Seems sure to appeal equally to fans of Polar Bear, Lockheart and the Duke.

State Rep. Matt Soper, a Delta Republican whose district covers Grand Junction, called the situation “appalling.”

This abundant board features tortellini skewers, prosciutto-melon skewers and stuffed mushrooms, as well as classic antipasti items.

Kamau Leverock’s Gujarat Greats went down by 5 wickets to the Manipal Tigers. Leverock was replaced by West Indies legend Chris Gayle who was making his first appearance in the 2024 tournament. Gujarat Greats batted first and were bowled out for 131, Mohammad Kaif was the top scorer with 34, Praveen Gupta was the pick […]

The Argus Group participated in the Keep Bermuda Beautiful [KBB] Coastal Clean-Up, with 30 employees volunteering their time to collect an estimated 480 pounds of trash along the coastline at Admiralty House. A spokesperson said, “The Argus Group is proud to announce its participation in the Keep Bermuda Beautiful [KBB] Coastal Clean-Up on September 29th, […]

The Bermuda Health Council is offering two training sessions to help healthcare organizations comply with the upcoming Personal Information Protection Act [PIPA]. A spokesperson said, “As Bermuda prepares for the full implementation of the Personal Information Protection Act [PIPA] on January 1, 2025, the Bermuda Health Council is offering two training sessions to help healthcare […]

“This year’s emancipation commemoration theme is ‘Reimagining Community: Snapshots of Our Past,’ Minister of Tourism, Culture and Sport Owen Darrell said. Speaking in the Senate, the Minister said, “I stand before you today to recognize one of the most significant milestones in our history – the emancipation of our ancestors from the bonds of enslavement. […]

A number of people have come together to issue a declaration commemorating the 190th anniversary of the 1834 Emancipation Act. A spokesperson said, “On July 29, 2024, we, the undersigned – personally or on behalf of organizations – join in this declaration regarding a most significant milestone for Bermuda and other jurisdictions. On August 1, […]

Deputy Premier and Minister of Home Affairs Walter Roban travelled overseas to attend the Green Overseas Climate Finance Forum. A Government spokesperson said, “The Ministry of Home Affairs is pleased to advise that the Deputy Premier and Minister of Home Affairs, the Hon. Walter Roban, JP, MP, travelled overseas this weekend to represent Bermuda at […]

The Bermuda Tourism Authority [BTA] is aiming to enroll 300 new participants in its AnchorBDA programme before the end of 2024. A spokesperson said, “The Bermuda Tourism Authority has launched a bold challenge, aiming to enroll 300 new participants in its AnchorBDA programme before the end of 2024. “This initiative seeks to enhance the skills […]

Apple today seeded the second public betas of upcoming iOS 18.2, iPadOS 18.2, and macOS Sequoia 15.2 updates, allowing the public to continue testing new features ahead of when the software launches. The public betas come a day after Apple provided developers with new betas.


Public beta testers can download the updates from the Settings app on each device after opting into the beta through Apple's public beta testing website. Note that Apple has also released public betas for watchOS 11.2, tvOS 18.2, and the latest HomePod software.

iOS 18.2, iPadOS 18.2, and ‌macOS Sequoia‌ introduce the next Apple Intelligence features, including the first image generation capabilities.

The update adds Image Playground, a new app for creating images based on text descriptions. You can enter anything you want, though Apple will suggest costumes, locations, items, and more to add to an image. There are options to create characters that resemble your friends and family, and you can choose a photo for ‌Image Playground‌ to use as inspiration to create a related image. Elements added to ‌Image Playground‌ creations are previewed, and there is a preview history so you can undo a change and go back to a prior version.

While ‌Image Playground‌ is a standalone app, it is also integrated into Messages, Notes, Freeform, and more. ‌Image Playground‌ does not make photorealistic images and is instead limited to animation or illustration styles.

The update also adds Genmoji, which are customizable emoji characters that you can create based on descriptions and phrases. Like ‌Image Playground‌ creations, you can base them on your friends and family, with the data pulled from the People album in Photos. You can also make characters using basic elements, and you'll get multiple ‌Genmoji‌ suggestions to choose from. You can create ‌Genmoji‌ using the emoji keyboard.

‌Genmoji‌ are limited to iOS 18.2 and iPadOS 18.2 right now, and will be coming to ‌macOS Sequoia‌ later.

Siri in iOS 18.2, iPadOS 18.2, and ‌macOS Sequoia‌ 15.2 has ChatGPT integration. If ‌Siri‌ is unable to provide an answer to a question, ‌Siri‌ will hand the request over to ChatGPT, though ‌Siri‌ will need user permission first. ChatGPT will answer the question and relay the information back through ‌Siri‌.

ChatGPT can be used to create content from scratch, including text and images. No account is required to use ChatGPT integration, and Apple and OpenAI do not store requests.

If you have an iPhone 16, there's a Visual Intelligence feature in iOS 18.2 that provides information about what's around you. Open up the camera and point it at a restaurant to get reviews, or point it at an item to search Google for it.

Some other Visual Intelligence capabilities include reading text out loud, detecting phone numbers and addresses to add them to Contacts, copying text, and summarizing text.

Apple added Writing Tools in iOS 18.1, but in iOS 18.2, you can more freely describe the tone or content change that you want to make, such as adding more action words, or turning an email into a poem.

‌Apple Intelligence‌ now supports localized English in Australia, Canada, New Zealand, South Africa, Ireland, and the UK in addition to U.S. English.

Wait List

If you've already been testing ‌Apple Intelligence‌ and are opted in, you will have access to Writing Tools, ChatGPT integration, and Visual Intelligence automatically.

There is a secondary waiting list for early access to use ‌Genmoji‌, ‌Image Playground‌, and Image Wand. You can sign up to get access in ‌Image Playground‌ or in the areas where you access ‌Genmoji‌ or Image Wand.

When you request access, you are added to a wait list for all three capabilities and you'll get a notification when the features are available for you to use. Apple will roll out access over time.

Availability and Compatibility

The public betas are available on all devices, but the ‌Apple Intelligence‌ features require a device capable of ‌Apple Intelligence‌.

Apple is still working on refining the new ‌Apple Intelligence‌ tools, and the company warns that ‌Genmoji‌, Image Wand, and ‌Image Playground‌ can sometimes give you results you weren't expecting. Apple is collecting feedback on these experiences and will refine them over time.

Release Date

Apple is expected to release the iOS 18.2, iPadOS 18.2, ‌macOS Sequoia‌ 15.2, watchOS 11.2, tvOS 18.2, and visionOS 2.2 updates in early December.
This article, "Apple Seeds Second Public Betas of iOS 18.2, iPadOS 18.2 and macOS Sequoia 15.2 With New Apple Intelligence Features" first appeared on MacRumors.com

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Glenn Greenwald: "So you have huge number of journalists who believe that, they have the right to lie and even when they get caught, they don't care because they know their audience won't hold it against them." Continue reading →

City Hall [US, Frederick Wiseman, 4] The latest of Wiseman’s distinctive epic-length observational documentaries studies the quotidian, procedural and human moments of human life as seen through the processes of municipal government in Boston, as held together by the thoughtful charisma of Mayor Martin Walsh. Improbably absorbing as always, this institutional cross-section offers a beguiling vision of an oasis of good government in the USA.

In a normal year I’d wait for the four and a half hour Wiseman documentary to arrive on television rather than taking up two time slots to watch it from the confines of a cinema seat at TIFF. But this is not such a year and with a digital screening you get a pause button when you need it. This is bound for PBS and due to the breadth of its subject matter will serve as an excellent introduction to those unfamiliar with this pillar of the documentary form. Or track down 2017’s Ex Libris, about the New York Public Library. In North America Wiseman’s filmography can be found on the Kanopy platform, which you may be able to access through your public library system.

The Father [UK, Florian Zeller, 4] Retired engineer (Anthony Hopkins) struggles to piece together the confusing reality of his living circumstances as his daughter (Olivia Colman) copes with his progressing dementia. Impeccably performed stage play adaptation puts the viewer inside the contradictory shifts of the protagonist’s subjective viewpoint.

Forget Draculas and Cthulhus. This is the real terror.

Summer of 85 [France, Francois Ozon, 4] Love between two young men in a French beach town leads to a bizarre crime. Teen emotions run high in a sunlit melodrama of Eros and Thanatos.

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Capsule review boilerplate: Ratings are out of 5. I’ll be collecting these reviews in order of preference in a master post the Monday after the fest. Films shown on the festival circuit will appear in theaters, disc and/or streaming over the next year plus.

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I don't think you have to be a commie trot to observe that calling it that is stupid.

Apple has released iOS 17.7.1 and iPadOS 17.7.1 for iPhone and iPad users who are not running iOS 18, which was just updated to includes support for Apple Intelligence with iOS 18.1 and iPadOS 18.1. The software updates include important security fixes, making them important updates to install if you’re still running the prior major ... Read More

Apple Intelligence is here on Mac, iPhone, and iPad, and while the system requirements are strict, the Apple devices that are new and powerful enough to use the AI tools now gain some really fantastic features. We’re going to show you six helpful Apple Intelligence features and uses that you’ll find beneficial to your workflow, ... Read More

The second beta versions of iOS 18.2, MacOS Sequoia 15.2, and iPadOS 18.2 are now available for users participating in the beta testing programs for Apple system software. The new betas continue to focus on additional Apple Intelligence features, expanding beyond the writing tools, smart replies, and summary features what was initially introduced in iOS ... Read More

The third betas of iOS 18.2, iPadOS 18.2, and MacOS Sequoia 15.2, are available for beta testers of Apple system software. The latest betas continue to emphasize on new Apple Intelligence features, including ChatGPT integration, Genmoji custom Emoji creation, Image Playground for AI image generation, and more. These new AI features are in addition to ... Read More

Mary G. McCoy
Jun 1, 2002; 43:921-929
Research Articles

IJ Goldberg
Apr 1, 1996; 37:693-707
Reviews

JP Segrest
Feb 1, 1992; 33:141-166
Reviews

Can global technology governance anticipate the future? Expert comment NCapeling 27 April 2021

Trying to govern disruption is perilous as complex technology is increasingly embedded in societies and omnipresent in economic, social, and political activity.

Technology governance is beset by the challenges of how regulation can keep pace with rapid digital transformation, how governments can regulate in a context of deep knowledge asymmetry, and how policymakers can address the transnational nature of technology.

Keeping pace with, much less understanding, the implications of digital platforms and artificial intelligence for societies is increasingly challenging as technology becomes more sophisticated and yet more ubiquitous.

To overcome these obstacles, there is an urgent need to move towards a more anticipatory and inclusive model of technology governance. There are some signs of this in recent proposals by the European Union (EU) and the UK on the regulation of online harms.

Regulation failing to keep up

The speed of the digital revolution, further accelerated by the pandemic, has largely outstripped policymakers’ ability to provide appropriate frameworks to regulate and direct technology transformations.

Governments around the world face a ‘pacing problem’, a phenomenon described by Gary Marchant in 2011 as ‘the growing gap between the pace of science and technology and the lagging responsiveness of legal and ethical oversight that society relies on to govern emerging technologies’.

This ever-growing rift, Marchant argues, has been exacerbated by the increasing public appetite for and adoption of new technologies, as well as political inertia. As a result, legislation on emerging technologies risks being ineffective or out-of-date by the time it is implemented.

Effective regulation requires a thorough understanding of both the underlying technology design, processes and business model, and how current or new policy tools can be used to promote principles of good governance.

Artificial intelligence, for example, is penetrating all sectors of society and spanning multiple regulatory regimes without any regard for jurisdictional boundaries. As technology is increasingly developed and applied by the private sector rather than the state, officials often lack the technical expertise to adequately comprehend and act on emerging issues. This increases the risk of superficial regulation which fails to address the underlying structural causes of societal harms.

The significant lack of knowledge from those who aim to regulate compared to those who design, develop and market technology is prevalent in most technology-related domains, including powerful online platforms and providers such as Facebook, Twitter, Google and YouTube.

For example, the ability for governments and researchers to access the algorithms used in the business model of social media companies to promote online content – harmful or otherwise – remains opaque so, to a crucial extent, the regulator is operating in the dark.

The transnational nature of technology also poses additional problems for effective governance. Digital technologies intensify the gathering, harvesting, and transfer of data across borders, challenging administrative boundaries both domestically and internationally.

While there have been some efforts at the international level to coordinate approaches to the regulation of – for example – artificial intelligence (AI) and online content governance, more work is needed to promote global regulatory alignment, including on cross-border data flows and antitrust.

Reactive national legislative approaches are often based on targeted interventions in specific policy areas, and so risk failing to address the scale, complexity, and transnational nature of socio-technological challenges. Greater attention needs to be placed on how regulatory functions and policy tools should evolve to effectively govern technology, requiring a shift from a reactionary and rigid framework to a more anticipatory and adaptive model of governance.

Holistic and systemic versus mechanistic and linear

Some recent proposals for technology governance may offer potential solutions. The EU publication of a series of interlinked regulatory proposals – the Digital Services Act, Digital Markets Act and European Democracy Action Plan – integrates several novel and anticipatory features.

The EU package recognizes that the solutions to online harms such as disinformation, hate speech, and extremism lie in a holistic approach which draws on a range of disciplines, such as international human rights law, competition law, e-commerce, and behavioural science.

It consists of a combination of light touch regulation – such as codes of conduct – and hard law requirements such as transparency obligations. Codes of conduct provide flexibility as to how requirements are achieved by digital platforms, and can be updated and tweaked relatively easily enabling regulations to keep pace as technology evolves.

As with the EU Digital Services Act, the UK’s recent proposals for an online safety bill are innovative in adopting a ‘systems-based’ approach which broadly focuses on the procedures and policies of technology companies rather than the substance of online content.

This means the proposals can be adapted to different types of content, and differentiated according to the size and reach of the technology company concerned. This ‘co-regulatory’ model recognizes the evolving nature of digital ecosystems and the ongoing responsibilities of the companies concerned. The forthcoming UK draft legislation will also be complemented by a ‘Safety by Design’ framework, which is forward-looking in focusing on responsible product design.

By tackling the complexity and unpredictability of technology governance through holistic and systemic approaches rather than mechanistic and linear ones, the UK and EU proposals represent an important pivot from reactive to anticipatory digital governance.

Both sets of proposals were also the result of extensive multistakeholder engagement, including between policy officials and technology actors. This engagement broke down silos within the technical and policy/legal communities and helped bridge the knowledge gap between dominant technology companies and policymakers, facilitating a more agile, inclusive, and pragmatic regulatory approach.

Coherence rather than fragmentation

Anticipatory governance also recognizes the need for new coalitions to promote regulatory coherence rather than fragmentation at the international level. The EU has been pushing for greater transatlantic engagement on regulation of the digital space, and the UK – as chair of the G7 presidency in 2021 – aims to work with democratic allies to forge a coherent response to online harms.

Meanwhile the OECD’s AI Policy Observatory enables member states to share best practice on the regulation of AI, and an increasing number of states such as France, Norway, and the UK are using ‘regulatory sandboxes’ to test and build AI or personal data systems that meet privacy standards.

Not all states currently have the organizational capacity and institutional depth to design and deliver regulatory schemes of this nature, as well as the resource-intensive consultation processes which often accompany them.

So, as an increasing number of states ponder how to ‘futureproof’ their regulation of tomorrow’s technology – whether 6G, quantum computing or biotechnology – there is a need for capacity building in governments both on the theory of anticipatory governance and on how it can be applied in practice to global technology regulation.

Phospholipase Cε (PLCε) is activated downstream of G protein–coupled receptors and receptor tyrosine kinases through direct interactions with small GTPases, including Rap1A and Ras. Although Ras has been reported to allosterically activate the lipase, it is not known whether Rap1A has the same ability or what its molecular mechanism might be. Rap1A activates PLCε in response to the stimulation of β-adrenergic receptors, translocating the complex to the perinuclear membrane. Because the C-terminal Ras association (RA2) domain of PLCε was proposed to the primary binding site for Rap1A, we first confirmed using purified proteins that the RA2 domain is indeed essential for activation by Rap1A. However, we also showed that the PLCε pleckstrin homology (PH) domain and first two EF hands (EF1/2) are required for Rap1A activation and identified hydrophobic residues on the surface of the RA2 domain that are also necessary. Small-angle X-ray scattering showed that Rap1A binding induces and stabilizes discrete conformational states in PLCε variants that can be activated by the GTPase. These data, together with the recent structure of a catalytically active fragment of PLCε, provide the first evidence that Rap1A, and by extension Ras, allosterically activate the lipase by promoting and stabilizing interactions between the RA2 domain and the PLCε core.

Investigations of bacterial resistance strategies can aid in the development of new antimicrobial drugs as a countermeasure to the increasing worldwide prevalence of bacterial antibiotic resistance. One such strategy involves the TipA class of transcription factors, which constitute minimal autoregulated multidrug resistance (MDR) systems against diverse antibiotics. However, we have insufficient information regarding how antibiotic binding induces transcriptional activation to design molecules that could interfere with this process. To learn more, we determined the crystal structure of SkgA from Caulobacter crescentus as a representative TipA protein. We identified an unexpected spatial orientation and location of the antibiotic-binding TipAS effector domain in the apo state. We observed that the α6–α7 region of the TipAS domain, which is canonically responsible for forming the lid of antibiotic-binding cleft to tightly enclose the bound antibiotic, is involved in the dimeric interface and stabilized via interaction with the DNA-binding domain in the apo state. Further structural and biochemical analyses demonstrated that the unliganded TipAS domain sterically hinders promoter DNA binding but undergoes a remarkable conformational shift upon antibiotic binding to release this autoinhibition via a switch of its α6–α7 region. Hence, the promoters for MDR genes including tipA and RNA polymerases become available for transcription, enabling efficient antibiotic resistance. These insights into the molecular mechanism of activation of TipA proteins advance our understanding of TipA proteins, as well as bacterial MDR systems, and may provide important clues to block bacterial resistance.

The dimeric ectonucleotidase CD73 catalyzes the hydrolysis of AMP at the cell surface to form adenosine, a potent suppressor of the immune response. Blocking CD73 activity in the tumor microenvironment can have a beneficial effect on tumor eradication and is a promising approach for cancer therapy. Biparatopic antibodies binding different regions of CD73 may be a means to antagonize its enzymatic activity. A panel of biparatopic antibodies representing the pairwise combination of 11 parental monoclonal antibodies against CD73 was generated by Fab-arm exchange. Nine variants vastly exceeded the potency of their parental antibodies with ≥90% inhibition of activity and subnanomolar EC50 values. Pairing the Fabs of parents with nonoverlapping epitopes was both sufficient and necessary whereas monovalent antibodies were poor inhibitors. Some parental antibodies yielded potent biparatopics with multiple partners, one of which (TB19) producing the most potent. The structure of the TB19 Fab with CD73 reveals that it blocks alignment of the N- and C-terminal CD73 domains necessary for catalysis. A separate structure of CD73 with a Fab (TB38) which complements TB19 in a particularly potent biparatopic shows its binding to a nonoverlapping site on the CD73 N-terminal domain. Structural modeling demonstrates a TB19/TB38 biparatopic antibody would be unable to bind the CD73 dimer in a bivalent manner, implicating crosslinking of separate CD73 dimers in its mechanism of action. This ability of a biparatopic antibody to both crosslink CD73 dimers and fix them in an inactive conformation thus represents a highly effective mechanism for the inhibition of CD73 activity.

Visual Abstract

Julia Knöckel
Dec 22, 2020; 0:RA120.002432v1-mcp.RA120.002432
Research

Matthias Schittmayer
Dec 1, 2020; 19:2104-2114
Research

Jianhua Wang
Nov 4, 2020; 0:RA120.002375v1-mcp.RA120.002375
Research

The subcellular localization of Arf family proteins is generally thought to be determined by their corresponding guanine nucleotide exchange factors. By promoting GTP binding, guanine nucleotide exchange factors induce conformational changes of Arf proteins exposing their N-terminal amphipathic helices, which then insert into the membranes to stabilize the membrane association process. Here, we found that the N-terminal amphipathic motifs of the Golgi-localized Arf family protein, Arfrp1, and the endosome- and plasma membrane–localized Arf family protein, Arl14, play critical roles in spatial determination. Exchanging the amphipathic helix motifs between these two Arf proteins causes the switch of their localizations. Moreover, the amphipathic helices of Arfrp1 and Arl14 are sufficient for cytosolic proteins to be localized into a specific cellular compartment. The spatial determination mediated by the Arfrp1 helix requires its binding partner Sys1. In addition, the residues that are required for the acetylation of the Arfrp1 helix and the myristoylation of the Arl14 helix are important for the specific subcellular localization. Interestingly, Arfrp1 and Arl14 are recruited to their specific cellular compartments independent of GTP binding. Our results demonstrate that the amphipathic motifs of Arfrp1 and Arl14 are sufficient for determining specific subcellular localizations in a GTP-independent manner, suggesting that the membrane association and activation of some Arf proteins are uncoupled.

Angiopoietin-like protein (ANGPTL)3 regulates plasma lipids by inhibiting LPL and endothelial lipase (EL). ANGPTL3 inactivation lowers LDL-C independently of the classical LDLR-mediated pathway and represents a promising therapeutic approach for individuals with homozygous familial hypercholesterolemia due to LDLR mutations. Yet, how ANGPTL3 regulates LDL-C levels is unknown. Here, we demonstrate in hyperlipidemic humans and mice that ANGPTL3 controls VLDL catabolism upstream of LDL. Using kinetic, lipidomic, and biophysical studies, we show that ANGPTL3 inhibition reduces VLDL-lipid content and size, generating remnant particles that are efficiently removed from the circulation. This suggests that ANGPTL3 inhibition lowers LDL-C by limiting LDL particle production. Mechanistically, we discovered that EL is a key mediator of ANGPTL3’s novel pathway. Our experiments revealed that, although dispensable in the presence of LDLR, EL-mediated processing of VLDL becomes critical for LDLR-independent particle clearance. In the absence of EL and LDLR, ANGPTL3 inhibition perturbed VLDL catabolism, promoted accumulation of atypical remnants, and failed to reduce LDL-C. Taken together, we uncover ANGPTL3 at the helm of a novel EL-dependent pathway that lowers LDL-C in the absence of LDLR.

For three decades, the LPL–specific monoclonal antibody 5D2 has been used to investigate LPL structure/function and intravascular lipolysis. 5D2 has been used to measure LPL levels, block the triglyceride hydrolase activity of LPL, and prevent the propensity of concentrated LPL preparations to form homodimers. Two early studies on the location of the 5D2 epitope reached conflicting conclusions, but the more convincing report suggested that 5D2 binds to a tryptophan (Trp)-rich loop in the carboxyl terminus of LPL. The same loop had been implicated in lipoprotein binding. Using surface plasmon resonance, we showed that 5D2 binds with high affinity to a synthetic LPL peptide containing the Trp-rich loop of human (but not mouse) LPL. We also showed, by both fluorescence and UV resonance Raman spectroscopy, that the Trp-rich loop binds lipids. Finally, we used X-ray crystallography to solve the structure of the Trp-rich peptide bound to a 5D2 Fab fragment. The Trp-rich peptide contains a short α-helix, with two Trps projecting into the antigen recognition site. A proline substitution in the α-helix, found in mouse LPL, is expected to interfere with several hydrogen bonds, explaining why 5D2 cannot bind to mouse LPL.

Despite the crucial function of the small intestine in nutrient uptake our understanding of the molecular events underlying the digestive function is still rudimentary. Recent studies demonstrated that enterocytes do not direct the entire dietary triacylglycerol toward immediate chylomicron synthesis. Especially after high-fat challenges, parts of the resynthesized triacylglycerol are packaged into cytosolic lipid droplets for transient storage in the endothelial layer of the small intestine. The reason for this temporary storage of triacylglycerol is not completely understood. To utilize lipids from cytosolic lipid droplets for chylomicron synthesis in the endoplasmic reticulum, stored triacylglycerol has to be hydrolyzed either by cytosolic lipolysis or lipophagy. Interestingly, triacylglycerol storage and chylomicron secretion rates are unevenly distributed along the small intestine, with the proximal jejunum exhibiting the highest intermittent storage capacity. We hypothesize that correlating hydrolytic enzyme activities with the reported distribution of triacylglycerol storage and chylomicron secretion in different sections of the small intestine is a promising strategy to determine key enzymes in triacylglycerol remobilization. We employed a serine hydrolase specific activity-based labeling approach in combination with quantitative proteomics to identify and rank hydrolases based on their relative activity in 11 sections of the small intestine. Moreover, we identified several clusters of enzymes showing similar activity distribution along the small intestine. Merging our activity-based results with substrate specificity and subcellular localization known from previous studies, carboxylesterase 2e and arylacetamide deacetylase emerge as promising candidates for triacylglycerol mobilization from cytosolic lipid droplets in enterocytes.

Les troubles gastro-intestinaux peuvent avoir un impact significatif sur la qualité de vie des patients. Ils engendrent en effet des symptômes variés et inconfortables allant de douleurs abdominales et nausées à des troubles plus graves comme les maladies inflammatoires chroniques de l’intestin. Quelles sont les principales pathologies rencontrées dans cette spécialité de la médecine ? À quel […]

L’article Quelles sont les principales pathologies en gastroentérologie ? est apparu en premier sur Ortho Doc France.

Malaria elimination is still pending on the development of novel tools that rely on a deep understanding of parasite biology. Proteins of all living cells undergo a myriad number of posttranslational modifications (PTMs) that are critical to multifarious life processes. An extensive proteome-wide dissection revealed a fine PTM map of most proteins in both Plasmodium falciparum, the causative agent of severe malaria, and the infected red blood cells. More than two-thirds of proteins of the parasite and its host cell underwent extensive and dynamic modification throughout the erythrocytic developmental stage. PTMs critically modulate the virulence factors involved in the host-parasite interaction and pathogenesis. Furthermore, P. falciparum stabilized the supporting proteins of erythrocyte origin by selective de-modification. Collectively, our multiple omic analyses, apart from having furthered a deep understanding of the systems biology of P. falciparum and malaria pathogenesis, provide a valuable resource for mining new antimalarial targets.

Sporozoites are a motile form of malaria-causing Plasmodium falciparum parasites that migrate from the site of transmission in the dermis through the bloodstream to invade hepatocytes. Sporozoites interact with many cells within the host, but the molecular identity of these interactions and their role in the pathology of malaria is poorly understood. Parasite proteins that are secreted and embedded within membranes are known to be important for these interactions, but our understanding of how they interact with each other to form functional complexes is largely unknown. Here, we compile a library of recombinant proteins representing the repertoire of cell surface and secreted proteins from the P. falciparum sporozoite and use an assay designed to detect extracellular interactions to systematically identify complexes. We identify three protein complexes including an interaction between two components of the p24 complex that is involved in the trafficking of glycosylphosphatidylinositol (GPI)-anchored proteins through the secretory pathway. Plasmodium parasites lacking either gene are strongly inhibited in the establishment of liver stage infections. These findings reveal an important role for the p24 complex in malaria pathogenesis and show that the library of recombinant proteins represents a valuable resource to investigate P. falciparum sporozoite biology.

Trump Media and Technology Group shares rose 15% in value on Tuesday as voters cast ballots on Election Day.

New cross-species research suggests a theory of mind is one thing that sets humans apart from apes

Researchers interviewed scores of principals in 19 states on how they’ve coped and the lessons they’re taking away from the pandemic’s disruption.

School districts are competing against each other for purchases of digital devices as remote learning expands to schools across the country.

Wendy Shirey, principal of Pinecrest Academy Horizon in Henderson, Nev., was awarded the $25,000 cash prize, which is known as the "Oscars of Teaching."

Teachers felt that iPads "provide no educational function in the classroom" and are often used to play games in class.

Middle and high schools in Maine are returning their iPads and switching back to laptops after a survey found that 88.5 percent of teachers and 74 percent of students in one district preferred laptops for schoolwork and instruction, reports the Lewiston-Auburn Sun Journal.

Students at Bellevue Elementary in Syracuse, N.Y., spend an extra 70 minutes at school each day, and their principal says the extended school day has improved their academic performance.

Dez-Ann Romain, a Brooklyn principal, is believed to be the first full-time, front-line educator to die from COVID-19.

The Tennessee department of education is proposing unsually comprehensive legislation that will require all current and new K-3 teachers, and those who train them, to know evidence-based reading instruction.