epl

Optimized incorporation of an unnatural fluorescent amino acid affords measurement of conformational dynamics governing high-fidelity DNA replication [DNA and Chromosomes]

By www.jbc.org
Published On :: 2020-12-11T00:06:21-08:00

DNA polymerase from bacteriophage T7 undergoes large, substrate-induced conformational changes that are thought to account for high replication fidelity, but prior studies were adversely affected by mutations required to construct a Cys-lite variant needed for site-specific fluorescence labeling. Here we have optimized the direct incorporation of a fluorescent un-natural amino acid, (7-hydroxy-4-coumarin-yl)-ethylglycine, using orthogonal amber suppression machinery in Escherichia coli. MS methods verify that the unnatural amino acid is only incorporated at one position with minimal background. We show that the single fluorophore provides a signal to detect nucleotide-induced conformational changes through equilibrium and stopped-flow kinetic measurements of correct nucleotide binding and incorporation. Pre-steady-state chemical quench methods show that the kinetics and fidelity of DNA replication catalyzed by the labeled enzyme are largely unaffected by the unnatural amino acid. These advances enable rigorous analysis to establish the kinetic and mechanistic basis for high-fidelity DNA replication.


Full Article

epl

A human cancer cell line initiates DNA replication normally in the absence of ORC5 and ORC2 proteins [DNA and Chromosomes]

By www.jbc.org
Published On :: 2020-12-11T00:06:20-08:00

The origin recognition complex (ORC), composed of six subunits, ORC1–6, binds to origins of replication as a ring-shaped heterohexameric ATPase that is believed to be essential to recruit and load MCM2–7, the minichromosome maintenance protein complex, around DNA and initiate DNA replication. We previously reported the creation of viable cancer cell lines that lacked detectable ORC1 or ORC2 protein without a reduction in the number of origins firing. Here, using CRISPR-Cas9–mediated mutations, we report that human HCT116 colon cancer cells also survive when ORC5 protein expression is abolished via a mutation in the initiator ATG of the ORC5 gene. Even if an internal methionine is used to produce an undetectable, N terminally deleted ORC5, the protein would lack 80% of the AAA+ ATPase domain, including the Walker A motif. The ORC5-depleted cells show normal chromatin binding of MCM2–7 and initiate replication from a similar number of origins as WT cells. In addition, we introduced a second mutation in ORC2 in the ORC5 mutant cells, rendering both ORC5 and ORC2 proteins undetectable in the same cells and destabilizing the ORC1, ORC3, and ORC4 proteins. Yet the double mutant cells grow, recruit MCM2–7 normally to chromatin, and initiate DNA replication with normal number of origins. Thus, in these selected cancer cells, either a crippled ORC lacking ORC2 and ORC5 and present at minimal levels on the chromatin can recruit and load enough MCM2–7 to initiate DNA replication, or human cell lines can sometimes recruit MCM2–7 to origins independent of ORC.


Full Article

epl

Polymerase {gamma} efficiently replicates through many natural template barriers but stalls at the HSP1 quadruplex [Enzymology]

By www.jbc.org
Published On :: 2020-12-18T00:06:18-08:00

Faithful replication of the mitochondrial genome is carried out by a set of key nuclear-encoded proteins. DNA polymerase γ is a core component of the mtDNA replisome and the only replicative DNA polymerase localized to mitochondria. The asynchronous mechanism of mtDNA replication predicts that the replication machinery encounters dsDNA and unique physical barriers such as structured genes, G-quadruplexes, and other obstacles. In vitro experiments here provide evidence that the polymerase γ heterotrimer is well-adapted to efficiently synthesize DNA, despite the presence of many naturally occurring roadblocks. However, we identified a specific G-quadruplex–forming sequence at the heavy-strand promoter (HSP1) that has the potential to cause significant stalling of mtDNA replication. Furthermore, this structured region of DNA corresponds to the break site for a large (3,895 bp) deletion observed in mitochondrial disease patients. The presence of this deletion in humans correlates with UV exposure, and we have found that efficiency of polymerase γ DNA synthesis is reduced after this quadruplex is exposed to UV in vitro.


Full Article

epl

Blood tests for colon cancer screening not ready to replace colonoscopy, study indicates

By www.upi.com
Published On :: Mon, 28 Oct 2024 17:29:27 -0400

New blood tests screen for colorectal cancer in a much less invasive way than colonoscopy, but deaths will increase if many people choose this alternative, a new study indicates.


Full Article

epl

DeepL to Debut Nvidia DGX SuperPOD with DGX GB200 Systems in Europe

By www.hpcwire.com
Published On :: Fri, 01 Nov 2024 13:21:40 +0000

COLOGNE, Germany, Nov. 1, 2024 — DeepL has announced it will be among the first to commercially deploy the Nvidia DGX SuperPOD with DGX GB200 systems. The Nvidia DGX SuperPOD, […]

The post DeepL to Debut Nvidia DGX SuperPOD with DGX GB200 Systems in Europe appeared first on HPCwire.


Full Article

epl

Could we replace data centers with … plant DNA? | Cliff Kapono and Keolu Fox

By www.ted.com
Published On :: Mon, 21 Oct 2024 14:51:23 +0000

Is it possible to meet the world's seemingly infinite demand for data storage while also caring for the natural environment? Biomedical researcher Keolu Fox and professional surfer and scientist Cliff Kapono believe that Indigenous knowledge combined with the science of genetics may offer such a solution: using the DNA of plant cells (like those found in sugar cane) as mini data warehouses. Learn more about the incredible potential of this technology — and how it could help foster ecosystem resilience in a high-tech world.


Full Article

epl

Rapid Deployment of Remote Learning: Lessons From 4 Districts

By www.edweek.org
Published On :: Thu, 19 Mar 2020 00:00:00 +0000

Chief technology officers are facing an unprecedented test of digital preparedness due to the coronavirus pandemic, struggling with shortfalls of available learning devices and huge Wi-Fi access challenges.


Full Article

epl

Rapid Deployment of Remote Learning: Lessons From 4 Districts

By www.edweek.org
Published On :: Thu, 19 Mar 2020 00:00:00 +0000

Chief technology officers are facing an unprecedented test of digital preparedness due to the coronavirus pandemic, struggling with shortfalls of available learning devices and huge Wi-Fi access challenges.


Full Article

epl

Utah high school to replace Braves mascot amid backlash

By www.edweek.org
Published On :: 2020-12-01T08:42:39-05:00


Full Article

epl

Alabama School Board Members Weigh In on Plan to Replace Them

By www.edweek.org
Published On :: Wed, 10 Jul 2019 00:00:00 +0000

State Board of Education members weighed in today about a proposal to eliminate their elected positions and replace the board with an appointed commission.


Full Article

epl

N.J. Supreme Court Rejects Gov. Christie's Motion to Replace Funding Formula

By blogs.edweek.org
Published On :: Tue, 31 Jan 2017 00:00:00 +0000

Gov. Christie has pushed to flatten the state's funding formula so that the state's impoverished urban districts would get the same amount of money wealthy suburban districts get.


Full Article

epl

Utah high school to replace Braves mascot amid backlash

By www.edweek.org
Published On :: Tue, 01 Dec 2020 00:00:00 +0000


Full Article

epl

A District-Level Effort to Replace the Common Core State Standards

By blogs.edweek.org
Published On :: Tue, 08 Jul 2014 00:00:00 +0000

The Manchester district in the Granite State has worked to develop its own content standards. How do they differ from the common core?


Full Article

epl

Rapid Deployment of Remote Learning: Lessons From 4 Districts

By www.edweek.org
Published On :: Thu, 19 Mar 2020 00:00:00 +0000

Chief technology officers are facing an unprecedented test of digital preparedness due to the coronavirus pandemic, struggling with shortfalls of available learning devices and huge Wi-Fi access challenges.


Full Article

epl

FAO in review: Building and deploying professional and practical expertise

By www.fao.org
Published On :: Fri, 02 Dec 2022 00:00:00 GMT

Read the seriesFull Article


epl

This London Blacksmith Forges Replicas of Medieval Swords

By www.smithsonianmag.com
Published On :: Fri, 04 Oct 2024 00:00:00 -0000

A London blacksmith has perfected a technique known as pattern welding to create elaborately-designed replica Saxon swords and knives. He demonstrates his technique on camera.


Full Article

epl

A Thief Replaced This Iconic Churchill Portrait With a Fake. Two Years Later, the Original Has Been Recovered

By www.smithsonianmag.com
Published On :: Mon, 16 Sep 2024 17:03:15 +0000

Investigators discovered that the original print of "The Roaring Lion" had been sold to a buyer in Italy


Full Article

epl

Walk Through a Full-Scale Replica of the Secret Annex Where Anne Frank's Family Took Shelter During the Holocaust

By www.smithsonianmag.com
Published On :: Tue, 22 Oct 2024 19:19:15 +0000

Featuring more than 100 original artifacts, a new immersive exhibition in New York City will explore the young Jewish diarist's life and legacy


Full Article

epl

Paris to deploy 4,000 police officers for Israel-France soccer match following violence in Amsterdam

By www.cbc.ca
Published On :: Sun, 10 Nov 2024 13:08:23 EST

Paris police said Sunday that 4,000 officers and 1,600 stadium staff will be deployed for a France-Israel soccer match to ensure security a week after violence against Israeli fans in Amsterdam.


Full Article

epl

X-Fingers Replace Lost Digits, Empower Patients with New Function

By www.solidworks.com
Published On :: Tue, 10 May 2011 00:00:00 -0500

SolidWorks Helps Make Replacement Fingers a Reality


Full Article

epl

Apple starts supplying replacement parts for iPhone 16 repairs

By appleinsider.com
Published On :: Sun, 10 Nov 2024 19:13:03 +0000

Repair parts for the iPhone 16 lineup are now available to order in the US and other countries, including for those wanting to fix their iPhone for themselves.


DIY repairs are well-suited to some, but can be labor-intensive and expensive.

Following the release of the repair manuals for the iPhone 16 in September, it's now possible to acquire replacement parts for repairs from Apple directly. This is a continuation of a move starting in 2022 towards more user repairability of its products.

Batteries, one of the most common replacement parts, sell for $99 for the iPhone 16 and iPhone 16 Plus, or $119 for the iPhone 16 Pro or Pro Max. Likewise, replacement camera assemblies cost $169 or $249, depending on the model.


Continue Reading on AppleInsider | Discuss on our Forums


Full Article

epl

News24 Business | Rand recovers to pre-election levels as Trumpmania is replaced by interest rate focus

By www.news24.com
Published On :: Thursday Nov 07 2024 12:04:26

The dollar edged lower on Thursday, while investors awaited policy decisions from the Federal Reserve and other central banks.


Full Article

epl

PSUbuy replaces Shop OnLion

By www.psu.edu
Published On :: Tue, 12 Nov 2024 12:12:58 -0500

Penn State has updated its procurement processes with the implementation of PSUbuy. The new system replaces Shop OnLion.


Full Article

epl

Saudi Arabia Replaces CEO Of Futuristic Mega-City NEOM Amid Rising Scepticism

By www.ndtv.com
Published On :: Wed, 13 Nov 2024 09:50:36 +0530

Saudi Arabia announced that it was replacing the chief executive of its futuristic mega-city NEOM as scepticism mounts over the Gulf kingdom's most ambitious development projects.


Full Article

epl

OnePlus 12R Android 15-Based OxygenOS 15 Stable Update Rolling Out for Global Users

By www.gadgets360.com
Published On :: Mon, 11 Nov 2024 14:13:30 +0530

OnePlus 12R was launched in India in January this year with a Snapdragon 8 Gen 2 chipset paired with up to 16GB of LPDDR5x RAM. It runs on Android 14-based OxygenOS 14 out-of-the-box. Now the stable version of the Android 15-based OxygenOS 15 update with updated features and fixes is rolling out to OnePlus 12R users.


Full Article

epl

OnePlus Ace 5 Series Tipped to Get Metal Middle Frame, Ceramic Body, 24GB RAM, More

By www.gadgets360.com
Published On :: Mon, 11 Nov 2024 19:06:09 +0530

OnePlus seems to be preparing to launch the OnePlus Ace 5 and Ace 5 Pro in China. The Chinese tech brand is yet to make an official announcement, but rumours about the duo continue to surface on the Web. As per a new leak, the OnePlus Ace 5 will run on the Snapdragon 8 Gen 3 chipset. The upcoming Ace 5 smartphones are also said to feature a metal middle frame.


Full Article

epl

Indiana Jones and the Great Circle Gameplay Deep Dive Details Combat, Exploration and Puzzles

By www.gadgets360.com
Published On :: Tue, 12 Nov 2024 13:26:20 +0530

Indiana Jones and the Great Circle received a gameplay deep dive Monday that detailed more of the game’s combat, exploration and puzzles. Publisher Bethesda also shed more light on the premise of the story that sees Indy join the chase for a priceless stolen relic.


Full Article

epl

Most Reliable Vendors To Buy Replica Rolex Super Clone Watches

By www.ndtv.com
Published On :: Tue, 28 Nov 2023 18:15:59 +0530

Here's all you need to know about the two vendors that deal with the finest quality Rolex replica watches


Full Article

epl

Saudi Arabia Replaces CEO Of Futuristic Mega-City NEOM Amid Rising Scepticism

By www.ndtv.com
Published On :: Wed, 13 Nov 2024 09:50:36 +0530

Saudi Arabia announced that it was replacing the chief executive of its futuristic mega-city NEOM as scepticism mounts over the Gulf kingdom's most ambitious development projects.


Full Article

epl

Session-Replay Analytics Could Be a GDPR Quagmire

By www.dmnews.com
Published On :: Fri, 25 May 2018 11:00:00 GMT

Here's a new angle on GDPR, likely one of many angles people haven't yet considered: Does web session recording count as collecting PII?


Full Article

epl

DNREC Awards Contract Replace Bancroft Bridge

By news.delaware.gov
Published On :: Wed, 28 Aug 2024 18:00:37 +0000

The Delaware Department of Natural Resources and Environmental Control announced that A-Del Construction of Newark has been awarded the contract for the replacement of the Bancroft Bridge in Alapocas Run State Park. Construction is tentatively scheduled to begin Oct. 1 and be completed in April 2025. Replacement of the existing Bancroft Bridge has been one of the DNREC Division of Parks and Recreation’s highest priorities since its emergency closure September 2021 when it was damaged beyond repair due to Hurricane Ida floodwaters.


Full Article

epl

OnePlus 8 Pro Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus 8 Pro Mobile Phones. Know detailed info about OnePlus 8 Pro configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus 8 Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus 8 Mobile Phones. Know detailed info about OnePlus 8 configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus U1 55-inch 4K HDR TV Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus U1 55-inch 4K HDR TV TV. Know detailed info about OnePlus U1 55-inch 4K HDR TV configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus Nord Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus Nord Mobile Phones. Know detailed info about OnePlus Nord configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus Buds Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus Buds Audio Video. Know detailed info about OnePlus Buds configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus 8T Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus 8T Mobile Phones. Know detailed info about OnePlus 8T configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus Band Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus Band Wearable Devices. Know detailed info about OnePlus Band configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus 9 Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus 9 Mobile Phones. Know detailed info about OnePlus 9 configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

Oneplus 9 Pro Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of Oneplus 9 Pro Mobile Phones. Know detailed info about Oneplus 9 Pro configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus 5T 8GB Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus 5T 8GB Mobile Phones. Know detailed info about OnePlus 5T 8GB configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus 9R Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus 9R Mobile Phones. Know detailed info about OnePlus 9R configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus Watch Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus Watch Wearable Devices. Know detailed info about OnePlus Watch configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus Nord CE 5G Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus Nord CE 5G Mobile Phones. Know detailed info about OnePlus Nord CE 5G configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus U1S TV Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus U1S TV TV. Know detailed info about OnePlus U1S TV configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus Buds Pro Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus Buds Pro Audio Video. Know detailed info about OnePlus Buds Pro configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus Buds Z2 Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus Buds Z2 Audio Video. Know detailed info about OnePlus Buds Z2 configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

Oneplus Nord CE 2 5g Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of Oneplus Nord CE 2 5g Mobile Phones. Know detailed info about Oneplus Nord CE 2 5g configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus Y1S Edge 43-inch FHD TV Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus Y1S Edge 43-inch FHD TV TV. Know detailed info about OnePlus Y1S Edge 43-inch FHD TV configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article

epl

OnePlus 10 Pro Review

By www.digit.in
Published On :: 2023-09-22T13:09:00+05:30

Read the in depth Review of OnePlus 10 Pro Mobile Phones. Know detailed info about OnePlus 10 Pro configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.


Full Article