Artificial intelligence yields new antibiotic

                              A Deep Learning Model Identifies a  New Drug That Can Kill 
                              Many Species of Anti-Resistant Bacteria

                                                             

Date:
February 20, 2020
Source:
Massachusetts Institute of Technology
Summary:
Using a machine-learning algorithm, researchers have identified a powerful new antibiotic compound. In laboratory tests, the drug killed many of the world's most problematic disease-causing bacteria, including some strains that are resistant to all known antibiotics. It also cleared infections in two different mouse models.
Share:
   
FULL STORY


Bacterial colony in dish (stock image).
Credit: © motorolka / Adobe Stock


Using a machine-learning algorithm, MIT researchers have identified a powerful new antibiotic compound. In laboratory tests, the drug killed many of the world's most problematic disease-causing bacteria, including some strains that are resistant to all known antibiotics. It also cleared infections in two different mouse models.

The computer model, which can screen more than a hundred million chemical compounds in a matter of days, is designed to pick out potential antibiotics that kill bacteria using different mechanisms than those of existing drugs.

"We wanted to develop a platform that would allow us to harness the power of artificial intelligence to usher in a new age of antibiotic drug discovery," says James Collins, the Termeer Professor of Medical Engineering and Science in MIT's Institute for Medical Engineering and Science (IMES) and Department of Biological Engineering. "Our approach revealed this amazing molecule which is arguably one of the more powerful antibiotics that has been discovered."

In their new study, the researchers also identified several other promising antibiotic candidates, which they plan to test further. They believe the model could also be used to design new drugs, based on what it has learned about chemical structures that enable drugs to kill bacteria.

"The machine learning model can explore, in silico, large chemical spaces that can be prohibitively expensive for traditional experimental approaches," says Regina Barzilay, the Delta Electronics Professor of Electrical Engineering and Computer Science in MIT's Computer Science and Artificial Intelligence Laboratory (CSAIL).

Barzilay and Collins, who are faculty co-leads for MIT's Abdul Latif Jameel Clinic for Machine Learning in Health, are the senior authors of the study, which appears today in Cell. The first author of the paper is Jonathan Stokes, a postdoc at MIT and the Broad Institute of MIT and Harvard.

A new pipeline

Over the past few decades, very few new antibiotics have been developed, and most of those newly approved antibiotics are slightly different variants of existing drugs. Current methods for screening new antibiotics are often prohibitively costly, require a significant time investment, and are usually limited to a narrow spectrum of chemical diversity.

"We're facing a growing crisis around antibiotic resistance, and this situation is being generated by both an increasing number of pathogens becoming resistant to existing antibiotics, and an anemic pipeline in the biotech and pharmaceutical industries for new antibiotics," Collins says.

To try to find completely novel compounds, he teamed up with Barzilay, Professor Tommi Jaakkola, and their students Kevin Yang, Kyle Swanson, and Wengong Jin, who have previously developed machine-learning computer models that can be trained to analyze the molecular structures of compounds and correlate them with particular traits, such as the ability to kill bacteria.

The idea of using predictive computer models for "in silico" screening is not new, but until now, these models were not sufficiently accurate to transform drug discovery. Previously, molecules were represented as vectors reflecting the presence or absence of certain chemical groups. However, the new neural networks can learn these representations automatically, mapping molecules into continuous vectors which are subsequently used to predict their properties.

In this case, the researchers designed their model to look for chemical features that make molecules effective at killing E. coli. To do so, they trained the model on about 2,500 molecules, including about 1,700 FDA-approved drugs and a set of 800 natural products with diverse structures and a wide range of bioactivities.

Once the model was trained, the researchers tested it on the Broad Institute's Drug Repurposing Hub, a library of about 6,000 compounds. The model picked out one molecule that was predicted to have strong antibacterial activity and had a chemical structure different from any existing antibiotics. Using a different machine-learning model, the researchers also showed that this molecule would likely have low toxicity to human cells.

This molecule, which the researchers decided to call halicin, after the fictional artificial intelligence system from "2001: A Space Odyssey," has been previously investigated as possible diabetes drug. The researchers tested it against dozens of bacterial strains isolated from patients and grown in lab dishes, and found that it was able to kill many that are resistant to treatment, including Clostridium difficile, Acinetobacter baumannii, and Mycobacterium tuberculosis. The drug worked against every species that they tested, with the exception of Pseudomonas aeruginosa, a difficult-to-treat lung pathogen.

To test halicin's effectiveness in living animals, the researchers used it to treat mice infected with A. baumannii, a bacterium that has infected many U.S. soldiers stationed in Iraq and Afghanistan. The strain of A. baumannii that they used is resistant to all known antibiotics, but application of a halicin-containing ointment completely cleared the infections within 24 hours.

Preliminary studies suggest that halicin kills bacteria by disrupting their ability to maintain an electrochemical gradient across their cell membranes. This gradient is necessary, among other functions, to produce ATP (molecules that cells use to store energy), so if the gradient breaks down, the cells die. This type of killing mechanism could be difficult for bacteria to develop resistance to, the researchers say.

"When you're dealing with a molecule that likely associates with membrane components, a cell can't necessarily acquire a single mutation or a couple of mutations to change the chemistry of the outer membrane. Mutations like that tend to be far more complex to acquire evolutionarily," Stokes says.

In this study, the researchers found that E. coli did not develop any resistance to halicin during a 30-day treatment period. In contrast, the bacteria started to develop resistance to the antibiotic ciprofloxacin within one to three days, and after 30 days, the bacteria were about 200 times more resistant to ciprofloxacin than they were at the beginning of the experiment.

The researchers plan to pursue further studies of halicin, working with a pharmaceutical company or nonprofit organization, in hopes of developing it for use in humans.

Optimized molecules

After identifying halicin, the researchers also used their model to screen more than 100 million molecules selected from the ZINC15 database, an online collection of about 1.5 billion chemical compounds. This screen, which took only three days, identified 23 candidates that were structurally dissimilar from existing antibiotics and predicted to be nontoxic to human cells.

In laboratory tests against five species of bacteria, the researchers found that eight of the molecules showed antibacterial activity, and two were particularly powerful. The researchers now plan to test these molecules further, and also to screen more of the ZINC15 database.

The researchers also plan to use their model to design new antibiotics and to optimize existing molecules. For example, they could train the model to add features that would make a particular antibiotic target only certain bacteria, preventing it from killing beneficial bacteria in a patient's digestive tract.


Story Source:

Materials provided by Massachusetts Institute of Technology. Original written by Anne Trafton. Note: Content may be edited for style and length.

Journal Reference:

Jonathan M. Stokes, Kevin Yang, Kyle Swanson, Wengong Jin, Andres Cubillos-Ruiz, Nina M. Donghia, Craig R. MacNair, Shawn French, Lindsey A. Carfrae, Zohar Bloom-Ackerman, Victoria M. Tran, Anush Chiappino-Pepe, Ahmed H. Badran, Ian W. Andrews, Emma J. Chory, George M. Church, Eric D. Brown, Tommi S. Jaakkola, Regina Barzilay, James J. Collins. A Deep Learning Approach to Antibiotic Discovery. Cell, 2020; 180 (4): 688 DOI: 10.1016/j.cell.2020.01.021

Cite This Page:

MLA
APA
Chicago
Massachusetts Institute of Technology. "Artificial intelligence yields new antibiotic: A deep-learning model identifies a powerful new drug that can kill many species of antibiotic-resistant bacteria." ScienceDaily. ScienceDaily, 20 February 2020. <www.sciencedaily.com/releases/2020/02/200220141748.htm>

Spring into New Recipes! Slow Cooker Chicken Teriyaki!

                                    Slow Cooker Chicken Teriyaki! It's Even Gluten Free!

                                                                         

3 pounds Boneless Skinless Chicken Breast, About 3 large
1/8 teaspoon Black Pepper, Fresh ground
1/2 cup Brown Sugar, Packed
1/2 cup Soy Sauce, Gluten free if necessary
2 tablespoons Rice Wine Vinegar
2 teaspoons Fresh Ginger, Minced
2 cloves Garlic, Crushed
1-2 tablespoons Cornstarch
1-2 tablespoons Water
Toasted Sesame Seeds, For garnish, optional
Directions
Place the chicken in the crock pot and season with the black pepper.
In a medium bowl, whisk together the brown sugar, soy sauce, vinegar, ginger and garlic. Pour over the chicken.
Cook the chicken on high for 2 hours and 15 minutes or low for 3-4 hours or until the internal temperature of the chicken reaches 165°F.
Remove the chicken from the liquid and shred or dice, set aside.
Pour the sauce in to a saucepan and heat until boiling. In a small bowl, combine the water and cornstarch. Use 1 tablespoon water and cornstarch for a thinner sauce, 2 for a thicker sauce. I prefer using 2 tablespoons of cornstarch and water. When the sauce begins to boil, whisk in the cornstarch slurry until it thickens. Add the chicken and sauce back into the crock pot and toss until the chicken is completely coated in the sauce.
Serve with rice and garnish with toasted sesame seeds.
Notes
 

The cook time listed is for cooking on high. If you'd prefer to cook on low, do so for 3 hours and 30 minutes.

Find More Recipes

Money as Christmas Gifts? Creative Ways to Give Cash!

                                                               

                                         

Little money, need last minute Christmas gifts? Think you're not creative, and oh so little time? Grab some cash, read on and choose one!

All ages:

"Money Gift Ideas"

Think about how many people don't carry cash ... how many kids have never even held cash in their hands? Like so many things, money has become "virtual." Money Gifts are thoughtful, creative and make a great gift for all ages.

"Money Book"

Items:

Small photo album. (Dollar General, Walmart, Target, Dollar Tree)Money: You decide.. One dollar bills, fives, tens, twenties...more? 

"Money Tree"

This little gem was found on "It's All About Rosie" Check out her cool tutorial on making a money tree, cheap, easy, quick and cute! 

Items:

9" high styrofoam cone (found in the floral section of the craft store)
Small flower pot or tin pail for the base
Approx 20 dollar bills
Bobby Pins
Topper  2 stars are cut and glued together back to back with a toothpick in between

For instructions and to find more creative ideas, click link below

https://itsallrosie.blogspot.com/2012/02/money-tree-tutorial.html

"Play-Doh"

How about putting a little cash in a "Play-Doh" in one of their containers! Surprise!

Items

All you need is an empty Play-Doh container and Whatever cash bills you choose to place in it! 

Bow or wrapping paper.

Gift Tag

"Money Gift Box"

This is easy. You can choose any box, small, medium, large. Place whatever bills in the box. A decorative box is usually easy to find. 

Items

Box of your choice

Wrapping paper or bow.

Gift tag.

Wnctimes Blog

Christmas Chimes by Erma Bombeck

                                 

                                                                         

                                                             

Everything is in readiness.

The tree is trimmed.  The cards taped to the door frame.  The boxes stacked in glittering disarray under the tree.

Why don’t I hear chimes?

Remember the small boy who made the chimes ring in a fictional story years ago?  As the legend went, the chimes would not ring unless a gift of love was placed on the altar.  Kings and men of great wealth placed untold jewels there, but year after year the church remained silent.

Then one Christmas Eve, a small child in a tattered coat made his way down the aisle, and without anyone noticing he took off his coat and placed it on the altar.  The chimes rang out joyously throughout the land to mark the unselfish giving of a small boy.

I used to hear chimes.

I heard them the year one of my sons gave me a tattered piece of construction paper on which he had crayoned two hands folded in prayer and a moving message, OH COME HOLY SPIT!

I heard them the year I got a shoe box that contained two baseball cards and the gum was still with them.

I heard them the Christmas they all got together and cleaned the garage.

They’re gone, aren’t they?  The years of the lace doilies fashioned into snowflakes … the hands traced in plaster of paris … the Christmas trees of pipe cleaners … the thread spools that held small candles.  They’re gone.

The chubby hands that clumsily used up $2 worth of paper to wrap a cork coaster are sophisticated enough to take a number and have the gift wrapped professionally.

The childish decision of when to break the ceramic piggy bank with a hammer to spring the 59 cents is now resolved by a credit card.

The muted thump of pajama-covered feet padding down the stairs to tuck her homemade crumb scrapers beneath the tree has given way to pantyhose and fashion boots to the knee.

It’ll be a good Christmas.  We’ll eat too much.  Make a mess in the living room.  Throw the warranties into the fire by mistake.  Drive the dog crazy taping bows to his tail.  Return cookies to the plate with a bite out of them.  Listen to Christmas music.

But Lord … what I would give to bend low and receive a gift of toothpicks and library paste and hear the chimes just one more time!

Benefits of Pets in the life of Older People

                                                      

I love pets! I love dogs! I love cats! They get me up and moving. They give me unconditional love. 

They listen to me, they are there when I am sad, mad, sick and are happy when I am happy.

I know I am a better person because they have been in my life. I think I try to live up to the person they think I am.

I have lost pets and the grief is beyond words. Getting another pet after losing one, it has felt like it diminishes the love, the value of the pets you miss. But it doesn't. They want us to be happy. And rescuing another pet is saving a life. 

The following is a study on the health benefits for older people of having pets. 

Share your positive thoughts about life with pets in the comments!

Source:
Taylor & Francis
Summary:
New research calls for increased understanding about older adults, the relationship between pet ownership and health, and the current barriers which limit older adults' chances to own a pet. The stud goes into detail about physical and financial risks for older adult pet ownership and how it can be diminished.

Research published in Activities, Adaption & Aging calls for increased understanding about older adults, the relationship between pet ownership and health, and the current barriers which limit older adults' chances to own a pet. The study, Fostering the Human-Animal Bond for Older Adults, goes into detail about physical and financial risks for older adult pet ownership and how it can be diminished.

Medical problems that arise with older adults, such as physical illness and emotional issues, have the potential to be mitigated by companionship of pets because it reduces social isolation and enhances physical activity. But illnesses that are often associated with aging, ranging from arthritis to diabetes, make it hard or impossible for older adults to provide routine care for their pets. Financial barriers are another issue that older pet owners face.

In the article, the researchers describe these common issues affecting older adults, particularly those living alone. They tell a story about Janet, a 75-year old obese woman who has diabetes and arthritis, but really wants a cat for company. Though she described herself as a "cat lady," she worries about the monetary investment and the fate of the feline should she fall ill or pass away.

When asked about what sparked the study, author Keith Anderson from the University of Montana commented "As a geriatric social work researcher, I've always been interested in finding creative, cost effective ways to improve the lives and well-being of older adults…My co-authors direct the Veterinary Outreach Program, affiliated with The Ohio State University, which provides mobile wellness care for the pets of older adults and/or homebound residents. Our interests overlapped and we began to discuss ways in which we could link pets in shelters with older adults who may benefit from pet ownership." The study was funded by the WALTHAM Foundation.

The researchers found that programs are beginning to arise to overcome these obstacles. "Programs are emerging that facilitate the adoption of pets by older adults. These programs match older adults with adult shelter animals and provide support throughout the adoption and ownership processes." 

Unfortunately, there are some drawbacks that these programs need to overcome, but the authors seem hopeful about finding potential solutions: "Lower-income older adults often live in buildings where there are fees and deposits associated with owning pets. We need creative solutions to address these financial barriers."

"Future researchers should continue to explore the human-animal bond for older adult populations, particularly for those with cognitive, physical, and financial limitations. There is so much potential benefit here for both pets and potential pet owners" wrote the research team.


Story Source:

Materials provided by Taylor & Francis. Note: Content may be edited for style and length.

Journal Reference:

Keith A. Anderson, Linda K. Lord, Lawrence N. Hill, Sandra McCune. Fostering the Human-Animal Bond for Older Adults: Challenges and Opportunities. Activities, Adaptation & Aging, 2015; 39 (1): 32 DOI: 10.1080/01924788.2015.994447

Cite This Page:

MLA
APA
Chicago
Taylor & Francis. "Pet ownership and its potential benefits for older adults." ScienceDaily. ScienceDaily, 23 June 2015. <www.sciencedaily.com/releases/2015/06/150623141736.htm>.

 

Self Help Tips for Holiday Blues

                                                               
Women of all ages experience holiday blues. We are blasted with "perfect people" on commercials. with "Perfect families. We may look back on past holidays, longing for those times again. We may look back on past sad holidays ... all of it can be a roller coaster ride!

I am not an expert, I do know what I experience in my own life. 

Some things that help me:

* Listening to "white noise" through earphones. I do this throughout the day. "Using earplugs or a white noise machine may also help drown out noise from outside the bedroom that could be keeping you awake. Not only do these behaviors promote sleep, but they can also helpease depression." (according to sleep.org)

* Watching youtube videos. I love watching short videos : funny pets, funny kids, people. I will take time to listen to music videos. I am amazed there are current artists out there who have some awesome music!

* Time Out. I have a childhood friend that I talk to at least once a week. We are more like sisters. She has always been kind of hyper. When I hear it in her voice, I remind her to take time out. Time to do nothing. Time to just be. I really find that it helps me. We are so overloaded with information, constant...just taking a few minutes each day to focus on being still is so important.

Below are some more suggestion. I will post the link to the full article below.

Self-help tips

1: Reach out and stay connected

If you’re depressed, you may not want to do anything or see anybody. But isolation only makes depression worse. On your own, it can be difficult to maintain perspective and sustain the effort required to beat depression. That’s why support matters—so make an effort to connect to others and limit the time you’re alone. If you can’t get out to socialize, invite loved ones to visit you, or keep in touch over the phone or email.

But remember: digital communication isn’t a replacement for face-to-face contact. Do your best to see people in person on a daily basis. Your mood will thank you! And remember, it’s never too late to build new friendships.

Get out in to the world. Try not to stay cooped up at home all day. Go to the park, take a trip to the hairdresser, have lunch with a friend, visit a museum, or go to a concert or a play.

Volunteer your time. Helping others is one of the best ways to feel better about yourself and expand your social network.

Join a depression support group. Being with others facing the same problems can help reduce your sense of isolation. It can also be inspiring to hear how others cope with depression.

Take care of a pet. A pet can keep you company, and walking a dog, for example, can be good exercise for you and a great way to meet people. Dog owners love to chat while their pets play together.

Take a class or join a club to meet like-minded people. Try joining a senior center, a book club, or another group of people with similar interests.

Create opportunities to laugh. Laughter provides a mood boost, so swap humorous stories and jokes with your loved ones, watch a comedy, or read a funny book.

Self Help Tip Guide

Positive relationships boost self-esteem and vice versa

                                                       

                                          

                              Robust reciprocal link found across life span

Date:
September 26, 2019
Source:
American Psychological Association
Summary:
Does having close friends boost your self-esteem, or does having high self-esteem influence the quality of your friendships? Both, according to a meta-analysis of more than two decades of research.

Does having close friends boost your self-esteem, or does having high self-esteem influence the quality of your friendships?

Both, according to a meta-analysis of more than two decades of research, published by the American Psychological Association.

"For the first time, we have a systematic answer to a key question in the field of self-esteem research: Whether and to what extent a person's social relationships influence his or her self-esteem development, and vice versa, and at what ages," said study author Michelle A. Harris, PhD, of The University of Texas at Austin. "The answer to what age groups is across the life span."

The research was published in the Journal of Personality and Social Psychology.

Harris and her co-author, Ulrich Orth, PhD, of the University of Bern, analyzed 52 studies involving more than 47,000 participants (54% female) looking at either the effect of self-esteem on social relationships over time or the reverse effect. The studies, all published between 1992 and 2016, included multiple countries (e.g., 30 samples from the United States, four from Switzerland, three from Germany, two each from Australia, Belgium, Canada, Finland, Greece, Russia and Sweden). Participants were 60% white, 2% Hispanic/Latino, 12% other predominantly another ethnicity and 19% mixed ethnicities. Samples ranged from early childhood to late adulthood.

The authors found that positive social relationships, social support and social acceptance help shape the development of self-esteem in people over time across ages 4 to 76. The authors also found a significant effect in the reverse direction. While earlier research had yielded inconsistent findings, the meta-analysis supports the classic and contemporary theories of the influence of self-esteem on social connections and the influence of social connections on self-esteem, according to Harris. The findings were the same after accounting for gender and ethnicity.

"The reciprocal link between self-esteem and social relationships implies that the effects of a positive feedback loop accumulate over time and could be substantial as people go through life," according to Harris.

The authors discuss the idea that positive relationships with parents may cultivate self-esteem in children, which leads to more positive relationships with peers in adolescence, which may further strengthen the self-esteem of emerging adults, and so on into late adulthood. However, the field is still in need of an integrated theory that can explain whether relationships have such a cumulative effect across life, or whether certain relationships become particularly important at certain ages.

When self-esteem or quality of social relationships is low, Harris noted, it can negatively affect the other factor, and set off a downward spiral, making clinical interventions especially important to offset this potentially adverse development.

"The fact that the effect did not differ significantly among studies with different sample characteristics strengthens confidence in the robustness of our findings," said Harris.

"We found a limited number of longitudinal studies on self-esteem and specific relationships in adulthood as well as studies using measures other than self-report, so our findings only begin to speak to these groups, and we look forward to future work oriented towards filling these gaps."


Story Source:

Materials provided by American Psychological Association. Note: Content may be edited for style and length.

Journal Reference:

Michelle A. Harris and Ulrich Orth. The Link Between Self-Esteem and Social Relationships: A Meta-Analysis of Longitudinal Studies. Journal of Personality and Social Psychology, 2019 DOI: 10.1037/pspp0000265

Cite This Page:

MLA
APA
Chicago
American Psychological Association. "Positive relationships boost self-esteem, and vice versa: Robust reciprocal link found across life span." ScienceDaily. ScienceDaily, 26 September 2019. <www.sciencedaily.com/releases/2019/09/190926092416.htm>.