Connect with us

This open access paper expands on earlier work on cellular senescence in long-lived naked mole-rats. Individuals of this species can live as much as nine times longer than equivalently sized rodents, and are near immune to cancer. In other mammals, senescent cells accumulate with age and disrupt tissue function via their inflammatory signaling. Evidence suggests that this is an important cause of degenerative aging, given that selective destruction of these errant cells produces rejuvenation and extended life span in mice.

Naked Mole Rat Senescent Cells are Unusually Vulnerable to Oxidative Stress

Image credit: Pixabay (Free Pixabay license)

In naked mole-rats, senescent cells exhibit very little of the harmful signaling that occurs in other mammals. These cells also also self-destruct more readily when stressed. That naked mole-rat senescent cells are more prone to self-destruction following oxidative stress is not just a benefit when it comes to getting rid of these harmful cells, but it also prevents damage to molecules caused by oxidative reactionsanother important mechanism of aging – from causing further harm to tissues.

Naked mole-rats (NMRs) are the longest-lived rodents, showing minimal aging phenotypes. An unsolved paradox is that NMRs exhibit low intracellular anti-oxidant defence despite minimal aging. Here, we explained a link between these “contradicting” features by a phenomenon termed “senescent cell death” – senescence induced cell death in NMR cells due to their inherent vulnerability to reactive oxygen species and unique metabolic system.

Generally, the “free radical theory of aging“, later modified to “mitochondrial free radical theory“, is the well-known theory of aging mechanism. Intracellular reactive oxygen species (ROS), deriving especially from mitochondria, damages macromolecules such as lipids, DNA, and proteins, and the accumulated damages in tissues are assumed to contribute aging process. Indeed, the mitochondrial ROS production rate is negatively correlated with the maximal lifespan of animal species.

However, previous insights on responses of long-lived NMRs to ROS are puzzling: 1) Several reports suggested that NMRs have stronger anti-oxidant mechanisms. 2) However, many other reports suggested that NMRs exhibit low anti-oxidant defence. From young ages, NMR suffers greater oxidative damages in tissue DNA, protein, and lipids than mice. Nevertheless, the level of oxidative damage does not increase further and remains constant for more than 20 years. Thus, at least in part, NMR exhibits low intracellular anti-oxidant defence despite their delayed aging. These complex but interesting observations raise a possibility that NMR may have developed a unique system to remove damaged cellular components or the cells that suffered the oxidative damage during aging.

In mammalian cells, one of the typical “damaged” cellular status along with elevated oxidative damage is cellular senescence. Cellular senescence is an irreversible cell proliferation arrest induced in response to stresses such as DNA damage, oncogene activation, and telomere shortening. Cellular senescence contributes to avoidance of cancer formation by stopping proliferation of damaged cells. In addition, cellular senescence has important roles in tissue homeostasis, embryonic development, and wound healing. On the other hand, accumulation of senescent cells promotes age-related physiological deterioration and disorders, by secreting a bioactive “secretome” called senescence-associated secretory phenotype (SASP).

In NMR skin, we observed few senescent cells during aging or after ultraviolet irradiation, suggesting suppression of senescent cell accumulation in NMR tissue. We discovered that senescent NMR fibroblasts induce senescent cell death through retinoblastoma protein activation accompanied by autophagy dysregulation, increased oxidative damage, and accelerated H2O2-releasing metabolic pathways.

Link: https://doi.org/10.1101/2020.07.02.155903

Source: Fight Aging!




Source link

0
Continue Reading

Technology

Immune Protein IL-17A Responsible for Lethal Side Effects of Gastric Cancer

1 4

The formation of scar tissue, or fibrosis, as gastric cancer disseminates throughout the peritoneum can be more lethal than the cancer itself and can interfere with chemotherapy. Researchers from Kanazawa University have now found that proinflammatory cytokine IL-17A from mast cells heavily influences the degree of fibrosis and causes structural changes in peritoneal cells. Preventing mast cells from releasing IL-17A may therefore be a promising treatment strategy for gastric cancer patients with peritoneal dissemination.

Immune Protein IL 17A Responsible for Lethal Side Effects of Gastric

Fig. 2 Expression of FAP was found in HPMCs treated with IL-17A using immunofluorescence staining. This means HPMCs were transformed into myofibroblast, so called CAF, by IL-17A. FAP: fibroblast activation protein as a marker of CAF. HPMCs: human peritoneal mesothelial cells. CAF: cancer associated fibroblast. Image credit: Kanazawa University

Gastric cancer, one of the leading causes of cancer-associated mortality worldwide, is renowned for its ability to disseminate throughout the peritoneal cavity. As well as causing secondary tumors in other organs, metastatic gastric cancer cells trigger extensive stromal fibrosis, or the formation of scar tissue, that can be more deadly than the cancer itself—bowel obstruction and hydronephrosis and jaundice are all common side effects of gastric cancer-associated fibrosis. What’s more, the densely packed scar tissue can disturb chemotherapy drugs from reaching their target due to intra-tumoral high pressure.

Preventing fibrosis could therefore improve the prognosis for gastric cancer patients. The problem is, researchers have yet to discover what causes fibrosis, let alone how to prevent it.

But in a study published recently in Gastric Cancer, researchers from Kanazawa University found that an inflammatory protein produced by mast cells, IL-17A, triggers cellular changes in the peritoneum, leading to stromal fibrosis in gastric cancer patients.

Lead author Katsuya Gunjigake from Kanazawa University’s Division of Cancer Medicine explains why the researchers targeted IL-17A.

“Over-stimulation of the immune system by IL-17A plays a major role in chronic inflammatory diseases such as rheumatoid arthritis and multiple sclerosis. It has also been associated with increased tumor growth and dissemination in various forms of cancer. Interestingly though, while studies had shown that IL-17A causes fibrosis in both Crohn’s disease and lung disease, no one had investigated the link between tissue fibrosis and IL-17A in cancer.”

By studying cancerous tissue from 70 gastric cancer patients with peritoneal dissemination, the researchers discovered that the degree of fibrosis was governed by the amount of IL-17A, and that IL-17A was being produced by a subgroup of white blood cells called mast cells.

Says Gunjigake, “Mast cells are most commonly associated with anaphylaxis but are also involved in pathogen defense and immune tolerance, among other things. They contain small particles called granules that are filled with molecules such as histamine, serotonin, and IL-17A that are released into the extracellular environment in a process known as degranulation.”

Immune Protein IL 17A Responsible for Lethal Side Effects of Gastric

Fig. 1 The number of IL-17A and MCT double positive cells correlated with the ratio of fibrotic area in the peritoneal tumors. This means IL-17A derived from mast cells may contribute tumor fibrosis. MCT: mast cell tryptase Fig. 2 Expression of FAP was found in HPMCs treated with IL-17A using immunofluorescence staining. This means HPMCs were transformed into myofibroblast, so called CAF, by IL-17A. FAP: fibroblast activation protein as a marker of CAF. HPMCs: human peritoneal mesothelial cells. CAF: cancer associated fibroblast. Fig. 3 Nude mouse was inoculated with human gastric cancer cell line MKN45-P cells intraperitoneally at day 0. Recombinant mouse IL-17A was administrated intraperitoneally at day 1, 3 and 7. Large and many peritoneal nodules were found at day 14. Fig. 4 Fibrosis in the peritoneal nodules was recognized as blue area by azan staining. Fibrous area in the tumor treated with IL-17A was wider than that without IL-17A. Image credit: Kanazawa University

The researchers then injected mice with human peritoneal cells and gastric cancer cells and examined the effects of IL-17A treatment, with interesting results.

“Not only did IL-17A increase tumor size and the degree of fibrosis, it also changed the structure of the peritoneal cells, enhancing their invasive and migratory capabilities,” explains responsible author Sachio Fushida.

“Given the obvious role of IL-17A in driving fibrosis, our results suggest that suppression of mast cell degranulation may be a promising treatment strategy for gastric cancer patients with peritoneal dissemination.”

Article

Interleukin-17A derived from mast cells contributes to fibrosis in gastric cancer with peritoneal dissemination

Journal: Gastric Cancer

Authors: Katsuya Gunjigake, Jun Kinoshita, Takahisa Yamaguchi, Hiroto Saito, Daisuke Fujimori, Toshihide Horiike, Shinichi Harada, Hidehiro Tajima, Itasu Ninomiya, Tetsuo Ohta, Sachio Fushida

DOI: 10.1007/s10120-020-01092-2

Funder

This work was supported by JSPS KAKENHI Grant Number 16K10494.

Source: Kanazawa University




Source link

0
Continue Reading

Technology

Opera for Android, Desktop Browsers Get Redesigned Sync Capabilities

Opera for android desktop 1600851955578

Opera has launched updated versions of its browsers for Android and desktop. Opera for Android version 60 and Opera for Desktop version 71 come with completely redesigned sync capabilities between them, the company says. The new feature uses a QR code scan to establish a connection between Opera on an Android device and the Opera desktop browser on Windows, macOS, or Linux. The Opera browser for Android also comes with the popular Flow feature as well as Suggested Sites feature on the homepage. In meanwhile, the Opera desktop browser now comes with the Easy Files feature.

Opera for Android 60

With Opera browser for Android, users can navigate to opera.com/connect on their PCs or tablets and scan the QR code displayed there with the QR code reader located in the search bar of the browser. As soon as this is done, the new Sync feature will start synchronising all their passwords, bookmarks, speed dials, typed browsing history and open tabs, as well as the newly-integrated Flow feature across devices.

The new Sync feature of Opera for Android does do not require any login credentials to sync data across devices.
Photo Credit: Opera

Stefan Stjernelund, Product Manager of Opera for Android, says that people don’t sync their phones with their PCs “because they hate the hassle of having to type in their logins and lengthy passwords.” He notes that the QR code scan feature can help users to quickly sync data across devices that do not require any login credentials. “Opera was the first browser to offer sync between mobile and desktop browsers 13 years ago. Today we’re taking a big step forward by making it easier than ever,” added Stjernelund.

Apart from the new syncing feature, Opera for Android 60 also gets the Flow feature from the Opera Touch browser. This feature allows users to share files, links, YouTube videos, photos, and personal notes with themselves, between their Opera mobile and desktop browsers. So, if you’re searching something on Opera on your Android smartphones, you can quickly share it on the desktop version. According to the brand, Flow is end-to-end encrypted so anything stored will only be known to the user. In Opera for Android, Flow can be accessed from the O-menu.

 

Opera for Android 60 now also comes with Suggested Sites feature that allows for “speed dials” in the browser. According to the brand, the speed dial section is now smarter and more dynamic as it identifies the user’s most frequently visited websites. It displays them just below the traditional speed dial section. “Suggested Sites gives us a quicker way to engage with relevant content without the need to manually add pages to the speed dial or bookmarks,” Stjernelund noted. Users have a choice to easily disable this feature.

Additionally, Opera for Android offers a built-in free unlimited browser VPN, a QR code scanner, a crypto wallet, and a cookie dialog blocker. You can download Opera for Android 60 via Google Play.

Opera for android desktop sync feature intext Opera for Android

Flow feature allows users to share files, links, videos and photos between their Opera mobile and desktop browsers
Photo Credit: Opera

Opera for Desktop 71

The Opera for Desktop version 71 browser comes with the Easy Files feature that offers most recently downloaded files that essentially makes attaching files in the Opera browser easy. It is also claimed to feature a high level of privacy and security. It features a built-in browser VPN, ad blocker, as well as built-in messengers, including WhatsApp, Telegram, Instagram and Facebook.


How are we staying sane during this Coronavirus lockdown? We discussed this on Orbital, our weekly technology podcast, which you can subscribe to via Apple Podcasts or RSS, download the episode, or just hit the play button below.

Source link

0
Continue Reading

Technology

The best hidden features in iOS 14

ios14 hidden features

Apple’s iOS 14 is full of new features, but some of the best gems are the ones in obscure places. Learn about the best hidden features in iOS 14 and how to use them on your iPhone and iPad.

Image: CNET

When Apple’s iOS 14 was released last week, many users and developers were surprised by the next-day availability. iOS 14 includes big changes that will forever change the way we use our iOS devices: From the widgets on the Home Screen, to the App Library, to the new automations in Shortcuts, iOS is clearly moving at a fast pace and bringing many new headlining features. Read about the best iOS 14 hidden features that many users skip over. 

SEE: Apple iPadOS: A cheat sheet (free PDF) (TechRepublic)

Listen for sounds

One accessibility feature that Apple added to iOS 14 was the ability for your iPhone to listen for particular sounds and then alert you whenever it encounters them. This feature is fantastic for hard of hearing or deaf users who need assistance in identifying when the door bell rings, an animal makes a noise, etc.

To enable this feature, perform the following steps: 

  1. Open the Settings app.
  2. Navigate to Accessibility | Sound Recognition.
  3. Select the toggle to ON.
  4. Select Sounds.
  5. Toggle on the sounds that you’d like your device to recognize and alert you to (Figure A).

Figure A

ios14-hidden-features-figure-a.jpg

Your iPhone can recognize multiple sounds on-device and alert you to them. This list of recognizable sounds will grow over time.

As of iOS 14, your phone can do on-device sound recognition of four different categories of sounds: Alarms, Animals, Household, and People. This set of sounds will grow over time based on advances in machine learning and device microphones. You can enable or disable the particular individual sounds you’re concerned with.

Apple notes that, with this feature enabled, your iPhone will continuously listen for sounds using on-device intelligence and notify you when the sounds are recognized. Because of this your battery life may take a slight hit, and this will also utilize on-device storage to process the sounds.

In addition, Apple notes that this shouldn’t be relied upon for emergency situations or navigation.

SEE: How to use widgets on the Home Screen in iOS 14 (TechRepublic)

New color picker

There’s a new color picker that you will encounter in both Apple and third-party apps that brings about a new way on iOS to select colors that we’re excited about. If you’ve spent any time in macOS, you’ve undoubtedly encounter the macOS Digital Color Meter that’s available systemwide. Apple now has a new color picker on iOS 14 that brings a few new ways of selecting colors, and saving them.

We’ll show how to do this in Notes, but the feature is also available in other apps. In Notes, select the drawing tool, then select the color picker icon. When you do this, the new color picker will appear (Figure B). 

Figure B

ios14-hidden-features-figure-b.jpg

The new iOS 14 color picker brings the same tools from macOS to iOS for picking colors.

The first section you’ll encounter is a standard color grid which shows a few hues to let you quickly pick a color. The next tab is the Spectrum, which lets you get more fine-grained control over every color available to pick on the device and it’s opacity. The last tab is Sliders, which we’re very excited about. This view lets you pick or enter RGB values, or a hex value to set the color—a feature that hasn’t been available on iOS except in speciality apps before.

SEE: iOS 14 App Library: How to use it on your iPhone (TechRepublic)

Lastly, you’ll notice the custom palette organizer at the bottom of the color picker. In this section, you can save your favorite colors by tapping the + button, or tap and hold on any of them to delete them. You can save up to 10 colors in this section for easily switching between apps, or projects.

Hide the Hidden Photos album

The Hidden photo album has been available in the Photos app for years, but it has been far from hidden on iOS devices. Rather, it was a folder called Hidden that just stored photos you didn’t want visible in your main Photo library. Now you can also hide this folder so that the hidden photos are truly hidden.

To do this, perform these steps:

  1. Open Settings.
  2. Navigate to Photos.
  3. Scroll near the bottom, and disable the toggle for Hidden Album.

With this option deselected, the Hidden album will no longer appear in the Albums tab of Photos. To show it again, re-enable the toggle. 

Dictation shortcut

On iPadOS 14, there’s a new way to assign a keyboard shortcut for text dictation. This lets you easily still use dictation even when an external keyboard is attached without the need to use the on-screen controls for dictation.

To enable this feature, perform these steps:

  1. Open Settings.
  2. Navigate to General | Keyboard | Dictation Shortcut.
  3. Select an available Shortcut (Figure C).

Figure C

ios14-hidden-features-figure-c.jpg

Selecting a dictation shortcut will let you easily double-tap the selected button on a hardware keyboard to start the dictation process without needing to use the on-screen controls.

The available shortcuts are either Control or Command. Select one or the other, then activate by quickly double-pressing the selected shortcut when your cursor is in a text field.

Hide Home Screens

Apple introduced the App Library for iPhone, and it allows a lot of customization and cleanup for iOS Home Screens for the first time in the history of the iPhone. You can still have multiple Home Screens in iOS 14, but sometimes you may want to disable messy Home Screens or Home Screens of apps that you don’t access frequently.

To disable a Home Screen on your iPhone:

  1. Tap and hold on the Home Screen to enter jiggle mode.
  2. Tap the dots denoting page numbers. 
  3. Tap the checkmark under the Home Screen to remove it, tap again to add it back (Figure D).

Figure D 

ios14-hidden-features-figure-d.jpg

Hiding Home Screens allows users to clean up their icons and hide pages of apps that aren’t always needed.

Select Done when finished and your changes will be saved. Any hidden pages will be skipped over when swiping left or right between Home Screens.

Back tap gesture

If you have an iPhone 8 or newer, then we saved the best feature for last in this tip lineup. That’s because the back tap feature is one of those hidden gems that will change your digital life once you’ve implemented it.

SEE: Apple releases iOS 14 without this privacy feature: What iPhone users and developers need to know (TechRepublic)

With this feature, you can assign a double- or triple-tap gesture to the back of your iPhone. When you tap the back of the device with your finger twice or three times, it can perform an action that you assign. Yes, you read that right, you can perform an action by just tapping the back of your iPhone with your finger, and it even works with a case.

To set up this feature:

  1. Open Settings.
  2. Navigate to Accessibility | Touch | Back Tap.
  3. Select Double Tap or Triple Tap to set up actions for one or both.
  4. Select an action (Figure E).

Figure E

ios14-hidden-features-figure-e.jpg

Myriad shortcuts are available to the back tap feature. You can even launch an app through a Shortcuts workflow.

There are many system, accessibility, scroll, and even app shortcuts available–you can even create your own Shortcut workflows and assign them to a double- or triple-tap gesture. The possibilities are limitless when it comes to assigning actions for this feature. 

Also see

Source link

0
Continue Reading

Trending