Looking back, Ellie Furuya says her wedding reception in Thailand was too adult-centric. If she could go back, she'd make it more kid-friendly.

The Internet Archive, an online repository of web pages, was offline Thursday after its founder confirmed a major cyberattack that exposed the data of millions of users and left the site defaced.

Any complaints, queries or suggestions about content on News24 may be sent to our public editor George Claassen.

While on a walk, a woman saw a tuxedo cat in a window and greeted it with a wave. But she never imagined the cat would return the greeting, lifting its paw to say "hey."

"How many aura points did I gain when I waved to a cat and it waved back," says the caption of her TikTok video, accompanied by footage of the surreal exchange. — Read the rest

The post Woah! Woman waves at a stranger's cat — and much to her surprise, it waves back (video) appeared first on Boing Boing.

I recently switched over to using a vinegar-based spray cleaner (just vinegar, water, and rubbing alcohol), to clean my kitchen. It works wonderfully for me, and I love that by using it I'm saving money and reducing my exposure to harsh chemicals. — Read the rest

The post The science of vinegar: what happens to bacteria under a microscope appeared first on Boing Boing.

[update 2011-01-18 @ 16:07:40: We're up!]

5by5 Live

Before Christ was a corporal, Dan Benjamin was already a bit of a hero to me.

Since the early aughts–long before his insanely great 5by5.tv podcast network–Dan’s Hivelogic Enkoder was saving us millions of spam messages. His thoughtful tutorials on OS X (including unmissable advice on doing sane installs of MySQL and Rails, among others) are among the best on the web. His CSS has been widely stolen and reused without acknowledgment by thieves as diverse as other people and me. And his polymath posts on everything from Buddhism to The Paleo Diet to how to record a “Double-ender” have shown a charming combination of curiosity and empathy that, amongst numerous other reasons, clearly makes Dan a better human than me.

A propos of nothing, Dan’s also the guy who conducted one of (mp3) the three best interviews with me in which it’s been my good fortune to participate.1

Today, I’m honored to say that Dan and I are starting a thing together.

If it suits you, drop by 5by5.tv/live in about 35 minutes–at Noon Eastern/9am Pacific–to find out what we’re up to. I think it might be good. I’ll just say I’m as excited about this as I’ve been about any new project I’ve started in the past year or so.

Anyway. You can judge for yourself. Whether you can tolerate me or otherwise, definitely do not miss the work Dan’s doing at 5by5. Because it really is outstanding and very polished stuff.

As for our thing? My own goal, to paraphrase a bit from that interview with Dan, is to help you get excited, get better–and then?–Back to Work.

More soon. Thanks.

And...we're up

Back to Work | Ep.#1: Alligator in the Bathroom

Download MP3 of "'Back to Work,' Ep. 1"

In the inaugural episode of Back to Work, Merlin Mann and Dan Benjamin discuss why they’re doing this show, getting back to work instead of buying berets, the lizard brain, and compare the Shadow of the Mouse to San Francisco, and eventually get to some practical tips for removing friction.

It's a start.

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Episode Links

• Welcome to BrettTerpstra.com, home of Brett Terpstra and his nerdery
• carlhuda/janus – GitHub
• practically efficient — technology, workflows, life
• MacSparky – Blog
• The Brooks Review
• And now it’s all this
• Dan Rodney’s List of Mac OS X Keyboard Shortcuts & Keystrokes
• 43f Podcast: John Gruber & Merlin Mann’s Blogging Panel at SxSW | 43 Folders
• waffle software · ThisService
• One Thing Well
• html2text: THE ASCIINATOR (aka html2txt)
• The Conversation #27: Missionless Statements – 5by5

There is a reason Joe Rogan became the world's largest podcaster. He doesn't take his audience -- or his guests -- for granted. He wants MEANINGFUL conversations.

The post Joe Rogan Officially Backs A Candidate… Could Be The Biggest Endorsement Yet appeared first on Clash Daily.

Trump asked the question: are you better now than when I was in office? America's answer could not have been more clear.

The post TRUMP TRIUMPHS: Victory Speech As He Completes The YUGE Comeback appeared first on Clash Daily.

Kamala was right about one thing: this election really DID deliver 'joy'... just not the way she expected.

The post EPIC: The ‘Songify’ Trend Of Clipping Speeches To Music Is Back… And AWESOME! appeared first on Clash Daily.

A.F. Branco Cartoon – After almost four years of Democrats trying to shove Marxism down Americans’ throats, We, The People,..

Shortly after President-elect Donald Trump appointed Tom Homan as “border czar,” the immigration hardliner’s hilarious 2019 smackdown of Democratic Rep. Alexandria Ocasio-Cortez of New York went viral on social media. […]

The post Flashback: Video of Tom Homan Taking Down AOC Resurfaces, Showing Why Trump Picked Him appeared first on The Western Journal.

Boris Macek
Feb 1, 2008; 7:299-307
Research

Egypt’s purchase of a Chinese fighter jet is a reminder Cold War tactics are back in the Middle East Expert comment LJefferson 18 October 2024

The Egyptian army is a formidable force lacking air superiority capabilities to match its size and ambitions. China understood this predicament and offered to help.

The reported agreement for Egypt to buy the Chinese Chengdu J-10C 4.5 generation fighter jets is part of a broader shift from focusing on modernizing ground troops to bolstering the air force. The details of the deal have not yet been published. Nonetheless, it reveals Egypt has two motivations beyond backing its arsenal with another fighter jet.

Elusive Western technology

The most important motivation for Egypt’s military diversification strategy (and the biggest source of frustration) is the perceived Western technology starvation.
   
A quick examination of the map around Egypt shows that the most significant perceived threats to its national security are located in remote places where Egypt doesn’t traditionally enjoy ground troops’ presence. These include Ethiopia, the Southern Red Sea, Libya and the vulnerability a potential Israel–Iran regional war would create. From the generals’ perspective in Cairo, this list is more than a catalyst to build a modern and capable long arm.

The race started in 2015 after the Obama administration paused an arms transfer to Cairo in 2013 that included four F-16C Block 52 fighter jets amid toppling the Muslim Brotherhood government. The psychological effect of Washington’s decision in Cairo increased Egypt’s risk tolerance towards challenging its military ties with the US by diversifying away from it. 

Egypt ordered the MiG-29M2 fighter jets from Russia and the French Rafales this same year. In 2018, Egypt negotiated a $2 billion deal with Russia to purchase the Su-35 fighter jet, seen in Washington as crossing a red line and triggering a warning to Egypt that it would impose sanctions under the Countering America’s Adversaries Through Sanctions Act (CAATSA). This caused the deal to collapse.

The main factor of the US military sales in the Middle East is the upholding of the Israel Military Qualitative Edge principle over its neighbours. This principle requires the US to ensure Israel is superior over other regional countries’ strategic military capabilities, especially in air power.

For Egypt, this has long been a strategic vulnerability. The US turned down multiple requests by Egypt to purchase the active radar long-range AIM-120 AMRAAM fire-and-forget missile that can be launched from the F-16 fighter jets, the main striking force in Egypt’s arsenal. 

Unlike the Gulf and other states (such as Jordan and Turkey), Egypt was only allowed the old AIM-7 Sparrow and the AIM-9 Sidewinders, which are shorter in range and technologically inferior. Israel also allegedly pressured the Trump administration to refuse Egypt’s request to buy the F-35 stealth fight jets in 2019.

The US and Israel reportedly pressured France to not sell to Egypt the MBDA’s Meteor 100 km air-to-air missile with the Rafale fighters. Instead, Egypt received the 80 km MICA missile as part of the deal to buy 30 Rafales in 2021. Acquiring this advanced radar system and long-range missiles was likely behind Cairo’s deal to purchase 24 Eurofighter Typhoon aircraft from Italy in 2022. However, it is unlikely that they will come with the full package.

Egypt thought the Chinese J-10C Vigorous Dragon fighter may solve this predicament. The Chinese fighter has a beyond-visual range AESA radar and can carry the PL-15 200 km air-to-air missile, similar to the Rafale’s Meteor. The J-10C’s price tag is attractive for Egypt at $40-50 million, much less than the F-16 and Rafales.

The Chinese fighters are also a hedge against Russia’s sanctioned fighter jets, traditionally a second choice for the Egyptian air force.

Risky manoeuvres 

This doesn’t mean Egypt is on a path to abandon its weapons purchases from its Western partners. Egyptian weapons procurement policy is not only motivated by technical considerations. It also serves political objectives. Egypt still receives $1.3 billion every year in military and economic aid from Washington. Regime security and backing are two objectives that will likely encourage Cairo to rely on Western weapons systems for decades. 

However, from Egypt’s military perspective, the time may have come to resort to the Cold War tactics of diversification and counterbalancing. Being forced to accept old technology during the significant modernization of its air force creates a technical and operational necessity to seek this technology elsewhere. 

The regional uncertainty since Hamas’s 7 October attack on Israel and the war that followed in Gaza, southern Lebanon, and Israel’s intermittent confrontations with Iran makes make it imperative for the Egyptian strategic planners to take risky manoeuvres while targeting specific capabilities they seem desperate to acquire. 

The threat to deploy CAATSA sanctions against Egypt in 2019 makes the J-10C deal with China an interesting case study for all Middle Eastern allies of the West. It shows an uptick in Egypt’s risk tolerance to overcome its technological dilemma. It allows other countries considering the Chinese fighters (mainly Saudi Arabia) to gauge Washington’s reaction and design their future approach accordingly.   

Another motivation is to pressure the US, UK, and their allies to reconsider their implicit embargo on certain advanced technology by showing that Cairo now has alternatives. This tactic seems to work. General Frank McKenzie, the former head of US Central Command, said during a congressional hearing in 2022 that Washington will finally provide Egypt with the F-15 heavy-weight air superiority fighter, a longstanding demand by Cairo.

Building favours

The J-10C fighter jet ticks all the boxes: It satisfies Cairo’s diversity strategy and technological needs. It is under the sanctions threshold since it is less technologically savvy than the most controversial J-20 5th generation fighters, the equivalent to Russia’s SU-35. And it takes Egypt’s military partnership with China to a new level.

The rumour that the Chinese fighters are bought to replace the ageing versions of Egypt’s significant F-16 fleet is a source of pride for Beijing since its military technology started to be seen as a competitor to Western technology. A heavyweight military power like Egypt relying on Chinese fighters would almost certainly boost China’s share in the regional weapons market, just like Cairo’s purchase of the Rafale boosted its popularity globally.

MS Brown
Jul 1, 1980; 21:505-517
Reviews

Jason M. Ridlon
Feb 1, 2006; 47:241-259
Reviews

Reactive oxygen species (ROS) are an unavoidable host environmental cue for intracellular pathogens such as Mycobacterium tuberculosis and Mycobacterium bovis; however, the signaling pathway in mycobacteria for sensing and responding to environmental stress remains largely unclear. Here, we characterize a novel CmtR-Zur-ESX3-Zn2+ regulatory pathway in M. bovis that aids mycobacterial survival under oxidative stress. We demonstrate that CmtR functions as a novel redox sensor and that its expression can be significantly induced under H2O2 stress. CmtR can physically interact with the negative regulator Zur and de-represses the expression of the esx-3 operon, which leads to Zn2+ accumulation and promotion of reactive oxygen species detoxication in mycobacterial cells. Zn2+ can also act as an effector molecule of the CmtR regulator, using which the latter can de-repress its own expression for further inducing bacterial antioxidant adaptation. Consistently, CmtR can induce the expression of EsxH, a component of esx-3 operon involved in Zn2+ transportation that has been reported earlier, and inhibit phagosome maturation in macrophages. Lastly, CmtR significantly contributes to bacterial survival in macrophages and in the lungs of infected mice. Our findings reveal the existence of an antioxidant regulatory pathway in mycobacteria and provide novel information on stress-triggered gene regulation and its association with host–pathogen interaction.

Expert

Recent studies have suggested that innate immune responses exhibit characteristics associated with memory linked to modulations in both vertebrates and invertebrates. However, the diverse evolutionary paths taken, particularly within the invertebrate taxa, should lead to similarly diverse innate immunity memory processes. Our understanding of innate immune memory in invertebrates primarily comes from studies of the fruit fly Drosophila melanogaster, the generality of which is unclear. Caenorhabditis elegans typically inhabits soil harboring a variety of fatal microbial pathogens; for this invertebrate, the innate immune system and aversive behavior are the major defensive strategies against microbial infection. However, their characteristics of immunological memory remains infantile. Here we discovered an immunological memory that promoted avoidance and suppressed innate immunity during reinfection with bacteria, which we revealed to be specific to the previously exposed pathogens. During this trade-off switch of avoidance and innate immunity, the chemosensory neurons AWB and ADF modulated production of serotonin and dopamine, which in turn decreased expression of the innate immunity-associated genes and led to enhanced avoidance via the downstream insulin-like pathway. Therefore, our current study profiles the immune memories during C. elegans reinfected by pathogenic bacteria and further reveals that the chemosensory neurons, the neurotransmitter(s), and their associated molecular signaling pathways are responsible for a trade-off switch between the two immunological memories.

Animals can sense the presence of microbes in their tissues and mobilize their own defenses by recognizing and responding to conserved microbial structures (often called microbe-associated molecular patterns (MAMPs)). Successful host defenses may kill the invaders, yet the host animal may fail to restore homeostasis if the stimulatory microbial structures are not silenced. Although mice have many mechanisms for limiting their responses to lipopolysaccharide (LPS), a major Gram-negative bacterial MAMP, a highly conserved host lipase is required to extinguish LPS sensing in tissues and restore homeostasis. We review recent progress in understanding how this enzyme, acyloxyacyl hydrolase (AOAH), transforms LPS from stimulus to inhibitor, reduces tissue injury and death from infection, prevents prolonged post-infection immunosuppression, and keeps stimulatory LPS from entering the bloodstream. We also discuss how AOAH may increase sensitivity to pulmonary allergens. Better appreciation of how host enzymes modify LPS and other MAMPs may help prevent tissue injury and hasten recovery from infection.

Iron is an essential micronutrient, and, in the case of bacteria, its availability is commonly a growth-limiting factor. However, correct functioning of cells requires that the labile pool of chelatable “free” iron be tightly regulated. Correct metalation of proteins requiring iron as a cofactor demands that such a readily accessible source of iron exist, but overaccumulation results in an oxidative burden that, if unchecked, would lead to cell death. The toxicity of iron stems from its potential to catalyze formation of reactive oxygen species that, in addition to causing damage to biological molecules, can also lead to the formation of reactive nitrogen species. To avoid iron-mediated oxidative stress, bacteria utilize iron-dependent global regulators to sense the iron status of the cell and regulate the expression of proteins involved in the acquisition, storage, and efflux of iron accordingly. Here, we survey the current understanding of the structure and mechanism of the important members of each of these classes of protein. Diversity in the details of iron homeostasis mechanisms reflect the differing nutritional stresses resulting from the wide variety of ecological niches that bacteria inhabit. However, in this review, we seek to highlight the similarities of iron homeostasis between different bacteria, while acknowledging important variations. In this way, we hope to illustrate how bacteria have evolved common approaches to overcome the dual problems of the insolubility and potential toxicity of iron.

Chorismate mutase (CM), an essential enzyme at the branch-point of the shikimate pathway, is required for the biosynthesis of phenylalanine and tyrosine in bacteria, archaea, plants, and fungi. MtCM, the CM from Mycobacterium tuberculosis, has less than 1% of the catalytic efficiency of a typical natural CM and requires complex formation with 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase for high activity. To explore the full potential of MtCM for catalyzing its native reaction, we applied diverse iterative cycles of mutagenesis and selection, thereby raising kcat/Km 270-fold to 5 × 105 m−1s−1, which is even higher than for the complex. Moreover, the evolutionarily optimized autonomous MtCM, which had 11 of its 90 amino acids exchanged, was stabilized compared with its progenitor, as indicated by a 9 °C increase in melting temperature. The 1.5 Å crystal structure of the top-evolved MtCM variant reveals the molecular underpinnings of this activity boost. Some acquired residues (e.g. Pro52 and Asp55) are conserved in naturally efficient CMs, but most of them lie beyond the active site. Our evolutionary trajectories reached a plateau at the level of the best natural enzymes, suggesting that we have exhausted the potential of MtCM. Taken together, these findings show that the scaffold of MtCM, which naturally evolved for mediocrity to enable inter-enzyme allosteric regulation of the shikimate pathway, is inherently capable of high activity.

Pectins are a major dietary nutrient source for the human gut microbiota. The prominent gut microbe Bacteroides thetaiotaomicron was recently shown to encode the founding member (BT1017) of a new family of pectin methylesterases essential for the metabolism of the complex pectin rhamnogalacturonan-II (RG-II). However, biochemical and structural knowledge of this family is lacking. Here, we showed that BT1017 is critical for the metabolism of an RG-II–derived oligosaccharide ΔBT1017oligoB generated by a BT1017 deletion mutant (ΔBT1017) during growth on carbohydrate extract from apple juice. Structural analyses of ΔBT1017oligoB using a combination of enzymatic, mass spectrometric, and NMR approaches revealed that it is a bimethylated nonaoligosaccharide (GlcA-β1,4-(2-O-Me-Xyl-α1,3)-Fuc-α1,4-(GalA-β1,3)-Rha-α1,3-Api-β1,2-(Araf-α1,3)-(GalA-α1,4)-GalA) containing components of the RG-II backbone and its side chains. We showed that the catalytic module of BT1017 adopts an α/β-hydrolase fold, consisting of a central twisted 10-stranded β-sheet sandwiched by several α-helices. This constitutes a new fold for pectin methylesterases, which are predominantly right-handed β-helical proteins. Bioinformatic analyses revealed that the family is dominated by sequences from prominent genera of the human gut microbiota, including Bacteroides and Prevotella. Our re-sults not only highlight the critical role played by this family of enzymes in pectin metabolism but also provide new insights into the molecular basis of the adaptation of B. thetaiotaomicron to the human gut.

Peptidoglycan (PG) is an essential constituent of the bacterial cell wall. During cell division, the machinery responsible for PG synthesis localizes mid-cell, at the septum, under the control of a multiprotein complex called the divisome. In Escherichia coli, septal PG synthesis and cell constriction rely on the accumulation of FtsN at the division site. Interestingly, a short sequence of FtsN (Leu75–Gln93, known as EFtsN) was shown to be essential and sufficient for its functioning in vivo, but what exactly this sequence is doing remained unknown. Here, we show that EFtsN binds specifically to the major PG synthase PBP1b and is sufficient to stimulate its biosynthetic glycosyltransferase (GTase) activity. We also report the crystal structure of PBP1b in complex with EFtsN, which demonstrates that EFtsN binds at the junction between the GTase and UB2H domains of PBP1b. Interestingly, mutations to two residues (R141A/R397A) within the EFtsN-binding pocket reduced the activation of PBP1b by FtsN but not by the lipoprotein LpoB. This mutant was unable to rescue the ΔponB-ponAts strain, which lacks PBP1b and has a thermosensitive PBP1a, at nonpermissive temperature and induced a mild cell-chaining phenotype and cell lysis. Altogether, the results show that EFtsN interacts with PBP1b and that this interaction plays a role in the activation of its GTase activity by FtsN, which may contribute to the overall septal PG synthesis and regulation during cell division.

Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (MTB), is one of the leading causes of death worldwide, especially in children. However, the mechanisms by which MTB infects its cellular host, activates an immune response, and triggers inflammation remain unknown. Mitochondria play important roles in the initiation and activation of the nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) inflammasome, where mitochondria-associated endoplasmic reticulum membranes (MAMs) may serve as the platform for inflammasome assembly and activation. Additionally, mitofusin 2 (MFN2) is implicated in the formation of MAMs, but, the roles of mitochondria and MFN2 in MTB infection have not been elucidated. Using mircroarry profiling of TB patients and in vitro MTB stimulation of macrophages, we observed an up-regulation of MFN2 in the peripheral blood mononuclear cells of active TB patients. Furthermore, we found that MTB stimulation by MTB-specific antigen ESAT-6 or lysate of MTB promoted MFN2 interaction with NLRP3 inflammasomes, resulting in the assembly and activation of the inflammasome and, subsequently, IL-1β secretion. These findings suggest that MFN2 and mitochondria play important role in the pathogen-host interaction during MTB infection.

Michael E. Abrams
Dec 1, 2020; 61:1538-1538
Images in Lipid Research

Mass spectrometry has become an indispensable tool for the characterization of glycosylation across biological systems. Our ability to generate rich fragmentation of glycopeptides has dramatically improved over the last decade yet our informatic approaches still lag behind. Although glycoproteomic informatics approaches using glycan databases have attracted considerable attention, database independent approaches have not. This has significantly limited high throughput studies of unusual or atypical glycosylation events such as those observed in bacteria. As such, computational approaches to examine bacterial glycosylation and identify chemically diverse glycans are desperately needed. Here we describe the use of wide-tolerance (up to 2000 Da) open searching as a means to rapidly examine bacterial glycoproteomes. We benchmarked this approach using N-linked glycopeptides of Campylobacter fetus subsp. fetus as well as O-linked glycopeptides of Acinetobacter baumannii and Burkholderia cenocepacia revealing glycopeptides modified with a range of glycans can be readily identified without defining the glycan masses before database searching. Using this approach, we demonstrate how wide tolerance searching can be used to compare glycan use across bacterial species by examining the glycoproteomes of eight Burkholderia species (B. pseudomallei; B. multivorans; B. dolosa; B. humptydooensis; B. ubonensis, B. anthina; B. diffusa; B. pseudomultivorans). Finally, we demonstrate how open searching enables the identification of low frequency glycoforms based on shared modified peptides sequences. Combined, these results show that open searching is a robust computational approach for the determination of glycan diversity within bacterial proteomes.

The histidine kinase Hik33 plays important roles in mediating cyanobacterial response to divergent types of abiotic stresses including cold, salt, high light (HL), and osmotic stresses. However, how these functions are regulated by Hik33 remains to be addressed. Using a hik33-deficient strain (hik33) of Synechocystis sp. PCC 6803 (Synechocystis) and quantitative proteomics, we found that Hik33 depletion induces differential protein expression highly similar to that induced by divergent types of stresses. This typically includes downregulation of proteins in photosynthesis and carbon assimilation that are necessary for cell propagation, and upregulation of heat shock proteins, chaperons, and proteases that are important for cell survival. This observation indicates that depletion of Hik33 alone mimics divergent types of abiotic stresses, and that Hik33 could be important for preventing abnormal stress response in the normal condition. Moreover, we found the majority of proteins of plasmid origin were significantly upregulated in hik33, though their biological significance remains to be addressed. Together, the systematically characterized Hik33-regulated cyanobacterial proteome, which is largely involved in stress responses, builds the molecular basis for Hik33 as a general regulator of stress responses.

In nucleotide excision repair, bulky DNA lesions such as UV-induced cyclobutane pyrimidine dimers are removed from the genome by concerted dual incisions bracketing the lesion, followed by gap filling and ligation. So far, two dual-incision patterns have been discovered: the prokaryotic type, which removes the damage in 11–13-nucleotide-long oligomers, and the eukaryotic type, which removes the damage in 24–32-nucleotide-long oligomers. However, a recent study reported that the UvrC protein of Mycobacterium tuberculosis removes damage in a manner analogous to yeast and humans in a 25-mer oligonucleotide arising from incisions at 15 nt from the 3´ end and 9 nt from the 5´ end flanking the damage. To test this model, we used the in vivo excision assay and the excision repair sequencing genome-wide repair mapping method developed in our laboratory to determine the repair pattern and genome-wide repair map of Mycobacterium smegmatis. We find that M. smegmatis, which possesses homologs of the Escherichia coli uvrA, uvrB, and uvrC genes, removes cyclobutane pyrimidine dimers from the genome in a manner identical to the prokaryotic pattern by incising 7 nt 5´ and 3 or 4 nt 3´ to the photoproduct, and performs transcription-coupled repair in a manner similar to E. coli.

Timely repair of DNA double-strand breaks (DSBs) is essential to maintaining genomic integrity and preventing illnesses induced by genetic abnormalities. We previously demonstrated that the E3 ubiquitin ligase SMURF2 plays a critical tumor suppressing role via its interaction with RNF20 (ring finger protein 20) in shaping chromatin landscape and preserving genomic stability. However, the mechanism that mobilizes SMURF2 in response to DNA damage remains unclear. Using biochemical approaches and MS analysis, we show that upon the onset of the DNA-damage response, SMURF2 becomes phosphorylated at Ser384 by ataxia telangiectasia mutated (ATM) serine/threonine kinase, and this phosphorylation is required for its interaction with RNF20. We demonstrate that a SMURF2 mutant with an S384A substitution has reduced capacity to ubiquitinate RNF20 while promoting Smad3 ubiquitination unabatedly. More importantly, mouse embryonic fibroblasts expressing the SMURF2 S384A mutant show a weakened ability to sustain the DSB response compared with those expressing WT SMURF2 following etoposide treatment. These data indicate that SMURF2-mediated RNF20 ubiquitination and degradation controlled by ataxia telangiectasia mutated–induced phosphorylation at Ser384 constitutes a negative feedback loop that regulates DSB repair.

Jerad Eickhoff took his latest first step on Sunday morning at Spectrum Field. He threw a bullpen session, his first since sustaining a setback last month following carpal tunnel surgery in October.

After undergoing surgery in late June to repair a torn left labrum in his left shoulder that required nine anchors to be inserted to keep everything in place, Zack Cozart is healthy and looking for a bounce-back season with the Angels.

Gorbachev's complex legacy is beyond the popular belief Expert comment NCapeling 3 September 2022

The last major figure with a decisive Cold War role, Mikhail Gorbachev was not as bad as Putin’s Russia portrays him, but also not as heroic as the West thinks.

Arguably the worst year of the Cold War since the Cuban Missile Crisis was 1983, with three major incidents which escalated East-West tensions – and any one of them could have led to a full-scale war.

The first was the Korean Airline KAL007 being shot down by an SU15 fighter aircraft for straying into Soviet airspace, killing all 269 passengers and crew. Then came the identification of signals from Soviet satellites as being incoming US intercontinental ballistic missiles – Colonel Stanislav Petrov, going against all protocols, thankfully decided to report them as a false alarm before he could be sure.

The third was perhaps the most dangerous, being the misinterpretation of a live-fire NATO exercise which was believed by some in both East Germany and Russia to be a front for an imminent attack.

All three incidents occurred in the few months following the infamous March 1983 ‘Star Wars’ speech by US president Ronald Reagan, in which he talked about nuclear arms control and laid out the US case for a ballistic missile defence programme.

At that time Mikhail Sergeyevich Gorbachev was the youngest serving member of the USSR Politburo, known to be a favourite of Soviet leader Yuri Andropov, and it is highly likely he had been aware of these close calls and was part of discussions within Kremlin decision-making circles.

A changemaker both inside and outside the USSR

Following the deaths of Andropov in 1984 and his replacement Konstantin Chernenko in 1985, Gorbachev’s appointment as general secretary of the Communist Party saw him immediately begin to change the Soviet Union from within – and also change relationships with the major Western powers, especially the US, Germany, and the UK.

His policies of glasnost (openness) and perestroika (restructuring) were primarily aimed at internal reforms but translated into a major reset of international relations and international security. During his six years as leader, Gorbachev initiated many arms control negotiations which resulted in treaties and increased both the transparency and the confidence between the USSR and the US.

These included the 1986 Stockholm Accord which emanated from the Helsinki Process and allowed for the observation and inspection of large-scale military exercises, the 1985 resumption of the Strategic Arms Reduction Talks which lead to START I, and the 1987 INF Treaty in which the USSR ‘out-yessed’ the US – the most open and transparent disarmament treaty in terms of notification and verification measures ever agreed.

There was also a reciprocal moratorium on nuclear weapons tests starting from 1985 – which laid the groundwork for the 1996 CTBT – the 1991 Chemical Weapons Convention, and the 1990 Conventional Forces in Europe (CFE) Treaty.

The most dramatic moment of all was when Gorbachev and Reagan met at a summit in Reykjavik and came close to deciding to eliminate nuclear weapons – but the initiative failed to reach agreement, mainly because Reagan could not drop his commitment to ballistic missile defences and Gorbachev could not accept the offer of joint development.

Nonetheless, all these nuclear arms control treaties led the way for their descendants which have kept nuclear weapons in check ever since and are still in place in the form of the New START agreement.

But despite these outstanding achievements, Gorbachev had blind spots – such as enabling rather than destroying the USSR bioweapons programme, unlike the US which had dismantled its own bioweapons offensive capability by 1973.

And it is now known that, despite negotiating the Chemical Weapons Convention, Russia withheld information on new chemical weapons agents – Novichoks – which have since been used to lethal effect by Russia in Salisbury and against figures opposing the current regime.

His misguided faith in a Soviet future

Gorbachev was markedly different to his predecessors as secretary general. He was neither as decrepit nor as hardline, and he understood from the outset that the Soviet Union was, by the 1980s, finally dying.

Using the intellectual abilities of Aleksandr Yakovlev, he forced through the reforms which simultaneously captured the imagination of the free world and liberated his countrymen and women.

But although he built solid relationships – even friendships – with the world’s major heads of state and improved the USSR’s human rights, releasing dissidents such as Andrei Sakharov, but many – especially Ukrainian dissidents – continued to languish in camps.

The greatest disappointment in Gorbachev’s legacy was he completely believed the USSR could be reformed and still survive as an entity while others, such as Boris Yeltsin and Ronald Reagan, understood it had to be dismantled.

This shortcoming is especially uncomfortable as today’s Russia continues to insist it has a given right to control other former Soviet states, to the extent it is willing to destroy them if they do not concede.

Canada ordered striking dock workers back to the ports of Vancouver, Prince Rupert and Montreal on Tuesday to clear out more than a week of container congestion bound for the United States and Canada.

The Carolina Panthers signed running back Chuba Hubbard to a four-year contract extension worth $33.2 million, a league source told UPI on Thursday.

Tua Tagovailoa and Daniel Jones are among UPI senior sports writer Alex Butler's five must-start fantasy football quarterbacks for Week 10.

Tyrone Tracy Jr. and Najee Harris are among UPI senior sports writer Alex Butler's four must-start fantasy football running backs for Week 10.

A struggling Detroit Lions offense awoke late, scoring 19-unanswered points to rally past the Houston Texans and improve to 8-1 this season. The Lions overcame a career-high five interceptions Jared Goff threw.

Veteran quarterback Dak Prescott will undergo season-ending surgery to repair his injured hamstring, Dallas Cowboys owner Jerry Jones announced Tuesday.

About 2.25 million U.S. middle- and high-school students this year say they use tobacco products, which is 500,000 fewer than a year ago, the Centers for Disease Control said Thursday.

While no candy is truly healthy, some options are better for your gut than others. And there are ways you can help wake your gut from its sugar "spell" after holiday indulgence.

Virtual yoga can be a successful and accessible way to manage chronic low back pain -- a common ailment with major consequences, a new study suggests.

Waiting is the hardest part. In the fall of 2023, HPCwire wrote about the new diverging Xeon processor strategy from Intel. Instead of a on-size-fits all approach; Intel has opted […]

The post Granite Rapids HPC Benchmarks: I’m Thinking Intel Is Back (Updated) appeared first on HPCwire.

A New York Supreme Court justice will decide Tuesday if President-elect Donald Trump's sentencing will move forward later this month.

Canada ordered striking dock workers back to the ports of Vancouver, Prince Rupert and Montreal on Tuesday to clear out more than a week of container congestion bound for the United States and Canada.

The U.S. military conducted retaliatory airstrikes Tuesday in Syria, targeting facilities of Iran-backed militias following rockets launched at U.S. forces in the Middle Eastern country.

SpaceX has scrubbed Tuesday's launch of 20 Starlink Internet satellites into orbit from the Vandenberg Space Force Base in California until Wednesday, adding to its massive constellation designed to provide online servic

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