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Comment by Dr. Krishna Kumari Challa on September 6, 2023 at 10:23am

Synchronizing your internal clocks may help mitigate jet lag, effects of aging

Traveling to faraway places is a great way to seek out new experiences, but jet lag can be an unpleasant side effect. Adjusting to a new time zone is often accompanied by fatigue, difficulty sleeping, and a host of other problems that can turn an otherwise exciting adventure into a miserable trip.

Jet lag is caused by a difference between the circadian system—the body's internal clock—and the surrounding environment. Around the turn of the century, scientists began to recognize that the body has multiple internal clocks, calibrated in different ways, and that jet lag-like symptoms can result when these clocks drift out of sync with each other. This can happen in several ways and grows more prevalent with age.

A team of scientists  developed a theoretical model to study the interactions between multiple internal clocks under the effects of aging and disruptions like jet lag. The article, "A minimal model of peripheral clocks reveals differential circadian re-entrainment in aging," appeared in the journal Chaos on Sept. 5, 2023.

Modern research has shown that circadian clocks are present in almost every cell and tissue in the body. Each relies on its own set of cues to calibrate; the brain's clock depends on sunlight, for instance, while the peripheral organs calibrate at mealtime.

Conflicting signals, such as warm weather during a short photoperiod or nighttime eating—eating when your brain is about to rest—can confuse internal clocks and cause desynchrony.

At this point, little is known about how the body's various internal clocks affect each other. The added complexity of accounting for multiple clocks means researchers tend to use simplified models. Most studies primarily focus on one particular time cue or a single clock. Important gaps remain in our understanding of the synchronization of multiple clocks under conflicting time cues.

Researchers now took a different approach, building a mathematical framework that accounts for this complex interplay between systems. Their model features two populations of coupled oscillators that mimic the natural rhythms of circadian cycles. Each oscillator influences the others while simultaneously adjusting based on unique external cues.

Using this model, the team was able to explore how such a coupled system could be disrupted and what makes the effect worse. They found that common symptoms of aging, such as weaker signals between circadian clocks and a lower sensitivity to light, result in a system that is more vulnerable to disruptions and slower to recover.

They also landed on a new method to speed up recovery from jet lag and similar disruptions. According to their results, the way to better sleep is through the stomach.

Having a larger meal in the early morning of the new time zone can help overcome jet lag. Constantly shifting meal schedules or having a meal at night is discouraged, as it can lead to misalignment between internal clocks. 

The authors plan to investigate the other side of the equation and identify the factors that result in more resilient internal clocks. Such discoveries could result in recommendations to prevent jet lag in the first place, or to keep the circadian system healthy into old age.

A minimal model of peripheral clocks reveals differential circadian re-entrainment in aging, Chaos An Interdisciplinary Journal of Nonlinear Science (2023). DOI: 10.1063/5.0157524

Comment by Dr. Krishna Kumari Challa on September 6, 2023 at 9:55am

Why are male kidneys more vulnerable to disease than female kidneys? Mouse study points to testosterone

Female kidneys are known to be more resilient to disease and injury, but males need not despair. A new  study published in Developmental Cell describes not only how sex hormones drive differences in male and female mouse kidneys, but also how lowering testosterone can "feminize" this organ and improve its resilience.

By exploring how differences emerge in male and female kidneys during development, we can better understand how to address sex-related health disparities for patients with kidney diseases.

Researchers identified more than 1,000 genes with different levels of activity in male and female mouse kidneys. The differences were most evident in the section of the kidney's filtering unit known as the proximal tubule, responsible for reabsorbing most of the nutrients such as glucose and amino acids back into the blood stream. Most of these sex differences in gene activity emerged as the mice entered puberty and became even more pronounced as they reached sexual maturity. Because female kidneys tend to fare better in the face of disease or injury, the researchers were interested how the gene activity of kidneys becomes "feminized" or "masculinized"—and testosterone appeared to be the biggest culprit. 

To feminize the kidneys of male mice, two strategies worked equally well: castrating males before puberty and thus lowering their natural testosterone levels, or removing the cellular sensors known as androgen receptors that respond to male sex hormones. Intriguingly, three months of calorie restriction—which is an indirect way to lower testosterone—produced a similar effect. Accordingly, calorie restriction has already been shown to mitigate certain types of kidney injuries in mice. To re-masculinize the kidneys of the castrated males, the researchers only needed to inject testosterone. Similarly, testosterone injection masculinized the kidneys of females who had their ovaries removed before puberty. The scientists performed some similar experiments with mouse livers. Although this organ also displays sex-related differences, the hormones and underlying factors driving these differences are very different than those at play in the kidney. This suggests that these sex-related organ differences emerged independently during evolution. To test whether the same genes are involved in sex-related kidney differences in humans, the scientists analyzed a limited number of male and female donor kidneys and biopsies. When it came to genes that differed in their activity between the sexes, there was a modest overlap of the human genes with the mouse genes.

Andrew P McMahon & colleagues, Direct androgen receptor control of sexually dimorphic gene expression in the mammalian kidney, Developmental Cell (2023). DOI: 10.1016/j.devcel.2023.08.010. www.cell.com/developmental-cel … 1534-5807(23)00406-9

Comment by Dr. Krishna Kumari Challa on September 5, 2023 at 7:46am

Eye movements decrease while effortfully listening to speech: study

After a certain age, approximately 40% of people experience some degree of hearing loss. While age-related hearing loss is most prevalent in adults over the age of 65, it can start occurring far earlier than that, when people are in their 40s or 50s.

Despite their widespread use, existing diagnostic techniques might be unable to detect earlier signs of hearing loss, such as the loss of the ability to hear speech in crowded or noisy environments. Some researchers have thus been trying to devise viable techniques to detect subtler forms of hearing loss, so that they can be addressed early, before they are irreparable. To this end, neuroscientists have recently been exploring the relationship between effortful listening and eye movements. Their most recent paper, published in The Journal of Neuroscience, suggests eye movements tend to decrease while young adults are placing greater effort in trying to hear speech.

Past studies highlighted several different physiological responses that occur while one is effortfully listening. One that is commonly mentioned in existing literature is a change in pupil size, which can be measured using pupillometry, a technique that relies on a camera to record eyes and calculate the diameter of pupils at different points in time.

 Research investigating the auditory cortex in animals—that is, the brain region responding to sound—found that when animals reduce their movements, the auditory cortex becomes more sensitive to sound.  so researchers thought that reduced eye movements could also be associated with higher auditory sensitivity to speech.

When researchers tested this,  they found that under the more effortful listening conditions, that is, when the degree of speech masking through background noise was high, individuals' eye movements decreased as reflected in longer fixation durations and reduced gaze dispersion, compared to more favorable listening conditions.

M. Eric Cui et al, Eye Movements Decrease during Effortful Speech Listening, The Journal of Neuroscience (2023). DOI: 10.1523/JNEUROSCI.0240-23.2023

Comment by Dr. Krishna Kumari Challa on September 4, 2023 at 8:55am

For the new paper, the authors conducted both a review, or meta-analysis, of previous research and their own original data analysis.

For the meta-analysis, they looked at 22 traits across 199 studies including millions of male-female co-parents, engaged pairs, married pairs or cohabitating pairs. The oldest study was conducted in 1903.

In addition, they used a dataset called the UK Biobank to study 133 traits, including many that are seldom studied, across almost 80,000 opposite-sex pairs in the United Kingdom.

Across both analyses, traits like political and religious attitudes, level of education, and certain measures of IQ showed particularly high correlations.

Traits around substance use also showed high correlations, with heavy smokers, heavy drinkers and teetotalers tending strongly to partner up with those with similar habits. Meanwhile, traits like height and weight, medical conditions and personality traits showed far lower but still positive correlations. For instance, the correlation for neuroticism was .11. For some traits, like extroversion, there was not much of a correlation at all. People have all these theories that extroverts like introverts or extroverts like other extroverts, but the fact of the matter is that it's about like flipping a coin: Extroverts are similarly likely to end up with extroverts as with introverts.

In the meta-analysis, the researchers found "no compelling evidence" on any trait that opposites attract. In the UK Biobank sample, they did find a handful of traits in which there seemed to be a negative correlation, albeit small.

Those included: chronotype (whether someone is a "morning lark" or "night owl"), tendency to worry and hearing difficulty.

More research must be done to unpack those findings.

These findings suggest that even in situations where we feel like we have a choice about our relationships, there may be mechanisms happening behind the scenes of which we aren't fully aware.

The authors note that couples share traits for a variety of reasons: Some grow up in the same area. Some are attracted to people who are similar to them. Some grow more similar the longer they are together.

Horwitz, T.B. et al, Evidence of correlations between human partners based on systematic reviews and meta-analyses of 22 traits and UK Biobank analysis of 133 traits. Nature Human Behavior (2023). DOI: 10.1038/s41562-023-01672-z www.nature.com/articles/s41562-023-01672-z

Part 2

Comment by Dr. Krishna Kumari Challa on September 4, 2023 at 8:52am

Evidence shows that, in love, opposites don't actually attract

Despite some conventional wisdom to the contrary, opposites don't actually attract.

That's the takeaway from a sweeping research  analysis of more than 130 traits and including millions of couples over more than a century.

The findings demonstrate that birds of a feather are indeed more likely to flock together.

The study, published today in the journal Nature Human Behaviour, confirms what individual studies have hinted at for decades, defying the age-old adage that "opposites attract."

It found that for between 82% and 89% of traits analyzed—ranging from political leanings to age of first intercourse to substance use habits—partners were more likely than not to be similar.

For only 3% of traits, and only in one part of their analysis, did individuals tend to partner with those who were different than them.

Aside from shedding light on unseen forces that may shape human relationships, the research has important implications for the field of genetic research. A lot of models in genetics assume that human mating is random. This study shows this assumption is probably wrong, noting that what is known as "assortative mating"—when individuals with similar traits couple up—can skew findings of genetic studies.

Part 1

Comment by Dr. Krishna Kumari Challa on September 4, 2023 at 8:46am

Fake world is not good!

'Smart' glasses skew power balance with non-wearers, say researchers

Someone wearing augmented reality (AR) or "smart" glasses could be Googling your face, turning you into a cat or recording your conversation—and that creates a major power imbalance, say researchers.

Currently, most work on AR glasses focuses primarily on the experience of the wearer. Researchers  explored how this technology affects interactions between the wearer and another person. Their explorations showed that, while the device generally made the wearer less anxious, things weren't so rosy on the other side of the glasses.

AR glasses superimpose virtual objects and text over the field of view to create a mixed-reality world for the user. Some designs are big and bulky, but as AR technology advances, smart glasses are becoming indistinguishable from regular glasses, raising concerns that a wearer could be secretly recording someone or even generating deepfakes with their likeness.

According to the wearers, the fun filters reduced their anxiety and put them at ease during the exercise. The non-wearers, however, reported feeling disempowered because they didn't know what was happening on the other side of the lenses. They were also upset that the filters robbed them of control over their own appearance. The possibility that the wearer could be secretly recording them without consent—especially when they didn't know what they looked like—also put the non-wearers at a disadvantage.

The non-wearers weren't completely powerless, however. A few demanded to know what the wearer was seeing, and moved their faces or bodies to evade the filters—giving them some control in negotiating their presence in the invisible mixed-reality world. 

Another issue is that, like many AR glasses, Spectacles have darkened lenses so the wearer can see the projected virtual images. This lack of transparency also degraded the quality of the social interaction, the researchers reported.

To create more positive experiences for people on both sides of the lenses, the study participants proposed that smart glasses designers add a projection display and a recording indicator light, so people nearby will know what the wearer is seeing and recording.

Ji Won Chung et al, Negotiating Dyadic Interactions through the Lens of Augmented Reality Glasses, Proceedings of the 2023 ACM Designing Interactive Systems Conference (2023). DOI: 10.1145/3563657.3595967

Comment by Dr. Krishna Kumari Challa on September 4, 2023 at 6:59am

Study discovers mechanism that inhibits a wide variety of viruses, similar to one already found in cancer drug
Researchers recently described a mechanism that inhibits virus replication and protects cells from damage. Interestingly, a drug that has already been approved could prove useful in combating various viruses.

AIDS, the flu, COVID-19—time and again, viral infections overtake entire regions of the world and cost human lives. To date, there are no drugs with a broad antiviral effect. Researchers want to change that.

In the journal PLOS Pathogens, they described a way to effectively inhibit the multiplication of a wide variety of viruses.

The fact that it is so tricky to fight viruses is partly due to their simple structure. They offer only a few points of attack for inhibiting agents. In addition, they repeatedly change in such a way that active agents no longer recognize their target.

Viruses, which consist of only a few components, use the body's own structures of their host, e.g. humans, for their reproduction. Also because severe effects of a viral infection are often due to an excessive reaction of the body's defense system, researchers are increasingly focusing their attention on the interaction between virus, human physiology and the defense system.

The goal is to find mechanisms in the body that can be therapeutically inhibited or enhanced to slow down a viral infection and alleviate its effects. Researchers  have now succeeded in influencing two mechanisms in human cells simultaneously so that both happen.

They are researching the body's own molecule itaconic acid. Some time ago, they discovered that a pharmacologically optimized variant of it, 4-octyl itaconate, is particularly efficient in activating a signaling pathway that controls various protective and defense mechanisms of human cells.

The switch for this signaling pathway is a protein called NRF2. However, their experiments repeatedly revealed evidence that 4-octyl itaconate directly impairs virus replication—independently of the NRF2 signaling pathway. To investigate these indications, they produced cells in the laboratory without NRF2 protein.

When the protective switch was missing, influenza viruses actually multiplied better. To their surprise, however, the researchers found that even without NRF2, 4-octyl itaconate inhibited the proliferation of influenza viruses just as strongly as in unmodified cells.

The researchers suspected that 4-octyl itaconate obstructed the transport of proteins and nucleic acids from the cell nucleus, which many viruses depend on.

To test their assumption, they compared the effect of 4-octyl itaconate with that of a cancer drug (selinexor) that blocks a transport channel from the cell nucleus. Both the cancer drug and the itaconic acid variant inhibited replication of an influenza virus. They prevented precursors of the newly formed virus particles from being transported out of the nucleus of the host cell. The unfinished viruses remained stuck in the cell nucleus, so to speak.

The authors of the current study also provide an explanation for their observation: In the structure of the transport channel, they found a site to which both 4-octyl itaconate and the anticancer drug bind. It is similar to the site where 4-octyl itaconate interacts with the protein that controls the NRF2 switch.

Using biochemical methods, the researchers proved that 4-octyl itaconate actually binds to the nuclear transporter in human cells, thereby blocking it. 

The now published findings open up new perspectives for the development of antiviral therapies.

Fakhar H. Waqas et al, NRF2 activators inhibit influenza A virus replication by interfering with nucleo-cytoplasmic export of viral RNPs in an NRF2-independent manner, PLOS Pathogens (2023). DOI: 10.1371/journal.ppat.1011506

Comment by Dr. Krishna Kumari Challa on September 2, 2023 at 12:03pm

Human ancestors nearly went extinct
Roughly 900,000 years ago, climate changes sweeping the globe might have pushed our distant ancestors to the brink of extinction. The unknown human-like species was reduced to just 1,280 breeding individuals, creating a genetic bottleneck that is still detectable in the DNA of modern-day humans. The population didn’t expand for more than 100,000 years, after which it bloomed again and the progenitors of our species and of our extinct relatives, the Denisovans and the Neanderthals, emerged.

The work, published in Science, suggests a drastic reduction in the population of our ancestors well before our species, Homo sapiens, emerged. The population of breeding individuals was reduced to just 1,280 and didn’t expand again for another 117,000 years.

About 98.7% of human ancestors were lost then.

The fossil record in Africa and Eurasia between 950,000 and 650,000 years ago is patchy and that “the discovery of this bottleneck may explain the chronological gap.

The researchers’ method allowed them to reconstruct ancient population dynamics on the basis of genetic data from present-day humans. By constructing a complex family tree of genes, the team was able to examine the finer branches of the tree with greater precision, identifying significant evolutionary events.

The technique put the spotlight on the period 800,000 to one million years ago — for which there is much unknown — in a way that hasn’t been done before.

Around 813,000 years ago, the population of pre-humans began to swell again. How our ancestors managed to survive, and what allowed them to flourish once more, remains unclear, though.

https://www.science.org/doi/10.1126/science.abq7487?utm_source=Natu...

Comment by Dr. Krishna Kumari Challa on September 2, 2023 at 11:54am

Groundwater depletion rates in India could triple in coming decades as climate warms, study warns

A new  study finds that farmers in India have adapted to warming temperatures by intensifying the withdrawal of groundwater used for irrigation. If the trend continues, the rate of groundwater loss could triple by 2080, further threatening India's food and water security.

Reduced water availability in India due to ground water depletion and climate change could threaten the livelihoods of more than one-third of the country's 1.4 billion residents and has global implications. India recently overtook China to become the world's most populous nation and is the second-largest global producer of common cereal grains including rice and wheat.

This is of concern, given that India is the world's largest consumer of groundwater and is a critical resource for the regional and global food supply.

Without policies and interventions to conserve groundwater, we find that warming temperatures will likely amplify India's already existing groundwater depletion problem, further challenging India's food and water security in the face of climate change.

 Nishan Bhattarai, Warming temperatures exacerbate groundwater depletion rates in India, Science Advances (2023). DOI: 10.1126/sciadv.adi1401. www.science.org/doi/10.1126/sciadv.adi1401

Comment by Dr. Krishna Kumari Challa on September 1, 2023 at 11:42am

Scientists Warn 1 Billion People on Track to Die From Climate Change

The fossil fuels that humanity burns today will be a death sentence for many lives tomorrow.

A recent review of 180 articles on the human death rate of climate change has settled on a deeply distressing number. Over the next century or so, conservative estimates suggest a billion people could die from climate catastrophes, possibly more.

As with most predictions for the future, this one is based on several assumptions.

One is a rough rule of thumb called the '1000-ton rule'. Under this framework, every thousand tons of carbon that humanity burns is said to indirectly condemn a future person to death.

If the world reaches temperatures 2°C above the average global preindustrial temperature, which is what we are on track for in the coming decades, then that's a lot of lives lost. For every 0.1 °C degree of warming from now on, the world could suffer roughly 100 million deaths.

If you take the scientific consensus of the 1,000-ton rule seriously, and run the numbers, anthropogenic global warming equates to a billion premature dead bodies over the next century.

Obviously, we have to act. And we have to act fast.

https://www.mdpi.com/1996-1073/16/16/6074

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