Bouchiba continued getting jobs at major studios like Pixar and Dreamworks even after being added to France's national sex offender registry in 2014.

Each episode cost nearly $14 million per episode to produce and market across its two-season, 18-episode run.

His style complements the whimsical narrative of a woman taking an unconventional cab ride to the moon.

Artists of all levels are invited to showcase their skills and creativity.

Improving organic traffic can sometimes be challenging, but if you apply the correct SEO strategies, the hard work will eventually pay off. Search engine traffic is great because it’s relevant and targeted. For most websites, organic traffic converts much better than traffic from social media or other sources. Another great advantage is that visits from […]

The post 10 Smart Ways To Increase Organic Traffic To A Website appeared first on RSSground.com.

Explore these NOVA resources to better understand the volcanology behind Tonga’s massive undersea eruption in January.

These are just a few of the geoglyphs in southern Peru, known as the Nazca lines, thought to be at least 2,000 years old.

With 23 short essays on creatures ranging from the wombat to the spider, Katherine Rundell's new book is essential reading for anyone whose wonder could use a jumpstart.

Natural Bonds is not only a home for animals, however: It is also a home for people. 

Behind the Bylines: Breaking news coverage is the backbone of news, and in Israel, it comes with the added intensity of wartime coverage within the war. Joanie Margulies has been doing just that.

Over a dozen flights cancelled or delayed between Bali and Australia

The hot Glass Animals from Oxford, England have carved a niche in the indie rock universe with their unique conceptual pop sound Their journey through career highs and lows of thrilling experiences about changing lives and birthed their most acclaimed project to date — the Dreamland album Dreamland The creative forces behind it came up with an equally ambitious project called Dreamland Tours. The Glass Animals Dreamland Tour has been hailed as an unparalleled experience for fans, going beyond the traditional concept of a concert. The tour is characterized by immersive visuals, interactive performances, and the tangible personal connection the band shares with its listeners This combination is a magical fan experience which continues to echo over the limits of the concert venue. As we delve into the highlights of the Glass Animals Dreamland Tour, we’ll see why it stands true to the ultimate fan experience.   Glass Animals Visiting the Land of Dreams: An Art Journey Glass helps with the back of the Dreamland album Musical journeys viewed by mirror animals Stained glass animals have made an indelible mark on the canvas of contemporary music. Rising from humble beginnings in 2010, the four-man band from Oxford have grown into a powerhouse with indie musical talent, marrying smooth beats and eclectic lyricism Their rise has been fueled by critically acclaimed albums, and taking on an ever-changing soundscape. Introduction to the Dreamland album and its themes “Dreamland,” their third album, due out in 2020, is a mosaic of memories, introspection and intimate stories. Explores topics such as nostalgia, personal growth, and the complexity of the human spirit. Songs like “Heat Waves” resonate with fans, not only because they are catchy, but because they are heartfelt. The transition to touring: The importance of dreamland in live performances The Dreamland Tour elevates the album from a purely listening experience to a multi-sensory event. Gives fans the chance to step into the world imagined by the lyrics on the album. The tour takes on more meaning as it marks the album’s life in a haunting place, inviting fans to share in the band’s most personal moments. Basically, a Dreamland tour isn’t just about performance. It’s a gateway to the true heartbeat of Glass Animals, delivering an immersive experience lifted straight from the kaleidoscopic world of the Dreamland album. The Unique Aspects of the Dreamland Tour Visuals and Stage Design One unmissable aspect of the Dreamland tour by Glass Animals is the impeccable visuals and stage design. Strikingly vivid and meticulously crafted, the stage becomes a living, pulsating extension of the Dreamland album itself. The stage setup incorporates a remarkable array of LED screens and lighting, bathed in a dreamy palette of pastels and bursts of neon. The visual effects transcend the typical, showcasing visuals that immerse fans in a psychedelic landscape filled with soaring palm trees and retro television sets. Imbued within these visuals are the specific themes and narratives of the Dreamland album, transforming songs into vibrant vignettes that captivate audiences. Interactive Performances Beyond the sensory feasts of the visuals and stage design, the Dreamland Tour stands out for its engaging and interactive performances. The band’s authenticity shines through each performance, fostering an intimate connection with the audience. During shows, the band members often break the metaphorical fourth wall, engaging directly with fans through candid banter, shared stories, and common jokes. Notable moments from the tour include frontman Dave Bayley’s famed crowd surfing, and encouragement for fans to join the band in singing along, creating a collective auditory experience. Setlist and Musical Arrangements The craft and care put into the setlist and musical arrangements have played a significant part in the tour’s resounding success. The setlist is composed not merely as a linear progression of songs but as a journey through Glass Animals’ discography, carefully curated to engage fans new and old. Signature hits from their previous albums such as “Gooey” from ZABA and “Youth” from How To Be A Human Being are woven seamlessly with tracks from Dreamland. Exclusive to the tour are special renditions of select tracks, including acoustic versions and extended instrumental segments that offer fans a unique and novel listening experience. In essence, the Dreamland Tour is marked by a synthesis of compelling visuals, engaging performances, and thoughtful setlist selection – offering fans a truly immersive and memorable experience. fan experiences and testimonials Personal information The Dreamland trip has left an indelible mark on fans, many of whom share fond stories of their experiences. These stories reflect not only the enjoyment of the concert, but also the deep emotional connection fans have made to the music of Glass Animals and the memories they remember while on tour Emotional resonance: A fan described a moment during “Heat Waves” when the crowd’s combined singing spoke of a sense of shared experience and understanding, bringing many to tears. Memorable connection: Another recounted a pre-concert meeting in which band member Dave Belle remembered their names from previous concerts, revealing the real connection the band has with its audience . community and stakeholders One of the outstanding features of the Dreamland tour is its ability to create a vibrant and inclusive community among fans. From the concert lineup to the final notes of fading music, belonging and shared passion is palpable. Before the concert: Fans often share information online, detailing their interests, clothing choices and itineraries, building anticipation and camaraderie even before the concert begins. During the performance: The interactive aspects of the show, such as music, crowd surfing, immediately become mainstream events in society, forcing connections with them the intensity of the desired interval. After the event: Social media platforms are buzzing with concert photos, videos and personal reflections, allowing the community to relive the experience and maintain the relationships built during the event. Through the power of music and shared experiences, the Dreamland tour has created a sense of community that extends beyond concert venues is not limited to Fans walking away with memories of a performance. Behind-the-Scenes Elements that Make the Tour Special Preparation and Inspiration The Dreamland Tour, as recounted by the members of Glass Animals, is not just a series of concerts but a deeply immersive experience designed to transport fans into the very essence of their latest album, Dreamland. The planning and creative process behind the tour was both exhaustive and exhilarating. Creative Process: The band members spent countless hours discussing and experimenting with different visual and auditory elements to ensure that the live experience would accurately reflect the album’s intimate and entrancing vibe. Band Quotes: “We wanted to pull the audience into Dreamland, to make them feel the nostalgia, the melancholy, and the euphoria that the album speaks to,” said Dave Bayley. “Every detail, from the visuals to the setlist, was crafted with this in mind.” Challenges and Triumphs Like many others, the Dreamland Tour faced its fair share of hurdles, most notably, the global pandemic. The uncertainties and health concerns posed significant challenges, leading to postponed dates and constant reevaluation of plans. Overcoming Obstacles: The band and their crew demonstrated remarkable resilience in the face of these challenges. With a deep commitment to their fans and the music, they navigated through the uncertainty, enforcing strict health protocols to ensure the safety of everyone involved. Milestones: Despite the initial setbacks, the tour emerged triumphant. Sold-out shows and critical acclaim became testaments to the band’s hard work and the fans’ undying enthusiasm. “Seeing fans come together safely after such a difficult time has been incredibly touching and reinforces why we do what we do,” Bayley commented on the success of the tour. The behind-the-scenes preparation, boundless creativity, and relentless determination to overcome challenges underscore the Dreamland Tour’s success, making it not just a series of live performances, but a truly memorable and impactful experience for both the band and their fans. The lasting impact of a visit to dreamland Glass Animals’ Dreamland Tour not only captivated audiences around the world, it left an indelible mark on the music industry and its fans. This volume explores the transformative power of touring and its contribution to live music. It’s about the music industry The Dreamland tour set a new standard for live music, emphasizing the importance of an immersive concert experience. Here are some of the initiatives that have impacted the industry. New platform activities: The tour introduced new forms of drama and visual storytelling, turning the concert into an emotional experience. Fan interaction: Leveraging technology and social media, the team created more interactive and personal experiences, setting the trend for future tours It’s about the fans and the attendees Beyond the phenomenon, the Dreamland tour created a deep and lasting connection with fans and impacted them in many profound ways: Emotional resonance: Many attendees described the concert as emotionally transformative, providing a sense of escape and connection during difficult times. Community building: The tour has been a catalyst for community building, and fans have bonded over shared experiences, both online and in concert. conclusion The key to appreciating the Dreamland Tour was its unique blend of immersive storytelling, interactive performances and profound emotional journey for attendees not just a series of concerts; It was a public trip to the heart of the Glass Animals’ musical universe, and a program was designed to provide the ultimate fan experience. Visiting Dreamland with innovative stage design, personalized fan interaction and exciting performances reaffirmed what it means to attend a live concert Its legacy extends beyond nights out under neon lights and businesses the standards it has raised Reflecting on the impact of the Dreamland tour, it’s clear that his legacy will continue to inspire fans and artists alike, shaping the future of live performance and fan engagement in the music industry.

The post Why the Glass Animals Dreamland Tour Is the Ultimate Fan Experience appeared first on Geeky Traveller.

Situated on the northwest coast of the picturesque island of Crete, Chania stands as a testament to a vibrant mix of cultures that have left their mark over the millennia Breathtaking, famous for rich historical fabrics and the warm hospitality of his people is not appropriate to the destination; It’s an experience waiting to be discovered. This blog post will be your gateway to why Chania, Greece is the paradise you have been searching for. What sets Chania apart? A mixture of histories The streets of Chania speak of the past, whispering stories of Venice, the Ottomans and the Egyptian conquerors, each of whom left behind them a piece of its culture, architecture and spirit and through this blend of influences no Chania becomes a living canvas with so much history and beauty. The Old Port of Venice, with its magnificent lighthouse, stands as a symbol of Chania’s enduring heritage, inviting visitors to walk and marvel at the texts carved into its ancient stones. Unsurpassed natural beauty From tranquil beaches with crystal-clear waters to majestic white mountains in the background, Chania offers natural landscapes as diverse as stunning with stunning white and pink sands like Balos The Lagoon and Elafonissi Beach are not heavenly. For adventure enthusiasts, the Samaria Gorge, one of the longest canyons in Europe, is both a challenge and a reward of unparalleled panoramic views Elegant Gastronomic Delights Chania’s cuisine is typical of Crete’s many dishes. With a culinary tradition that emphasizes innovation and local ingredients, Chania offers a quality and divine culinary experience. Olive oil, wild herbs, fresh herbs and catch of the day feature prominently, delivering authenticity. The heart of Chania: its people Perhaps, though, what really sets Chania apart is the kindness and hospitality of its people. Guests are welcomed with open arms and treated as part of the family, making every experience in Chania feel personal and authentic. Whether it’s through shared meals, guided tours or casual conversation, Chanias make sure you take a piece of their heart with you when you leave Why choose Chania for your next vacation Chania, a picturesque town on the northwest coast of Crete, Greece, captures the heart of every traveler with its breathtaking beauty, rich history and crystal clear beaches If you want to relax, you relax or go deeper into history, Chania has something special in store for you. Pristine Beaches Balos Lagoon and Elafonissi Beach Balos Lagoon: Nestled between the Gramvousa Peninsula and the coast of Crete, Balos Lagoon is famed for its wild natural beauty, exotic turquoise waters, and fine white sand. This beach is accessible by boat or a short hike, offering stunning views that are worth the journey. Elafonissi Beach: Known for its unique pink sand, Elafonissi Beach is located on the southwestern tip of Crete. The beach is a protected nature reserve, providing shallow crystal-clear waters perfect for families. The island opposite the beach is accessible by foot through shallow water, revealing rare plant species and an environment unspoiled by human activity. These beaches are not just places to sunbathe and swim; they are destinations where nature’s artistry is on full display, featuring: Crystal-clear blue waters Exotic landscapes Unique natural environments Rich History and Culture Chania is a city soaked in history, with its roots stretching back to ancient civilizations. Walking through Chania is akin to traversing through time, with each step uncovering a new layer of its past. Overview of Chania’s History From the Minoan civilization to Byzantine times, followed by Venetian, Ottoman, and Egyptian influence, Chania is a living museum showcasing the rich tapestry of human history. This diverse historical influence has shaped the city’s architecture, culture, and traditions, making it a fascinating place to explore. Historical Sites The Old Venetian Harbor: The heart of Chania, this harbor is lined with historic buildings, bustling cafes, and quaint shops. The striking lighthouse, built by the Venetians and reconstructed by the Egyptians, is one of the most iconic images of Chania. The Ancient Ruins of Aptera: Located a few kilometers outside of Chania, the ancient city of Aptera presents a captivating site with ruins dating back to the Minoan era. Visitors can explore ancient temples, Roman baths, and impressive fortifications that offer a glimpse into the past. Exquisite Cuisine Step into Chania, and you’ll be welcomed with a feast not just for the eyes, but for the palate too. Cretan cuisine is a journey of taste, freshness, and tradition. Local Specialties: Dakos: A rustic appetizer featuring barley rusk topped with crushed tomato, mizithra cheese, and a drizzle of olive oil. Moussaka: A rich casserole layered with potatoes, eggplant, minced meat, and a creamy béchamel sauce. Kalitsounia: Sweet or savory cheese pies unique to the region. Health Benefits of the Mediterranean Diet: Rich in olive oil, legumes, and fresh produce, the Cretan diet is renowned for its health-promoting qualities. Dishes like Greek Salad and Grilled Seafood provide nutrients and antioxidants linked to longevity. Where to Find Local Cuisine: Tavernas in the Old Harbor serve fresh, local dishes with scenic views. Street vendors and local bakeries offer quick, delicious bites. Breathtaking Landscapes Chania’s dramatic landscapes invite both awe and adventure. Mountains and Gorges: The White Mountains: A towering range that gives you hiking trails and caves to explore. Samaria Gorge: A 16 km trek through a World Biosphere Reserve. Outdoor Activities: Guided treks are available for all levels of hikers. Boat trips allow you to appreciate the coastline from the water. Local Hospitality and Authentic Experiences The warmth of Chania’s people makes every moment spent here feel genuinely welcoming. Warm Hospitality Offered by Locals: Visitors are often greeted with a heartfelt “Kalimera” (good morning) and a smile. Many locals are eager to share stories or help guide you to the best spots. Immersive Experiences: Traditional Cretan Nights: Enjoy vibrant folk music and dancing. Local Markets: Visit the Agora (central market) to buy local honey, cheeses, and herbs. Planning Your Trip to Chania Nestled on the northwest coast of Crete, Greece, Chania is a captivating blend of scenic beauty, rich history, and vibrant culture. Planning your trip requires thoughtful consideration of when to visit, where to stay, how to navigate the city, and what experiences you shouldn’t miss. Best Time to Visit Analyzing Chania’s Weather Patterns: Spring (April to June): The weather starts warming up, making it ideal for outdoor activities without the summer crowds. Summer (July to August): Peak season with sunny days perfect for beach outings, but expect higher prices and more tourists. Autumn (September to October): Warm and less crowded. The sea remains warm enough for swimming. Winter (November to March): Cooler temperatures and occasional rain, suitable for those seeking tranquility and interested in exploring Chania’s cultural sites. Accommodations Chania offers a breadth of accommodation options to suit every taste and budget. Overview of Accommodation Options: Luxury Resorts: Beachfront properties providing exclusive amenities and breathtaking views. Boutique Hotels: Nestled in the Old Town, offering unique charm and close proximity to historical sites. Budget-Friendly Stays: Hostels and guesthouses that don’t compromise on comfort and provide excellent value. Getting Around Navigating Chania and its surrounding areas can be both fun and convenient. Tips on Navigating Chania: Public Transport: City buses are reliable for local travel. For adventures beyond the city, consider the KTEL buses that connect Chania to other parts of Crete. Car Rental: Offers the freedom to explore remote beaches and mountain villages at your pace. International driving permits are usually required for visitors. Must-Have Experiences Chania brims with activities and sights that cater to all interests. Curated List of Not-to-Miss Experiences: Old Venetian Harbor: Stroll around and enjoy the sunset views. Samaria Gorge: A challenging but rewarding hike offering stunning natural landscapes. Beaches: Balos Lagoon and Falassarna Beach are must-visits for beach lovers. Cretan Cuisine Tasting: Explore local tavernas for an authentic taste of Crete. conclusion Chania, with its perfect blend of climate, accommodation options, easy navigation and unique experiences, promises a memorable getaway. Chania is not just another holiday destination; It’s a place where every corner holds a story, every meal a celebration, every moment like heaven. Whether you’re wandering its cobblestone streets, sunbathing on its pristine beaches, or exploring its rich cultural heritage, Chania invites you to immerse yourself in its beauty, history and warmth is not just a place to visit; There is a world to experience. Make Chania your next holiday destination and discover a paradise that captures your heart.

The post Why Chania, Greece Should Be Your Next Paradise Vacation Destination appeared first on Geeky Traveller.

O ex-presidente Jair Bolsonaro e seus aliados políticos tentam reverter a inelegibilidade até 2030 imposta pela Justiça eleitoral com recursos e tentativas de mudar a legislação.

"Customers must be able to reevaluate their willingness to have their genome data shared outside the original intent.”

The post Patronis Questions DNA Testing Companies’ User Confidentiality appeared first on Shark Tank.

A new expedition finds that a large part of the railing at the ship's front has fallen away.

The Sphinx, a patch of snow thought to be the longest-lasting in the UK, has melted for the fourth consecutive year.

Described by some as an "enigma", Mrs Trump is expected to return to her White House duties "on her own terms".

DR Congo-born Dikembe Mutombo has been hailed for his humanitarian work across Africa following his death aged 58 from brain cancer.

Australian airlines say it is unsafe to fly after Mount Lewotobi Laki-laki spewed ash.

1. Pakistani TikToker Imsha Rehman deactivates social media accounts after explicit video leaked online  Hindustan Times
2. Pakistani Influencer Imsha Rehman Deactivates Social Media Accounts After Private Video Leaks  NDTV
3. Now Pakistani TikToker Imsha Rehman’s alleged obscene video leaked online  The Times of India
4. After Minahil Malik, another Pakistani TikTok star Imsha Rehman’s X-rated video goes viral; here's how she  The Economic Times
5. Imsha Rehman viral video: Why Pakistani TikToker has deactivated her account? What’s there in the ‘explicit’ clip?  Mint

1. Manipur on boil: 2 more bodies found, 6 missing  The Times of India
2. Additional paramilitary forces rushed to Manipur amid spike in ethnic violence  Hindustan Times
3. Three women, three children missing after Jiribam gunfight; Meiteis and Kukis hold bandhs in Manipur  The New Indian Express
4. Letters to The Editor — November 13, 2024  The Hindu
5. Centre rushes 20 more CAPF companies to Manipur after fresh violence  Deccan Herald

The CEO of a California gay charity has been charged with embezzling almost a million bucks of the organization’s money. The charity official, Jacob Joseph Aaron Rostovsky, has been charged with 53 felony counts including fraudulent claims, grand theft, misappropriation of public funds, insurance fraud, perjury and money laundering, according to KTLA-TV. The DA said […]

The post CEO of Gay Nonprofit Charged for Stealing Organization’s Money appeared first on The Lid.

The US military has carried out strikes against targets in Syria in what the United States Central Command (CENTCOM) said was a response to recent attacks on US forces by "Iranian-aligned targets" in the country.

United Nations Secretary-General Antonio Guterres told world leaders at the COP29 summit on Tuesday to "pay up" to prevent climate-led humanitarian disasters, and said time was running out to limit a destructive rise in global tempera

velocityconf: RT @oreillyanimals Vote Instant Wild's Digital Eyes & Ears for Wildlife Protection to win Google Global Impact Award http://t.co/Z0EetiQshZ

velocityconf: RT @OReillyAnimals Advice, please! Elephant Listening Project asks for ideas/solutions/help with 3 practical problems http://t.co/Y90YP3maoz

Teachers can assess young students’ literacy skills and knowledge by encouraging them to produce books based on animal facts.

A new children's book transforms a sad, scared and anxious little boy into a superhero. The book is called "Cape," in honor of the bright-red cape the little boy wears and finds comfort in following the death of his father. "Cape" is Kevin Johnson's debut picture book, and it's vividly illustrated by artist Kitt Thomas.

"I think they say they want autonomy. I think their actions don't say the same thing," Airbnb CEO Brian Chesky recently said in an interview.

Amazon has been scrutinized in the past over workplace safety. An Amazon spokesperson said the accident will be investigated.

Companies have continued to cut jobs in 2024 after a wave of layoffs last year. Meta, Goldman Sachs, Google, and Tesla are among those shedding staff.

We are doing what we do best when something threatens the consumer supply chain: rushing to buy mountains of toilet paper. Experts say the dockworkers' strike won't result in shortages, but the panic-buying might so long as the panic-buying lasts.

"They cleaned out the toilet paper at my local Walmart in Virginia.

— Read the rest

The post Toilet paper buying panic recommences as dockworkers strike appeared first on Boing Boing.

A quick note to point you toward this piece I wrote for P&G’s Signal publication. Since its inception, I’ve been co-editor of the monthly outlet, which covers innovation in large enterprise. This month I went in search of proof that the hype around generative AI – fueled in large part by both Google and Microsoft … Continue reading "Can GenAI Change Big Companies?"

I’m still digging through some of the pieces I posted at the now defunct NewCo Shift, and found this piece, adapted from a talk I gave at the Thrival Humans X Tech conference in Pittsburgh back in September of 2018. I was alarmed by trends that I saw intensifying – a push by the tech … Continue reading "Technology, Humanity, and the Existential Test"

Melania Trump will not be traveling with her husband to Washington on Wednesday when President-elect Donald Trump and President Joe Biden have a formal transition meeting, according to multiple reports. […]

The post Melania Trump to Give Jill Biden the Cold Shoulder This Week: Report appeared first on The Western Journal.

An important mechanism of resistance to β-lactam antibiotics is via their β-lactamase–catalyzed hydrolysis. Recent work has shown that, in addition to the established hydrolysis products, the reaction of the class D nucleophilic serine β-lactamases (SBLs) with carbapenems also produces β-lactones. We report studies on the factors determining β-lactone formation by class D SBLs. We show that variations in hydrophobic residues at the active site of class D SBLs (i.e. Trp105, Val120, and Leu158, using OXA-48 numbering) impact on the relative levels of β-lactones and hydrolysis products formed. Some variants, i.e. the OXA-48 V120L and OXA-23 V128L variants, catalyze increased β-lactone formation compared with the WT enzymes. The results of kinetic and product studies reveal that variations of residues other than those directly involved in catalysis, including those arising from clinically observed mutations, can alter the reaction outcome of class D SBL catalysis. NMR studies show that some class D SBL variants catalyze formation of β-lactones from all clinically relevant carbapenems regardless of the presence or absence of a 1β-methyl substituent. Analysis of reported crystal structures for carbapenem-derived acyl-enzyme complexes reveals preferred conformations for hydrolysis and β-lactone formation. The observation of increased β-lactone formation by class D SBL variants, including the clinically observed carbapenemase OXA-48 V120L, supports the proposal that class D SBL-catalyzed rearrangement of β-lactams to β-lactones is important as a resistance mechanism.

Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an α/β-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (compound 1) and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A Trp-186/Trp-187/Tyr-247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in α/β-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, whereas the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single-crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U and provided a new approach for engineering regioselective epoxide hydrolases.

Mitochondria are specialized compartments that produce requisite ATP to fuel cellular functions and serve as centers of metabolite processing, cellular signaling, and apoptosis. To accomplish these roles, mitochondria rely on the genetic information in their small genome (mitochondrial DNA) and the nucleus. A growing appreciation for mitochondria's role in a myriad of human diseases, including inherited genetic disorders, degenerative diseases, inflammation, and cancer, has fueled the study of biochemical mechanisms that control mitochondrial function. The mitochondrial transcriptional machinery is different from nuclear machinery. The in vitro re-constituted transcriptional complexes of Saccharomyces cerevisiae (yeast) and humans, aided with high-resolution structures and biochemical characterizations, have provided a deeper understanding of the mechanism and regulation of mitochondrial DNA transcription. In this review, we will discuss recent advances in the structure and mechanism of mitochondrial transcription initiation. We will follow up with recent discoveries and formative findings regarding the regulatory events that control mitochondrial DNA transcription, focusing on those involved in cross-talk between the mitochondria and nucleus.

Martin R. Larsen
Jul 1, 2005; 4:873-886
Technology

Despite its major importance in human health, the metabolic potential of the human gut microbiota is still poorly understood. We have recently shown that biosynthesis of Ruminococcin C (RumC), a novel ribosomally synthesized and posttranslationally modified peptide (RiPP) produced by the commensal bacterium Ruminococcus gnavus, requires two radical SAM enzymes (RumMC1 and RumMC2) catalyzing the formation of four Cα-thioether bridges. These bridges, which are essential for RumC's antibiotic properties against human pathogens such as Clostridium perfringens, define two hairpin domains giving this sactipeptide (sulfur-to-α-carbon thioether–containing peptide) an unusual architecture among natural products. We report here the biochemical and spectroscopic characterizations of RumMC2. EPR spectroscopy and mutagenesis data support that RumMC2 is a member of the large family of SPASM domain radical SAM enzymes characterized by the presence of three [4Fe-4S] clusters. We also demonstrate that this enzyme initiates its reaction by Cα H-atom abstraction and is able to catalyze the formation of nonnatural thioether bonds in engineered peptide substrates. Unexpectedly, our data support the formation of a ketoimine rather than an α,β-dehydro-amino acid intermediate during Cα-thioether bridge LC–MS/MS fragmentation. Finally, we explored the roles of the leader peptide and of the RiPP precursor peptide recognition element, present in myriad RiPP-modifying enzymes. Collectively, our data support a more complex role for the peptide recognition element and the core peptide for the installation of posttranslational modifications in RiPPs than previously anticipated and suggest a possible reaction intermediate for thioether bond formation.

HIV Type 1 (HIV-1) and simian immunodeficiency virus (SIV) display differential replication kinetics in macrophages. This is because high expression levels of the active host deoxynucleotide triphosphohydrolase sterile α motif domain and histidine-aspartate domain–containing protein 1 (SAMHD1) deplete intracellular dNTPs, which restrict HIV-1 reverse transcription, and result in a restrictive infection in this myeloid cell type. Some SIVs overcome SAMHD1 restriction using viral protein X (Vpx), a viral accessory protein that induces proteasomal degradation of SAMHD1, increasing cellular dNTP concentrations and enabling efficient proviral DNA synthesis. We previously reported that SAMHD1-noncounteracting lentiviruses may have evolved to harbor RT proteins that efficiently polymerize DNA, even at low dNTP concentrations, to circumvent SAMHD1 restriction. Here we investigated whether RTs from SIVmac239 virus lacking a Vpx protein evolve during in vivo infection to more efficiently synthesize DNA at the low dNTP concentrations found in macrophages. Sequence analysis of RTs cloned from Vpx (+) and Vpx (−) SIVmac239–infected animals revealed that Vpx (−) RTs contained more extensive mutations than Vpx (+) RTs. Although the amino acid substitutions were dispersed indiscriminately across the protein, steady-state and pre-steady-state analysis demonstrated that selected SIVmac239 Vpx (−) RTs are characterized by higher catalytic efficiency and incorporation efficiency values than RTs cloned from SIVmac239 Vpx (+) infections. Overall, this study supports the possibility that the loss of Vpx may generate in vivo SIVmac239 RT variants that can counteract the limited availability of dNTP substrate in macrophages.

This article is by Toni Šušnjar.

Strategy and Enemies

The structure of an army will depend on the strategy, as strategy will determine the army’s role and tasks. A state which carries out expansion through outright territorial conquest will have large numbers of heavy infantry, combat engineers and artillery, and possibly some heavy cavalry as well (e.g. Roman Empire, 10th century Byzantine Empire). If conquest is done by slowly destroying an opponent’s economic and social structures through constant raiding (such as chevauchee or razzia / ghazw), then majority of the army will be light cavalry, with some heavy cavalry support (e.g. Seljuk and Ottoman Empires), and light infantry will be used if terrain is unsuitable for cavalry. If a state is defending against cavalry raids, then light cavalry will be dominant (e.g. 15th century Hungary), whereas heavy cavalry will predominate if enemy raiders are primarily infantry. If enemy armies are too powerful to face in the field, light and heavy cavalry will be used to harass the invading army and cut off its supplies and foraging. In terrain unsuitable for cavalry operations, heavy infantry will be used instead.

Raiding — as a strategy — is generally preferred against a peer opponent, especially if a state cannot have a developed logistical support system.

Continue reading Building a Fantasy Army — Strategy & Organization at Mythic Scribes.

The aftermath: Navigating a Taliban-led Afghanistan Expert comment NCapeling 20 August 2021

In the coming weeks, governments and international organizations must work through an approach to the Taliban takeover of Afghanistan. It will not be simple.

A failure to acknowledge that the legitimate, elected representatives of Afghanistan are no longer in control of territory or institutions, and to refuse to deal with those that are, will only make for further misery for a population which has already endured decades of violence and poverty.

But to recognize the Taliban risks condemning tens of thousands of Afghan women, children, and men to brutal repression and, for some, potential death, as well as mocking the human rights and rule of law which the US and its allies sought to promote in Afghanistan, and globally, as cornerstones of values-based foreign policies.

The dilemma western governments find themselves in is one they have studiously sought to avoid despite mounting evidence that, without a negotiated deal, a Taliban takeover was only a matter of time. As late as 6 August, the UN Security Council refused to countenance appeals by the UN mission and Afghan civil society activists to press the Taliban and the government to negotiate a ceasefire.

The US reiterated its refrain that it ‘will not accept a military takeover of Afghanistan’ and the UK stressed the Taliban’s only route to power was through meaningful engagement in a peace process. Meanwhile, not until 11 August did Germany and the Netherlands stop deporting Afghan migrants despite the pleas of Afghan authorities and refugee organizations that the country was on the brink of crisis.

Delaying the inevitable

Belief that a military takeover was still some months away may have led diplomats to view dealing with the Taliban as a distant task. The unilateral nature of the US deal with the Taliban and the resistance of the Ghani government to any suggestion of power-sharing arrangements compounded a lack of international coordination and planning on what the conditions for engagement might be.

It cannot be delayed further. The scale of the humanitarian crisis in Afghanistan is daunting, with more than half a million displaced by fighting in 2021 alone, almost 17 million facing crisis levels of food insecurity, and nearly half of all children under five malnourished as a consequence of drought and the COVID-19 pandemic.

With one of the highest global refugee populations and an estimated up 20-30,000 Afghans fleeing the country weekly – even before the government collapsed – Afghanistan evokes still raw memories of the 2015 Syria migrant crisis for Europe. Pakistan and Turkey, home to some of the largest Afghan refugee communities, have already closed their borders to more.

The ongoing chaos at Kabul airport highlights the challenges ahead. But there is a small window – before the UN Security Council is scheduled to review the mandate of the UN mission in Afghanistan by 17 September – for the US and its allies to craft an approach to dealing with the Taliban.

Formal recognition of a Taliban-led government is simply not an option, even for those maintaining a diplomatic presence in Kabul such as China, Iran, Pakistan, and Russia. Technically the Afghan republic has not yet dissolved with vice-president Amrullah Saleh, reportedly in hiding in the Panjshir valley, claiming he is the country’s ‘caretaker’ president.

Conditions for international acceptance

Afghanistan’s ‘enduring partners’ must now focus on building a consensus around five conditions for international acceptance of a Taliban-administered Afghanistan and prevent the Taliban again reaping the benefits of international divisions. The G7 began to articulate some of these conditions but they need to be set out and negotiated with Afghanistan’s neighbours before being formally articulated by the UN Security Council.

1. Adherence to Afghanistan’s human rights obligations. This must specify the rights of women and girls to education and work, the protection of ethnic and religious minorities, and safe passage for all Afghans and internationals leaving the country.
2. Amnesty for all individuals who worked for the Afghan government or international embassies, forces, or aid organizations since 2001.
3. No harbouring of terrorist groups. This has been the central condition for the US deal with the Taliban, and the overriding concern for both China and Russia.
4. Non-lethal public order. The provision of public order to enable supply routes to open, evacuations to continue, and aid to be delivered, is essential and one that Russia has made as a condition for its future relations.
5. Negotiation of inclusive political arrangements with Afghanistan’s political and ethnic factions.

The UN mission in Afghanistan, including its human rights component, and the Al-Qaida Sanctions Committee’s Analytical Support and Sanctions Monitoring Team should be mandated with reporting monthly on the progress toward these five conditions. Their assessments should form the basis for any reconsideration of the Taliban’s status as a terrorist organization. And a negotiated political settlement must be a precondition to the release of the government’s foreign reserves, estimated to be $9.5 billion.

Before this, the humanitarian and development aid on which Afghanistan is almost completely reliant must be recalibrated to flow through international agencies. Models such as Hamas-run Gaza, Assad’s Syria, or Aristide’s Haiti, show that while far from effective, it is possible to provide urgent assistance outside government channels.

This is one of the reasons why the Taliban has sought to retain a strong UN presence across Afghanistan and why the UN must be given a more significant political mandate and resources. The World Bank-administered Afghan Reconstruction Trust Fund should remain the principal channel for international funds.

It is difficult in the short-term to see the US leading this collective effort, given its defensive and domestic-focused position. It could be a moment for the UK and EU to demonstrate their multilateral commitments and forge a coordinated conditions-based approach to a Taliban-administered Afghanistan at the UN.

Going beyond handwringing or gesture politics will be difficult and messy and, ultimately, Afghanistan’s future must be decided by Afghans. Until that day, however, this will save lives.

Independent Thinking: Humanitarian disaster in Syria and Turkey Audio NCapeling 16 February 2023

Episode 15 of our weekly podcast examines the far-reaching consequences of the earthquakes which struck Turkey and Syria on the region’s fragile geopolitics.

With thousands killed and international aid flooding in, what hope is there for the many thousands of people in Syria and Turkey caught between the groups and governments involved in conflict for more than a decade.

The panel aslo discusses the political impact within Turkey, as fears grow that President Recep Tyap Erdogan may postpone the upcoming election amid outcries over corruption and the devastating loss of life.

Joining Bronwen this week is Lina Sinjab, Syrian filmmaker and BBC journalist covering the Middle East, Charles Lister, senior fellow and director of the Syria programme at the Middle East Institute, and Ziya Meral, senior associate fellow on Turkey at the Royal United Services Institute (RUSI).

About Independent Thinking

A weekly podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.