Near-atomic ‘maps’ reveal structure for maintaining pH balance in cells

For the first time, scientists have visualized a new class of molecular gates that maintain pH balance within brain cells, a critical function that keeps cells alive and helps prevent stroke and other brain injuries.

These gates, called proton-activated chloride channels (PAC), nest within cell membranes and regulate the passage of small molecules called chloride ions into and out of cells. This allows cells to sense and respond to their environment.

“Proton-activated chloride channels have only recently been described but they are critical for cell survival, particularly in the brain,” said Wei Lü, Ph.D., a Van Andel Institute assistant professor and co-corresponding author of the study, which was published today in Nature. “Our new images, coupled with our findings into how these channels work, provide much-needed molecular blueprints that will help answer long-standing questions in the field and provide new insights into how these channels may be therapeutically targeted in disease.”

The images reveal a wedding bouquet-like structure, with parts that change configuration in response to environmental pH. When pH shifts from alkaline to acidic, a key pH sensor moves from its “resting” location and is inserted in an “acidic pocket,” which signals that the gate allowing ions in and out of the cell should be open. This specific mechanism has never before been described.

This study is a collaboration between the Lü Lab at Van Andel Institute and a group led by Zhaozhu Qiu, Ph.D., an assistant professor at Johns Hopkins University School of Medicine and co-corresponding author of the paper. The Johns Hopkins team first reported the discovery of PAC in Science last year.

Solving PAC structures are another important, early step toward an understanding that may one day impact human health.

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Materials provided by Van Andel Research Institute. Note: Content may be edited for style and length.

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Eradicating black rats on Palmyra Atoll uncovers eye-opening indirect effects

The black rats weren’t supposed to be there, on Palmyra Atoll. Likely arriving at the remote Pacific islet network as stowaways with the U.S. Navy during World War II, the rodents, with no natural predators, simply took over. Omnivorous eating machines, they dined on seabird eggs, native crabs and whatever seed and seedling they could find.

When the atoll’s managers — the U.S. Fish and Wildlife Service, The Nature Conservancy and Island Conservation — were planning to conduct a rat eradication project, UC Santa Barbara community ecologist Hillary Young and her research group saw it as an unusual opportunity. They had already been visiting Palmyra regularly to track another non-native species — the coconut palm — to see whether it was spreading invasively in the area, potentially impacting the nesting seabird population and changing the island’s soil composition. They had plots where they were monitoring trees in various stages of growth and survival; how would the vegetation respond to the eradication of the island’s main seed and seedling eater?

“Prior to the eradication, most of the understory of Palmyra was either bare ground — sandy soil or coral rubble — or covered in a carpet of ferns,” said Ana Miller-ter Kuile, a graduate student researcher in the Young Group and lead author of a study that appears in the journal Biotropica. The rats were quick to eat seeds and young plants coming out of the ground, and they frequented the canopy as well, often nesting in the coconut palms and eating coconuts.

Eradication of the rats — which was conducted in 2011 — did in fact result in a resurgence of vegetation on Palmyra. And not only that. The Asian tiger mosquito was wiped out, while two species of land crab emerged, adding to the atoll’s biodiversity.

But rarely is ecology easily untangled. In the years that followed eradication, Palmyra’s understory did indeed fill with juvenile trees as seeds that hit the ground were allowed to take root. Only they were often not the Pisonia or other native trees that would have been the more ideal forests for the native seabirds and animals of Palmyra.

“I was on the island in 2012, just after the eradication and could easily navigate through the open jungle understory,” Miller-ter Kuile said. “Two years later when I went back, I was wading through an infuriating carpet of seedlings that were taller than me, tripping over piles of coconuts.” While the researchers found a 14-fold increase in seedling biomass, most of these new seedlings were juvenile coconut palms, their proliferation left unchecked by the removal of the rats.

“Rats were basically eating almost every nut before it even reached the forest floor,” Miller-ter Kuile said. “I knew that rats could have an impact, I just didn’t expect it to be this large.” In the absence of rats, according to a population model the researchers built based on a decades’ worth of data on coconut seed production, growth and survival, the coconut palms’ population growth rate increased by 10% — enough to eventually overtake the island, had the managers not stepped in with an aggressive coconut palm removal project.

The coconut palm invasion is a problem for places like Palmyra Atoll, as it shifts the island’s ecology away from native plants and animals.

“Coconuts have a very different ‘nutritional’ profile from the native tree species on this island, with much more carbon and less nitrogen,” Miller-ter Kuile said. “When these trees die, because they have different nutrient profiles from native plants, they are likely to break down differently — and more slowly — and influence rates of decomposition.” In addition, she said, native seabirds do not nest in coconut palms, which would deprive the atoll of the nutrients in their guano, which, in turn, “would lead to what would likely be a fairly nutrient-poor system, which discourages other native plants from growing in those areas.”

Continuing their restoration of the island, Palmyra’s managers were working to remove the vast majority of the island’s millions of coconut palms to give local species a chance to dominate, a project that is currently on hold due to the COVID-19 pandemic.

Anticipating the indirect downstream effects, such as potential shifts in ecology toward other invasive species, could become part of a more holistic island rodent eradication effort, Miller-ter Kuile said.

“Wildlife management, in particular, has a history of being single-species focused, which often means that a lot of time and energy is put into producing or controlling a species without considering the broader effects of that management effort on all of the rest of the species in that ecosystem,” she said. According to the study, “documenting the variation in invasive rodent diet items, along with long-term surveys, can help prioritize island eradications where restoration is most likely to be successful.”

“The ‘accidental experiment’ of our long-term monitoring of trees in this project I think provides a rare opportunity to quantify the immediate and longer-term effects of eradication,” she said.

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New research traces the origins of trench fever

First observed among British Expeditionary Forces in 1915, trench fever sickened an estimated 500,000 soldiers during World War I. Since then, the disease has become synonymous with the battlefield. But now, new research from an international team of scientists has uncovered evidence challenging this long-held belief.

The research, published this week in PLOS ONE, outlines the discovery of DNA evidence of the disease in civilian remains predating WWI by thousands of years. In total, the team analyzed bone fragments and teeth of 145 individuals alive between the 1st and 19th centuries. Approximately 20% of those remains contained traces of Bartonella quintana, the bacteria responsible for trench fever.

Davide Tanasi, an associate professor with USF’s History Department and member of the Institute for the Advanced Study of Culture and the Environment, excavated remains for this project from a Roman cemetery in Syracuse, Sicily. Tanasi, who is also the director of USF’s Institute for Digital Exploration, first began work at the site to better understand the dietary habits and health of the Christian population living there during the 3rd and 4th centuries. Through a collaboration with French epidemiologists, researchers used real-time polymerase chain reaction testing to detect B. quintana DNA within the remains.

“Once contracted, there are diseases, like trench fever, that can leave traces within your DNA and can integrate your DNA with further information,” Tanasi said. “This means that once a person dies, even as far back as 2,000 years ago, it is still possible to find traces of the bacterium that infected them.”

Tanasi says the discovery sheds light on the complex history of trench fever and begins answering historical questions about the lives of Christian citizens in this region during the 3rd and 4th centuries.

“Archaeology isn’t just the study of the past, but it’s something that can make the present better through the study of the past,” he said. “The more we understand about the behavior of these bacteria in the past, the more we can design plans to address them, contain them and eliminate them in the present.”

While most associate this disease with WWI and WWII, occurrences of trench fever are still reported today, most prominently within homeless populations. The bacteria are spread to humans through contact with body lice (Pediculus humanus corporis), making poor personal hygiene a primary factor in its spread and infection rate. Researchers hope that by tracing the progression of B. quintana through history, they’re able to identify ways to better manage the spread of the disease today.

For Tanasi, his work with the remains excavated in Sicily continues. Through stable-isotope analysis, his research group examines the diet and lives of those who once lived in the region. He hopes this work will further answer questions about the lifestyle and health of the Christian community of Roman Syracuse.

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Materials provided by University of South Florida (USF Innovation). Note: Content may be edited for style and length.

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Covid: New care home visits guidance in England defended by minister

Critics say fresh measures in England including screens, pods and window visits are not practical.

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Obedience Test Results

Four days ago I posted a simple obedience test. I’m still getting more responses each day, but it looks like the patterns have become clear enough to share what I’ve learned thus far.

The basic idea was that I commanded people who read that post to read 5 more articles from my website on that same day and then to send me feedback about their experience. They could choose to obey the command or not.

Why the Obedience Test?

It was a simple idea that popped into my mind at the time, and I opted to run with it. That’s likely because I’ve been thinking about the theme of obedience lately. Much of the time whatever is churning in my mind provides the inspiration for new blog posts.

As some people guessed, obedience is a theme that I’m exploring in the novel I’m writing, particularly with respect to how humans relate to AI. It’s not the only theme I’m exploring, but it’s one of the major ones. That could change as I get further into the writing though. I’m only about 5K words into it so far.

Today much of the AI we interact with, such as “smart” assistants like Siri (still dumb as a stump) or Alexa (getting there), behaves rather obediently. It does what we tell it to do, or at least it tries. But what if that Master-servant relationship begins to shift, towards one of equals and perhaps shifting even beyond that? How might humans respond to this shift? Will they obey smarter AI, especially if it’s to their benefit? Or will they resist?

Would you let an AI decide what you get to eat? Would you let an AI plan your exercise? What if obeying the AI in this way greatly improves your health? There are lots of ways we can envision that being ornery towards AI might just slow you down, such as by refusing to do your AI-generated workouts.

This shift is already showing up today, is it not? How many people are obeying other companies and services without even realizing how they’re being conditioned? And how many people rebel against science and logic, even when it’s ultimately detrimental to them?

Also, how many people willingly assume roles of obedience in human relationships, such as by having a boss telling them what to do? How might AI affect these relationships over time? Will AI level the playing field or create even bigger power imbalances? We might see both aspects coming into play.

What human instincts, mindsets, and behaviors actually get in our way and slow us down, both individually and collectively? How could AI help us? How might it hurt us, such as by amplifying addictions?

With the election happening, I’ve also been thinking about people’s obedience to politicians and political parties as well. Where does obedience help us? Where does it hurt us? Are people succumbing to falsehoods because they’re being too obedient? Are they buying into conspiracy theories because they’re being too rebellious?

And lastly, I’ve had a long history in my relationship with obedience, from being raised in a religion with strict rules of conduct to going through a wild and rebellious phase to going decades without a boss to getting into D/s play. So I was also curious to see where some of my blog readers landed in terms of this relationship with obedience.

I also just thought it would be a fun thing to try and to see how people responded. I imagined that some people would act like ornery rebels and others would find value in obedience, perhaps playfully. That’s pretty much what happened.

Results

The results were varied but not surprising.

It was pretty close to 50-50 between the rebels and the obeyers. There was some gray area in the middle with a few people semi-obeying, like reading a few articles or skimming instead of fully reading, but most people reported that they either read 5+ more articles or read none.

I also noted that everyone who replied technically obeyed the second command to send feedback. A true rebel wouldn’t have bothered to reply, so of course I don’t get to see those responses.

Among the rebels who did reply, the most common response pattern was from people who said that they hate being told what to do and rejected the command because of that. Some seemed to take pride in their rebelliousness, like they were spiting me by not obeying. They responded as if I was their Mom or Dad telling them to clean up their room.

A few rebels also said that they were intending to read more articles on my site that day before reading the obedience test, but after being commanded to read more, they declared that they weren’t going to read any more that day. They couldn’t do it because then it would mean something different, like they were being obedient.

The rebel mindset is still a reactive one, wouldn’t you say? It strikes me that people are less free when they think like this. Tell a rebel to do something, and now they can’t do it.

Who set up the obey-or-disobey framing? I did, and these rebels still bought into it, which in my view is actually an obedient act. They let me define the frame, which limited their options by constricting the meaning they’d assign to different actions. So they obeyed my frame, and then they tried to rebel within that frame, which of course looks a bit silly: Oh yeah… just for that I’m not gonna read any more articles today, even though I was originally going to. So there!

If you let someone dictate the meaning you assign to an event or decision, you become less free. Even as these people thought they were being rebellious, they were actually just giving away their power.

If they had declined to accept my framing offer, they could have decided to read or not read more articles for their own reasons, not for the reasons I suggested. You don’t have to buy into the meaning that someone else offers.

Some rebels even caught onto the fact that they were obeying the second command to share feedback, and then they had to justify why they were obeying that part but not the first part. They typically framed the second part as a request that they were choosing to accept, being more sensitive to the “command” framing of the first part. I’d say you’re still less free if you have a negative reaction to being commanded. It’s a framing offer that you can accept or decline regardless of how someone labels it.

Not all rebels seemed very triggered though. Some declined easily without expressing much feeling about it, usually saying that it didn’t align with how they wanted to spend their time.

Consider that someone could tell or command you to do something that would actually be good for you, and if you frame this as something you must resist, you’re holding yourself back. It makes you a less coachable and teachable person since you’re likely to encounter something that makes you want to rebel and resist sooner or later, even within the scope of well-intentioned advice.

It’s hard to give advice to a reactive rebel, so such rebels tend to teach the people around them not to give them advice – and often not to give them invitations either.

Another drawback to the rebel mindset is that rebels often have trouble assuming command and telling other people what to do. They figure that other people will be resistant in much the same way, which isn’t true. Some people enjoy being told what to do, even when it’s framed as a command. Hence rebels often have a hard time delegating.

And of course in certain situations, some people like to play and dance with the concept of obedience, which may or may not include playful forms of rebellion.

The limitations of the rebel mindset are pretty easy for me to spot because I used to be very much like that myself. It was a phase I went through for many years. It helped me grow away from some aspects of my upbringing that were problematic, but it also introduced new problems that slowed me down. Rebelliousness can be a fun and rewarding mindset to explore for a while – and beneficial too – but I wouldn’t want to stay there for decades. This mindset too often gets in the way of making discerning and intelligent choices, and it chokes off some otherwise good opportunities.

Obeyers

On the obeyers side, I could mostly divide the responses into two types:

  1. Some people playfully embraced this framing and just went with the command, feeling little or no resistance to it.
  2. Some people felt some resistance to the obedience frame, so they shared extra justifications for following the command anyway, such as curiosity, potential benefits, trusting me, or wanting to share and participate in the experiment.

What I noticed most of all with the obeyers is that by and large, they seemed to like and enjoy the experience way more than the rebels did. They clearly had more fun with it. Some reported synchronicities and extra value received from the articles they read. There was more appreciation. And they wrote longer responses on average, often sharing extra details, stories, and personal updates.

Whereas the feedback from rebels was usually more curt and direct, the obeyers’ feedback was generally more open, friendly, and playful. So I’d say that between these two groups, the obeyers had a better overall experience.

The obeyers were less likely to be triggered by the command and obedience framing. They largely regarded it as an invitation or a suggestion, even a playful one. Some reported some mild negativity towards this framing, but it wasn’t nearly as severe as what the rebels shared, and the obeyers didn’t have to stretch too far to find a way to justify taking action in spite of some resistance.

I found it interesting how people came up with different reasons and justifications to overcome their resistance. Not everyone needed to do that though.

Some people didn’t feel any resistance to the obedience framing. They basically played back at me and went with the role-playing aspect of it. These people seemed to enjoy the experience most of all.

My Inner Reaction

I also paid attention to how I internally reacted to people’s reactions. Put yourself in my shoes, and imagine that you received the types of responses I just described. How do you think you’d have reacted to them?

This probably won’t surprise you, but I felt most connected to the obeyers. Their playing-back-at-me responses were the warmest and most fun to read. I felt a stronger heart connection to them too.

The rebels framed the experiment as something they had to resist or reject. I didn’t take this personally, especially since I anticipated that many people would respond this way. Even so, I felt less connected to them. They seemed more shielded and less trusting whereas the obeyers’ replies often made me smile or laugh.

I mostly felt a bit sad for the rebels because they seemed the least free, the least flexible, the least happy, and the most trapped. That may be because it reminded me of how limiting it was when I was in my super rebellious phase.

Playing With Obedience

I think what we really want to aim for here is freedom, conscious choice, and also good discernment.

If you’re too obedient and not discerning about it, that can be bad of course. You could be led astray by someone who doesn’t have your best interests at heart.

If you’re too rebellious and not discerning about it, that can also be bad. You’re going to miss out on some good opportunities, and you’ll reject some good advice and invitations if they’re framed in ways that trigger you.

My recommendation is to see if you can remove the heat from words like command and obedience. Realize that being told what to do isn’t an attack. It’s just an invitation. You can accept or decline any such invitation, but don’t let your reactive triggers make those decisions for you.

If you struggle with negative reactions to the obedience and command framing, you’ll likely have a harder time obeying your own commands. Part of you will frequently rebel against yourself. You’ll often see your inner rebel resisting your inner commander. Then your inner commander will become flabby too, not wanting to give orders to your rebellious side. This makes you less free and less capable. It wastes energy to internally fight with yourself.

To flow through life with more ease and action, it’s helpful to recognize that there’s nothing wrong with commanding, and there’s nothing wrong with obeying. It’s important not to overweight these factors, so you can give more weight to the decisions and results you’d like to experience.

This month I’m doing NaNoWriMo to write my novel. This is a 30-day challenge that someone else created. I’m obeying the challenge, and I’m obeying my own command to do it. My inner rebel remains calm and untriggered. Even though I don’t have to, I find it worthwhile to frame the challenge as having aspects of command and obedience. This helps me continue to reduce resistance related to both aspects, and that in turn helps me get better results. It’s really hard for rebels to successfully complete a challenge like this.

Consider that if you can’t do a challenge with the command-and-obey framing, you may also be weak at doing it with some other framing like self-interest, self-discipline, or personal achievement. It’s so easy to accidentally trigger your inner rebel, making you want to resist even when it would be better if you persisted with the challenge.

So consider that it might be best for you in the long run if you can develop a healthier, non-triggered relationship with command and obedience. Take the sting out of this framing. Let yourself see both sides as forms of play, and notice that a more playful relationship with this framing gives you more options, more freedom, and better results.

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Covid-19: NHS in England moves to highest alert level

Health bosses are ‘seriously concerned’ about winter, with free beds expected to be used up in weeks.

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Coronavirus: Extremely vulnerable advised not to go to work from Thursday

The advice for people at higher risk from Covid-19 is to stay at home as much as possible for a month.

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Leaf-cutter bees as plastic recyclers? Not a good idea, say scientists

Plastic has become ubiquitous in modern life and its accumulation as waste in the environment is sounding warning bells for the health of humans and wildlife. In a recent study, Utah State University scientist Janice Brahney cited alarming amounts of microplastics in the nation’s national parks and wilderness areas.

Bioengineers around the world are working to develop plastic-eating “super” enzymes that can break down the human-made material’s molecular structure faster to aid recycling efforts. In another research effort published in 2019, entomologists noted leaf-cutter bees were using plastic waste to construct their nests. The researchers suggested such behavior could be an “ecologically adaptive trait” and a beneficial recycling effort.

Not so fast, says USU evolutionary ecologist Joseph Wilson. Just because bees can use plastic, doesn’t mean they should.

Wilson and undergraduate researcher Sussy Jones, along with colleagues Scott McCleve, a naturalist and retired math teacher in Douglas, Arizona, and USU alum and New Mexico-based independent scientist Olivia Carril ’00, MS’06, jointly authored an observational paper in the Oct. 9, 2020 issue of Science Matters, exploring the nest building behavior of bees in the genus Megachile.

“Leaf-cutter bees are among the most recognizable of solitary bees, because of their habit of cutting circles out of leaves to build their cylindrical nests,” says Wilson, associate professor of biology at USU-Tooele. “We’ve heard reports of these bees using plastic, especially plastic flagging primarily in construction and agriculture, and we decided to investigate.”

The researchers don’t yet know how widespread the use of plastic by leaf-cutter bees is and they also know little about plastic’s effects on the insects.

“Building from plastic could change the dynamics and environment of the bee’s nest cells, because plastic doesn’t breathe like natural materials,” says Wilson, who produced a video about the phenomenon. “In the 1970s, some researcher let leaf-cutter bees nest in plastic straws and found ninety percent of the bees’ offspring died because of fungal growth. The plastic sealed in the moisture and didn’t allow gas exchange.”

To deter bees’ use of flagging, Wilson suggests use of fabric ribbons made from natural fibers.

“These materials are biodegradable and, if used by bees, will likely avoid the harmful moisture-capturing effects of plastic,” he says.

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Materials provided by Utah State University. Original written by Mary-Ann Muffoletto. Note: Content may be edited for style and length.

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Covid: Destructive rules only current option, says Chris Whitty

England’s chief medical officer defends lockdowns as a further 397 coronavirus deaths are recorded.

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Researchers pioneer more effective way to block malaria transmission in mosquitoes

Employing a strategy known as “population modification,” which involves using a CRISPR-Cas9 gene drive system to introduce genes preventing parasite transmission into mosquito chromosomes, University of California researchers have made a major advance in the use of genetic technologies to control the transmission of malaria parasites.

University of California, Irvine postdoctoral researcher Adriana Adolfi, in collaboration with colleagues at UCI, UC Berkeley and UC San Diego, followed up on the group’s pioneering effort to develop CRISPR-based gene drive systems for making mosquito vectors resistant to transmitting malaria parasites by increasing gene drive effectiveness in female mosquito progeny.

“This work mitigates a big issue with the first gene drive systems, which is the accumulation of drive-resistant mosquitoes that could still transmit malaria parasites,” said UCI vector biologist Anthony James, the Donald Bren Professor of Microbiology & Molecular Genetics and Molecular Biology & Biochemistry, who was a co-primary investigator on the study.

“The second-generation gene drive system described in this paper can be applied to any of the several thousand genes that are essential for insects to survive or reproduce,” said UC San Diego Distinguished Professor Ethan Bier, a co-author of the study and science director at the Tata Institute for Genetics and Society. “While it was developed in fruit flies, this system is readily transportable to a broad selection of insect species that serve as vectors for devastating disorders such as Chagas disease, sleeping disease, leishmaniasis and arboviral diseases.”

They describe a highly efficient second-generation version of the team’s original gene drive, developed for the Indo-Pakistani malaria vector mosquito Anopheles stephensi. The 2015 work, published in Proceedings of the National Academy of Sciences, was the first demonstration of a CRISPR-based gene drive in mosquitoes.

In that first study, the gene drive was transmitted to about 99 percent of progeny when the parent in which the gene drive was inserted was a male but only 60 to 70 percent of offspring when the parent in which the gene drive was inserted was a female. A significant number of drive-resistant chromosomes are generated in females; this, in principle, could allow those females to continue to transmit parasites.

Adolfi, lead author of the new study, and collaborators solved the failure to drive efficiently through females by equipping the gene drive with a functional copy of the target gene into which the drive is inserted. Normal function of this target gene is required in this mosquito species for female survival and fertility after she feeds on blood, and its functionality is usually disrupted when the drive system is inserted into the gene.

The resulting female mosquitoes showed strong and consistent drive in a population cage study and negligible production of drive-resistant chromosomes. This strategy of inserting a gene drive into a gene essential for viability or fertility and at the same time including a functional gene that rescues the loss of viability or fertility provides a general solution to drive resistance through females. Also, as with a catalytic converter removing combustion pollution from automobiles, the new system efficiently eliminates genetic errors made in the drive process.

This gene drive system — in combination with genes for blocking parasite transmission — can now be used to design field-ready strains of mosquitoes. Thorough testing is required to demonstrate safety and efficacy before advancing to field testing.

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Materials provided by University of California – Irvine. Note: Content may be edited for style and length.

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