How bacteria live -- whether as independent cells or in a communal biofilm -- determines how they evolve antibiotic resistance, which could lead to more personalized approaches to antimicrobial therapy and infection control.
University of Pittsburgh School of Medicine researchers repeatedly exposed bacteria to the antibiotic ciprofloxacin to force rapid evolution. As expected, the bacteria developed resistance to the drug, but surprisingly, their lifestyle affected which specific adaptations emerged, according to a study published today in eLife.
"What we're simulating in the lab is happening in the wild, in the clinic, during the development of drug resistance," said senior author Vaughn Cooper, Ph.D., director of the Center for Evolutionary Biology and Medicine at Pitt. "Our results show that biofilm growth shapes the way drug resistance evolves." According to study lead author Alfonso Santos-Lopez, Ph.D., a postdoctoral researcher in Cooper's lab, this finding could uncover vulnerabilities that may prove useful when treating drug-resistant infections.
"Antibiotic resistance is one of our main problems in medicine," Santos-Lopez said. "We have to develop new treatments, and one idea is to take advantage of what the field calls 'collateral sensitivity.' When bacteria evolve resistance to one drug, it can expose a vulnerability to a different class of antibiotics that can effectively kill the bacteria."
Knowing these evolutionary push-and-pull relationships could take the guesswork out of prescribing antibiotics, Santos-Lopez said.
In this experiment, when the biofilm evolved resistance to ciprofloxacin, it became defenseless against cephalosporins. The free-floating bacteria did not develop this same chink in their armor, even though they became 128 times more resistant to ciprofloxacin than the biofilm-grown bacteria.
According to study coauthor Michelle Scribner, a doctoral student in Cooper's lab, these findings highlight the importance of studying bacteria as they naturally occur, in biofilms.
"Biofilms are a more clinically relevant lifestyle," Scribner said. "They're thought to be the primary mode of growth for bacteria living in the body. Most infections are caused by biofilms on surfaces."
From Science Daily
Oct 23, 2019
Looking inside the body with inderect light
Light provides all our visual information, but it reaches our eyes in different ways. Direct light comes unperturbed, coming straight from the source, whereas indirect light bounces off different surfaces, such as walls or ceilings, before entering our eyes. Extracting information from these two pathways has significant implications in diagnostic imaging and other applications. A multinational collaboration led by Nara Institute of Science and Technology Assistant Professor Hiroyuki Kubo, Arizona State University Assistant Professor Suren Jayasuriya, and Carnegie Mellon University Professor Srinivasa G. Narasimhan has successfully captured and analyzed indirect light with commercially available cameras to create images of blood vessels in living human beings in real time at extraordinary resolution.
While direct light provides information like depth and colour, allowing us to see a person's skin and other superficial features, indirect light, explains Kubo, can reveal otherwise unseen details just under the surface.
"Light on skin has strong subsurface scattering. By capturing indirect light, we can see details of invisible objects underneath the skin like blood vessels," he says.
The new technique exploits the epipolar geometry on which light travels by creating a synchronization delay between the light source and camera. A new nonlinear algorithm developed by the researchers then demultiplexes the information to provide a sharper image.
"Our imaging system illuminates the scene with epipolar planes corresponding to projector rows. We vary two key parameters to capture the light transport: the offset between the projecting row and camera row in the rolling shutter, or synchronization delay, and the exposure of the camera row," explains Kubo.
The result was the imaging of blood vessels at a much finer resolution than standard medical instruments. It also extracted details in circumstances that have been challenging in medical imaging, such as darker toned or hairy skin.
"We captured the basilic and cephalic veins in the inner forearm, which are about 1-5 mm deep," observes Kubo.
The hardware comes at a low cost and is portable. That and the ability to reveal new details of blood vessels non-invasively will improve the quality of care to a wider patient population such as patients who cannot have agents injected into their blood vessels, like children or the elderly.
Overall, Kubo is optimistic that this technique adds to vascular image quality in just about any condition seen in clinics.
Read more at Science Daily
While direct light provides information like depth and colour, allowing us to see a person's skin and other superficial features, indirect light, explains Kubo, can reveal otherwise unseen details just under the surface.
"Light on skin has strong subsurface scattering. By capturing indirect light, we can see details of invisible objects underneath the skin like blood vessels," he says.
The new technique exploits the epipolar geometry on which light travels by creating a synchronization delay between the light source and camera. A new nonlinear algorithm developed by the researchers then demultiplexes the information to provide a sharper image.
"Our imaging system illuminates the scene with epipolar planes corresponding to projector rows. We vary two key parameters to capture the light transport: the offset between the projecting row and camera row in the rolling shutter, or synchronization delay, and the exposure of the camera row," explains Kubo.
The result was the imaging of blood vessels at a much finer resolution than standard medical instruments. It also extracted details in circumstances that have been challenging in medical imaging, such as darker toned or hairy skin.
"We captured the basilic and cephalic veins in the inner forearm, which are about 1-5 mm deep," observes Kubo.
The hardware comes at a low cost and is portable. That and the ability to reveal new details of blood vessels non-invasively will improve the quality of care to a wider patient population such as patients who cannot have agents injected into their blood vessels, like children or the elderly.
Overall, Kubo is optimistic that this technique adds to vascular image quality in just about any condition seen in clinics.
Read more at Science Daily
Achieving quantum supremacy
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| Quantum computing concept illustration |
"A computation that would take 10,000 years on a classical supercomputer took 200 seconds on our quantum computer," said Brooks Foxen, a graduate student researcher in the Martinis Group. "It is likely that the classical simulation time, currently estimated at 10,000 years, will be reduced by improved classical hardware and algorithms, but, since we are currently 1.5 trillion times faster, we feel comfortable laying claim to this achievement."
The feat is outlined in a paper in the journal Nature.
The milestone comes after roughly two decades of quantum computing research conducted by Martinis and his group, from the development of a single superconducting qubit to systems including architectures of 72 and, with Sycamore, 54 qubits (one didn't perform) that take advantage of the both awe-inspiring and bizarre properties of quantum mechanics.
"The algorithm was chosen to emphasize the strengths of the quantum computer by leveraging the natural dynamics of the device," said Ben Chiaro, another graduate student researcher in the Martinis Group. That is, the researchers wanted to test the computer's ability to hold and rapidly manipulate a vast amount of complex, unstructured data.
"We basically wanted to produce an entangled state involving all of our qubits as quickly as we can," Foxen said, "and so we settled on a sequence of operations that produced a complicated superposition state that, when measured, returns bitstring with a probability determined by the specific sequence of operations used to prepare that particular superposition. The exercise, which was to verify that the circuit's output correspond to the equence used to prepare the state, sampled the quantum circuit a million times in just a few minutes, exploring all possibilities -- before the system could lose its quantum coherence.
'A complex superposition state'
"We performed a fixed set of operations that entangles 53 qubits into a complex superposition state," Chiaro explained. "This superposition state encodes the probability distribution. For the quantum computer, preparing this superposition state is accomplished by applying a sequence of tens of control pulses to each qubit in a matter of microseconds. We can prepare and then sample from this distribution by measuring the qubits a million times in 200 seconds."
"For classical computers, it is much more difficult to compute the outcome of these operations because it requires computing the probability of being in any one of the 2^53 possible states, where the 53 comes from the number of qubits -- the exponential scaling is why people are interested in quantum computing to begin with," Foxen said. "This is done by matrix multiplication, which is expensive for classical computers as the matrices become large."
According to the new paper, the researchers used a method called cross-entropy benchmarking to compare the quantum circuit's output (a "bitstring") to its "corresponding ideal probability computed via simulation on a classical computer" to ascertain that the quantum computer was working correctly.
"We made a lot of design choices in the development of our processor that are really advantageous," said Chiaro. Among these advantages, he said, are the ability to experimentally tune the parameters of the individual qubits as well as their interactions.
While the experiment was chosen as a proof-of-concept for the computer, the research has resulted in a very real and valuable tool: a certified random number generator. Useful in a variety of fields, random numbers can ensure that encrypted keys can't be guessed, or that a sample from a larger population is truly representative, leading to optimal solutions for complex problems and more robust machine learning applications. The speed with which the quantum circuit can produce its randomized bit string is so great that there is no time to analyze and "cheat" the system.
"Quantum mechanical states do things that go beyond our day-to-day experience and so have the potential to provide capabilities and application that would otherwise be unattainable," commented Joe Incandela, UC Santa Barbara's vice chancellor for research. "The team has demonstrated the ability to reliably create and repeatedly sample complicated quantum states involving 53 entangled elements to carry out an exercise that would take millennia to do with a classical supercomputer. This is a major accomplishment. We are at the threshold of a new era of knowledge acquisition."
Looking ahead
With an achievement like "quantum supremacy," it's tempting to think that the UC Santa Barbara/Google researchers will plant their flag and rest easy. But for Foxen, Chiaro, Martinis and the rest of the UCSB/Google AI Quantum group, this is just the beginning.
"It's kind of a continuous improvement mindset," Foxen said. "There are always projects in the works." In the near term, further improvements to these "noisy" qubits may enable the simulation of interesting phenomena in quantum mechanics, such as thermalization, or the vast amount of possibility in the realms of materials and chemistry.
In the long term, however, the scientists are always looking to improve coherence times, or, at the other end, to detect and fix errors, which would take many additional qubits per qubit being checked. These efforts have been running parallel to the design and build of the quantum computer itself, and ensure the researchers have a lot of work before hitting their next milestone.
Read more at Science Daily
Oct 22, 2019
Training parents is key to helping children eat a variety of foods
Families dealing with the stress and frustration of their child's overly picky eating habits may have a new addition to their parental toolbox. Pediatric researchers recently described a brief group cognitive-behavioral therapy program that provides parents with specific techniques to improve their child's mealtime behaviors and expand the range of foods their children will eat. Although the study size was small, the parents involved reported "life-changing" improvements.
Researchers from Children's Hospital of Philadelphia (CHOP) and The University of Pennsylvania published this study in the August 2019 issue of Cognitive and Behavioral Practice.
"Our research shows the acceptability, feasibility and positive outcomes of the Picky Eaters Clinic, a seven-session, parent-only, group-based intervention intended to train parents of children with Avoidant/Restrictive Food Intake Disorder (ARFID)," said study leader Katherine Dahlsgaard, PhD, ABPP, Clinical Director of the Anxiety Behaviors Clinic at CHOP. "In the Clinic, parents are taught to act as behavioral therapists who promote long-term improvements in food acceptance and positive mealtime behaviors."
This study included 21 patients and their parents, who were referred to the Picky Eaters Clinic at CHOP. Families, including the child, attended a diagnostic evaluation and were assessed for treatment eligibility. The children ranged in age from 4 to 12 years and were diagnosed with ARFID, due to excessive picky eating and associated functional impairment.
The families reported that picky eating caused considerable stress. Parental stress resulted from: diet containing less than 20 foods; refusal of entire food groups (typically vegetables, meats or fruits); the need to make a separate meal; difficulty traveling, socializing or going to restaurants; high child distress/refusal to eat when presented with a new or non-preferred food; and lack of child's motivation to change or unwillingness to receive treatment.
The seven clinic sessions occurred over a 6-month period. The first four sessions were held one week apart; the fifth and sixth were spaced two 3 to 4 weeks apart, allowing families time to practice the assigned behavior strategies at home. Children were challenged at home to chew and swallow a portion of a new or non-preferred food and a successful challenge resulted in a post-meal reward. The majority chose screen time.
The seventh "reunion" session was held 3 months later, to allow parents to catch up and share gains. The researchers administered post-treatment feeding measures and a parent satisfaction survey at the last sessions.
Read more at Science Daily
Researchers from Children's Hospital of Philadelphia (CHOP) and The University of Pennsylvania published this study in the August 2019 issue of Cognitive and Behavioral Practice.
"Our research shows the acceptability, feasibility and positive outcomes of the Picky Eaters Clinic, a seven-session, parent-only, group-based intervention intended to train parents of children with Avoidant/Restrictive Food Intake Disorder (ARFID)," said study leader Katherine Dahlsgaard, PhD, ABPP, Clinical Director of the Anxiety Behaviors Clinic at CHOP. "In the Clinic, parents are taught to act as behavioral therapists who promote long-term improvements in food acceptance and positive mealtime behaviors."
This study included 21 patients and their parents, who were referred to the Picky Eaters Clinic at CHOP. Families, including the child, attended a diagnostic evaluation and were assessed for treatment eligibility. The children ranged in age from 4 to 12 years and were diagnosed with ARFID, due to excessive picky eating and associated functional impairment.
The families reported that picky eating caused considerable stress. Parental stress resulted from: diet containing less than 20 foods; refusal of entire food groups (typically vegetables, meats or fruits); the need to make a separate meal; difficulty traveling, socializing or going to restaurants; high child distress/refusal to eat when presented with a new or non-preferred food; and lack of child's motivation to change or unwillingness to receive treatment.
The seven clinic sessions occurred over a 6-month period. The first four sessions were held one week apart; the fifth and sixth were spaced two 3 to 4 weeks apart, allowing families time to practice the assigned behavior strategies at home. Children were challenged at home to chew and swallow a portion of a new or non-preferred food and a successful challenge resulted in a post-meal reward. The majority chose screen time.
The seventh "reunion" session was held 3 months later, to allow parents to catch up and share gains. The researchers administered post-treatment feeding measures and a parent satisfaction survey at the last sessions.
Read more at Science Daily
The secret of classic Belgian beers? Medieval super yeasts!
An international team of scientists, led by Prof. Kevin Verstrepen (VIB-KU-Leuven) and Prof. Steven Maere (VIB-UGent), has discovered that some of the most renowned classic Belgian beers, including Gueuze and Trappist ales, are fermented with a rare and unusual form of hybrid yeasts. These yeasts combine DNA of the traditional ale yeast, Saccharomyces cerevisiae, with that of more stress-resistant feral yeasts such as Saccharomyces kudriavzevii.
Mixed origins
"These yeasts are hybrids between two completely different species" says Dr. Jan Steensels (VIB -- KU Leuven Center for Microbiology), who coordinated the lab work of this study. "Think of lions and tigers making a super-baby."
Such interspecific hybridizations are rare and seem to be favored by the domestication process. In this case, the new hybrid yeasts combined important characteristics of both parental species, with the fermentation capacity of normal beer yeasts and the stress tolerance and capacity to form special aromas of more feral ancient yeasts like S. kudriavzevii that haphazardly made their way into the brewery.
The team, from the VIB-KU Leuven Center for Microbiology and the University of Munich, supported by industrial partners, has spent five years characterizing the different yeasts used in today's production of beer, wine, bread and biofuels. The genetic analysis of these yeasts was quite a piece of work, because none of the existing pipelines for DNA sequencing can deal with such mixed origins.
For this the team could, surprisingly, count on the plant expertise of professor Steven Maere, a bioinformatics expert from the VIB-UGent Center for Plant Systems Biology. Maere explains: "Plants have some of the most complex genomes of all living organisms. It is fascinating that complex interspecific hybrids with doubled genomes feature prominently both among domesticated yeasts and domesticated plants."
A surprise in DNA
"It was a bit of a surprise for us" says Dr. Brigida Gallone (VIB-KU Leuven Center for Microbiology), the lead author on the paper that appeared today in Nature Ecology and Evolution. "In 2016, we reported that most industrial yeasts belong to, or arose from the species Saccharomyces cerevisiae, the traditional baker's and brewer's yeast. We found that these industrial yeasts are quite different from their wild progenitors, with different subfamilies having adapted to beer, wine and bakery environments. We also noticed that some of the yeasts that were isolated from ancient Belgian beer styles, like Gueuze and Trappist beers, are even more unusual and contained DNA of two different yeast species."
"It really seems that these unique natural yeasts allowed the development of some of the most renowned beers that Belgium is so famous for," says Dr. Philippe Malcorps, Senior Scientist at the Global Innovation and Technology Center of AB InBev, the world's largest brewer. The team of Malcorps helped with the isolation of yeasts from some of their spontaneous fermentation beer cellars. Those natural super-yeasts are living witnesses of brewing from pre-industrial ages, adapted to harsh conditions of fermentation of the strong Trappist beers, or survival in the long lagering typical for Gueuze beers.
"One could say that the unique habitat in wooden fermentation barrels created by adventurous Medieval Belgian brewers allowed these new species to thrive until today," says Prof. Kevin Verstrepen (VIB-KU Leuven Center for Microbiology).
A history of yeasts
Apart from the special Belgian yeasts, the team also collected a large number of hybrids from S. eubayanus and S. cerevisiae, or from S. uvarum strongly adapted to cold fermentation. While it was already known that lager yeasts were hybrids, the complete DNA analysis of a large number of these yeasts showed how these specific hybrids originated in medieval Germany and later spread across different European breweries as the pilsner beers grew more popular.
"It is no coincidence that the origin of today's beer yeasts lies in Belgium and Germany, arguably the two countries that are most associated with the art of brewing," says Prof. Mathias Hutzler (TU Munich).
Read more at Science Daily
Mixed origins
"These yeasts are hybrids between two completely different species" says Dr. Jan Steensels (VIB -- KU Leuven Center for Microbiology), who coordinated the lab work of this study. "Think of lions and tigers making a super-baby."
Such interspecific hybridizations are rare and seem to be favored by the domestication process. In this case, the new hybrid yeasts combined important characteristics of both parental species, with the fermentation capacity of normal beer yeasts and the stress tolerance and capacity to form special aromas of more feral ancient yeasts like S. kudriavzevii that haphazardly made their way into the brewery.
The team, from the VIB-KU Leuven Center for Microbiology and the University of Munich, supported by industrial partners, has spent five years characterizing the different yeasts used in today's production of beer, wine, bread and biofuels. The genetic analysis of these yeasts was quite a piece of work, because none of the existing pipelines for DNA sequencing can deal with such mixed origins.
For this the team could, surprisingly, count on the plant expertise of professor Steven Maere, a bioinformatics expert from the VIB-UGent Center for Plant Systems Biology. Maere explains: "Plants have some of the most complex genomes of all living organisms. It is fascinating that complex interspecific hybrids with doubled genomes feature prominently both among domesticated yeasts and domesticated plants."
A surprise in DNA
"It was a bit of a surprise for us" says Dr. Brigida Gallone (VIB-KU Leuven Center for Microbiology), the lead author on the paper that appeared today in Nature Ecology and Evolution. "In 2016, we reported that most industrial yeasts belong to, or arose from the species Saccharomyces cerevisiae, the traditional baker's and brewer's yeast. We found that these industrial yeasts are quite different from their wild progenitors, with different subfamilies having adapted to beer, wine and bakery environments. We also noticed that some of the yeasts that were isolated from ancient Belgian beer styles, like Gueuze and Trappist beers, are even more unusual and contained DNA of two different yeast species."
"It really seems that these unique natural yeasts allowed the development of some of the most renowned beers that Belgium is so famous for," says Dr. Philippe Malcorps, Senior Scientist at the Global Innovation and Technology Center of AB InBev, the world's largest brewer. The team of Malcorps helped with the isolation of yeasts from some of their spontaneous fermentation beer cellars. Those natural super-yeasts are living witnesses of brewing from pre-industrial ages, adapted to harsh conditions of fermentation of the strong Trappist beers, or survival in the long lagering typical for Gueuze beers.
"One could say that the unique habitat in wooden fermentation barrels created by adventurous Medieval Belgian brewers allowed these new species to thrive until today," says Prof. Kevin Verstrepen (VIB-KU Leuven Center for Microbiology).
A history of yeasts
Apart from the special Belgian yeasts, the team also collected a large number of hybrids from S. eubayanus and S. cerevisiae, or from S. uvarum strongly adapted to cold fermentation. While it was already known that lager yeasts were hybrids, the complete DNA analysis of a large number of these yeasts showed how these specific hybrids originated in medieval Germany and later spread across different European breweries as the pilsner beers grew more popular.
"It is no coincidence that the origin of today's beer yeasts lies in Belgium and Germany, arguably the two countries that are most associated with the art of brewing," says Prof. Mathias Hutzler (TU Munich).
Read more at Science Daily
Unique brain cells linked to OCD and anxiety
According to the National Institute of Mental Health, 1 in 3 people experience debilitating anxiety -- the kind that prevents someone from going about their normal life. Women are also more at risk to suffer from anxiety. Yet the roots of anxiety and other anxiety-related diseases, such as Obsessive Compulsive Disorder (OCD), are still unclear. In a new study, University of Utah scientists discovered a new lineage of specialized brain cells, called Hoxb8-lineage microglia, and established a link between the lineage and OCD and anxiety in mice.
Mice with disabled Hoxb8-lineage microglia exhibited excessive overgrooming behavior. The symptom resembles behavior in humans with a type of OCD called trichotillomania, a disorder that causes people to obsessively pluck out their own hair. Their experiments proved that Hoxb8-lineage microglia prevent mice from displaying OCD behaviors. Additionally, they found that female sex hormones caused more severe OCD behaviors and induced added anxiety in the mice.
"More women than men experience debilitating anxiety at some point in their lives. Scientists want help these people to get their lives back. In this study were able to link anxiety to a dysfunction in a type of microglia, and to female sex hormones," said lead author Dimitri Traenkner, research assistant professor in the School of Biological Sciences at the University of Utah. "It opens up a new avenue for thinking about anxiety. Since we have this model, we have a way to test new drugs to help these mice and hopefully at some point, this will help people."
The study published today in Cell Reports.
Discovery of a new microglia lineage
Microglia are crucial during brain development in the womb -- they ensure that brain structures and neural circuitry all wire together correctly. Traenkner and colleagues showed that microglia belong to least two distinct sub-lineages of cells. One lineage called Hoxb8-lineage microglia makes up about 30% of all microglia in the brain but until now, no one knew whether they had any unique function.
Mario Capecchi, Nobel laureate and senior author of the study, had long suspected that Hoxb8-microglia were special. In previous research, he disabled Hoxb8-lineage microglia expecting some impact on development. But the mice seemed fine.
'We didn't really know what to make of the fact that mice without Hoxb8 appear so normal, until we noticed that they groom significantly more and longer than what would be considered healthy. And that's how the whole thing started," said Capecchi, who is also a distinguished professor of human genetics at the University of Utah Health.
This is the first study to describe microglia's role in OCD and anxiety behaviors in mice.
"Researchers have long suspected that microglia have a role in anxiety and neuropsychological disorders in humans because this cell type can release substances that may harm neurons. So, we were surprised to find that microglia actually protect from anxiety, they don't cause it," added Traenkner.
Female sex hormones drive symptom severity
The mice showed sex-linked severity in their symptoms; female mice's OCD symptoms were consistently more dramatic than in the males. Females also exhibited an additional anxiety symptom that was lacking in male mice -- the researchers designed and validated a new test showing that the pupils of female mice dilated dramatically, triggered by a fight-or-flight stress response.
To test whether sex hormones drove OCD and anxiety symptoms, Traenkner and colleagues manipulated estrogen and progesterone levels in the mice. They found that at male-levels, female mice's OCD and anxiety behaviors resembled the male response, and at female hormone levels, male mice's OCD behaviors looked more like the female's severe symptoms, and showed signs of anxiety.
"Our findings strongly argue for a mechanistic link between biological sex and genetic family history in the risk to develop an anxiety disorders," said Traenkner.
What does this mean for humans?
For many, anxiety drastically impacts their work, friends, family and lifestyle. Scientists and health care professionals are always looking for ways to help people get their lives back. This study of mouse models links anxiety to dysfunctional microglia. Down the line, the findings could spark new microglia-focused studies in patients with anxiety and, eventually, help to better treat this debilitating disorder.
Read more at Science Daily
Mice with disabled Hoxb8-lineage microglia exhibited excessive overgrooming behavior. The symptom resembles behavior in humans with a type of OCD called trichotillomania, a disorder that causes people to obsessively pluck out their own hair. Their experiments proved that Hoxb8-lineage microglia prevent mice from displaying OCD behaviors. Additionally, they found that female sex hormones caused more severe OCD behaviors and induced added anxiety in the mice.
"More women than men experience debilitating anxiety at some point in their lives. Scientists want help these people to get their lives back. In this study were able to link anxiety to a dysfunction in a type of microglia, and to female sex hormones," said lead author Dimitri Traenkner, research assistant professor in the School of Biological Sciences at the University of Utah. "It opens up a new avenue for thinking about anxiety. Since we have this model, we have a way to test new drugs to help these mice and hopefully at some point, this will help people."
The study published today in Cell Reports.
Discovery of a new microglia lineage
Microglia are crucial during brain development in the womb -- they ensure that brain structures and neural circuitry all wire together correctly. Traenkner and colleagues showed that microglia belong to least two distinct sub-lineages of cells. One lineage called Hoxb8-lineage microglia makes up about 30% of all microglia in the brain but until now, no one knew whether they had any unique function.
Mario Capecchi, Nobel laureate and senior author of the study, had long suspected that Hoxb8-microglia were special. In previous research, he disabled Hoxb8-lineage microglia expecting some impact on development. But the mice seemed fine.
'We didn't really know what to make of the fact that mice without Hoxb8 appear so normal, until we noticed that they groom significantly more and longer than what would be considered healthy. And that's how the whole thing started," said Capecchi, who is also a distinguished professor of human genetics at the University of Utah Health.
This is the first study to describe microglia's role in OCD and anxiety behaviors in mice.
"Researchers have long suspected that microglia have a role in anxiety and neuropsychological disorders in humans because this cell type can release substances that may harm neurons. So, we were surprised to find that microglia actually protect from anxiety, they don't cause it," added Traenkner.
Female sex hormones drive symptom severity
The mice showed sex-linked severity in their symptoms; female mice's OCD symptoms were consistently more dramatic than in the males. Females also exhibited an additional anxiety symptom that was lacking in male mice -- the researchers designed and validated a new test showing that the pupils of female mice dilated dramatically, triggered by a fight-or-flight stress response.
To test whether sex hormones drove OCD and anxiety symptoms, Traenkner and colleagues manipulated estrogen and progesterone levels in the mice. They found that at male-levels, female mice's OCD and anxiety behaviors resembled the male response, and at female hormone levels, male mice's OCD behaviors looked more like the female's severe symptoms, and showed signs of anxiety.
"Our findings strongly argue for a mechanistic link between biological sex and genetic family history in the risk to develop an anxiety disorders," said Traenkner.
What does this mean for humans?
For many, anxiety drastically impacts their work, friends, family and lifestyle. Scientists and health care professionals are always looking for ways to help people get their lives back. This study of mouse models links anxiety to dysfunctional microglia. Down the line, the findings could spark new microglia-focused studies in patients with anxiety and, eventually, help to better treat this debilitating disorder.
Read more at Science Daily
New drug-delivery technology promises efficient, targeted cancer treatment
A precise and non-toxic treatment that targets lung cancer cells at the nanoscale is able to effectively kill the cells even at a low dose.
Researchers from Washington State University and the Department of Energy's Pacific Northwest National Laboratory (PNNL) used tiny tubes made from organic molecules called peptoids to deliver cancer-killing drugs in a targeted manner.
The research, led by Yuehe Lin, professor in WSU's School of Mechanical and Materials Engineering, and Chun-Long Chen, a senior research scientist at PNNL and a joint faculty fellow at the University of Washington, was published as the cover story in the journal Small.
The biologically-inspired nanotubes, which are about a hundred thousand times thinner than a human hair, were rolled up from membrane-like nanosheets. The drug molecules, fluorescent dyes and cancer-targeting molecules were precisely placed within the nanotubes, enabling them to track the efficiency of drug delivery into the cancer cells.
The new technology allows the two drugs -- one for chemotherapy and the other for a less-invasive photodynamic therapy treatment -- to be delivered directly to the cancer cells. Photodynamic therapy uses a chemical that, when exposed to light, releases reactive oxygen species (ROS) that kill cancer cells. The researchers' dual-drug approach enabled the use of a lower dose of the cancer drugs than using a single drug, leading to effective killing of cancer cells with low toxicity.
"By precisely engineering these nanotubes with fluorescent dyes and cancer targeting molecules, scientists can clearly locate tumor cells and track how the drug regimen is performing," said Lin. "We can also track how nanotubes enter and deliver the drugs inside the cancer cell."
The team tested the nanotubes on lung cancer cells and found that they delivered the chemotherapy drug doxorubicin directly into the fast-dividing cancer cells, resulting in highly efficient cancer killing while using less chemotherapy drugs.
"This is a promising approach for precision targeting with little damage to healthy surrounding cells," said Lin.
While other nanomaterials, such as carbon nanotubes, have been used to deliver and track cancer-killing drugs, researchers have found that they are toxic to the body. Furthermore, they didn't do well at precisely recognizing molecules.
"By using these peptoids, we were able to develop highly programmable nanotubes and a biocompatible delivery mechanism," said Chen. "We also harnessed the high stability of peptoid and its well-controlled packing to develop nanotubes that are highly stable."
Read more at Science Daily
Researchers from Washington State University and the Department of Energy's Pacific Northwest National Laboratory (PNNL) used tiny tubes made from organic molecules called peptoids to deliver cancer-killing drugs in a targeted manner.
The research, led by Yuehe Lin, professor in WSU's School of Mechanical and Materials Engineering, and Chun-Long Chen, a senior research scientist at PNNL and a joint faculty fellow at the University of Washington, was published as the cover story in the journal Small.
The biologically-inspired nanotubes, which are about a hundred thousand times thinner than a human hair, were rolled up from membrane-like nanosheets. The drug molecules, fluorescent dyes and cancer-targeting molecules were precisely placed within the nanotubes, enabling them to track the efficiency of drug delivery into the cancer cells.
The new technology allows the two drugs -- one for chemotherapy and the other for a less-invasive photodynamic therapy treatment -- to be delivered directly to the cancer cells. Photodynamic therapy uses a chemical that, when exposed to light, releases reactive oxygen species (ROS) that kill cancer cells. The researchers' dual-drug approach enabled the use of a lower dose of the cancer drugs than using a single drug, leading to effective killing of cancer cells with low toxicity.
"By precisely engineering these nanotubes with fluorescent dyes and cancer targeting molecules, scientists can clearly locate tumor cells and track how the drug regimen is performing," said Lin. "We can also track how nanotubes enter and deliver the drugs inside the cancer cell."
The team tested the nanotubes on lung cancer cells and found that they delivered the chemotherapy drug doxorubicin directly into the fast-dividing cancer cells, resulting in highly efficient cancer killing while using less chemotherapy drugs.
"This is a promising approach for precision targeting with little damage to healthy surrounding cells," said Lin.
While other nanomaterials, such as carbon nanotubes, have been used to deliver and track cancer-killing drugs, researchers have found that they are toxic to the body. Furthermore, they didn't do well at precisely recognizing molecules.
"By using these peptoids, we were able to develop highly programmable nanotubes and a biocompatible delivery mechanism," said Chen. "We also harnessed the high stability of peptoid and its well-controlled packing to develop nanotubes that are highly stable."
Read more at Science Daily
Oct 21, 2019
DNA-reeling bacteria yield new insight on how superbugs acquire drug-resistance
A new study from Indiana University has revealed a previously unknown role a protein plays in helping bacteria reel in DNA in their environment -- like a fisherman pulling up a catch from the ocean.
The discovery was made possible by a new imaging method invented at IU that let scientists see for the first time how bacteria use their long and mobile appendages -- called pili -- to bind to, or "harpoon," DNA in the environment. The new study, reported Oct. 18 in the journal PLOS Genetics, focuses on how they reel their catch back in.
By revealing the mechanisms involved in this process, the study's authors said the results may help hasten work on new ways to stop bacterial infection.
"The issue of antibiotic resistance is very relevant to this work since the ability of pili to bind to, and 'reel in,' DNA is one of the major ways that bacteria evolve to thwart existing drugs," said Ankur Dalia, an assistant professor in the IU Bloomington College of Arts and Sciences' Department of Biology, who is senior author on the study. "An improved understanding of this 'reeling' activity can help inform strategies to stop it."
The act of gobbling up and incorporating genetic material from the environment -- known as natural transformation -- is an evolutionary process by which bacteria incorporate specific traits from other microorganisms, including genes that convey antibiotic resistance.
The need for new methods to stop bacterial infection is growing since overuse of existing antibiotics, which speeds how quickly infectious organisms evolve to outsmart these drugs, is causing the world to quickly run out of effective treatments. By 2050, it's estimated that 10 million people could die each year from antimicrobial resistance.
Although they may look like tiny arms under a microscope, Dalia said, pili are actually more akin to an erector set that is quickly put together and torn down over and over again. Each "piece" in the structure is a protein sub-unit called the major pilin that assembles into a filament called the pilus fiber.
"There are two main motors that had previously been implicated in this polymerization and depolymerization process," added Jennifer Chlebek, a Ph.D. student in Dalia's lab, who led the study. "In this study, we show that there is a third motor involved in the depolymerization process, and we start to unravel how it works."
The two previously characterized "motors" that control the pili's activity are the proteins PilB, which constructs the pili, and PilT, which deconstructs it. These motors run by utilizing ATP, a source of cellular energy. In this study, IU researchers showed that stopping this process, which switches off the power to PilT, does not prevent the retraction of the pili, as previously thought.
Instead, they found that a third motor protein, called PilU, can power pilus retraction even if PilT is inactive, although this retraction occurs about five times more slowly. The researchers also found that switching off power to both retraction proteins slows the retraction process to a painstaking rate of 50 times slower. An unaltered pilus retracts at a rate of one-fifth of a micron per second.
Moreover, the study found that switching off PilU affects the strength of pilus retraction, which was measured by collaborators at Brooklyn College. The study also showed that PilU and PilT do not form a "hybrid" motor, but instead that these two independent motors somehow coordinate with one another to mediate pilus retraction.
"While the PilU protein had previously been implicated in pilus activity, its exact role has been difficult to determine because cells that lack this protein generally only have very subtle effects," Chlebek added. "Our observation that PilU can support pilus retraction in a mutant strain, when we threw a wrench in the PilT motor, was the key to unlocking how this protein aids in the depolymerization of pili."
The ability to precisely measure the pili's retraction rate -- and therefore precisely measure the impact of altering the proteins that affect this process -- was made possible by the ability to see pili under a microscope, which was not possible until the breakthrough imaging method invented at IU.
"The ability to fluorescently dye the pili was huge," Dalia said. "It allowed us to not only see the pili's activity but also measure it in ways which simply would not have been possible in the past."
Read more at Science Daily
The discovery was made possible by a new imaging method invented at IU that let scientists see for the first time how bacteria use their long and mobile appendages -- called pili -- to bind to, or "harpoon," DNA in the environment. The new study, reported Oct. 18 in the journal PLOS Genetics, focuses on how they reel their catch back in.
By revealing the mechanisms involved in this process, the study's authors said the results may help hasten work on new ways to stop bacterial infection.
"The issue of antibiotic resistance is very relevant to this work since the ability of pili to bind to, and 'reel in,' DNA is one of the major ways that bacteria evolve to thwart existing drugs," said Ankur Dalia, an assistant professor in the IU Bloomington College of Arts and Sciences' Department of Biology, who is senior author on the study. "An improved understanding of this 'reeling' activity can help inform strategies to stop it."
The act of gobbling up and incorporating genetic material from the environment -- known as natural transformation -- is an evolutionary process by which bacteria incorporate specific traits from other microorganisms, including genes that convey antibiotic resistance.
The need for new methods to stop bacterial infection is growing since overuse of existing antibiotics, which speeds how quickly infectious organisms evolve to outsmart these drugs, is causing the world to quickly run out of effective treatments. By 2050, it's estimated that 10 million people could die each year from antimicrobial resistance.
Although they may look like tiny arms under a microscope, Dalia said, pili are actually more akin to an erector set that is quickly put together and torn down over and over again. Each "piece" in the structure is a protein sub-unit called the major pilin that assembles into a filament called the pilus fiber.
"There are two main motors that had previously been implicated in this polymerization and depolymerization process," added Jennifer Chlebek, a Ph.D. student in Dalia's lab, who led the study. "In this study, we show that there is a third motor involved in the depolymerization process, and we start to unravel how it works."
The two previously characterized "motors" that control the pili's activity are the proteins PilB, which constructs the pili, and PilT, which deconstructs it. These motors run by utilizing ATP, a source of cellular energy. In this study, IU researchers showed that stopping this process, which switches off the power to PilT, does not prevent the retraction of the pili, as previously thought.
Instead, they found that a third motor protein, called PilU, can power pilus retraction even if PilT is inactive, although this retraction occurs about five times more slowly. The researchers also found that switching off power to both retraction proteins slows the retraction process to a painstaking rate of 50 times slower. An unaltered pilus retracts at a rate of one-fifth of a micron per second.
Moreover, the study found that switching off PilU affects the strength of pilus retraction, which was measured by collaborators at Brooklyn College. The study also showed that PilU and PilT do not form a "hybrid" motor, but instead that these two independent motors somehow coordinate with one another to mediate pilus retraction.
"While the PilU protein had previously been implicated in pilus activity, its exact role has been difficult to determine because cells that lack this protein generally only have very subtle effects," Chlebek added. "Our observation that PilU can support pilus retraction in a mutant strain, when we threw a wrench in the PilT motor, was the key to unlocking how this protein aids in the depolymerization of pili."
The ability to precisely measure the pili's retraction rate -- and therefore precisely measure the impact of altering the proteins that affect this process -- was made possible by the ability to see pili under a microscope, which was not possible until the breakthrough imaging method invented at IU.
"The ability to fluorescently dye the pili was huge," Dalia said. "It allowed us to not only see the pili's activity but also measure it in ways which simply would not have been possible in the past."
Read more at Science Daily
Gimme six! Researchers discover aye-aye's extra finger
 |
| Aye-aye. |
Aye-ayes are unusual animals from the get-go: these extremely rare lemurs are known for their constantly growing incisors, large ears, and strange hands -- particularly for the slender, elongated middle fingers that they use for locating and spearing grubs inside trees.
"The aye-aye has the craziest hand of any primate," says Adam Hartstone-Rose, associate professor of biological sciences at NC State and lead author of a paper describing the work. "Their fingers have evolved to be extremely specialized -- so specialized, in fact, that they aren't much help when it comes to moving through trees. When you watch them move, it looks like a strange lemur walking on spiders."
Hartstone-Rose and NC State post-doctoral researcher Edwin Dickinson were studying the tendons that lead to the aye-aye's unusual hands when they noticed that one of the tendons branched off toward a small structure on the wrist. Using traditional dissection digital imaging techniques on six aye-ayes, the researchers found that the structure in question is composed of both bone and cartilage, and has musculature that allows it to move in three directions -- much the same way that human thumbs move.
"Using these digital techniques allows us to visualize these structures in three dimensions, and to understand the organization of the muscles which provide movement to the digit," says Dickinson, who built the digital model of the anatomy and is co-first author of the paper.
"The pseudothumb is definitely more than just a nub," Hartstone-Rose says. "It has both a bone and cartilaginous extension and three distinct muscles that move it. The pseudothumb can wriggle in space and exert an amount of force equivalent to almost half the aye-aye's body weight. So it would be quite useful for gripping."
The team examined aye-aye specimens from both sexes, ranging in age from juvenile to adult, and found the same structure in both the left and right hands of each one.
According to Hartstone-Rose and Dickinson, the aye-aye may have developed the pseudothumb to compensate for its other, overspecialized fingers.
"Other species, like the panda bear, have developed the same extra digit to aid in gripping because the standard bear paw is too generalized to allow the dexterity necessary for grasping," Hartstone-Rose says. "And moles and some extinct swimming reptiles have added extra digits to widen the hand for more efficient digging or swimming. In this case, the aye-aye's hand is so specialized for foraging an extra digit for mobility became necessary.
Read more at Science Daily
'Artificial leaf' successfully produces clean gas
A widely-used gas that is currently produced from fossil fuels can instead be made by an 'artificial leaf' that uses only sunlight, carbon dioxide and water, and which could eventually be used to develop a sustainable liquid fuel alternative to petrol.
The carbon-neutral device sets a new benchmark in the field of solar fuels, after researchers at the University of Cambridge demonstrated that it can directly produce the gas -- called syngas -- in a sustainable and simple way.
Rather than running on fossil fuels, the artificial leaf is powered by sunlight, although it still works efficiently on cloudy and overcast days. And unlike the current industrial processes for producing syngas, the leaf does not release any additional carbon dioxide into the atmosphere. The results are reported in the journal Nature Materials.
Syngas is currently made from a mixture of hydrogen and carbon monoxide, and is used to produce a range of commodities, such as fuels, pharmaceuticals, plastics and fertilisers.
"You may not have heard of syngas itself but every day, you consume products that were created using it. Being able to produce it sustainably would be a critical step in closing the global carbon cycle and establishing a sustainable chemical and fuel industry," said senior author Professor Erwin Reisner from Cambridge's Department of Chemistry, who has spent seven years working towards this goal.
The device Reisner and his colleagues produced is inspired by photosynthesis -- the natural process by which plants use the energy from sunlight to turn carbon dioxide into food.
On the artificial leaf, two light absorbers, similar to the molecules in plants that harvest sunlight, are combined with a catalyst made from the naturally abundant element cobalt.
When the device is immersed in water, one light absorber uses the catalyst to produce oxygen. The other carries out the chemical reaction that reduces carbon dioxide and water into carbon monoxide and hydrogen, forming the syngas mixture.
As an added bonus, the researchers discovered that their light absorbers work even under the low levels of sunlight on a rainy or overcast day.
"This means you are not limited to using this technology just in warm countries, or only operating the process during the summer months," said PhD student Virgil Andrei, first author of the paper. "You could use it from dawn until dusk, anywhere in the world."
The research was carried out in the Christian Doppler Laboratory for Sustainable SynGas Chemistry in the University's Department of Chemistry. It was co-funded by the Austrian government and the Austrian petrochemical company OMV, which is looking for ways to make its business more sustainable.
"OMV has been an avid supporter of the Christian Doppler Laboratory for the past seven years. The team's fundamental research to produce syngas as the basis for liquid fuel in a carbon neutral way is ground-breaking," said Michael-Dieter Ulbrich, Senior Advisor at OMV.
Other 'artificial leaf' devices have also been developed, but these usually only produce hydrogen. The Cambridge researchers say the reason they have been able to make theirs produce syngas sustainably is thanks the combination of materials and catalysts they used.
These include state-of-the-art perovskite light absorbers, which provide a high photovoltage and electrical current to power the chemical reaction by which carbon dioxide is reduced to carbon monoxide, in comparison to light absorbers made from silicon or dye-sensitised materials. The researchers also used cobalt as their molecular catalyst, instead of platinum or silver. Cobalt is not only lower-cost, but it is better at producing carbon monoxide than other catalysts.
The team is now looking at ways to use their technology to produce a sustainable liquid fuel alternative to petrol.
Syngas is already used as a building block in the production of liquid fuels. "What we'd like to do next, instead of first making syngas and then converting it into liquid fuel, is to make the liquid fuel in one step from carbon dioxide and water," said Reisner, who is also a Fellow of St John's College.
Although great advances are being made in generating electricity from renewable energy sources such as wind power and photovoltaics, Reisner says the development of synthetic petrol is vital, as electricity can currently only satisfy about 25% of our total global energy demand. "There is a major demand for liquid fuels to power heavy transport, shipping and aviation sustainably," he said.
Read more at Science Daily
The carbon-neutral device sets a new benchmark in the field of solar fuels, after researchers at the University of Cambridge demonstrated that it can directly produce the gas -- called syngas -- in a sustainable and simple way.
Rather than running on fossil fuels, the artificial leaf is powered by sunlight, although it still works efficiently on cloudy and overcast days. And unlike the current industrial processes for producing syngas, the leaf does not release any additional carbon dioxide into the atmosphere. The results are reported in the journal Nature Materials.
Syngas is currently made from a mixture of hydrogen and carbon monoxide, and is used to produce a range of commodities, such as fuels, pharmaceuticals, plastics and fertilisers.
"You may not have heard of syngas itself but every day, you consume products that were created using it. Being able to produce it sustainably would be a critical step in closing the global carbon cycle and establishing a sustainable chemical and fuel industry," said senior author Professor Erwin Reisner from Cambridge's Department of Chemistry, who has spent seven years working towards this goal.
The device Reisner and his colleagues produced is inspired by photosynthesis -- the natural process by which plants use the energy from sunlight to turn carbon dioxide into food.
On the artificial leaf, two light absorbers, similar to the molecules in plants that harvest sunlight, are combined with a catalyst made from the naturally abundant element cobalt.
When the device is immersed in water, one light absorber uses the catalyst to produce oxygen. The other carries out the chemical reaction that reduces carbon dioxide and water into carbon monoxide and hydrogen, forming the syngas mixture.
As an added bonus, the researchers discovered that their light absorbers work even under the low levels of sunlight on a rainy or overcast day.
"This means you are not limited to using this technology just in warm countries, or only operating the process during the summer months," said PhD student Virgil Andrei, first author of the paper. "You could use it from dawn until dusk, anywhere in the world."
The research was carried out in the Christian Doppler Laboratory for Sustainable SynGas Chemistry in the University's Department of Chemistry. It was co-funded by the Austrian government and the Austrian petrochemical company OMV, which is looking for ways to make its business more sustainable.
"OMV has been an avid supporter of the Christian Doppler Laboratory for the past seven years. The team's fundamental research to produce syngas as the basis for liquid fuel in a carbon neutral way is ground-breaking," said Michael-Dieter Ulbrich, Senior Advisor at OMV.
Other 'artificial leaf' devices have also been developed, but these usually only produce hydrogen. The Cambridge researchers say the reason they have been able to make theirs produce syngas sustainably is thanks the combination of materials and catalysts they used.
These include state-of-the-art perovskite light absorbers, which provide a high photovoltage and electrical current to power the chemical reaction by which carbon dioxide is reduced to carbon monoxide, in comparison to light absorbers made from silicon or dye-sensitised materials. The researchers also used cobalt as their molecular catalyst, instead of platinum or silver. Cobalt is not only lower-cost, but it is better at producing carbon monoxide than other catalysts.
The team is now looking at ways to use their technology to produce a sustainable liquid fuel alternative to petrol.
Syngas is already used as a building block in the production of liquid fuels. "What we'd like to do next, instead of first making syngas and then converting it into liquid fuel, is to make the liquid fuel in one step from carbon dioxide and water," said Reisner, who is also a Fellow of St John's College.
Although great advances are being made in generating electricity from renewable energy sources such as wind power and photovoltaics, Reisner says the development of synthetic petrol is vital, as electricity can currently only satisfy about 25% of our total global energy demand. "There is a major demand for liquid fuels to power heavy transport, shipping and aviation sustainably," he said.
Read more at Science Daily
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