Kadian Morgan was overwhelmed with grief as she leaned against a wall outside her gate on Jackson Lane, East Kingston, yesterday, tears streaming down her face. Her 19-year-old son, Kayshan 'Bem Bem' Smith, was lying in the morgue after being...

For many Jamaicans, the deceased are more than just loved ones who have passed on; they are cherished family members who deserve to look as presentable as they did in life. In a culture where the appearance of the deceased is paramount, morticians...

As I walked into the embalming room at Jones Funeral Home and Supplies in Kingston on Sunday, I immediately felt the weight of the room. The air was thick with the scent of various chemicals used in the trade permeating the space. Tools such as...

Clostridium difficile is an anaerobic and spore-forming bacterium responsible for 15–25% of postantibiotic diarrhea and 95% of pseudomembranous colitis. Peptidoglycan is a crucial element of the bacterial cell wall that is exposed to the host, making it an important target for the innate immune system. The C. difficile peptidoglycan is largely N-deacetylated on its glucosamine (93% of muropeptides) through the activity of enzymes known as N-deacetylases, and this N-deacetylation modulates host–pathogen interactions, such as resistance to the bacteriolytic activity of lysozyme, virulence, and host innate immune responses. C. difficile genome analysis showed that 12 genes potentially encode N-deacetylases; however, which of these N-deacetylases are involved in peptidoglycan N-deacetylation remains unknown. Here, we report the enzymes responsible for peptidoglycan N-deacetylation and their respective regulation. Through peptidoglycan analysis of several mutants, we found that the N-deacetylases PdaV and PgdA act in synergy. Together they are responsible for the high level of peptidoglycan N-deacetylation in C. difficile and the consequent resistance to lysozyme. We also characterized a third enzyme, PgdB, as a glucosamine N-deacetylase. However, its impact on N-deacetylation and lysozyme resistance is limited, and its physiological role remains to be dissected. Finally, given the influence of peptidoglycan N-deacetylation on host defense against pathogens, we investigated the virulence and colonization ability of the mutants. Unlike what has been shown in other pathogenic bacteria, a lack of N-deacetylation in C. difficile is not linked to a decrease in virulence.

Sirtuin 6, SIRT6, is critical for both glucose and lipid homeostasis and is involved in maintaining genomic stability under conditions of oxidative DNA damage such as those observed in age-related diseases. There is an intense search for modulators of SIRT6 activity, however, not many specific activators have been reported. Long acyl-chain fatty acids have been shown to increase the weak in vitro deacetylase activity of SIRT6 but this effect is modest at best. Herein we report that electrophilic nitro-fatty acids (nitro-oleic acid and nitro-conjugated linoleic acid) potently activate SIRT6. Binding of the nitro-fatty acid to the hydrophobic crevice of the SIRT6 active site exerted a moderate activation (2-fold at 20 μm), similar to that previously reported for non-nitrated fatty acids. However, covalent Michael adduct formation with Cys-18, a residue present at the N terminus of SIRT6 but absent from other isoforms, induced a conformational change that resulted in a much stronger activation (40-fold at 20 μm). Molecular modeling of the resulting Michael adduct suggested stabilization of the co-substrate and acyl-binding loops as a possible additional mechanism of SIRT6 activation by the nitro-fatty acid. Importantly, treatment of cells with nitro-oleic acid promoted H3K9 deacetylation, whereas oleic acid had no effect. Altogether, our results show that nitrated fatty acids can be considered a valuable tool for specific SIRT6 activation, and that SIRT6 should be considered as a molecular target for in vivo actions of these anti-inflammatory nitro-lipids.

S-Acylation, a reversible post-translational lipid modification of proteins, controls the properties and function of various proteins, including ion channels. Large conductance Ca2+-activated potassium (BK) channels are S-acylated at two sites that impart distinct functional effects. Whereas the enzymes that attach lipid groups are known, the enzymes mediating lipid removal (i.e. deacylation) are largely unknown. Here, McClafferty et al. identify two enzymes, ABHD17a and ABHD17c, that excise BK channel lipid groups with remarkable precision. These findings lend insights into mechanisms that orchestrate the (de)acylation that fine-tunes ion channel function in physiology and disease.

S-Acylation, the reversible post-translational lipid modification of proteins, is an important mechanism to control the properties and function of ion channels and other polytopic transmembrane proteins. However, although increasing evidence reveals the role of diverse acyl protein transferases (zDHHC) in controlling ion channel S-acylation, the acyl protein thioesterases that control ion channel deacylation are very poorly defined. Here we show that ABHD17a (α/β-hydrolase domain-containing protein 17a) deacylates the stress-regulated exon domain of large conductance voltage- and calcium-activated potassium (BK) channels inhibiting channel activity independently of effects on channel surface expression. Importantly, ABHD17a deacylates BK channels in a site-specific manner because it has no effect on the S-acylated S0–S1 domain conserved in all BK channels that controls membrane trafficking and is deacylated by the acyl protein thioesterase Lypla1. Thus, distinct S-acylated domains in the same polytopic transmembrane protein can be regulated by different acyl protein thioesterases revealing mechanisms for generating both specificity and diversity for these important enzymes to control the properties and functions of ion channels.

The EGFR tyrosine kinase inhibitor gefitinib is commonly used for lung cancer patients. However, some patients eventually become resistant to gefitinib and develop progressive disease. Here, we indicate that ecto-ATP synthase, which ectopically translocated from mitochondrial inner membrane to plasma membrane, is considered as a potential therapeutic target for drug-resistant cells. Quantitative multi-omics profiling reveals that ecto-ATP synthase inhibitor mediates CK2-dependent phosphorylation of DNA topoisomerase IIα (topo IIα) at serine 1106 and subsequently increases the expression of long noncoding RNA, GAS5. Additionally, we also determine that downstream of GAS5, p53 pathway, is activated by ecto-ATP synthase inhibitor for regulation of programed cell death. Interestingly, GAS5-proteins interactomic profiling elucidates that GAS5 associates with topo IIα and subsequently enhancing the phosphorylation level of topo IIα. Taken together, our findings suggest that ecto-ATP synthase blockade is an effective therapeutic strategy via regulation of CK2/phospho-topo IIα/GAS5 network in gefitinib-resistant lung cancer cells.

The Phillies continued to bolster their infield depth on Friday by signing versatile veteran Sean Rodriguez to a Minor League contract with an invite to big league Spring Training, MLB.com has learned.

Aaron Nola established himself as one of the best pitchers in baseball in 2018. The Phillies ensured on Wednesday that he will be the ace in their rotation for possibly the next five seasons.

The Angels agreed to terms with right-hander reliever Daniel Hudson on a Minor League deal to add bullpen depth, a source confirmed to MLB.com on Friday.

The Angels added a veteran lefty reliever, as Dan Jennings officially signed a Minor League deal on Saturday and joined the club for workouts at the club's Spring Training complex. Jennings will earn $1 million, plus incentives, if he makes the club.

Afonso Dhlakama’s Death Changes the Calculation for Peace Prospects in Mozambique Expert comment sysadmin 4 May 2018

If politicians continue to act in good faith, the death of the opposition leader may be a significant opportunity to finally draw a line under Mozambique’s long war.

The unexpected death of opposition and ex-rebel leader Afonso Dhlakama on 3 May is a game changer for Mozambique’s politics and an almost-completed peace process. The 65-year old Dhlakama, who died of a heart attack, had led Renamo for 38 years and had totally dominated his party. Dhlakama regularly boasted that he was Mozambique’s ‘father of democracy’, despite not allowing competition within his own party, and he leaves a legacy of more than 30 years of struggle, through both armed action and peaceful politics.

A long war

Originally Renamo had been a tool for the white minority regimes of Rhodesia and apartheid South Africa to challenge the socialist Frelimo political party that took power in Mozambique in 1975. But under Dhlakama’s command, by the late 1980s Renamo had become increasingly independent and rooted in Mozambique. After Renamo’s long war with Frelimo ground to a hurting stalemate, a transition led to Mozambique’s first multiparty elections in 1994, and the creation of a new joint army. A ‘pay and scatter’ programme successfully dispersed and reintegrated many thousands of ex-combatants.

But early post-election gains did not translate to lasting peace. Disarmament was a time-limited, technical process, and devoted declining resources and attention to clusters of ex-combatants that failed to disperse. In addition, Dhlakama was allowed to maintain an armed militia under the guise of a presidential guard.

Mounting economic inequality, notably in opposition strongholds such as central Mozambique, saw Renamo made political gains and Dhlakama nearly won the 1999 presidential elections. (Some believe he did.) The result focused Frelimo’s attention on the threat that Renamo posed and, ultimately, a strategy of pursuing total Frelimo domination across the country, culminating in a crushing Frelimo victory at the 2009 elections.

This humiliated and marginalized former Renamo rebels, resulting in Dhlakama ordering their return to targeted armed violence in 2013. Frelimo’s new leader, President Filipe Nyusi, took power in 2015 and sought direct dialogue with Dhlakama. Five rounds of internationally mediated peace talks took place from July to December. Finally, in late December 2016, Dhlakama announced a unilateral truce, which was extended twice and subsequently made indefinite.

New peace talks also started and, in August 2017 and February 2018, President Nyusi and Dhlakama showed the courage to meet in person, near Renamo’s base in central Mozambique, to build up mutual trust and discuss the details of the emerging peace deal – including the demobilization or integration into government security forces for Renamo’s now mostly middle-aged gunmen.

Dhlakama the ‘Big Man’

Dhlakama’s sudden death has fundamentally changed the negotiation dynamics. He never allowed for any serious succession planning, and ensured all key decisions were his and his alone. Renamo had already decided that he would be its presidential candidate for the 2019 national elections.

His party is significantly weakened by his death and unlikely able to fully recover – but needs to try and reach consensus quickly on a successor, as it will also compete in municipal elections in October and was expecting significant gains. There will be a number of contenders to succeed him including from the parliamentary wing, led by his niece Ivone Soares, its secretary general, Manuel Bissopo, and a few others.

But Renamo’s key leverage for now remains some 1,000 middle-aged gunmen in central Mozambique who have been stoically loyal to Dhlakama since the 1980s and who have little respect for the younger generation of professional politicians based in Maputo. Some may be bought off by government offers, others integrated into localised organized crime groups and others into internal Renamo sectarianism. The risk of fragmentation is real.

Renamo’s weakness could also embolden Frelimo hardliners to seek a return to unilateral domination of Mozambique’s political landscape, and to undermine the peace process. That would be a serious tactical mistake by Frelimo, as a lasting deal is close and the death of Dhlakama could actually assist in making this settlement lasting. Dhlakama was quixotic and prone to changing his mind, often influenced by the last person he spoke to – his death potentially introduces greater predictability in negotiations and in any post-deal implementation.

President Nyusi is clearly aware of this as he hailed on state television TVM that Dhlakama was ‘a citizen who has always worked for Mozambique’ and said he was distraught at the news of his death. He stated, ‘I hope that we as Mozambicans can continue to do everything so things do not go down.’ He also addressed Renamo’s support base by saying that ‘[Dhlakama] did everything so that there would be peace. The last time he spoke to me, he said he was not going to miss out anything in peace negotiations.’

Renamo’s gunmen are fatigued and want to retire with dignity but are vulnerable to manipulation and political miscalculation by Mozambican’s positioning politicians. International partners and investors can engage, by emphasizing that sustainable peace is the only pathway to poverty reduction and inclusive economic development.

This includes assisting development and reconciliation projects in areas impacted by the renewed conflict since 2013. Long-term investment for development in Renamo’s key constituencies could help avoid fragmentation at a critical time – faith groups and NGOs may also have a key role to play.

If Mozambique’s politicians continue to act in good faith, the death of Dhlakama may constitute a significant opportunity to finally draw a line under Mozambique’s long war.

SpaceX has reportedly struck a deal with LG Energy Solution Ltd. to supply cylindrical lithium-ion batteries for Elon Musk's Starship rocket, expected to launch early next year, according to industry sources.

Q-CTRL, the Australia-based start-up focusing on quantum infrastructure software, today announced that its performance-management software, Fire Opal, will be natively integrated into four of the world’s most advanced quantum computing […]

The post Quantum Software Specialist Q-CTRL Inks Deals with IBM, Rigetti, Oxford, and Diraq appeared first on HPCwire.

Deaths from cardiovascular disease have surged among adults ages 25 to 64 living in rural areas, a new study shows.

SpaceX has reportedly struck a deal with LG Energy Solution Ltd. to supply cylindrical lithium-ion batteries for Elon Musk's Starship rocket, expected to launch early next year, according to industry sources.

Kevin Costner says he didn't know about his "Yellowstone" character John Dutton's death until after the episode aired on Sunday.

A man drove a vehicle into a crowd at a sports center in Zhuhai, China, killing 35 people and injuring 43 others, police said.

Call for papers: SJDM, San Francisco, Nov 17-20, 2023. Submission deadline June 22, 2023

The rapid shift to tech-driven, remote learning this spring has infused more technology into K-12 education, but AI tools still remain on the fringe.

As the bizarre becomes ordinary, don't forget what's at stake for America's teachers during the COVID-19 pandemic, writes Justin Minkel.

With many school buildings closed for the rest of the academic year—and more to follow—district leaders turn their attention to making up for what may be deep learning losses.

With many school buildings closed for the rest of the academic year—and more to follow—district leaders turn their attention to making up for what may be deep learning losses.

The shooting death of a 10-year-old spectator at a high school football game exposes a critical vulnerability and crucial responsibility for schools: keeping people safe at events outside school buildings.

With many school buildings closed for the rest of the academic year—and more to follow—district leaders turn their attention to making up for what may be deep learning losses.

Wisconsin's $3 billion Foxconn deal is an economic and workforce loser for the state and its residents, argues Marc Tucker.

Florida's governor declares a standards overhaul would "remove all vestiges" of the common core. But it remains unclear how much is really changing under the Florida Benchmarks for Excellent Student Thinking.

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Thousands of Indiana teachers are scrambling to begin renewing their professional teaching licenses before new rules that state lawmakers approved this spring take effect July 1.

When Scott Gann learned his son Dustin had dyslexia, he was shocked at the school's reaction. No one there wanted to use the word.

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Neuronal cytotoxic edema is implicated in neuronal injury and death, yet mitigating brain edema with osmotic and surgical interventions yields poor clinical outcomes. Importantly, neuronal swelling and its downstream consequences during early brain development remain poorly investigated, and new treatment approaches are needed. We explored Ca²⁺-dependent downstream effects after neuronal cytotoxic edema caused by diverse injuries in mice of both sexes using multiphoton Ca²⁺ imaging in vivo [Postnatal Day (P)12–17] and in acute brain slices (P8–12). After different excitotoxic insults, cytosolic GCaMP6s translocated into the nucleus after a few minutes in a subpopulation of neurons, persisting for hours. We used an automated morphology-detection algorithm to detect neuronal soma and quantified the nuclear translocation of GCaMP6s as the nuclear to cytosolic intensity (N/C ratio). Elevated neuronal N/C ratios occurred concurrently with persistent elevation in Ca²⁺ loads and could also occur independently from neuronal swelling. Electron microscopy revealed that the nuclear translocation was associated with the increased nuclear pore size. The nuclear accumulation of GCaMP6s in neurons led to neocortical circuit dysfunction, mitochondrial pathology, and increased cell death. Inhibiting calpains, a family of Ca²⁺-activated proteases, prevented elevated N/C ratios and neuronal swelling. In summary, in the developing brain, we identified a calpain-dependent alteration of nuclear transport in a subpopulation of neurons after disease-relevant insults leading to long-term circuit dysfunction and cell death. The nuclear translocation of GCaMP6 and other cytosolic proteins after acute excitotoxicity can be an early biomarker of brain injury in the developing brain.

Building captive colonies for eventual re-introduction to the wild, scientists from Atlanta rescue endangered frogs and other amphibians threatened with extinction by a fatal fungus spreading through South American forests

In 1967, a horrific fire broke out during a routine pre-launch test for the Apollo 1 mission at Cape Kennedy, Florida. It would claim the lives of three NASA astronauts

The Black Death of 1348 was a devastating event, wiping out half the population of Britain. And in churches like this one, drawings on the wall provide a haunting visual record of the scale of the tragedy.

In this time-lapse video, watch how workers built a visitor’s center in South Africa using ancient Roman techniques such as the arched ceiling, or vault

Smithsonian magazine commissioned Drew Gardner for a project that connects Black Americans today to their lost ancestry. Read about Gardner’s project and process, as well as more details about the subjects of this incredible series here: https://www.smithsonianmag.com/history/descendants-black-civil-war-heroes-wear-heritage-pride-180983397/ Video produced by Sierra Theobald. Special thanks to Drew Gardner Additional credits: Emma MacBeath, WikiTree US Black Heritage project; Ottawa Goodman, research and coordinator; Sam Dole, Penumbra Foundation; Elizabeth Zuck, set design; Calvin Osbourne, props and costume; Angela Huff, hair and make up; Diego Huerta, Lexia Krebs, behind-the-scenes filming; background prints by Fujifilm USA

What caused the Plague? And what methods did people use to combat the spread? Learn about its origins, past outbreaks (including the Black Death), and the long-lasting impact of its legacy today. --- For more videos from Smithsonian Magazine: https://www.smithsonianmag.com/videos/ Digital Editorial Director: Brian Wolly Supervising Producer & Scriptwriter: Michelle Mehrtens Producer: Nicki Marko Producer: Sierra Theobald Video Editor: Natalie Cline Graphic Designer: Kevin Schoenblum

Uncover the dark and curious truth behind the death of one of America's most beloved authors, Edgar Allan Poe. For centuries, the circumstances surrounding his death have remained shrouded in mystery, sparking endless speculation and debate. Was it murder, disease, or something even more sinister? ___ A little more information: In 1849, Edgar Allan Poe was found delirious on the streets of Baltimore. He was taken to a hospital but died four days later, with no clear explanation for his condition. Theories about his demise range from alcoholism to rabies to a neurological disorder. Some suggest a more sinister plot, involving foul play or a conspiracy. Despite extensive speculation, Poe's death ultimately remains an enigma, adding to the haunting allure of his literary legacy. #unsolvedmysteries #gothicliterature #theraven #edgarallanpoe #truecrime #Smithsonianmagazine Subscribe: https://www.youtube.com/@SmithsonianMagazine Read more about the mystery of Edgar Allan Poe’s death here: https://www.smithsonianmag.com/history/still-mysterious-death-edgar-allan-poe-180952936/ How did Edgar Allan Poe become such a prolific and popular storyteller, even after his death? Learn more about his history here: https://www.smithsonianmag.com/arts-culture/edgar-allan-poe-became-era-premier-storyteller-180971001/ For more videos from Smithsonian Magazine: https://www.smithsonianmag.com/videos/ Get More Smithsonian Magazine: Official Site: https://www.smithsonianmag.com/ Facebook: https://www.facebook.com/smithsonianmagazine/ X: https://x.com/smithsonianmag Instagram: https://www.instagram.com/SmithsonianMagazine/ Digital Editorial Director: Brian Wolly Director of Programming: Nicki Marko Manager of Programming: Michelle Mehrtens Scriptwriter: Dan Wolf Video Editor and Narrator: Adam Benavides

In WW2, the British made destroying German dams a key strategic target in order to kneecap the German industrial effort. To accomplish this, they needed a special plane to deliver the payload: the Lancaster Bomber.

In this clip from the documentary, see how Cassady embodied the spirit of Jack Kerouac's iconic character from On the Road

This feed is dead. Stop polling it!

A new paper analyzes three decades of fatalities around the world and predicts how "superbugs" will affect human health in the future

Kleptoparasitism, in which a bird harasses another to steal its food, might introduce avian flu to the continent, currently the only one without the severe H5N1 strain