Culture

A material way to make Mars habitable

image: Polar ice caps on Mars are a combination of water ice and frozen CO2. Like its gaseous form, frozen CO2 allows sunlight to penetrate while trapping heat. In the summer, this solid-state greenhouse effect creates pockets of warming under the ice, seen here as black dots in the ice.

Image: 
Harvard SEAS

People have long dreamed of re-shaping the Martian climate to make it livable for humans. Carl Sagan was the first outside of the realm of science fiction to propose terraforming. In a 1971 paper, Sagan suggested that vaporizing the northern polar ice caps would "yield ~10 s g cm-2 of atmosphere over the planet, higher global temperatures through the greenhouse effect, and a greatly increased likelihood of liquid water."

Sagan's work inspired other researchers and futurists to take seriously the idea of terraforming. The key question was: are there enough greenhouse gases and water on Mars to increase its atmospheric pressure to Earth-like levels?

In 2018, a pair of NASA-funded researchers from the University of Colorado, Boulder and Northern Arizona University found that processing all the sources available on Mars would only increase atmospheric pressure to about 7 percent that of Earth - far short of what is needed to make the planet habitable.

Terraforming Mars, it seemed, was an unfulfillable dream.

Now, researchers from the Harvard University, NASA's Jet Propulsion Lab, and the University of Edinburgh, have a new idea. Rather than trying to change the whole planet, what if you took a more regional approach?

The researchers suggest that regions of the Martian surface could be made habitable with a material -- silica aerogel -- that mimics Earth's atmospheric greenhouse effect. Through modeling and experiments, the researchers show that a two to three-centimeter-thick shield of silica aerogel could transmit enough visible light for photosynthesis, block hazardous ultraviolet radiation, and raise temperatures underneath permanently above the melting point of water, all without the need for any internal heat source.

The paper is published in Nature Astronomy.

"This regional approach to making Mars habitable is much more achievable than global atmospheric modification," said Robin Wordsworth, Assistant Professor of Environmental Science and Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Department of Earth and Planetary Science. "Unlike the previous ideas to make Mars habitable, this is something that can be developed and tested systematically with materials and technology we already have."

"Mars is the most habitable planet in our Solar System besides Earth," said Laura Kerber, Research Scientist at NASA's Jet Propulsion Laboratory. "But it remains a hostile world for many kinds of life. A system for creating small islands of habitability would allow us to transform Mars in a controlled and scalable way."

The researchers were inspired by a phenomenon that already occurs on Mars.

Unlike Earth's polar ice caps, which are made of frozen water, polar ice caps on Mars are a combination of water ice and frozen CO2. Like its gaseous form, frozen CO2 allows sunlight to penetrate while trapping heat. In the summer, this solid-state greenhouse effect creates pockets of warming under the ice.

"We started thinking about this solid-state greenhouse effect and how it could be invoked for creating habitable environments on Mars in the future," said Wordsworth. "We started thinking about what kind of materials could minimize thermal conductivity but still transmit as much light as possible."

The researchers landed on silica aerogel, one of the most insulating materials ever created.

Silica aerogels are 97 percent porous, meaning light moves through the material but the interconnecting nanolayers of silicon dioxide infrared radiation and greatly slow the conduction of heat. These aerogels are used in several engineering applications today, including NASA's Mars Exploration Rovers.

"Silica aerogel is a promising material because its effect is passive," said Kerber. "It wouldn't require large amounts of energy or maintenance of moving parts to keep an area warm over long periods of time."

Using modeling and experiments that mimicked the Martian surface, the researchers demonstrated that a thin layer of this material increased average temperatures of mid-latitudes on Mars to Earth-like temperatures.

"Spread across a large enough area, you wouldn't need any other technology or physics, you would just need a layer of this stuff on the surface and underneath you would have permanent liquid water," said Wordsworth.

This material could be used to build habitation domes or even self-contained biospheres on Mars on Mars.

"There's a whole host of fascinating engineering questions that emerge from this," said Wordsworth.

Next, the team aims to test the material in Mars-like climates on Earth, such as the dry valleys of Antarctica or Chile.

Wordsworth points out that any discussion about making Mars habitable for humans and Earth life also raises important philosophical and ethical questions about planetary protection.

"If you're going to enable life on the Martian surface, are you sure that there's not life there already? If there is, how do we navigate that," asked Wordsworth. "The moment we decide to commit to having humans on Mars, these questions are inevitable."

Credit: 
Harvard John A. Paulson School of Engineering and Applied Sciences

Stripping down bacterial armor: A new way to fight anthrax

A new study led by Dr. Antonella Fioravanti in the lab of Prof. Han Remaut (VIB-VUB Center for Structural Biology) has shown that removing the armor of the bacterium that causes anthrax slows its growth and negatively affects its ability to cause disease. This work will be published in the prestigious journal Nature Microbiology can lead the way to new, effective ways of fighting anthrax and various other diseases.

A deadly disease

Anthrax is a deadly and highly resilient disease, caused by the spore-forming bacterium Bacillus anthracis. Historically, it was a major cause of death in humans and cattle. Today it is much less prevalent thanks to better hygiene and the immunization of cattle. Nevertheless, anthrax remains a naturally occurring disease that affects wildlife and livestock animals around the world. In humans, it presents a health concern primarily as a skin infection in people handling contaminated animal products, or more rarely as deadly systemic infection when ingested or inhaled.

The toughness of the spores and the lethality of an anthrax infection via inhalation unfortunately spurred its development as biological weapon in the mid-twentieth century. Although the development and stockpiling of anthrax as a bio-weapon has been banned by the international community, these regulations are violated at times. Because treatment options are limited and not effective in most cases, this means anthrax remains a potential bioterrorism threat.

A weapon-evading armor

As part of its strategy to evade the weapons of the immune system, the anthrax bacterium cloaks itself with a complex, dynamic armor. A poorly understood component of this armor is the Sap S-layer, a single layer of protein that forms a shell around the bacterium. In this study, researchers successfully applied Nanobodies® - small antibody fragments - to control the assembly of the bacterial armor and study its structure. The Nanobodies were not only effective in preventing the armor from forming, but also proved highly efficient in breaking down existing S-layers. When applied to live bacteria, breaking down the armor slowed bacterial growth and led to drastic changes in the surface of the bacterial cell.

Antonella Fioravanti (VIB-VUB), who led the research, shares her excitement: "I was over the moon. I created these Nanobodies as a tool to study the Sap S-layer, but that they would also inhibit bacterial growth was an unexpected bonus".

The effects were so striking that the Nanobodies were tested as a treatment in mice infected with B. anthracis. "The results were amazing, all treated mice recovered from lethal anthrax within days," says Filip Van Hauwermeiren, who performed the infection studies. "We had been studying ways to stop the lethality of anthrax but had never seen such striking effects as with these Nanobodies," adds his supervisor Mohamed Lamkanfi (previously VIB-UGhent Center for Inflammation Research, now at Janssen Pharmaceutica and Ghent University).

New targets in an old battle

These findings represent a step forward in a quest that started in the 19th century. When Robert Koch proved in 1876 that bacteria were causal agents of infectious disease, it was B. anthracis he was studying. In 1881, Louis Pasteur famously showed the public that exposure to inactivated B. anthracis protected livestock against anthrax. Still, a safe anthrax vaccine is not available to the broad public and treating acute infections in non-vaccinated persons is problematic. It requires long treatments with antibiotics which have poor success rates. Therapeutics derived from the Nanobodies discovered in this study may one day fill this treatment gap. Moreover, targeting the S-layer with Nanobodies may be successful in the fight against other bacteria with an S-layer armor. For example, the lab is currently exploring S-layer targeting Nanobodies in Clostridium difficile which causes life-threatening colitis.

Finally, the success of the experiments in this study have motivated researchers to look for other vulnerable targets on bacterial cell surfaces. Prof. Han Remaut explains: "Proteins on the surface of bacteria are interesting antibacterial targets because they are directly accessible. Targeting these proteins means that we have to worry less about that various ways that bacteria are preventing drugs from getting into the cell."

Credit: 
VIB (the Flanders Institute for Biotechnology)

Environment, not evolution, might underlie some human-ape differences

Apes' abilities have been unfairly measured, throwing into doubt the assumed belief that human infants are superior to adult chimpanzees, according to a new study by leaders in the field of ape cognition.

Researchers studied published work comparing human and ape social cognition and came to the conclusion the studies had got it wrong.

They say it should come as no surprise that apes raised in institutions would not perform well compared with humans raised in western families, especially when tested with western cultural practices, for example, gestures such as pointing.

The study is by Professor Kim Bard, a Comparative Developmental Psychologist at the University of Portsmouth, Professor Bill Hopkins, at University of Texas MD Anderson Cancer Center, in the USA, and lead author Dr David Leavens, at University of Sussex.

It is published in the current edition of Animal Cognition.

The researchers argue that it's possible that apes and humans are equally capable in some aspects of social cognition, for example, social signalling - pointing at a desired object - and scientists have misjudged their abilities because of an underlying bias and poor experimental designs.

They also suggest that without a rigorous, scientific approach to designing experiments and interpreting results, comparative psychology fails to contribute to our understanding of human uniqueness.

Professor Bard said: "Children are taught in primary school how to design a scientific experiment so that the results can be trusted and are reliable, for example, to demonstrate that sunlight is necessary for plants to grow. If you want to know whether sunflowers or tomato plants grow faster in a classroom, therefore, you have to give them equal amounts of sunlight. A bad experiment would be to put all the tomato pots in a dark corner and all the sunflower pots near a sunlit window. You can't answer the question because the tomato and sunflower plants were treated differently in the amount of sunlight they got.

"In social cognition tests, previous experience with cultural practices, like pointing, enhances performance. What has happened in countless studies comparing human and ape social cognition is the rules of experimental design have been forgotten. Studies have combined experience and species, for example, designing an experiment comparing humans (who, in our culture, have been given pointing experience) and apes (raised without any pointing experience) and then claiming (falsely) to have demonstrated a species difference in social cognition.

"Most studies, comparing apes with human children, for instance, have been poorly designed, with different relevant experiences given to each species, testing them at different ages in many cases, and then claiming to have found a difference in social cognition between humans and apes, but the species haven't been treated similiarly before or during the tests.

"These studies suffer from the same type of prejudice that once existed in studies of human intelligence, which started from a biased position of assuming northern Europeans were innately more intelligent than southern Europeans. We argue the same type of bias is apparent in cross-species studies."

The researchers say it's vital scientists realise that environmental experiences vary among humans (both between children and adults, and between people with different cultural experiences) and among apes (also from young to old, and between apes with different experiences).

Examples of the widespread weakness, or a 'pervasive collapse' in how experiments are being designed and in how the results are interpreted include samples being of different ages, being set markedly different tests, and being tested in different conditions. Time and again, such studies have attributed differences in results to evolutionary history, when the experimental design has not made alll other relevant variables comparable.

Professor Bard said: "Historically, many researchers have claimed humans are superior to apes in social intelligence, but the research is based on studies of captive adult apes isolated from European-style social interaction and human (usually children) from rich western cities. These experiment designs are simply not valid for the comparative study of species differences.

"If an ape from an ape orphanage doesn't appear to understand a communicative signal that western, middle class humans commonly use, it might not mean the ape is socially less able than a human, because there are many non-western humans that also don't use these signals. To truly understand the abilities of each species, research needs to examine specific individual learning histories within specific ecological circumstances for both humans and for apes.

"We urge researchers to stop using fallacious research designs and reasoning in studies of comparative cognition."

Credit: 
University of Portsmouth

Study demonstrates stress reduction benefits from petting dogs, cats

image: WSU students interact with a dog.

Image: 
WSU

College is stressful. Students have classes, papers, and exams. But they also often have work, bills to pay, and so many other pressures common in modern life.

Many universities have instituted "Pet Your Stress Away" programs, where students can come in and interact with cats and/or dogs to help alleviate some of the strain.

Scientists at Washington State University have recently demonstrated that, in addition to improving students' moods, these programs can actually get "under the skin" and have stress-relieving physiological benefits.

"Just 10 minutes can have a significant impact," said Patricia Pendry, an associate professor in WSU's Department of Human Development. "Students in our study that interacted with cats and dogs had a significant reduction in cortisol, a major stress hormone."

Pendry published these findings with WSU graduate student Jaymie Vandagriff last month in AERA Open, an open access journal published by the American Educational Research Association.

This is the first study that has demonstrated reductions in students' cortisol levels during a real-life intervention rather than in a laboratory setting.

The study involved 249 college students randomly divided into four groups. The first group received hands-on interaction in small groups with cats and dogs for 10 minutes. They could pet, play with, and generally hang out with the animals as they wanted.

To compare effects of different exposures to animals, the second group observed other people petting animals while they waited in line for their turn. The third group watched a slideshow of the same animals available during the intervention, while the fourth group was "waitlisted."

Those students waited for their turn quietly for 10 minutes without their phones, reading materials, or other stimuli, but were told they would experience animal interaction soon.

Several salivary cortisol samples were collected from each participant, starting in the morning when they woke up. Once all the data was crunched from the various samples, the students who interacted directly with the pets showed significantly less cortisol in their saliva after the interaction. These results were found even while considering that some students may have had very high or low levels to begin with.

"We already knew that students enjoy interacting with animals, and that it helps them experience more positive emotions," Pendry said. "What we wanted to learn was whether this exposure would help students reduce their stress in a less subjective way. And it did, which is exciting because the reduction of stress hormones may, over time, have significant benefits for physical and mental health."

Now Pendry and her team are continuing this work by examining the impact of a four-week-long animal-assisted stress prevention program. Preliminary results are very positive, with a follow-up study showing that the findings of the recently published work hold up.

They hope to publish the final results of that work in the near future.

Credit: 
Washington State University

Does rearranging chromosomes affect their function?

image: The pyramids represent chromatin domains in the wild-type situation. The reflection in the water below represents the rearrangements in the mutant fruit fly chromosomes. At first glance the (regulatory) landscapes look very similar, but there are lots of changes to the topology, and yet these have little impact on the nature of the landscape (gene expression) in many cases.
Beata Edyta Mierzwa in collaboration with EMBL.

Image: 
Beata Edyta Mierzwa in collaboration with EMBL

Molecular biologists long thought that domains in the genome's 3D organisation control how genes are expressed. After studying highly rearranged chromosomes in fruit flies, EMBL researchers now reveal that while this is the case for some genes, their results challenge the generality of this for many others. Their results, published in Nature Genetics on 15 July, reveal an uncoupling between the 3D genome organisation - also called chromatin topology - and gene expression.

Our chromosomes are compartmentalised into domains. Regulatory regions of the DNA that control gene expression - so-called enhancers - are often located in the same chromatin domains (called topologically associated domains) as their target genes. To date, there are a number of interesting examples where domains restrict the activity of enhancers to only the genes within their domain.

To test the generality of these findings more systematically, researchers from the Furlong and Korbel groups at EMBL took advantage of genetic tools in the fruit fly to study highly rearranged mutant chromosomes. Yad Ghavi-Helm, Alek Jankowski, Sascha Meiers and colleagues found that changes in chromatin domains were not predictive of changes in gene expression. This means that besides domains, there must be other mechanisms in place that control the specificity of interactions between enhancers and their target genes.

Shaking the dogma

"These results question the generality of a current dogma in the field, that chromatin domains (TADs) are essential to constrain and restrict enhancer function," says Eileen Furlong, the EMBL group leader who led the study.

"We were able to show that major changes in the 3D organisation of the genome had surprisingly little effect on the expression of most genes, at least in this biological context. The results indicate that while some genes are affected, many appear resistant to rearrangements in their chromatin domain, and that only a small fraction of genes are sensitive to such changes in their topology."

Enhancers are not that promiscuous

This raises many interesting questions in the field of chromatin topology, for example: what are these other mechanisms that control the interactions between enhancers and their target genes? Many enhancers do not appear to be promiscuous: they do not link to just any target gene, but rather have preferred partners. The team will continue to dissect this by using genetics, optogenetics (a technique to control protein activity with laser light) and single-cell approaches. This will allow them to study the impact of many more perturbations to chromatin topology in both cis and trans.

Credit: 
European Molecular Biology Laboratory

Wearing hearing aid may help protect brain in later life

A new study has concluded that people who wear a hearing aid for age-related hearing problems maintain better brain function over time than those who do not.

It builds on important research in recent years pulled together by the Lancet Commission on Dementia Prevention, Intervention and Care, through which hearing loss emerged as an important risk factor for dementia. This research suggests that wearing a hearing aid may mitigate that risk.

The research was conducted by the University of Exeter and King's College London and is presented at the Alzheimer's Association International Conference in LA. In the PROTECT online study of 25,000 people aged 50 or over.

The findings provide early evidence that encouraging people to wear an effective hearing aid may help to protect their brains and reduce their risk of dementia.

Both groups undertook annual cognitive tests over two years. After that time, the group who wore hearing aids performed better in measures assessing working memory and aspects of attention than those who did not. On one attention measure, people who wore hearing aids showed faster reaction times - in everyday terms, this is a reflection of concentration, for example, 'straining to hear a sound', 'peering closely at an object of great interest', 'listening intently to someone speaking'.

PROTECT lead Dr Anne Corbett, from the University of Exeter, said: "Previous research has shown that hearing loss is linked to a loss of brain function, memory and an increased risk of dementia. Our work is one of the largest studies to look at the impact of wearing a hearing aid, and suggests that wearing a hearing aid could actually protect the brain. We now need more research and a clinical trial to test this and perhaps feed into policy to help keep people healthy in later life."

Professor Clive Ballard, of the University of Exeter Medical School, said: "We know that we could reduce dementia risk by a third if we all took action from mid life. This research is part of an essential body of work to find out what really works to keep our brains healthy. This is an early finding and needs more investigation, yet it has exciting potential. The message here is that if you're advised you need a hearing aid, find one that works for you. At the very least it will improve your hearing and it could help keep your brain sharp too."

Credit: 
University of Exeter

Algae as a resource: Chemical tricks from the sea

image: This is Christian Stanetty.

Image: 
Clemens Cziegler / TU Wien

Algae form the basis of the marine ecosystem, and store more carbon than all land plants put together. The algae's carbohydrates are broken down by bacteria, which thereby turn them into an important energy source for the entire marine food chain. What exactly happens chemically during this degradation of algae biomass was, however, previously unknown.

Now, an international research team has succeeded in analysing and understanding the entire route of degradation of an important polysaccharide. A large number of enzymes is required for this process and now, for the first time, is has been possible to clarify their biochemical function. With this knowledge, it will become possible to use algae as a resource: they can be used for fermentations, to produce valuable types of sugar or, in the future, even be processed towards bioplastics. The overall aim is to achieve an environmentally friendly circular economy in which renewable raw materials are used in as diverse a manner as possible.

The research project was led by the University of Greifswald, in collaboration with TU Wien, the Max Planck Institute for Marine Microbiology (Bremen), the University of Bremen, research centre MARUM - Center for Marine Environmental Sciences (Bremen) and Roscoff Marine Station (France). The results of the research were recently published in the specialist journal Nature Chemical Biology.

Breaking down macromolecules into their building blocks

For most people, algae usually seem rather unattractive - for instance, when they proliferate to form a colossal algal bloom near the coast, and in particular close to beaches. However, in future, carpets of algae may be used as a valuable source of material for industry. "In order to use algae, you need to break down the large molecules that they produce into usable individual components," explains Christian Stanetty from the Institute of Applied Synthetic Chemistry at TU Wien. "This is a highly complicated process but, fortunately, we have nature as an example: that's to say, certain bacteria can do this brilliantly."

The international research team deciphered the way the marine bacteria Formosa agariphila degrades the polysaccharide ulvan, which is produced by the algae Ulva in up to 30% of its dry weight. This degradation process is a little chemical magic trick: in a series of steps, twelve different enzymes are employed to break down the macromolecule into ever smaller building blocks. "Our task at TU Wien was to clarify, with the help of nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry, what these building blocks look like, exactly," says Christian Stanetty. "There were a few surprises along the way with several of the degradation products looking different to what we had expected. This demonstrated that the bacteria take different chemical pathways during the degradation of the sugar than we had expected."

In this way, the researchers were able to find out which enzymes the bacteria use in the respective steps. "As a result, we now not only understand how these microorganisms gain access to this source of nutrition. We now also have access to a toolbox consisting of a whole spectrum of new biocatalysts, thus opening up the possibility of using this complex marine polysaccharide in a targeted manner as a resource for fermentations," says Prof. Uwe Bornscheuer from the University of Greifswald.

The utilisation of algae to synthesise hydrocarbons is 100% carbon-neutral. If this method can be successfully used to create products that had previously been produced using fossil-based resources, it would be an important step for climate protection. "This is absolutely feasible," believes Prof. Marko Mihovilovic from TU Wien. "Initially, simple products, such as special types of sugars, can be targeted. But with an increasing understanding of the chemistry involved, the more success we will have in using these algae as precursors for complex syntheses, all the way to bioplastics."

The aim: a circular economy of biogenic resources

Interdisciplinary cooperation was crucial to the success of the project: "From a scientific point of view, it is only possible to answer research questions of this complexity by collaboration," underlines Marko Mihovilovic. "We have been working with our partners from Germany for some time now, with great success. We will also continue to do so in the future - this should allow us to make significant progress, and ultimately to progress towards sustainable chemistry that will enable a genuine, environmentally sound circular economy."

Credit: 
Vienna University of Technology

Study shows advantages for stress urinary incontinence surgery

ROCHESTER, Minn. ­­­-- One of the most commonly performed surgeries to treat stress urinary incontinence in women may have better long-term results than another common surgical technique, according to a study led by Mayo Clinic researchers.

The retrospective study of more than 1,800 cases at Mayo Clinic from 2002 to 2012 found that the need for additional surgery was twice as high after a transobturator sling surgery compared with a retropubic sling procedure. Reoperation rates within eight years after surgery were 11.2% for patients in the transobturator group compared with 5.2% in the retropubic group, according to the study, which will be published in the journal Obstetrics and Gynecology in August.

The failure rate for the transobturator procedure was even higher among women who had the sling combined with vaginal prolapse repair, says Emanuel Trabuco, M.D., a Mayo Clinic urogynecologist.

"These findings would suggest that the retropubic procedure has better long-term results compared to the transobturator sling," says Dr. Trabuco, lead author of the study.

Stress urinary incontinence, the involuntary loss of urine associated with daily activities, such as exercise, and simple incidents, such as coughing or sneezing, is common among middle-aged women and can greatly affect quality of life. Physical therapy or vaginal inserts are helpful for some women, while others choose to have surgical repair. The two most common surgeries are the retropubic sling, which involves placing a mesh sling under the urethra and behind the pubic bone, and the transobturator sling, which places the sling at a less acute angle by placing the mesh through the thigh area.

The study found that both procedures were safe with few complications. "Given that in the U.S. alone, 200,000 procedures are performed each year to treat stress urinary incontinence, the data in this study should help guide informed discussions with women who are considering surgical treatment, especially if the patient also is having prolapse repairs," says Dr. Trabuco, a surgeon who specializes in vaginal prolapse and urinary and fecal incontinence in women.

The Food and Drug Administration has issued two public health warnings regarding the use of vaginal mesh kits for treating pelvic organ prolapse, which Dr. Trabuco says has created confusion and anxiety regarding the use of mesh for procedures, such as retropubic and transobturator slings. The FDA ban does not apply to midurethral slings for treating urinary incontinence.

The extremely low complication rates that necessitated reoperation -- 3.2% due to problems with bladder emptying and 1.9% due to mesh exposure in the vagina -- should reassure providers and patients of the safety of midurethral slings, according to the study.

Both urinary and fecal incontinence have been underreported in the medical literature because of embarrassment or stigma, Dr. Trabuco says. "We're hopeful that the findings in this study will encourage women to talk to a provider about the surgical and nonsurgical options to treat their conditions, which can greatly affect a woman's daily activities."

Credit: 
Mayo Clinic

A legal framework for vector-borne diseases and land use

Vector-borne diseases cause more than 700,000 deaths and affect hundreds of millions of people per year. These illnesses - caused by parasites, viruses, and bacteria transmitted by insects and animals - account for more than 17% of all infectious diseases on Earth.

While many emerging infectious diseases (EIDs) are preventable through informed protective measures, the way that humans alter our landscape - such as for farming and urban growth - is making this task more difficult.

Human-induced land use change is the primary driver of EIDs, including those carried by mosquitoes such as malaria, dengue, Zika, EEE, and West Nile. Why, then, does land-use planning often fail to recognize the effects these changes have on the risk of spreading disease?

Patricia Farnese, an associate professor of law at the University of Saskatchewan, will offer a legal perspective on infectious disease management with specific reference to vector-borne diseases at the Ecological Society of America's Annual Meeting in August.

"My goal is both to educate and to discuss how land-use planning can be different," says Farnese, who teaches property, agriculture, and wildlife law and researches ethical questions that arise when conservation and human rights collide.

When humans use more land for agriculture like farming, new pathways are introduced for EIDs to spread. Farnese says providing farm animals with sanitary, appropriate living conditions that are not overcrowded is extremely important. "You also want to make sure that farm animals are separated from wild animals," she says. "The spread of chronic wasting disease (CWD), for instance, is directly tied to the contact between wild animals and with captive animals that have CWD. It's not transferable to humans, although there are fears that it will mutate and infect humans or animals in agriculture."

People who are the poorest often suffer the most. The growth of urban slums is another land use change largely driving the spread of EIDs. Unsafe water, poor housing conditions and poor sanitation are standard conditions for those living in urban slums that contribute to the spread of EIDs. Inadequate waste management allows mosquitoes to easily breed and spread disease to large populations.

Farnese says there are many reasons that land-use planning often fails take human health into consideration and to recognize the risk of spreading disease, including the fact that the legal jurisdictions for health and land-use are often not held by the same level of government. Most land-use planning occurs at the local level, while action to prevent and mitigate infectious diseases often needs to be taken at a broader scale to be effective.

The biggest failing, according to Farnese, is that there are no legal mechanisms requiring land-use planning to do so. "Current frameworks for land-use planning are very good at protecting current uses, especially in urban areas," she explains. "But what of the rest of the environment? Rarely do places other than extraordinary places, such as national parks, get land-use planning attention."  

In the face of increasing EIDs as land-uses change in response to a changing climate, Farnese calls for improved models and legal guidelines for land-use planning that are adaptive to future uses and that address natural landscapes outside of urban areas. Specifically, she calls for legal frameworks that mandate both planning at the landscape scale and consideration of not just desired human land-uses, but also how they impact disease risk.

Credit: 
Ecological Society of America

Combined breast and gynecologic surgery: Study says not so fast

image: Sarah Tevis, MD, and colleagues argue against combined breast and gynecologic surgical procedures.

Image: 
University of Colorado Cancer Center

Breast cancer patients and women undergoing cancer-preventive breast surgeries may consider combining these procedures with hysterectomy and/or ovarian removal. However, a University of Colorado Cancer Center study published in Breast Journal argues against this combined approach: Patients undergoing coordinated breast and gynecologic procedures had a significantly longer length of hospital stay, and higher complication, readmission, and reoperation rates compared with patients who underwent single site surgery.

"This is something I talk with patients about on a weekly basis. Patients have the impression, 'I just want to have one surgery and have everything done.' But complication rates are higher with that approach. In patients at high risk of developing breast cancer and ovarian cancer, 2e recommend doing the prophylactic bilateral mastectomy along with breast reconstruction, but then trying to keep gynecologic surgery separate. It's safer and easier to do them separately," says Sarah Tevis, MD, CU Cancer Center investigator and breast surgeon at UCHealth University of Colorado Hospital.

The study used the National Surgery Quality Improvement Program (NSQIP) database to identify 77,030 women who had undergone breast surgery from 2011 to 2015, of whom 124 also had concurrent gynecologic surgery. Interestingly, it was generally younger, healthier women who chose to have combined breast and gynecologic surgeries, "and still their rate of complications was higher," Tevis says.

In addition to a higher rate of complications, choosing combined surgery may lead to treatment delays. First, the need to coordinate three surgeons - breast, reconstructive, and gynecologic - plus the need to schedule a full day in an operating room often leads to pushing back the date of surgery. Second, breast cancer patients are often treated with chemotherapy following surgery, and complications can delay the start of this important chemotherapy, leading to worse outcomes for patients.

"A few times, a patient has a medical problem that makes it better, for example, to only have one anesthesia. But outside these rare cases, we recommend separating breast and reconstructive surgery from gynecologic surgery," Tevis says.

Tevis and colleagues hope the current study shows the baseline level of complications associated with these surgical strategies. Future work will seek to discover features that may predict individual women who fare better and worse with each approach.

Credit: 
University of Colorado Anschutz Medical Campus

Extinct human species likely breast fed for a year after birth, NIH-funded study suggests

Infants of the extinct human species Australopithecus africanus likely breast fed for up to a year after birth, similar to modern humans but of shorter duration than modern day great apes, according to an analysis of fossil teeth funded in part by the National Institutes of Health. The findings provide insight into how breast feeding evolved among humans and may inform strategies to improve modern breast-feeding practices. The study appears in Nature.

Like trees, teeth contain growth rings that can be counted to estimate age. Teeth rings also incorporate dietary minerals as they grow. Breast milk contains barium, which accumulates steadily in an infant's teeth and then drops off after weaning. Study author Christine Austin, Ph.D., of the Icahn School of Medicine in New York, developed a method to analyze trace minerals in teeth with funding from NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

In the current study, researchers examined two sets of fossilized A. africanus teeth from the Sterkfontein Cave outside Johannesburg, South Africa. They found patterns of barium accumulation, suggesting that infants of this early human species likely breast fed for about a year--an interval which may have helped them overcome seasonal food shortages. A. africanus lived in southern Africa more than 2 million years ago. The species resided in savannahs with wet summers, when food was likely abundant, and dry winters, when food was scarce. Cyclical accumulations of lithium in the specimens' teeth suggest the species endured food scarcity during the dry season, which may have contributed to its eventual extinction.

Industrialization and the introduction of infant formula changed breast feeding practices. Analysis of the fossil record and remains from preindustrial societies can provide insight into the nature of those changes and their effects on infant development.

The NICHD grant to Dr. Austin funded a project to identify biomarkers identifying the transition from breast feeding to formula feeding. Among other projects, the method she developed has been used to identify changes in zinc and copper metabolism preceding autism symptoms in young children and linking exposure to manganese in the womb with larger birth size.

Credit: 
NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development

City College-led experts develop flood prediction model

The duration of floods can be determined by river flow, precipitation and atmospheric blocking. Now an international team of researchers led by Nasser Najibi and Naresh Devineni at The City College of New York is offering a novel physically based Bayesian network model for inference and prediction of flood duration. The model also accurately examines the timescales of flooding.

Conceptualized by Najibi and tested on the Missouri River Basin, the statistical model is based on data in the area from the last 50 years. They found that long duration floods first require high flow conditions in rivers created by recurrent high intensity rainfall events, which is then followed by a large stable long-lived low-pressure system -- a storm cell. These conditions may then result in large-scale devastating floods. In shorter duration floods, however, this land-atmospheric coupling is negligible thus explaining why not all storms result in widespread flooding.

"It is possible to predict the duration of floods by coupling atmospheric dynamics and land surface conditions in the watershed," summed up Najibi, a PhD candidate majoring in civil and environmental engineering (water resources engineering) in CCNY's Grove School of Engineering.

On the benefits of this new development, Najibi and Devineni said they are are able to mitigate potential risk imposed by longer duration floods on critical infrastructure systems such as flood control dams, bridges and power plants. It is also possible to predict how long the duration of flooding and inundation will be.

Najibi and his team plan to expand their study, which appeared in the "Nature" research journal "npj Climate and Atmospheric Science," across the United States. This work is part of Devineni's DOE Early Career project funded by the U.S. Department of Energy.

Devineni is an associate professor in the Grove School and NOAA CREST. Other collaborators in the research include Mengqian Lu (Hong Kong University of Science and Technology) and Rui A. P. Perdigão (Universtät Wien, Austria/ University of Lisbon, Portugal).

Credit: 
City College of New York

Sex, lies and crustaceans: New study highlights peculiar reproductive strategies of Daphnia

image: This graphic shows the unusual reproductive strategy used by the organism. In this system, known as cyclic parthenogenesis, Daphnia can alternate between sexual and parthenogenetic (asexual) reproduction.

Image: 
Shireen Dooling

Flourishing in spectacular numbers in lakes and ponds around the world, tiny creatures known as Daphnia play an essential role in freshwater ecology. Daphnia, a type of planktonic crustacean, are the primary consumers of algae and are an important food source for fish and other aquatic life.

Daphnia are ubiquitous in freshwater sources, but their mode of reproduction, known as cyclic parthenogenesis--which involves alternating phases of both sexual and asexual reproduction-- is an evolutionary puzzle. A further mystery surrounding Daphnia is that in some populations, up to 50% of females do not produce male offspring.

Now, Arizona State university's Michael Lynch and his colleagues, including lead author Zhiqiang Ye, believe they have identified a variation in a single gene (unique to Daphnia) that accounts for the non-male-producing (NMP) trait. Isolation of this NMP dominant allele sheds new light on the behavior of this important model organism as well as broader genetic mechanisms of male offspring production. Eventually, new insights into such mechanisms could spur innovations in fertility treatment or alternately, in pest management.

"What we discovered is that there are members of some Daphnia populations that are incapable of producing boys," Lynch says. "We have a chemical that we use called methyl farnesoate that we squirt in the water to induce male production and they don't even respond to that. So there are two flavors of individual in the population--one that produces daughters and sons and one that can only produce daughters."

Michael Lynch directs the Biodesign Center for Mechanisms of Evolution and is a professor at ASU's School of Life Sciences. The group's research on Daphnia appears in the current issue of the journal PNAS.

Beneath the surface

Daphnia, while just visible to the naked eye, are best observed under the microscope, where their translucent forms allow a clear view of internal structure. A heart that beats at a brisk 300 pulses per minute can clearly be seen along with the creature's five pairs of legs, which Daphnia use to sweep algae and organic detritus into their digestive tract. (Daphnia's cleanly visible structure coupled with their essential role in freshwater ecosystems have made them a vital organism for the study of ecology and physiology for over 100 years.)

Daphnia measure roughly 1-3 millimeters in length and feature prominent compound eyes sensitive to sunlight striking pond and lake surfaces, a durable carapace, antennae and a pair of hair-like abdominal structures known as setae.

Also visible in Daphnia is a brood chamber, where offspring resulting from sexual and asexual or parthenogenetic reproduction develop before birth. The movements of immature young can often be seen in the brood chamber.

Daphnia are prolific egg producers and it is estimated their numbers would quickly overpopulate a pond, were they not perpetually eaten by other aquatic life. Their rapid, abbreviated movements in the water are somewhat flea-like and they are often referred to as water fleas, though they are microcrustaceans, not insects.

While there are over 200 species in the Daphnia genus, the most common (and the subject of the current study) are D. pulex. (Precise taxonomy of Daphnia remains controversial, partly due to hybridization, phenotypic plasticity and other factors.)

Innovations in sex

Daphnia use a combined strategy of asexual and sexual reproduction during their life cycle. During most of the growth season, females reproduce asexually, producing diploid eggs (bearing two sets of chromosomes and producing genetically identical offspring). These eggs typically hatch after two to three days after being transferred to the Daphnia's brood pouch.

Late in the season, as environmental conditions change, the reproductive lifestyle of Daphnia shifts. Females begin producing males and what are known as resting eggs (or winter eggs). These are highly durable and capable of surviving intact--through extreme cold, drought or periods of scarce nutrients--for years or even decades, until environmental conditions become favorable for their hatching and development. Resting eggs are fertilized internally by male Daphnia before being deposited in the brood capsule.

Searching for clues

The new study examines a subset of clones of Daphnia pulex with a peculiar attribute: they only produce female offspring. Careful examination of these non-male producing Daphnia (NMP) identified some 3500 specific genomic markers found only in the NMP individuals. The researchers successively narrowed the field of candidate markers, comparing them with other NMP populations and looking for overlap, finally identifying just 5 protein-coding variants exclusively associated with the NMP Daphnia, all of which belong to a single gene.

Although some Daphnia populations have no members carrying the NMP variant, Lynch and his colleagues got lucky on their first try, sequencing 100 individuals, roughly half of which were non-male producers. Further, the NMP markers were all found in a confined region of the Daphnia genome, near the tip of chromosome 1. The variant that appears to be responsible for the NMP trait occurs on a gene labelled 8960, about which many questions remain. The gene is not present in other arthropods and appears unique to Daphnia.

"We have a huge Daphnia genome project," Lynch says. "We've sequenced about 2000 Daphnia genomes and we're continuing to do so. It's one of the biggest genome projects--maybe the biggest, except for the human genome project."

Zhiqiang Ye, a post-doc in Lynch's lab and lead author of the new study carried out much of the laboratory work. He examined gene expression in the male-producing and non-male producing alleles, and demonstrated that the NMP allele was largely non-responsive to methyl farnesoate, a critical hormone responsible for conferring male traits in Daphnia offspring.

Reproductive quandary

In evolutionary terms, the rationale for creating NMP Daphnia remains speculative. Intriguingly, the NMP trait appears to have originally been imported from a sister species of D. pulex, known as D. pulicaria. The NMP allele may act to limit the deleterious effects of too much inbreeding in Daphnia populations or simply help maintain an equilibrium of male production. The study, Lynch points out, may offer new clues concerning the origins and lifeways of obligate asexual organisms, (i.e. those that rely exclusively on asexual reproduction, a major conundrum in evolutionary biology).

The NMP phenotype bears similarity to a reproductive strategy found in so-called gynodioecious plants. "In a gynodioecious system, you have individuals who produce both male and female gametes and some that are only female," Lynch says. "In a superficial sense, it's very much like the Daphnia system."

In future research, Lynch and colleagues will apply the CRISPR-Cas9 gene editing methodology to the study of Daphnia, opening a new avenue of research into the genetics and genomics of this model organism. One proposed experiment will use the technique to knock out the gene responsible for male production or edit the NMP allele, to definitively establish gene 8960 as the culprit for the NMP trait in Daphnia.

Credit: 
Arizona State University

Helping transplanted stem cells stick around and do their jobs

Bone marrow transplants of hematopoietic stem cells have become standard treatment for a host of conditions including cancers of the blood and lymphatic systems, sickle cell anemia, inherited metabolic disorders, and radiation damage. Unfortunately, many bone marrow transplants fail due to rejection by the patient's immune system or graft-versus-host disease (in which the transplanted marrow cells attack the patient's healthy cells), both of which can be fatal. Mesenchymal stromal cells (MSCs) are known to secrete compounds that modulate the immune system and have shown promise in mitigating these problems in animal trials. However, clinical results with MSCs have been disappointing thus far, as they are rapidly cleared from the body and can draw attack from patients' immune systems, and efforts to encapsulate MSCs in protective biomaterials have resulted in large, bulky hydrogels that cannot be given intravenously and compromise the cells' functions.

Today, in a scientific first, researchers from the Wyss Institute for Biologically Inspired Engineering, Harvard's John A. Paulson School of Engineering and Applied Sciences (SEAS), and the Harvard Stem Cell Initiative (HSCI) demonstrate a single-cell encapsulation technology that effectively protects transplanted MSCs from clearance and immune attack and improves the success of bone marrow transplants in mice. The work is published in PNAS.

"To our knowledge, this is the first example of single-cell encapsulation being used to improve cell therapies, which are becoming more widespread as treatments for a number of diseases," said first author Angelo Mao, Ph.D., a former graduate student in the lab of Wyss Core Faculty member and lead of the Wyss Immuno-Materials Platform David Mooney, Ph.D. who is now a postdoc with Wyss Core Faculty member James Collins, Ph.D. "And, our encapsulated cells can be frozen and thawed with minimal impact on the cells' performance, which is critical in the context of hospitals and other treatment centers."

This advance builds on a method the team previously developed that uses a microfluidic device to coat individual living cells with a thin layer of an alginate-based hydrogel, creating what they term "microgels." The process encapsulates cells with 90% efficiency, and the resulting microgels are small enough that they can be delivered intravenously, unlike the bulky hydrogels created by other methods. When injected into mice, MSCs encapsulated using this technique remained in the animals' lungs ten times longer than "bare" MSCs, and remained viable for up to three days.

Because a large amount of MSCs' clinical appeal lies in their secretion of compounds that modulate the body's immune system, the researchers needed to test how microgel encapsulation affects MSCs' ability to function and resist immune attack. They modified their original alginate microgel by adding another compound that cross-links to the alginate and makes the microgel stiffer and better able to resist the body's immune system and clearance mechanisms. They also cultured the MSCs after encapsulation to encourage them to divide and produce more cells. When these new microgels were injected into mice, their persistence increased five-fold over the previous microgel design and an order of magnitude over bare MSCs.

To induce an immune response against the MSCs, the team incubated encapsulated cells in a medium containing fetal bovine serum, which is recognized by the body as foreign, before introducing them into mice. While the clearance rate of the encapsulated MSCs was higher than that observed without immune activation, it was still five times lower than that of bare MSCs. The microgels also outperformed bare MSCs when injected into mice that had a preexisting immune memory response against MSCs, which mimics human patients who are given multiple infusions of stem cells.

MSCs exposed to inflammatory cytokines respond by increasing their expression of immune-modulating genes and proteins, so the researchers next tested whether encapsulation in their new microgels impacted this response. They found that bare and encapsulated MSCs had comparable levels of gene expression when exposed to the same cytokines, demonstrating that the microgels did not impair MSC performance.

For their pièce de résistance, the team injected their MSC-containing microgels into mice along with transplanted bone marrow, half of which was immune-compatible with the recipient mouse and half of which was allogeneic, or an immune mismatch. Mice that received encapsulated MSCs had more than double the fraction of allogeneic bone marrow cells in their marrow and blood after nine days compared with mice that did not receive MSCs. Encapsulated MSCs also led to a greater degree of engraftment of the allogeneic cells into the host bone marrow compared to bare MSCs.

"One of the strong points of this work is that it uses a completely non-genetic approach to dramatically increase cell survival in transplant contexts, where it's sorely needed," said Mooney, who is also the Robert P. Pinkas Family Professor of Bioengineering at SEAS. "This technology nicely complements genetic engineering approaches, and in fact could be more efficient than attempting to directly modify immune cells themselves."

The Wyss Institute's Validation Project Program is supporting advancement of this approach as a possible treatment for ischemia (narrowing of blood vessels) in human patients, and hopes to demonstrate clinical viability in the near future. Validation Projects are technologies with potential high-impact applications that have successfully progressed through significant concept refinement and meet predefined technical, product development, and intellectual property criteria.

"This technology simultaneously resolves multiple issues with bone marrow transplants and stem cell therapies using an elegant, biomaterials-based approach that represents the kind of cross-disciplinary thinking that we value so greatly at the Wyss Institute," said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at SEAS. "We are excited to support this project as it moves toward clinical validation, and we look forward to other potential applications of microencapsulation to address drug and cell delivery problems."

Credit: 
Wyss Institute for Biologically Inspired Engineering at Harvard

Researchers describe new ALS biomarkers, potential new drug targets

Amyotrophic lateral sclerosis, or ALS, is an adult-onset neurodegenerative disease that causes paralysis and ultimately death when the nerves enervating the lungs cease to carry the signals needed for breathing. The disease has what is called a "focal onset," where paralysis starts with an arm or a leg and spreads throughout the body as motor neurons in the spinal cord and brain die off.

Early diagnosis of the disease has not been possible because of a lack of known biomarkers indicative of ALS, but scientists believe that cellular changes within spinal neurons occur before symptoms are detectable, and these changes could serve as useful biomarkers that can aid in earlier diagnosis.

Now, researchers at the University of Illinois at Chicago have described unique populations of neurons and associated cells in the spinal cords of patients who died of ALS.

When symptoms of ALS begin with the paralysis of an arm or a leg, it means that the disease has affected the motor neurons that enervate that arm or leg and which originate in a specific region along the spinal cord. For example, neurons that innervate the arm originate in the upper part of the spinal cord. In ALS, where symptoms first appear in the arm, the motor neurons in the upper spine region die off. Motor neurons above and below that region begin to die off next as the disease spreads up and down the spine, causing paralysis of other parts of the body.

The researchers, led by Fei Song, associate professor of neurology and rehabilitation in the UIC College of Medicine, found that patients with focal-onset ALS had different types of neurons in areas of the spinal cord that are less affected by the disease compared with patients without neurological disorders. They also found that spinal neurons in less affected regions of patients who died of focal-onset ALS were associated with cells called microglia and astrocytes. They report their findings in the journal Neurobiology of Disease.

"Since there must be cellular changes occurring in spinal cord regions adjacent to areas where the disease has clearly affected motor neurons in the spine, we wanted to look at neurons from these adjacent areas to determine if they are different from healthy tissue," Song said. "The debilitating disease has no effective treatment to stop the disease progression and there are only two medications that can prolong patient survival by a few months. So, new drug targets, especially ones that could be given in the earlier stages of the disease, are very much needed."

Song had worked with Dr. John Ravits, professor of clinical neurosciences at the University of California, San Diego, on ALS research in the past. Ravits sees patients with ALS and runs a biorepository that includes nerve tissue from patients who died of ALS and consented to have their nerve tissue collected after death.

Ravits published a paper in 2010 analyzing the expression of genes in spinal motor neurons taken from 12 patients whose ALS started focally compared with nerves of patients without neurological disorders. Motor neurons were collected from less affected regions of the spinal cord where the tissue was assumed to be in the earlier stages of disease.

While significant differences were found, Song wanted to reanalyze the genetic data using a new technique that could shed light on different cell types that may have been present in the samples collected by Ravits. Song and colleague Fabien Dachet, a research specialist with bioinformatics expertise in the UIC department of neurology and rehabilitation, applied a novel bioinformatics analysis to the genetic data.

"When we examined the data, it was clear that the mixture of cells from the ALS patients was very different from patients with no neurodegenerative disease," Song said.

They found that in samples from patients with focal-onset ALS, there were different types of motor neurons compared with control samples from patients without neurological disease. They also saw other cells called microglia and infiltrated macrophages associated with motor neurons from the ALS patients, where these cells were absent in similar samples from patients without neurological disease.

"We found a novel and unique subtype of motor neurons in these patients never before reported," Song said. "Now that we have identified new subtypes of motor neurons and microglia present in ALS patients, we can begin to further study their roles in contributing to disease progression."

Credit: 
University of Illinois Chicago