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.

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.

Multidrug resistance (MDR) in cancer arises from cross-resistance to structurally- and functionally-divergent chemotherapeutic drugs. In particular, MDR is characterized by increased expression and activity of ATP-binding cassette (ABC) superfamily transporters. Sphingolipids are substrates of ABC proteins in cell signaling, membrane biosynthesis, and inflammation, for example, and their products can favor cancer progression. Glucosylceramide (GlcCer) is a ubiquitous glycosphingolipid (GSL) generated by glucosylceramide synthase, a key regulatory enzyme encoded by the UDP-glucose ceramide glucosyltransferase (UGCG) gene. Stressed cells increase de novo biosynthesis of ceramides, which return to sub-toxic levels after UGCG mediates incorporation into GlcCer. Given that cancer cells seem to mobilize UGCG and have increased GSL content for ceramide clearance, which ultimately contributes to chemotherapy failure, here we investigated how inhibition of GSL biosynthesis affects the MDR phenotype of chronic myeloid leukemias. We found that MDR is associated with higher UGCG expression and with a complex GSL profile. UGCG inhibition with the ceramide analog d-threo-1-(3,4,-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (EtDO-P4) greatly reduced GSL and monosialotetrahexosylganglioside levels, and co-treatment with standard chemotherapeutics sensitized cells to mitochondrial membrane potential loss and apoptosis. ABC subfamily B member 1 (ABCB1) expression was reduced, and ABCC-mediated efflux activity was modulated by competition with nonglycosylated ceramides. Consistently, inhibition of ABCC-mediated transport reduced the efflux of exogenous C6-ceramide. Overall, UGCG inhibition impaired the malignant glycophenotype of MDR leukemias, which typically overcomes drug resistance through distinct mechanisms. This work sheds light on the involvement of GSL in chemotherapy failure, and its findings suggest that targeted GSL modulation could help manage MDR leukemias.

European dominance in U.S. immigration flows has decreased significantly since World War II, a result of economic, demographic, and policy trends on both sides of the Atlantic. Today, migration from European Union Member States to the United States, while small, is characterized by a substantial numbers of European scientists, professionals, and businesspeople.

Written from, different angles and spaces, the poems below testify to the great force of motherhood, which nurtures, strengthens, and manifests love. Happy Mother’s Day – Ann-Margaret Lim Words My mother loved words. Not necessarily in...

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...

While many Red Stripe Premier League (RSPL) players are finding it very difficult to stay motivated and maintain their training regime until the league is able to restart, Portmore defender Romaine Breakenridge remains highly motivated and eager...

Declaring it has been “pained” by the Jodian Fearon situation, the embattled Andrews Memorial Hospital (AMH) is speaking out, saying it has never been approached for or rejected efforts at registration or certification since it began operating 76...

For drummer Conroy Gordon, the hardest part of being locked away day after day in the narrow confines of a stranded cruise ship is his inability to tell his two daughters when Daddy will be home. For the past month, he has been battling this...

To say Judith-Miranda Townsend has a special love for children would not even begin to capture the essence of the Westmoreland supermom. Affectionately called ‘Mama Sweetie’ by foster children and members of the Holly Hill community in Darliston,...

This report finds that the 813,000 U.S. children under the age of 10 who have Black immigrant parents from Africa or the Caribbean generally fall in the middle of multiple well-being indicators, faring less well than Asian and white children but better than their native-born Black and Hispanic peers. Citizenship status, English proficiency, parental characteristics, poverty, housing, and access to social supports are examined.

Immigration from the Caribbean to the United States is a relatively recent phenomenon, beginning largely after 1965. This report provides a demographic profile of the 1.7 million Caribbean immigrants in the United States: their geographic settlement, education and workforce characteristics, earnings, modes of entry, and more.

This report focuses on the development of children of Black immigrants in the United States, comparing against the outcomes for their peers in native-born and other immigrant families. It also compares these U.S. children to those in the United Kingdom, where there is a large Black immigrant population but a notably different policy context of reception.

This report draws on a six-year longitudinal study of Palm Beach County, FL, examining parenting, child care enrollment, and other factors that encourage early school success. The authors find kindergarten-age children of Black immigrants have significantly higher odds of being ready for school than children of Latina immigrant or Black U.S.-born mothers.

Using a nationally representative U.S. birth-cohort study, this report examines levels of school readiness among young children by race/ethnicity and nativity. The authors identify the contextual factors — such as family circumstances, parenting practices, and enrollment in center-based child care — that encourage early school success.

ADVISORY COLUMN: SMALL BUSINESS On Thursday, May 7, the RJR/GLEANER Communications group staged a virtual town hall meeting on Television Jamaica titled “COVID-19...

Recent calls by the Jamaica Manufacturing and Exporters Association, JMEA, for more targeted concessions on raw materials that are processed for re-export sent Jamaica Agricultural Commodities Regulatory Authority, JACRA, back to the drawing board...

Simply put, motherhood is a beautiful thing. As one person puts it, all love begins and ends there. And though many who have had the opportunity to experience the beloved state boldly admit that it’s not always roses, the bottom line remains that...

Mother’s Day is usually a much-anticipated, celebratory day for Trinette Lilly and her siblings. However, this year, they were not looking forward to today because it marks the first anniversary of the brutal slaying of their mother, Antonette...

This volume, by a former senior counsel to the 9/11 Commission, argues that the U.S. approach to immigration and border security is off-kilter and not keeping pace with the scope and complexity of people’s movement around the world, nor with expectations regarding freedom of movement.

Each summer, Marcia Salmon would spend much time studying her son’s itinerary as he embarked on one of his tours to countries around the world. This year, Marcia does not have to deal with that bittersweet experience of watching her son, Kabaka...

This year’s Mother’s Day has undoubtedly been impacted by the COVID-19 virus. Plans to show appreciation to the one you call ‘mama’ have been thwarted due to worldwide quarantine conditions. But while there may not be the usual elaborate dinner at...

This report provides an overview of several commonly used translation and interpretation technologies. It aims to assist language access practitioners in understanding and identifying which systems would best meet their agency’s language access needs.

The discovery of an inhibitory memory circuit could lead to novel treatments for conditions such as PTSD

In order to remember, we must forget. Recent research shows that when your brain retrieves newly encoded information, it suppresses older related information so that it does not interfere with the process of recall. Now a team of European researchers has identified a neural pathway that induces forgetting by actively erasing memories. The findings could eventually lead to novel treatments for conditions such as post-traumatic stress disorder (PTSD).

We’ve known since the early 1950s that a brain structure called the hippocampus is critical for memory formation and retrieval, and subsequent work using modern techniques has revealed a great deal of information about the underlying cellular mechanisms. The hippocampus contains neural circuits that loop through three of its sub-regions – the dentate gyrus and the CA3 and CA1 areas – and it’s widely believed that memories form by the strengthening and weakening of synaptic connections within these circuits.

Related: Light switches memories on and off | Mo Costandi

Related: The Homer Simpson effect: forgetting to remember

“Badass” new method uses a magnetised protein to activate brain cells rapidly, reversibly, and non-invasively

Researchers in the United States have developed a new method for controlling the brain circuits associated with complex animal behaviours, using genetic engineering to create a magnetised protein that activates specific groups of nerve cells from a distance.

Understanding how the brain generates behaviour is one of the ultimate goals of neuroscience – and one of its most difficult questions. In recent years, researchers have developed a number of methods that enable them to remotely control specified groups of neurons and to probe the workings of neuronal circuits.

Related: Remote control of brain activity with heated nanoparticles

Related: Researchers read and write brain activity with light

New research reveals the secret behind the remarkable intelligence of some bird species

Related: Blind cave fish evolved a shrunken brain to save energy

Calling someone “bird brain” used to be considered as an insult. Birds’ brains are very small compared to those of mammals, and what’s more, they lack the heavily wrinkled cerebral cortex, which is characteristic of the human brain, and widely believed to the seat of intelligence. It was, therefore, widely assumed that birds aren’t very clever creatures, but recently this has started to change.

Related: Ravens cooperate with friends not foes

New research shows that the rhythm of breathing directly impacts neural activity in a network of brain areas involved in smell, memory and emotions

The rhythm of breathing co-ordinates electrical activity across a network of brain regions associated with smell, memory, and emotions, and can enhance their functioning, according to a new study by researchers at Northwestern University. The findings, published in the Journal of Neuroscience, suggest that breathing does not merely supply oxygen to the brain and body, but may also organise the activity of populations of cells within multiple brain regions to help orchestrate complex behaviours.

Related: Your nose knows death is imminent | Mo Costandi

Related: A cooler way to evaluate brain surgery patients

New research shows that we can train our brains to become memory champions

To many of us, having to memorize a long list of items feels like a chore. But for others, it is more like a sport. Every year, hundreds of these ‘memory athletes’ compete with one another in the World Memory Championships, memorising hundreds of words, numbers, or other pieces of information within minutes. The current world champion is Alex Mullen, who beat his competitors by memorizing a string of more than 550 digits in under 5 minutes.

You may think that such prodigious mental feats are linked to having an unusual brain, or to being extraordinarily clever. But they are not. New research published in the journal Neuron shows that you, too, can be a super memorizer with just six weeks of intensive mnemonic training, and also reveals the long-lasting changes to brain structure and function that occur as a result of such training.

Related: The Homer Simpson effect: forgetting to remember

Related: A neural pathway that erases memories

Ok, so I have tried and do not get the same as as the book (1.6m). Can someone show the forces diagram or something , please?

happy, sad, meh, mad, or what?

Examples being: XTro (UK), Oldboy (S.Korea), Girl With a Dragon Tattoo (Sweden), Predestination (Australia) ... something like these

Feminism is a lie and useless in modern America, patriarchy is a good thing and natural order of society. Women be like I'm oppressed cause I don't always get my way and choose careers that pay less

Military Entrance Processing Stations won't process individuals who have had COVID-19 for military service, even if they've fully recovered from the virus, the Pentagon confirmed this week.

Tesla filed a lawsuit Saturday against Alameda County, Calif., and CEO Elon Musk threatened to move the company's headquarters and operations out of state.

On May 10, 1908, Mother's Day was observed for the first time in the United States.

Musician Bono turns 60 and race car driver Helio Castroneves turns 45, among the famous birthdays for May 10.

This report analyzes how recent immigrants to France fare in the country's labor market over time. The research shows that new arrivals initially face a hostile labor market and ultimately improve their employment outcomes—but their process of labor market insertion and advancement is a slow one.

This report analyzes the labor market integration of recent immigrants to the United Kingdom. During the 2000s, a large influx of labor from Eastern European countries transformed the United Kingdom's immigrant population and labor market. The report finds that over time, these new arrivals showed some progress in moving out of the lowest-skilled jobs.

This report analyzes the labor market integration of newcomers to Germany, who tend to have different national origins and higher levels of education than earlier waves of migrants. These new immigrants have had varying levels of success in finding employment and transitioning into higher-skilled jobs.

The global economic crisis and changing migration patterns in Europe bring up questions about how well immigrants are able to find employment and progress into better jobs over time. This overview report caps a series of six country case studies evaluating the employment outcomes for foreign-born workers during their first decade in the Czech Republic, France, Germany, Spain, Sweden, and the United Kingdom.

Immigrants in the United Kingdom find work easily thanks to a flexible labor market, but often have trouble moving up the ladder into middle-skilled work. This report examines how workforce and integration policies affect immigrant workers in the United Kingdom.

Part of a series exploring issues likely to be addressed by the new National Integration Plan, this webinar, with perspectives from MPI, the National Partnership for New Americans, and the National Skills Coalition, looks at the role of adult education and English language and skills training in the immigrant integration process.