A combination of two substances secreted by the immune system can cure and prevent rotavirus infection, as well as potentially treat other viral infections that target epithelial cells, which cover body surfaces such as skin, blood vessels, organs and the urinary tract, according to researchers in the Institute for Biomedical Sciences at Georgia State University.
Rotavirus, which causes severe, life-threatening diarrhea in young children and moderate gastrointestinal distress in adults, leads to thousands of deaths in children annually, particularly in developing countries where rotavirus vaccines are only moderately effective. Rotavirus is an RNA virus that primarily infects intestinal epithelial cells.
The substances identified in the study, officially known as cytokines, are interleukin 18 (IL-18) and interleukin 22 (IL-22). IL-18 and IL-22 are produced when the body detects a protein in the whip-like appendage of bacteria.
The study, which investigated how these cytokines inhibit rotavirus infection, found when mice were treated with both IL-18 and IL-22, the cytokines promoted each other’s expression, but also impeded rotavirus by independent, distinct mechanisms that involved activating receptors in intestinal epithelial cells. These actions resulted in rapid and complete expulsion of rotavirus, even in hosts with severely compromised immune systems. The therapy was also found to be effective for norovirus, a contagious virus that causes vomiting and diarrhea. The findings are published in the journal Science Immunology.
“Our study reports a novel means of eradicating a viral infection, particularly viruses that infect epithelial cells,” said Dr. Andrew Gewirtz, senior author of the study and a professor in the Institute for Biomedical Sciences at Georgia State. “The results suggest that a cocktail that combines IL-18 and IL-22 could be a means of treating viral infections that target short-lived epithelial cells with high turnover rates.”
The study is funded by grants from the National Institutes of Health.
Patients receiving care for advanced cancer at Moores Cancer Center at UC San Diego Health were more likely to survive or experience a longer period without their disease progressing if they received personalized cancer therapy, report University of California San Diego School of Medicine researchers.
Led by Razelle Kurzrock, MD, director of the Center for Personalized Cancer Therapy at Moores Cancer Center and senior author of the study, a multidisciplinary molecular tumor board was established to advise treating physicians on course of care using an individual patient’s molecular tumor makeup to design precision medicine strategies.
“Patients who underwent a molecular tumor board-recommended therapy were better matched to genomic alterations in their cancer and had improved outcomes,” said Kurzrock. “The three-year survival for patients with the highest degree of matching and who received a personalized cancer therapy was approximately 55 percent compared to 25 percent in patients who received therapy that was unmatched or had low degrees of matching.”
Of 429 patients evaluated by the molecular tumor board, 62 percent were matched to at least one drug, report the researchers in the October 2, 2020 online issue of Nature Communications. Twenty percent of patients matched to all recommended drugs, including combination therapies.
The tumor board acted in an advisory role and treating physicians chose not to use the board’s recommended strategy in 38 percent of cases, opting instead for a standard therapy approach that might have been unmatched to the patient’s genetic alterations or had a low degree of matching. These patients experienced a lower progression-free survival and overall survival rates.
The use of next-generation sequencing allows for the identification of novel potential targets for patients with cancer to improve outcomes, but there are challenges to using this approach widely, said Shumei Kato, MD, associate professor of medicine at UC San Diego School of Medicine and first author.
“One of the hurdles is that every cancer patient appears to be carrying different molecular and genomic patterns despite having the same cancer type,” said Kato, a Moores Cancer Center medical oncologist specializing in rare and gastrointestinal cancers. “This can be challenging since we are customizing therapy based on the unique genomic pattern patients have, and thus it is difficult to predict the response. In addition, this approach requires multidisciplinary expertise as well as access to drugs or clinical trials not always available in smaller practices.”
For the month of September, I maintained a daily time log, as described in the post called Long-Term Time Logging. Now I can share some insights from what I learned.
In this case it actually wasn’t that helpful to see where my time went. I was pretty aware of that already, so reviewing the logs didn’t give me many insights there. My logs matched up pretty closely with my assumptions and expectations.
What was surprising was what gave me the most joy. At the end of each day, I asked a simple question and briefly answered it at the bottom of the day’s time log. That question was:
Do I love this day?
I had assumed that by asking this question, it would help me become aware of which days I felt best about, and then I could deliberately embrace more of those positive patterns. That turned out to be true, but the surprising part was what actually created a day I loved versus a day I didn’t love.
I figured going into this that I’d love my most productive days. If I got a lot of work done, that should give me a sense of accomplishment, and then I’d feel great at the end of the day, right?
Wrong actually. My most productive day was the day I appreciated the least. Looking back, I was pleased that I got a lot done, but that satisfaction was so much at a mental level. That mental satisfaction didn’t reach into my heart and make me feel like I could genuinely say I loved the day.
The days I loved most when I reflected back on them had more to do with being than with doing. All that was required for me to love the whole day was to recall one delightful event from it, and these events were usually very simple and not particularly effortful.
One Delightful Event
Even if most of the activities of a day were routine or so-so, if I experienced one delightful event during the day, I would always feel a heartfelt sense of appreciation for the day when I reflected back on it afterwards. So my appreciation ultimately came down to simple moments.
Mostly these delightful events involved something new – usually not wildly different but with just enough novelty to create a special memory for that day.
Here are some examples of small but delightful events that made me reflect back on the day with feelings of love and appreciation:
Running a different route than I’d run before, along a new street that had just recently been paved on the western edge of the city. The streetlights were working, but the sidewalks and landscaping hadn’t been added yet. It felt special to be one of the first people to run down a new road that wasn’t open to car traffic, like it was my own private running route. On one side was a wall with newly built houses behind it, and on the other side was open desert. (See the photo below, taken during my first run down that street.)
Playing some new video games with Rachelle, especially A Short Hike and Untitled Goose Game – the goose game made us laugh a lot.
Going to the Apple Store with Rachelle, getting new Apple Watches, and chatting with the employees. The store had been closed for many weeks and just reopened last week, so the vibe was upbeat and happy.
Returning a monitor that broke (while under warranty) to that same Apple Store and getting a replacement for it, which made me appreciate it more.
Going for a longer than usual run with new running shoes one morning.
Cleaning up some parts of the house to restore them to a nicer state of cleanliness and order.
Watching Cobra Kai with Rachelle. The show is set in an area where I used to live, and it reconnected me with fond memories of martial arts training.
Discovering some useful insights during journaling sessions.
Participating in a weekend intensive with a coaching group on Zoom.
Connecting with CGCers during coaching calls.
Attending a live script reading of The Princess Bride with many of the original cast members, along with more than 100K other people.
Listening to Kevin Smith’s Tough Sh*t audiobook, laughing a lot, and loving all the geeky references.
Yummy sex.
Having a good dentist appointment and chatting with the hygienist. (I actually like going to the dentist since the people there are so friendly and down-to-earth.)
One day when I exercised for 150+ minutes – it felt good to move a lot.
Attending a diversity committee call for the Transformational Leadership Council – nice to connect with like-minded friends who care.
Watching the final episode of The Good Place with Rachelle and seeing her getting teary-eyed at the end.
September was a pretty happy month for me, probably because I paid extra attention to happiness. I realized that big accomplishments don’t fuel my happiness as much as I thought, but small delights do.
A nice morning run, an insightful journaling session, a fun video game – these are all good ways to create a day I’ll appreciate. But what seems to help the most is including some form of novelty in a day. Newness made me happier than routine.
It’s more special to play a new video game than one I’ve played many times before. It’s more special to try a new brand of running shoes that I’ve never worn before. It’s more special to go a slightly different direction instead of following a familiar route.
It’s okay if my experiences are rooted to familiar places and situations, but one little twist in the direction of novelty somehow makes me appreciate the experience – and the day – more than I otherwise would.
Just running down a different street instead of running one of my standard routes can make a meaningful difference in how I feel about the whole day. I could have the laziest day ever, but if I just had one new experience that day, it elevated my relationship with the day. That surprised me. I didn’t think novelty was so meaningful.
Work-wise I felt better about the days when I didn’t use a system or routine to get things done. I had more appreciation for the days when I went with the flow of inspiration, especially when it led to engaging with work a bit differently. This makes me really curious about how to leverage this further. Would I be more productive if instead of trying to systematize my approach to work, I went in the opposite direction and did something to make each day truly unique?
Note that having a routine and embracing novelty are not necessarily contradictory approaches. You can follow a structure and still include some novelty, like how many movies adhere to genre standards and then try to add some unique twists. A good structure often becomes invisible, so you’ll probably notice and appreciate the novel aspects more.
What I gained from this 30-day experiment is a greater respect for small delights created through novelty. When I feel a nudge to lean in the direction of doing something new, I’m more likely to trust that impulse now. When I have that thought to run a different route one morning, I trust that it serves a good purpose. Doing something even slightly new makes the activity more memorable, and it’s the memory that I appreciate.
I’m less likely to appreciate a very routine day because the day is harder to remember. When reviewing my time log entries, it’s hard to recall the details of a day filled with familiar items, even when I have a written record of the activities for that day. When there’s even one item that’s semi-unique though, I somehow remember the day with a smile.
Another realization is that newness stimulates more growth. Running a familiar route isn’t as stimulating for my body and mind as running a new route. Would I improve faster if I ran different routes more often instead of sticking with my familiar favorites? Probably.
I encourage you to do your own time logging experiment for at least a month, so you can discover your own insights, which won’t necessarily align with mine. Some readers have started their own logging practices within the past few weeks, and they’ve been emailing me to say that they’re finding it valuable too.
Biology textbooks may need to be re-written, with scientists finding a new piece of DNA essential to forming male sex organs in mice.
An international research collaboration with The University of Queensland found the Y-chromosome gene that makes mice male is made up of two different DNA parts, not one, as scientists had previously assumed.
UQ’s Institute of Molecular Biosciences Emeritus Professor Peter Koopman said the critical DNA fragment had been hidden from researchers for more than 30 years.
“Expression of the Y chromosomal gene Sry is required for male development in mammals and since its discovery in 1990 has been considered a one-piece gene,” he said.
“Sry turns out to have a cryptic second part, which nobody suspected was there, that is essential for determining the sex of male mice. We have called the two-piece gene Sry-T.”
The scientists tested their theory and found that male mice (XY) lacking in Sry-T developed as female, while female mice (XX) carrying a Sry-T transgene developed as male.
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The success rate for the experiments was almost 100 per cent.
Emeritus Professor Koopman said the discovery would change how basic biology and evolution was taught around the world.
“For the last 30 years, we’ve been trying to figure out how this works,” he said.
“Sry is a master switch gene because it flicks the switch for male development, it gets the ball rolling for a whole series of genetic events that result in a baby being born as a male instead of female.
“This new piece of the gene is absolutely essential for its function; without that piece, the gene simply doesn’t work.
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“We’ve discovered something massively important in biology here, because without Sry there can be no sexual reproduction and hence no propagation and survival of mammalian species.”
The discovery may apply to efforts to manipulate sex ratios in agriculture or for biological pest management. But Emeritus Professor Koopman was quick to point out that, for ethical and practical reasons, the discovery cannot be utilised on human embryos.
“Once we understand better how males and females are specified in non-human species of mammals, then it offers the opportunity to influence that process,” he said.
“The ability to select for the desired sex could dramatically increase efficiencies for agricultural industries such as the dairy industry (females) or the beef industry (males).
“People have been trying to figure out ways to skew to the desired sex in these industries for a long time, and now that we understand more about the fundamental mechanism of Sry it may be possible through genetic means.”
fecal transplants could one day be used as a therapy to restore cognitive function in the elderly — according to new research from the University of East Anglia, the University of Florence and the Quadram Institute.
A new study published today shows how fecal transplants from older to younger mice altered their gut microbiome, which in turn impacted their spatial learning and memory.
The research team hope that reversing the procedure could one day see fecal transplantation used to combat cognitive decline among the elderly.
Dr David Vauzour, from UEA’s Norwich Medical School, said: “Ageing is an inevitable process that starts immediately after birth and ultimately leads to physical health problems as well as a decline in psychological well-being and cognitive function.
“Research has shown that the aging process may be linked with age-related changes in our gut microbiota.
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“Recently, the existence of two-way communication between the gut and the brain — known as the ‘gut-brain axis’ — has emerged as an important player in shaping aspects of behaviour and cognitive function.
“We wanted to see whether transferring gut microbes from older to younger mice could affect parts of the central nervous system associated with ageing.”
The research team performed fecal transplants from older adult mice to younger adult mice and then assessed the young adults for markers such as anxiety, exploratory behaviour and memory.
After the transplantation, the team found significant differences in the young mice’s microbial profiles.
While the young adults showed no significant changes in markers of anxiety, explorative behaviour or locomotor activity, they did show impaired spatial learning and memory as measured in a maze test.
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These changes were paralleled by alterations in the expression of proteins associated with synaptic plasticity and neuro transmission, and changes to cells in the hippocampus part of their brains — responsible for learning and memory.
Dr Vauzour said: “Our research shows that a fecal transplantation from an old donor to a young recipient causes an age-associated shift in the composition of gut microbiota.
“The procedure had an impact on the expression of proteins involved in key functions of the hippocampus — an important part of the brain that has a vital role in a variety of functions including memory, learning but also in spatial navigation and emotional behaviour and mood.
“In short, the young mice began to behave like older mice, in terms of their cognitive function.”
Prof Claudio Nicoletti, from the University of Florence, Italy, said: “While it remains to be seen whether transplantation from very young donors can restore cognitive function in aged recipients, the findings demonstrate that age-related shifts in the gut microbiome can alter components of the central nervous system.
“This work highlights the importance of the gut-brain axis in ageing and provides a strong rationale to devise therapies aiming to restore a young-like microbiota to improve cognitive functions and quality of life in the elderly,” he added.
“Manipulating the microbiome is increasingly being seen as a way of improving or maintaining human health, and these results are an exciting indication of its potential for helping us age healthily” said Prof Arjan Narbad from the Quadram Institute.
“We have established an FMT service on the Norwich Research Park to treat serious gut infections and now want to explore in humans its effectiveness in combating a number of age-related conditions, including cognitive decline.”
The research was led by a team at UEA and the University of Florence, in collaboration with colleagues at the University of Milan, the Earlham Institute, University of Siena, the Quadram Institute, and Nottingham Trent University.
Animal acoustic signals are amazingly diverse. Researchers from the University of Zurich and the University of Saint-Etienne, together with French, American and Dutch collaborators, explored the function and diversification of animal acoustic signals and the mechanisms underlying the evolution of animal communication systems.
To this end, they used Shannon & Weaver’s ‘Mathematical Theory of Communication’ originally applied to telecommunications in 1949, which has transformed the scientific understanding of animal communication. This theory allows the amount of information in a signal to be quantified. The researchers were the first to use this framework within an evolutionary perspective to explore the biological information encoded in an animal signal.
How drumming structure evolves over time
In deciding which biological model to choose, the researchers selected the woodpeckers’ drumming as their ideal candidate. This bird family is known for rapidly striking their beaks on tree trunks to communicate. The team combined acoustic analyses of drumming from 92 species of woodpeckers, together with theoretic calculations, evolutionary reconstructions, investigations at the level of ecological communities as well as playback experiments in the field.
“We wanted to test whether drumming has evolved to enhance species-specific biological information, thereby promoting species recognition,” says lead author Maxime Garcia of the UZH Department of Evolutionary Biology and Environmental Studies.
Constant amount of information for 22 million years
Results demonstrate the emergence of new drumming types during woodpeckers evolution. Yet, despite these changes in drumming structure, the amount of biological information about species identity has remained relatively constant for 22 million years. Selection towards increased biological information thus does not seem to represent a major evolutionary driver in this animal communication system. How then can biological information be concretely maintained in nature? Analyses of existing communities around the globe show that ecological arrangements facilitate the efficiency of drumming signals: Communities are composed of only a few species, which distribute their drumming strategies to avoid acoustic overlap. “The responses to different drumming structures seen in our experimental approach show the ability of individuals to recognize their own species based on acoustic cues about species identity found in drumming signals,” says Garcia. This way, biological information about species identity can be maintained without necessarily inducing a strong evolutionary pressure on drumming signals.
The present study shows that random and unpredictable changes in the structure of communication signals over time can occur while maintaining the signals overall informative potential within and across species. This work leads the way to further investigate the evolution of meaning associated with communicating through multiple communication channels.
One interesting frame shared in the book The Courage to Be Disliked is: All problems are interpersonal relationship problems.
That isn’t necessarily a true statement, but you can think of it as a lens for viewing problems. Personally I think it’s a bit exaggerated as far as lenses go. I prefer a similar but more flexible one: All problems, challenges, and situations can be framed as relationships.
Not everything translates well to an interpersonal relationship, but you can translate any situation to some type of relationship. This can include your relationships with:
yourself
other people
reality
life
your work
money
skills
your body
and more
Moreover, when working on your goals and habits, it’s helpful to translate your goals and habits into growth experiences for one or more of your relationships with different parts of life. This helps goals feel more personal and meaningful, so they aren’t just the mental “stuck in your head” types of goals that don’t really get accomplished.
For example, I could frame my daily exercise as a discipline-based habit that I have to push myself to do each day, but that’s a lame approach that isn’t very sustainable. That mindset looks especially weak when viewed through the relationship lens. Who wants to maintain a habit if the relationship is based on force and struggle against some kind of resistance? That kind of relationship is headed for a breakup sooner or later.
Instead of pushing myself to exercise more or exercise harder, I focused on improving my relationship with exercise. I asked questions like these:
What would make this relationship better?
What could I do to increase the enjoyment of exercise, so I naturally want to do it without having to force myself?
Where is there friction in the relationship, and how can I reduce or eliminate that resistance?
How could I keep improving this relationship over time, so it keeps getting better year after year?
This approach worked nicely. I have a very positive relationship with exercise, and it’s improved even more this year. Here are some aspects of the relationship that I focused on improving:
Running different routes for variety and different levels of challenge, so it doesn’t feel too routine or stale
Continuing to develop new routes that I’ve never run before, so I feel a sense of abundance in having different routes to pick from
Tuning into my body and mind to decide which route to run based on what kind of experience I want (a run with more people, a more solitary run, a run where I’ll see the sunrise, a run where I can expect to see plenty of rabbits, a run with more parks, running near the baseball stadium, running along the western edge of the city, etc)
Listening to really good audiobooks while I run, on topics that appeal to me, including sometimes listening to audiobooks about running from runners who love to run
Enjoying the views while running through the hills that overlook the whole Vegas Valley
Investing in quality running shoes and testing different kinds of shoes to discover my personal favorites
Heading out before dawn and being greeted by the rising sun
Sometimes picking out planets like Venus or Jupiter when I look up at the dark sky while first starting out
Using an Apple Watch to track my progress as I go (time, distance, pacing, heart rate, etc) – and getting a new one each year, so I always have the latest version
Mostly running for the enjoyment of it but occasionally setting interesting goals for distance or speed
Feeling a sense of accomplishment for sometimes running to spots farther out than I’ve run to before
Waving or nodding to other runners and cyclists I pass along the way, which gives a little feeling of social connection with the people in the neighborhood (it’s encouraging to see people exercising)
Feeling good when I finish running and switch to a cool down walking pace
Enjoying the alone time, which feels more like being than doing
Reminding myself to feel grateful that my body can do this (seeing it as a beautiful gift, not to be taken for granted)
Lately I’ve been running 60-70 minutes most mornings. Interestingly it feels more motivating to run for an hour or more than it used to feel to run for 30-45 minutes. One reason is that as I increased the duration, I focused more on the relationship with running rather than the discipline or habit of running. Another reason could be that these longer runs do an even better job of rebalancing hormones and neurotransmitters, so I feel even happier.
Instead of pushing myself to run farther, which I’ve done many times before but which didn’t lead to sustainably longer runs, I sought to connect more deeply with the love and beauty of running. I focused on improving my relationship with running. I leaned towards the principle of love more than the principle of power here. This worked very nicely.
There are so many other ways to apply the relationship frame to create and maintain improvements in different areas of your life. Instead of pushing yourself to work harder or with more discipline, you can focus instead on improving your relationship with your work. Same goes for your relationships with any other kinds of tasks.
More than two decades ago, this type of framing helped me a lot with improving the flow of money through my life. Instead of trying to make more money in ways that were only semi-aligned, I worked on fixing my alignment problems with money. I invested in improving my personal relationship with money. That relationship was weak – I saw money as something annoying that I shouldn’t have to deal with. But I learned to appreciate its role in life and to enjoy earning and spending it. These days I think of money as fun and playful – it feels lighter and less stressful than it used to. Having a better relationship with money makes it easier to earn it, and it’s more fun to spend it as well.
Look at an area where you tend to struggle or have a hard time accomplishing your goals. What do you see when you use the relationship frame on that area? Is your relationship based on trying to force yourself to push through resistance? If so, how could you improve the relationship over time, so you naturally enjoy engaging with this area of life? This simple reframe can generate powerful insights that can radically transform your results.
