Research published in The Lancet Public Health indicated that alcohol use disorder is a major risk factor for dementia, especially early-onset dementia.

“The relationships between alcohol use and cognitive health in general, and dementia in particular, are complex,” Michaël Schwarzinger, MD, of the Translational Health Economics Network, France, and colleagues wrote. “Moderate drinking has been consistently associated with detrimental effects on brain structure, and nearly every review describes methodological problems of underlying studies, such as inconsistent measurement of alcohol use or dementia, or both, and insufficient control of potential confounders. By contrast, heavy drinking seems detrimentally related to dementia risk, whatever the dementia type.”

To determine how alcohol use disorders effect dementia risk, especially among those aged younger than 65 years, researchers conducted a nationwide retrospective cohort of hospitalized adults in France discharged with alcohol-related brain damage, vascular dementia or other dementias between 2008 and 2013. Alcohol use disorder was the primary exposure, and dementia was the main outcome. Using the French National Hospital Discharge database, they studied the prevalence of early-onset dementia and determined whether alcohol use disorders or other risk factors were associated with dementia onset.

In total, 1,109,343 adults discharged from hospital in France were diagnosed with dementia and included in the study. Of those, 35,034 cases of dementia were attributable to alcohol-related brain damage, and 52,625 cases had other alcohol use disorders. Among the 57,353 early-onset dementia cases, 22,338 (38.9%) were attributable to alcohol-related brain damage and 10,115 (17.6%) had an additional diagnosis of alcohol use disorders.

Analysis revealed that alcohol use disorders were linked to a threefold increased risk for all types of dementia and “were the strongest modifiable risk factor for dementia onset” (adjusted HR = 3.34 [95% CI, 3.28–3.41] for women; HR = 3.36 [95% CI, 3.31–3.41] for men). Alcohol use disorders remained associated with an increased risk for vascular and other dementias even after excluding alcohol-related brain damage, according to the findings. Furthermore, chronic heavy drinking was also linked to all other independent risk factors for dementia onset, including tobacco smoking, high blood pressure, diabetes, lower education, depression and hearing loss.

“Our findings suggest that the burden of dementia attributable to alcohol use disorders is much larger than previously thought, suggesting that heavy drinking should be recognized as a major risk factor for all types of dementia,” Schwarzinger said in a press release. “A variety of measures are needed, such as reducing availability, increasing taxation and banning advertising and marketing of alcohol, alongside early detection and treatment of alcohol use disorders.”

Previous research has largely focused on modest alcohol use, and its possible beneficial effect, thus overlooking the effect of heavy alcohol use as a modifiable risk factor for dementia, according to a related comment written by Clive Ballard, MBChB, MRCPsych, and Iain Lang, PhD, of the University of Exeter Medical School, U.K.

“Although many questions remain, several can be answered using existing data, which would provide an opportunity to refine our understanding of the pathways of modifiable risk and develop optimal prevention strategies,” Ballard and Lang wrote. “In our view, this evidence is robust, and we should move forward with clear public health messages about the relationship between both alcohol use disorders and alcohol consumption, respectively, and dementia.” – by Savannah Demko

https://www.healio.com/psychiatry/alzheimers-disease-dementia/news/online/%7B90f5e375-9dd3-4715-9206-7c148d563d80%7D/heavy-drinking-may-increase-risk-for-dementia?utm_source=selligent&utm_medium=email&utm_campaign=psychiatry%20news&m_bt=1162769038120

Advertisements

Longer duration of untreated psychosis was associated with accelerated hippocampal atrophy during initial antipsychotic treatment of first-episode schizophrenia, suggesting that psychosis may have persistent, negative effects on brain structure, according to finding published in JAMA Psychiatry.

“Several factors … have been linked to early psychosis and could mediate an association between [duration of untreated psychosis] and hippocampal volume loss, but evidence from longitudinal studies is lacking,” Donald C. Goff, MD, department of psychiatry, New York University Langone Medical Center, and colleagues wrote. “Whereas the negative association of [duration of untreated psychosis] with clinical course is attenuated by the initiation of antipsychotic treatment, the evidence is mixed as to whether antipsychotics contribute to loss of brain volume or protect against it.”

The extent to which loss of brain volume early in psychosis treatment reflects an illness effect, a drug effect or both remains unknown, according to the researchers. Therefore, Goff and colleagues examined loss of hippocampal volume during the first 8 weeks of treatment for schizophrenia, its link to duration of untreated psychosis and molecular biomarkers related to hippocampal volume loss and duration of untreated psychosis.

At Shanghai Mental Health Center in China, researchers conducted a longitudinal study with age- and sex-matched healthy controls between Mar. 5, 2013, and Oct. 8, 2014. They assessed 71 patients with nonaffective first-episode psychosis treated with second-generation antipsychotics and 73 controls. They reassessed 31 participants with psychosis and 32 controls 8 weeks later, measuring hippocampal volumetric integrity (HVI), duration of untreated psychosis, 13 molecular biomarkers and 14 single-nucleotide polymorphisms from 12 candidate genes.

Participants in the first-episode psychosis group had lower baseline median left HVI (n = 57) compared with those in the control group (n = 54; P = .001). Left HVI decreased in 24 participants with psychosis at a median annualized rate of –.03791 throughout the 8 weeks of treatment, whereas left HVI increased in 31 controls at a rate of 0.00115 (P = .001). Furthermore, researchers observed an inverse association between the change in left hippocampal volume and duration of untreated psychosis (P = .002).

Although they observed similar results in the right HVI, the relationship between change in right HVI and duration of psychosis was not significant. According to the results of analyses that looked at left-side hippocampal volume only, left HVI was associated with molecular biomarkers of inflammation, oxidative stress, brain-derived neurotrophic factor, glial injury and those reflecting dopaminergic and glutamatergic transmission.

“We found significantly lower HVI at baseline in participants with [first episode psychosis] compared with healthy controls and additional HVI reduction during antipsychotic treatment that correlated with [duration of untreated psychosis], consistent with a persistent, possibly deleterious, effect of untreated psychosis on brain structure,” Goff and colleagues wrote. “Larger longitudinal studies of longer duration are needed to examine the association between [duration of untreated psychosis], hippocampal volume and clinical outcomes.” – by Savannah Demko

https://www.healio.com/psychiatry/schizophrenia/news/online/%7Bf6c3c940-fe57-41d1-9eb7-7c835e3c48ea%7D/longer-duration-of-untreated-psychosis-linked-to-loss-of-brain-volume?utm_source=selligent&utm_medium=email&utm_campaign=psychiatry%20news&m_bt=1162769038120

For years, scientists have known that mitochondria—the power source of cells—play a role in brain disorders such as depression, bipolar disorder, anxiety and stress responses. But recently scientists at the University of Maryland School of Medicine (UMSOM) have identified significant mitochondrial changes in brain cells that take place in cocaine addiction, and they have been able to block them.

In mice exposed repeatedly to cocaine, UMSOM researchers were able to identify an increase in a molecule that plays a role in mitochondria division (or fission) in a reward region of the brain. Researchers were able to block this change by using a special chemical, Mdivi-1. The researchers also blocked responses to cocaine by genetically manipulating the fission molecule within the mitochondria of brain cells, according to research published in Neuron.

“We are actually showing a new role for mitochondria in cocaine-induced behavior, and it’s important for us to further investigate that role,” said Mary Kay Lobo, PhD, Associate Professor of Anatomy and Neurobiology.

The researchers initially studied the mitochondria in cocaine-exposed mice and determined that mitochondria fission increased in the major reward region of the brain. To confirm this same change in humans, researchers were able to identify similar changes in the mitochondrial fission molecule in tissue collected from post mortem individuals who were cocaine dependents.

Dr. Lobo said that this latest research could help UMSOM researchers better understand changes in brain cells and mitochondria from other addictive disorders. “We are interested to see if there are mitochondrial changes when animals are taking opiates. That is definitely a future direction for the lab,” she said.

“This research is another great example of our ground-breaking work at the University of Maryland School of Medicine to better understand the biology behind drug addiction,” said E. Albert Reece, MD, PhD, MBA, University Executive Vice President of Medical Affairs and the John Z. and Akiko K. Bowers Distinguished Professor and Dean at the University of Maryland School of Medicine.

http://www.medschool.umaryland.edu/news/2018/University-of-Maryland-School-of-Medicine-Researchers-Discover-Key-Link-Between-Mitochondria-and-Cocaine-Addiction.html


Germany’s Green Belt is one of Europe’s most unique open spaces: a once heavily militarized stretch of the Iron Curtain that’s now a natural wonderland filled with a variety of threatened animal species.

by Matt Hickman

Although the Berlin Wall came crashing down on Nov. 9, 1989, there’s another important milestone for a reunified Germany that was ushered in this month. As of Feb. 5, 2018, the heavily fortified concrete barrier that divided the German capital beginning in 1961 has now been down longer than it was up: 28 years, two months and 27 days.

That being said, it’s sometimes easy to forget that the physical and ideological divide between East and West wasn’t just limited to a famous 90-some-mile wall in Berlin.

Predating the Berlin Wall by 16 years and located nearly 100 miles east, the Inner German Border was the true physical manifestation of the Iron Curtain: a 870-mile frontier that ran the entire length of the divided country from the Baltic Sea in the north to the former Czechoslovakia in the south. On one side of this 650-foot-wide strip of land stood the Federal Republic of Germany (FRG) and on the other — just beyond an extensive network of dog runs, minefields, concrete watchtowers, bunkers, booby traps and forbidding electrified barbed wire fences — stood the German Democratic Republic (GDR), a communist dictatorship that remained firmly in the grasp of the Soviet Union until the dissolution of the Eastern Bloc.

Remnants of the “Death Strip” that once severed Germany still exist — so called because hundreds of East Germans perished while attempting to flee the GDR for less totalitarian pastures. Many of the old watchtowers, fortifications and short stretches of fence have been preserved. Here, history, no matter how painful, hasn’t been paved over and replaced with shopping malls and tract housing. And as such, the scars of a divided Germany remain. But what unusual and beautiful scars they are.

Almost the entirety of the Inner German Border has been reclaimed by Mother Nature as part of a sprawling wildlife reserve and outdoor recreation area known as Das Grüne Band — the Green Belt. Encompassing large swaths of undisturbed countryside and farmland in addition to the border zone, in some ways the Green Belt — often described as a “living monument to reunification” and a “memory landscape” — remains a no man’s land given that a wide variety of plants and animals, many rare and endangered, positively rule.


Germany’s Green Belt isn’t entirely continuous. However, most of this exclusion zone-turned-wildlife haven remains in a near-natural state.

From ‘death zone into a lifeline’

Rich in biodiversity and largely unhampered by 21st century human development, the Green Belt is a project of German environmental group Bund Naturschutz (BUND) that dates back to 1989. However, work had begun on the non-fortified western side of the border zone much earlier after conservationists noticed that this woeful place was also a wildlife magnet. “The division of Germany was a travesty that robbed people of their freedom, but a positive side effect was the way the sealed border allowed nature to flourish,” Eckhard Selz, a park ranger hailing from the former East Germany, explained to the Guardian in 2009.

In a 2017 NBC News profile, conservationist Kai Frobel, considered by many to be the father of the Green Belt, explained that “nature essentially has been given a 40-year holiday” in the erstwhile border area, which itself has been transformed from a “death zone into a lifeline.”

“When we grew up in this area, we all thought that this monster of a border line had been built for eternity,” 58-year-old Frobel says of his teenage years spent as a budding conservationist hailing from Colburg, a Bavarian town located on the western side of the border but largely surrounded by the GDR. “No one, really no one, believed in German reunification at the time.”

When the Iron Curtain collapsed, Frobel and his fellow conservationists, including many from the former East Germany, rushed to protect and preserve the border zone. The worry was that the largely untouched area would give way to roads, housing and massive commercial farming operations — a “brown belt,” if you will. Vital wildlife habitats just recently discovered would be lost.

With governmental backing, the Green Belt became the first German nature conservation project to involve parties from both sides of a nation that had just been fused back together. Decades later, an impressive 87 percent of the Green Belt, which passes through nine of Germany’s 16 states, remains in an undeveloped or near-natural state. While there are some gaps in this unusually elongated wildlife refuge, BUND is continually working to restore them and prevent other sections from giving way to development.

“You will find no other place in Germany with the richness of habitats and species that the Green Belt provides,” Frobel tells NBC News.


A Cold War era concrete watchtower still stands along the eastern section of what was once the notorious Inner German Border.

The one upside of a nation-dividing no man’s land

In October of last year, Frobel, along with Inge Sielman and Hubert Weiger, were awarded the German government’s top environmental prize for their tireless work preserving and protecting the old Inner German Border and environs. (The trio received a combined 245,00 euros or roughly $284,300.)

As Deutsche Welle explains, the Green Belt’s dual function as a historical site and wildlife refuge is more vital today than ever. Many animals, forced to seek out new habitats due to encroaching development in outlying areas of the German countryside, are flocking to the protected area in record numbers.

“The Green Belt is now home to countless natural wonders that have been crowded out in other areas,” German President Frank-Walter Steinmeir explained at October’s Germany Environmental Prize ceremony, held in the city of Brunswick.


Tranquil, sobering and biologically diverse, the Green Belt is popular amongst hikers, cyclists, birders and history buffs alike.

In total, conservationists believe the Green Belt to be home to upwards of 1,200 plant and animal species that are endangered or near-extinct in Germany, including the lady’s slipper orchid, the Eurasian otter, wildcats and the European tree frog. The Green Belt also hosts a large number of rare and threatened birds such as the black stork.
“We discovered that over 90 percent of the bird species that were rare or highly endangered in Bavaria — such as the whinchat, the corn bunting and the European nightjar — could be found in the Green Belt. It became a final retreat for many species, and it still is today,” Frobel tells Deutsche Welle.

One less rare species found in growing abundance throughout the Green Zone are tourists. Germany has long touted the region as a sustainable “soft” tourism hotspot, particularly in recent years. Laced with hiking trails and dotted with nature viewing areas along with a fair number of memorials, museums, quaint villages and a handful of crumbling leftovers from the Cold War era, the Green Zone passes through already tourism-friendly nature regions including the Franconian and Thuringian forests, the Harz Mountains and the verdant floodplain of the river Elbe.

In addition to local conservation groups, a number of local tourism authorities are working alongside BUND to promote the natural splendors of the once inaccessible border region. “Numerous cycling and hiking trails along the Green Belt connect special points of experience and information,” reads the Green Belt tourism page. “You can see cranes and northern geese from observation ramparts, conquer castles and palaces, descend into diminutive mining pits, climb border towers, dart along old border trails in the dark, or be inspired by works of art.”


With informative signs guiding the way and pointing out important sights, the Green Belt is described as a ‘memory landscape.

A model for something much bigger

Of course, Germany wasn’t the only country cracked by the Iron Curtain.

For nearly four decades, the entire European continent was split between East and West with little movement between the two sides. And much like the heralded conservation area that’s flourishing in a once-divided Deutschland, the European Green Belt Initiative aims to protect biodiversity along the line of former Iron Curtain but on a much more ambitious scale.

Stretching from the Barents Sea on the Russian/Norwegian border and along the Baltic coast before cutting through the heart of Central Europe and terminating at the Adriatic and Black seas, the 7,500-mile European Green Belt links 24 individual countries through a winding necklace of national parks, nature preserves and other protected areas.

As in Germany, many of these European border regions were largely restricted/avoided during their existence. And so, wildlife moved in and flourished in relative solitude.

“Unwittingly, the once-divided Europe encouraged the conservation and development of valuable habitats. The border area served as a retreat for many endangered species,” explains the European Green Belt website.

Founded in 2003 and very much modeled on the work of BUND in Germany, the European Green Belt Initiative is a burgeoning grassroots movement comprised of around 150 governmental and non-governmental conservation organizations hailing from a diverse number of countries.

And in addition to inspiring a band of protected wilderness that bisects the European continent, the many successes of Germany’s Green Belt have also inspired South Korean officials to reach out to Frobel and his colleagues and discuss ways that the Korean Demilitarized Zone could some day (emphasis on some day) be transformed into a protected wildlife area.

“Conservationists are already preparing a so-called Green Belt Korea, and are in close consultation with us,” Frobel told Deutsche Welle in a 2017 interview with Deutsch Welle. He points out that the Korean Demilitarized Zone, home to “a well-preserved biodiverse habitat,” is the “only region in the world that can be compared with Germany before 1989.”

“They are using Germany’s Green Belt as its model for when reunification comes — even though the situation doesn’t look too good at the moment,” says Frobel.

https://www.mnn.com/earth-matters/wilderness-resources/blogs/germany-nation-dividingdeath-zone-reimagined-nature-reserve

In one of the first successes of its kind, researchers from Case Western Reserve University School of Medicine and six other institutions have inhibited the spreading of cancer cells from one part of the body to another. In doing so, they relied on a new model of how cancer metastasizes that emphasizes epigenetics, which examines how genes are turned on and off.

In a study published in Nature Medicine, the investigators—including scientists from the National Cancer Institute and Cleveland Clinic—used innovative epigenetic-centered techniques to halt the spread of bone cancer (osteosarcoma) cells to the lungs in mice.

The large majority of deaths associated with osteosarcoma are due to the spreading of the cancer to the lungs, a process known as metastasis. Most human osteosarcoma cases occur in children and young adults between the ages of 10 and 30, with teens the most frequently affected age group. Clinical outcomes for patients with osteosarcoma have not improved for more than 30 years, and there are currently no approved targeted anti-metastatic therapies for the disease in wide clinical use.

“More than 90 percent of all cancer deaths are the result of tumor metastasis, not primary-site tumors,” said the study’s senior author, Peter Scacheri, professor of genetics and genome sciences at Case Western Reserve University School of Medicine and member of the Case Comprehensive Cancer Center. “While many of the genes responsible for metastasis have been identified, the mechanisms that control these genes are not well defined. Our findings demonstrate that altered gene-enhancer activity is fundamental to a cancer cell’s ability to metastasize.”

Gene enhancers are short segments of DNA that, when bound by specialized proteins called transcription factors, function like switches to activate genes. This process is critical for normal development, as when a single fertilized egg develops into the many different cell types that comprise the body.

There are tens of thousands of gene enhancers in each cell, far more than the number of genes; they will be in different “on” and “off” positions in, for example, eye and heart cells (or gradients thereof, like a dimmer switch’s effects on the brightness-level of a light). These distinctive “on and off” profiles lend cells their unique characteristics, even though they all have the same DNA.

But faulty enhancer regulation appears to contribute to tumor-formation and subsequent spreading of cancer cells. In addition, different cancers are distinguishable by different enhancer patterns.

In this new study, the authors show that the on-off switches of cancer cells that have metastasized are in different positions than in the cells of the source tumor.

“Metastasis results from a complex set of traits acquired by tumor cells, distinct from those necessary for tumors to form in the first place,” said the study’s lead author, James J. Morrow, a medical student in the Medical Scientist Training Program at Case Western Reserve University School of Medicine. “Unfortunately, searching for gene mutations that drive metastasis has not substantially improved outcomes for patients with metastatic disease. Five-year survival rates for cancer patients with regional or localized disease have significantly improved for many types of cancer. But with few exceptions, outcomes for patients with metastatic cancer have remained stagnant.

“It is well established that primary tumor formation is driven by a combination of genetic and epigenetic events,” he continued. “So based on the knowledge that enhancers drive both normal cell development and tumor-formation, we hypothesized that they may play a similar role in the transition of cancer cells from one developmentally distinct tissue to another during metastatic progression.”

Through epigenomic profiling experiments, the Case Western Reserve-led researchers consistently identified certain bunched clusters of enhancers—known as metastatic variant enhancer loci (Met-VELs)—near cancer genes in lung metastases of patients with osteosarcoma, indicating that they were central to the metastatic process. Using experimental mouse models, the researchers then showed that growth of osteosarcoma cells in the lung can be mitigated by using BET inhibitors (anti-cancer drugs currently in clinical trials), which broadly interrupt the function of Met-VELs in driving gene expression.

Second, they demonstrated that the metastatic capacity of osteosarcoma cells can be diminished by blocking expression of individual genes regulated by Met-VELs or the transcription factors driving that regulation. They verified that a particular Met-VEL-linked gene, Tissue Factor (F3), is essential for metastatic colonization. Specifically, interrupting the signaling and pro-coagulant (blood clotting) functions of F3 with antibodies inhibiting these functions was sufficient to prevent metastasis. Additionally, they showed that deleting a single Met-VEL regulating F3 expression via the TALEN gene-editing process achieved a similar effect.

“Our experiments show that removing a single enhancer of the F3 gene in tumor cells virtually eliminates their ability to metastasize in mice,” said Scacheri. “Collectively, our findings establish that enhancer elements endow tumor cells with metastatic capacity and that targeted inhibition of genes associated with enhancer alterations, or deleting altered enhancers themselves is sufficient to block metastatic colonization and proliferation. While our work focused on lung metastasis in osteosarcoma, the findings have implications for other types of metastatic cancer as well.”

The Case Western Reserve University School of Medicine focus on epigenetics in the new study represents a break with the prevailing model for metastasis, which largely explores mutations in the genes—not if or how certain genes are turned on or off. And the preponderance of current cancer research takes place on the early stages of disease, such as how tumors are formed and on what distinguishes cancer cells from normal cells, and not on metastasis. Additionally, most cancer medications and treatments today were developed to kill primary tumors, not cancer cells that have spread elsewhere.

http://thedaily.case.edu/researchers-inhibit-cancer-metastases-via-novel-steps/

Scientists at The Scripps Research Institute (TSRI) have achieved a major milestone toward designing a safe and effective vaccine to both treat heroin addiction and block lethal overdose of the drug. Their research, published today in the journal Molecular Pharmaceutics, shows how a new anti-heroin formulation that is safe in animal models remains stable at room temperature for at least 30 days. As a result, the vaccine is close to being ready for human testing.

“The heroin vaccine is one step closer to clinical evaluation,” says Candy S. Hwang, PhD, first author of the study and a research associate at TSRI.

According to the National Institute on Drug Abuse, 15,446 Americans died from heroin overdose between 2000 and 2016, and the mortality rates are increasing. Heroin abuse has been further fueled by a rise in prescription opioid abuse—studies show that opioid pain reliever users are 40 times more likely to abuse heroin.

The first formulation of the heroin vaccine was developed in 2013 by a team led by Kim D. Janda, PhD, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI. It has been shown to be effective—and safe—in both mouse and non-human primate models.

The vaccine works by training the immune system antibodies to recognize and bind to heroin molecules, blocking the drug from reaching the brain to cause a “high.” Researchers believe that blocking the high of heroin will help eliminate the motivation for many recovering addicts to relapse into drug use.

The heroin molecule does not naturally prompt an antibody response, so researchers attach it to a carrier protein that alerts the immune system to start making antibodies. Scientists also add an ingredient called an adjuvant to the vaccine, which boosts the immune response and makes the vaccine more effective.

Hwang says, “Our goal was to prepare a vaccine that could be advanced to clinical trials. As such, we were looking for the best combination of ‘hapten’ (the heroin molecule), carrier protein and adjuvant to keep the vaccine both stable for transport and storage but still efficacious.”

For the new study, the researchers investigated how 20 different carrier protein/adjuvant combinations worked, including shelf stability based on temperature and storage time and whether the formulation was a liquid or powder.

Their experiments in rodent models showed that the best vaccine formulation contained a carrier protein called tetanus toxoid (TT) and adjuvants called alum and CpG ODN. The discovery that alum worked best as an adjuvant was especially significant since alum is one of the few adjuvants used in vaccines already approved by the U.S. Food and Drug Administration. The researchers also found that there was no difference in how well it worked between the liquid and powder versions of this formulation.

Hwang notes that the best vaccine formulation showed protection against lethal doses of heroin. This is particularly important as many heroin addicts have succumb to overdose and death during their attempts to quit the drug.

With this new study, the researchers have shown that the vaccine is safe and effective in animal models, stable under clinical conditions and reliant on an already-approved adjuvant. The next step is to find a producer to make the vaccine on a large scale.

“We believe that a heroin vaccine would be tremendously beneficial for people who have a heroin substance use disorder but have found difficulty in trying to quit,” says Hwang.

In addition to Hwang and Janda, authors of the study, “Enhancing Efficacy and Stability of an Anti-Heroin Vaccine: Examination of Antinociception, Opioid Binding Profile, and Lethality,” were Paul T. Bremer, Cody J. Wenthur, Beverly Ellis and Bin Zhou of The Scripps Research Institute; and Sam On Ho, SuMing Chiang and Gary Fujii of Molecular Express, Inc.

The study was supported by the National Institutes of Health (grants UH3DA041146, F32AI126628, F32DA043323, R42DA040422 and R44AI094770).

https://www.scripps.edu/news/press/2018/20180213janda.html


An Amazon molly, Poecilia formosa, an asexual fish species native to Texas that is entirely female.

By Shana Hutchin

Highlights

The Amazon molly has flourished by defying nature’s odds to reproduce asexually, cloning themselves by duping the male fish of another species to waste their germplasm

Females steal the entire genome of their host males, keep it for one generation and then throw it out again

The existence of Amazon mollies back anywhere from 100,000 to 200,000 years ago to a sexual reproduction event involving two different species of fish

Faculty Fellow Dr. Manfred Schartl led the international team that recently sequenced the first Amazon molly fish genome

No species is immune from the suffering of unrequited love, but scientists expect to learn volumes about the biological basis of sex from the newly sequenced genome of an all-female, asexual Texas native – the Amazon molly fish – that has thrived as a master of male manipulation over millennia.

The fresh waters along the Texas-Mexico border serve as home to this evolutionary anomaly – a fish that has flourished by defying nature’s odds to reproduce asexually through a natural form known as parthenogenesis in which growth and development of embryos occurs without fertilization, resulting only in daughters that are true clones of their mothers.

Texas A&M University Hagler Institute for Advanced Study (HIAS) Faculty Fellow Dr. Manfred Schartl led the international team that recently sequenced the first Amazon molly genome and the genomes of the original parental species that created this unique fish in an effort to better understand how its reproduction deviates from the male-female sexual norm and why the Amazon molly as a species has fared so well in the process.

The evolution of sex

The findings from their National Institutes of Health-funded research are published online today (Feb. 12) in the Nature research journal Nature Ecology & Evolution.

“The existence of two sexes, male and female, is one of the oldest and most widespread phenomena in biology,” says Schartl, a world leader in cellular and molecular biology of Xiphophorus model systems including platyfish and swordtails. “Studies on the exceptional case of asexuality helps us to better understand the biological meaning and evolution of sex.”

Animals that reproduce asexually are rare, compared to the overwhelming majority of species that exist as males and females and reproduce sexually. Because it was long thought that vertebrates would not be able to exist in such a way, Schartl says it was a sensation when the Amazon molly was the first asexual vertebrate discovered in 1932.

But even the most independent females occasionally need a male – in the Amazon molly’s case, to kick-start the parthenogenensis process. They seduce males from related sexual species for this service, which Schartl notes lacks the regular benefit for these males, which do not contribute their genes to the next generation.


An Amazon molly (right), caught in action while seducing a male Sailfin molly to steal sperm.

Thriving by cloning

“In essence, mollies repeatedly clone themselves by duping the male fish of another species to waste their germplasm,” Schartl says. “This reminds one of the tribe of female warriors in the Greek mythology, from which their name is derived.”

The team’s research traces the existence of Amazon mollies back anywhere from 100,000 to 200,000 years ago to a sexual reproduction event involving two different species of fish, an Atlantic molly and a Sailfin molly.

“That’s about 500,000 generations if you calculate it out to the present day, which makes them genetically older than humans,” Schartl says. “This is unexpected because asexuals are expected to be at disadvantage compared to their sexual counterparts.”

Schartl notes that one of the theories as to why asexual reproduction is incompatible with a species’ sustainability is the idea that if no new DNA is introduced during reproduction, then harmful gene mutations can accumulate over successive generations, leading to eventual extinction. Another hypothesis states that asexual reproduction is not like sexual reproduction, where the different genomes of the two parents are newly combined and create new genomes with every offspring. Because the absence of recombination in asexuals limits genetic diversity within a species, he says it gets more and more difficult to adapt to changes in the environment.

“Unexpectedly, we did not find the signs of genomic decay as predicted,” Schartl adds. “Our findings suggest that the molly’s thriving existence can be explained by the fact that the fish has a hardy genetic makeup that is often rare in nature and gives the animals some survival benefits.”

Schartl says the hybridization of the Atlantic and Sailfin mollies’ two different species genomes into a new one created a situation well known in the animal and plant breeding world — an artificial hybrid that is bigger, more colorful and capable of generating more and better products than the purebred parents, a phenomenon known as hybrid vigor.

https://today.tamu.edu/2018/02/12/texas-am-biologist-leads-international-team-that-sequences-first-amazon-molly-fish-genome/