular calcium ([Ca2+]i), we show that various CLL-specific PLCγ2 variants such as PLCγ2S707Y are hyper-responsive to activated BTK, even in the absence of BTK's catalytic activity and independently of enhanced PLCγ2 phospholipid substrate supply. At high levels of B-cell receptor (BCR) activation, which may occur in individual CLL patients, catalytically-inactive BTK restored the ability of the BCR to mediate increases in [Ca2+]i. Because catalytically-inactive BTK is insensitive to active-site BTK inhibitors, the mechanism involving the noncatalytic BTK uncovered here may contribute to preexisting reduced sensitivity or even primary resistance of CLL to these drugs.

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

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

Reactive oxygen and nitrogen species have been implicated in many biological processes and diseases, including immune responses, cardiovascular dysfunction, neurodegeneration, and cancer. These chemical species are short-lived in biological settings, and detecting them in these conditions and diseases requires the use of molecular probes that form stable, easily detectable, products. The chemical mechanisms and limitations of many of the currently used probes are not well-understood, hampering their effective applications. Boronates have emerged as a class of probes for the detection of nucleophilic two-electron oxidants. Here, we report the results of an oxygen-18–labeling MS study to identify the origin of oxygen atoms in the oxidation products of phenylboronate targeted to mitochondria. We demonstrate that boronate oxidation by hydrogen peroxide, peroxymonocarbonate, hypochlorite, or peroxynitrite involves the incorporation of oxygen atoms from these oxidants. We therefore conclude that boronates can be used as probes to track isotopically labeled oxidants. This suggests that the detection of specific products formed from these redox probes could enable precise identification of oxidants formed in biological systems. We discuss the implications of these results for understanding the mechanism of conversion of the boronate-based redox probes to oxidant-specific products.

Expert

A person needing a kidney transplant may have a friend or relative who volunteers to be a living donor, but whose kidney is incompatible, forcing the person to wait for a transplant from a deceased donor. In the U.S. alone, thousands of people die each year without ever finding a suitable kidney. A new technique applies graph theory to groups of incompatible patient-donor pairs to create the largest possible number of paired-donation exchanges. These exchanges, in which a donor paired with Patient A gives a kidney to Patient B while a donor paired with Patient B gives to Patient A, will dramatically increase transplants from living donors. Since transplantation is less expensive than dialysis, this mathematical algorithm, in addition to saving lives, will also save hundreds of millions of dollars annually. Naturally there can be more transplants if matches along longer patient-donor cycles are considered (e.g., A.s donor to B, B.s donor to C, and C.s donor to A). The problem is that the possible number of longer cycles grows so fast hundreds of millions of A >B>C>A matches in just 5000 donor-patient pairs that to search through all the possibilities is impossible. An ingenious use of random walks and integer programming now makes searching through all three-way matches feasible, even in a database large enough to include all incompatible patient-donor pairs. For More Information: Matchmaking for Kidneys, Dana Mackenzie, SIAM News, December 2008. Image of suboptimal two-way matching (in purple) and an optimal matching (in green), courtesy of Sommer Gentry.

"Pollinators were the key," says Edgar Mora, reflecting on the decision to recognise every bee, bat, hummingbird and butterfly as a citizen of Curridabat during his 12-year spell as mayor.

Huai-Liang Chang and Mu-lin Li
Trans. Amer. Math. Soc. 373 (2020), 3669-3691.
Abstract, references and article information

(University of Illinois Grainger College of Engineering) Three Nick Holonyak Jr., Micro and Nanotechnology Lab (HMNTL) faculty members received NSF Rapid Response Research (RAPID) program grants, all of which aim to shorten the amount of time it takes to process a COVID-19 test with less false negatives. Current tests can take as long as five days for results to be.

Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton's tyrosine kinase (BTK), such as ibrutinib, is limited by primary or secondary resistance to this drug. Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK's catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-γ2 (PLCγ2). The PLCγ2 variants typically do not exhibit constitutive activity in cell-free systems, leading to the suggestion that in intact cells they are hypersensitive to Rac family small GTPases or to the upstream kinases spleen-associated tyrosine kinase (SYK) and Lck/Yes-related novel tyrosine kinase (LYN). The sensitivity of the PLCγ2 variants to BTK itself has remained unknown. Here, using genetically-modified DT40 B lymphocytes, along with various biochemical assays, including analysis of PLCγ2-mediated inositol phosphate formation, inositol phospholipid assessments, fluorescence recovery after photobleaching (FRAP) static laser microscopy, and determination of intracellular calcium ([Ca2+]i), we show that various CLL-specific PLCγ2 variants such as PLCγ2S707Y are hyper-responsive to activated BTK, even in the absence of BTK's catalytic activity and independently of enhanced PLCγ2 phospholipid substrate supply. At high levels of B-cell receptor (BCR) activation, which may occur in individual CLL patients, catalytically-inactive BTK restored the ability of the BCR to mediate increases in [Ca2+]i. Because catalytically-inactive BTK is insensitive to active-site BTK inhibitors, the mechanism involving the noncatalytic BTK uncovered here may contribute to preexisting reduced sensitivity or even primary resistance of CLL to these drugs.

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

Tenants of the EcoPark, country park refreshment kiosks and the Hong Kong Wetland Park will benefit from increased rental concessions for government premises.

To help tenants cope with the economic impact of the COVID-19 epidemic, rental concessions of government premises from April to September will be increased from 50% to 75%.

The Environment Bureau said tenants of the EcoPark, country park refreshment kiosks and the Hong Kong Wetland Park will receive additional rental concessions of about $3.6 million.

Together with the 50% rental concessions provided by the Government from last October to March, these tenants will receive concessions of more than $17 million within 12 months, the bureau said.

Meanwhile, tenants of the Hong Kong Wetland Park will receive a full rental waiver during the park’s closure.