Biologist warn of early stages of Earth's sixth mass extinction event

The planet's current biodiversity, the product of 3.5 billion years of evolutionary trial and error, is the highest in the history of life. But it may be reaching a tipping point.

African elephant with calf, Amboseli National Park. Elephants and other large animals face an increased risk of extinction

Credit: © EcoView / Fotolia

In a new review of scientific literature and analysis of data published in Science, an international team of scientists cautions that the loss and decline of animals is contributing to what appears to be the early days of the planet's sixth mass biological extinction event.
Since 1500, more than 320 terrestrial vertebrates have become extinct. Populations of the remaining species show a 25 percent average decline in abundance. The situation is similarly dire for invertebrate animal life.
And while previous extinctions have been driven by natural planetary transformations or catastrophic asteroid strikes, the current die-off can be associated to human activity, a situation that the lead author Rodolfo Dirzo, a professor of biology at Stanford, designates an era of "Anthropocene defaunation."
Across vertebrates, 16 to 33 percent of all species are estimated to be globally threatened or endangered. Large animals -- described as megafauna and including elephants, rhinoceroses, polar bears and countless other species worldwide -- face the highest rate of decline, a trend that matches previous extinction events.
Larger animals tend to have lower population growth rates and produce fewer offspring. They need larger habitat areas to maintain viable populations. Their size and meat mass make them easier and more attractive hunting targets for humans.
Although these species represent a relatively low percentage of the animals at risk, their loss would have trickle-down effects that could shake the stability of other species and, in some cases, even human health.
For instance, previous experiments conducted in Kenya have isolated patches of land from megafauna such as zebras, giraffes and elephants, and observed how an ecosystem reacts to the removal of its largest species. Rather quickly, these areas become overwhelmed with rodents. Grass and shrubs increase and the rate of soil compaction decreases. Seeds and shelter become more easily available, and the risk of predation drops.
Consequently, the number of rodents doubles -- and so does the abundance of the disease-carrying ectoparasites that they harbor.
"Where human density is high, you get high rates of defaunation, high incidence of rodents, and thus high levels of pathogens, which increases the risks of disease transmission," said Dirzo, who is also a senior fellow at the Stanford Woods Institute for the Environment. "Who would have thought that just defaunation would have all these dramatic consequences? But it can be a vicious circle."
The scientists also detailed a troubling trend in invertebrate defaunation. Human population has doubled in the past 35 years; in the same period, the number of invertebrate animals -- such as beetles, butterflies, spiders and worms -- has decreased by 45 percent.
As with larger animals, the loss is driven primarily by loss of habitat and global climate disruption, and could have trickle-up effects in our everyday lives.
For instance, insects pollinate roughly 75 percent of the world's food crops, an estimated 10 percent of the economic value of the world's food supply. Insects also play a critical role in nutrient cycling and decomposing organic materials, which helps ensure ecosystem productivity. In the United States alone, the value of pest control by native predators is estimated at $4.5 billion annually.
Dirzo said that the solutions are complicated. Immediately reducing rates of habitat change and overexploitation would help, but these approaches need to be tailored to individual regions and situations. He said he hopes that raising awareness of the ongoing mass extinction -- and not just of large, charismatic species -- and its associated consequences will help spur change.
"We tend to think about extinction as loss of a species from the face of Earth, and that's very important, but there's a loss of critical ecosystem functioning in which animals play a central role that we need to pay attention to as well," Dirzo said. "Ironically, we have long considered that defaunation is a cryptic phenomenon, but I think we will end up with a situation that is non-cryptic because of the increasingly obvious consequences to the planet and to human wellbeing."
The coauthors on the report include Hillary S. Young, University of California, Santa Barbara; Mauro Galetti, Universidade Estadual Paulista in Brazil; Gerardo Ceballos, Universidad Nacional Autonoma de Mexico; Nick J.B. Isaac, of the Natural Environment Research Council Centre for Ecology and Hydrology in England; and Ben Collen, of University College London.

Journal Reference:

1. R. Dirzo, H. S. Young, M. Galetti, G. Ceballos, N. J. B. Isaac, B. Collen. Defaunation in the Anthropocene. Science, 2014; 345 (6195): 401 DOI: 10.1126/science.1251817 

Courtesy: ScienceDaily

Researchers eliminate HIV from cultured human cells for first time

HIV-1, the most common type of the virus that causes AIDS, has proved to be tenacious, inserting its genome permanently into its victims' DNA, forcing patients to take a lifelong drug regimen to control the virus and prevent a fresh attack. Now, a team of Temple University School of Medicine researchers has designed a way to snip out the integrated HIV-1 genes for good.

This scanning electron micrograph revealed the presence of the human immunodeficiency virus (HIV-1) (spherical in appearance), which had been co-cultivated with human lymphocytes.

Credit: CDC/C. Goldsmith, P. Feorino, E. L. Palmer, W. R. McManus

 

 

 

 

"This is one important step on the path toward a permanent cure for AIDS," says Kamel Khalili, PhD, Professor and Chair of the Department of Neuroscience at Temple. Khalili and his colleague, Wenhui Hu, MD, PhD, Associate Professor of Neuroscience at Temple, led the work which marks the first successful attempt to eliminate latent HIV-1 virus from human cells. "It's an exciting discovery, but it's not yet ready to go into the clinic. It's a proof of concept that we're moving in the right direction," added Dr. Khalili, who is also Director of the Center for Neurovirology and Director of the Comprehensive NeuroAIDS Center at Temple.

In a study published July 21 by the Proceedings of the National Academy of Sciences, Khalili and colleagues detail how they created molecular tools to delete the HIV-1 proviral DNA. When deployed, a combination of a DNA-snipping enzyme called a nuclease and a targeting strand of RNA called a guide RNA (gRNA) hunt down the viral genome and excise the HIV-1 DNA. From there, the cell's gene repair machinery takes over, soldering the loose ends of the genome back together -- resulting in virus-free cells.

"Since HIV-1 is never cleared by the immune system, removal of the virus is required in order to cure the disease," says Khalili, whose research focuses on the neuropathogenesis of viral infections. The same technique could theoretically be used against a variety of viruses, he says.

The research shows that these molecular tools also hold promise as a therapeutic vaccine; cells armed with the nuclease-RNA combination proved impervious to HIV infection.

Worldwide, more than 33 million people have HIV, including more than 1 million in the United States. Every year, another 50,000 Americans contract the virus, according to the U.S. Centers for Disease Control and Prevention.

Although highly active antiretroviral therapy (HAART) has controlled HIV-1 for infected people in the developed world over the last 15 years, the virus can rage again with any interruption in treatment. Even when HIV-1 replication is well controlled with HAART, the lingering HIV-1 presence has health consequences. "The low level replication of HIV-1 makes patients more likely to suffer from diseases usually associated with aging," Khalili says. These include cardiomyopathy -- a weakening of the heart muscle -- bone disease, kidney disease, and neurocognitive disorders. "These problems are often exacerbated by the toxic drugs that must be taken to control the virus," Khalili adds.

Researchers based the two-part HIV-1 editor on a system that evolved as a bacterial defense mechanism to protect against infection, Khalili says. Khalili's lab engineered a 20-nucleotide strand of gRNA to target the HIV-1 DNA and paired it with Cas9. The gRNA targets the control region of the gene called the long terminal repeat (LTR). LTRs are present on both ends of the HIV-1 genome. By targeting both LTRs, the Cas9 nuclease can snip out the 9,709-nucleotides that comprise the HIV-1 genome. To avoid any risk of the gRNA accidentally binding with any part of the patient's genome, the researchers selected nucleotide sequences that do not appear in any coding sequences of human DNA, thereby avoiding off-target effects and subsequent cellular DNA damage.

The editing process was successful in several cell types that can harbor HIV-1, including microglia and macrophages, as well as in T-lymphocytes. "T-cells and monocytic cells are the main cell types infected by HIV-1, so they are the most important targets for this technology," Khalili says.

The HIV-1 eradication approach faces several significant challenges before the technique is ready for patients, Khalili says. The researchers must devise a method to deliver the therapeutic agent to every single infected cell. Finally, because HIV-1 is prone to mutations, treatment may need to be individualized for each patient's unique viral sequences.

"We are working on a number of strategies so we can take the construct into preclinical studies," Khalili says. "We want to eradicate every single copy of HIV-1 from the patient. That will cure AIDS. I think this technology is the way we can do it."

Journal Reference:

1. W. Hu, R. Kaminski, F. Yang, Y. Zhang, L. Cosentino, F. Li, B. Luo, D. Alvarez-Carbonell, Y. Garcia-Mesa, J. Karn, X. Mo, K. Khalili. RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1405186111

Courtesy: ScienceDaily

Genetic risk for autism stems mostly from common genes

Using new statistical tools, Carnegie Mellon University's Kathryn Roeder has led an international team of researchers to discover that most of the genetic risk for autism comes from versions of genes that are common in the population rather than from rare variants or spontaneous glitches.

The bulk of risk, or liability, for autism spectrum disorders was traced to inherited variations in the genetic code shared by many people. These and other (unaccounted) factors dwarfed contributions from rare inherited, non-additive and spontaneous (de novo) genetic factors.

Published in the July 20 issue of the journal Nature Genetics, the study found that about 52 percent of autism was traced to common genes and rarely inherited variations, with spontaneous mutations contributing a modest 2.6 percent of the total risk. The research team -- from the Population-Based-Autism Genetics and Environment Study (PAGES) Consortium -- used data from Sweden's universal health registry to compare roughly 3,000 subjects, including autistic individuals and a control group. The largest study of its kind to date, the team also showed that inheritability outweighs environmental risk.

"From this study, we can see that genetics plays a major role in the development of autism compared to environmental risk factors, making autism more like height than we thought -- many small risk factors add up, each pushing a person further out on the spectrum," said Roeder, professor of statistics and computational biology at Carnegie Mellon and a leading expert on statistical genomics and the genetic basis of complex disease. "These findings could not have happened without statistics, and now we must build off of what we learned and use statistical approaches to determine where to put future resources, and decide what is the most beneficial direction to pursue to further pinpoint what causes autism."

Although autism is thought to be caused by an interplay of genetic and other factors, including environmental forces, consensus on their relative contributions and the outlines of its genetic architecture has remained elusive, until now. With this new study, the researchers believe that autism genetics is beginning to catch up.

Led by Roeder, the researchers used new statistical methods -- such as machine learning techniques and dimension reduction tools -- that allowed them to more reliably sort out the inheritability of the disorder. In addition, they were able to compare their results with a parallel family-based study in the Swedish population, which took into account data from twins, cousins, and factors like age of the father at birth and parents' psychiatric history. A best-fit statistical model took form, based mostly on additive genetic and non-shared environmental effects.

"Thanks to the boost in statistical power that comes with ample sample size, autism geneticists can now see the forest for the trees," said Thomas R. Insel, director of the National Institute of Mental Health (NIMH). "Knowing the nature of the genetic risk will help focus the search for clues to the molecular roots of the disorder."

Thomas Lehner, chief of the NIMH's Genomics Research Branch, agreed and added, "This is a different kind of analysis than employed in previous studies. Data from genome-wide association studies was used to identify a genetic model instead of focusing just on pinpointing genetic risk factors. The researchers were able to pick from all of the cases of illness within a population-based registry."

Now that the genetic architecture is better understood, the researchers are identifying specific genetic risk factors detected in the sample, such as deletions and duplications of genetic material and spontaneous mutations. The researchers said even though such rare spontaneous mutations accounted for only a small fraction of autism risk, the potentially large effects of these glitches make them important clues to understanding the molecular underpinnings of the disorder.

"Within a given family, the mutations could be a critical determinant that leads to the manifestation of ASD in a particular family member," said Joseph Buxbaum, the study's first author and professor of psychiatry, neuroscience, genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai (ISMMS). "The family may have common variation that puts it at risk, but if there is also a 'de novo' mutation on top of that, it could push an individual over the edge. So for many families, the interplay between common and spontaneous genetic factors could be the underlying genetic architecture of the disorder."

Current studies have not been large enough to reveal the many common genetic variants that increase the risk of autism. On their own, none of these common variants will have sufficient impact to cause autism.

"Our group in Pittsburgh is working to develop a model that predicts the genetic risk for a family based on a myriad of small effects. Such a score could provide clinical benefit to families," Roeder said.

Journal Reference:

1. Trent Gaugler, Lambertus Klei, Stephan J Sanders, Corneliu A Bodea, Arthur P Goldberg, Ann B Lee, Milind Mahajan, Dina Manaa, Yudi Pawitan, Jennifer Reichert, Stephan Ripke, Sven Sandin, Pamela Sklar, Oscar Svantesson, Abraham Reichenberg, Christina M Hultman, Bernie Devlin, Kathryn Roeder, Joseph D Buxbaum. Most genetic risk for autism resides with common variation. Nature Genetics, 2014; DOI: 10.1038/ng.3039 

Courtesy: ScienceDaily

More than glitter: How gold nanoparticles easily penetrate cells, making them useful for delivering drugs

A special class of tiny gold particles can easily slip through cell membranes, making them good candidates to deliver drugs directly to target cells. Scientists explain how gold nanoparticles easily penetrate cells, making them useful for delivering drugs.

MIT engineers created simulations of how a gold nanoparticle coated with special molecules can penetrate a membrane. At left, the particle (top) makes contact with the membrane. At right, it has fused to the membrane.

A new study from MIT materials scientists reveals that these nanoparticles enter cells by taking advantage of a route normally used in vesicle-vesicle fusion, a crucial process that allows signal transmission between neurons. In the July 21 issue of Nature Communications, the researchers describe in detail the mechanism by which these nanoparticles are able to fuse with a membrane.
The findings suggest possible strategies for designing nanoparticles -- made from gold or other materials -- that could get into cells even more easily.
"We've identified a type of mechanism that might be more prevalent than is currently known," says Reid Van Lehn, an MIT graduate student in materials science and engineering and one of the paper's lead authors. "By identifying this pathway for the first time it also suggests not only how to engineer this particular class of nanoparticles, but that this pathway might be active in other systems as well."
The paper's other lead author is Maria Ricci of École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland. The research team, led by Alfredo Alexander-Katz, an associate professor of materials science and engineering, and Francesco Stellacci from EPFL, also included scientists from the Carlos Besta Institute of Neurology in Italy and Durham University in the United Kingdom.
Most nanoparticles enter cells through endocytosis, a process that traps the particles in intracellular compartments, which can damage the cell membrane and cause cell contents to leak out. However, in 2008, Stellacci, who was then at MIT, and Darrell Irvine, a professor of materials science and engineering and of biological engineering, found that a special class of gold nanoparticles coated with a mix of molecules could enter cells without any disruption.
"Why this was happening, or how this was happening, was a complete mystery," Van Lehn says.
Last year, Alexander-Katz, Van Lehn, Stellacci, and others discovered that the particles were somehow fusing with cell membranes and being absorbed into the cells. In their new study, they created detailed atomistic simulations to model how this happens, and performed experiments that confirmed the model's predictions.
Stealth entry
Gold nanoparticles used for drug delivery are usually coated with a thin layer of molecules that help tune their chemical properties. Some of these molecules, or ligands, are negatively charged and hydrophilic, while the rest are hydrophobic. The researchers found that the particles' ability to enter cells depends on interactions between hydrophobic ligands and lipids found in the cell membrane.
Cell membranes consist of a double layer of phospholipid molecules, which have hydrophobic lipid tails and hydrophilic heads. The lipid tails face in toward each other, while the hydrophilic heads face out.
In their computer simulations, the researchers first created what they call a "perfect bilayer," in which all of the lipid tails stay in place within the membrane. Under these conditions, the researchers found that the gold nanoparticles could not fuse with the cell membrane.
However, if the model membrane includes a "defect" -- an opening through which lipid tails can slip out -- nanoparticles begin to enter the membrane. When these lipid protrusions occur, the lipids and particles cling to each other because they are both hydrophobic, and the particles are engulfed by the membrane without damaging it.
In real cell membranes, these protrusions occur randomly, especially near sites where proteins are embedded in the membrane. They also occur more often in curved sections of membrane, because it's harder for the hydrophilic heads to fully cover a curved area than a flat one, leaving gaps for the lipid tails to protrude.
"It's a packing problem," Alexander-Katz says. "There's open space where tails can come out, and there will be water contact. It just makes it 100 times more probable to have one of these protrusions come out in highly curved regions of the membrane."
Mimicking nature
This phenomenon appears to mimic a process that occurs naturally in cells -- the fusion of vesicles with the cell membrane. Vesicles are small spheres of membrane-like material that carry cargo such as neurotransmitters or hormones.
The similarity between absorption of vesicles and nanoparticle entry suggests that cells where a lot of vesicle fusion naturally occurs could be good targets for drug delivery by gold nanoparticles. The researchers plan to further analyze how the composition of the membranes and the proteins embedded in them influence the absorption process in different cell types. "We want to really understand all the constraints and determine how we can best design nanoparticles to target particular cell types, or regions of a cell," Van Lehn says.
"One could use the results from this paper to think about how to leverage these findings into improved nanoparticle delivery vehicles -- for instance, perhaps new surface ligands for nanoparticles could be engineered to have improved affinity for both surface groups and lipid tails," says Catherine Murphy, a professor of chemistry at the University of Illinois at Urbana-Champaign who was not involved in the study.
The research was funded by the National Science Foundation and the Swiss National Foundation.
Video: http://www.youtube.com/watch?v=jxRTYOdR654
 

Journal Reference:

1. Reid C. Van Lehn, Maria Ricci, Paulo H.J. Silva, Patrizia Andreozzi, Javier Reguera, Kislon Voïtchovsky, Francesco Stellacci, Alfredo Alexander-Katz. Lipid tail protrusions mediate the insertion of nanoparticles into model cell membranes. Nature Communications, 2014; 5 DOI: 10.1038/ncomms5482 

Courtesy: ScienceDaily
 

Global temperature reaches record high in June following record warmth in May

According to NOAA scientists, the globally averaged temperature over land and ocean surfaces for June 2014 was the highest for June since record keeping began in 1880. It also marked the 38th consecutive June and 352nd consecutive month with a global temperature above the 20th century average. The last below-average global temperature for June was in 1976 and the last below-average global temperature for any month was February 1985.

June 2014 Blended Land and Sea Surface Temperature Percentiles.

Most of the world experienced warmer-than-average monthly temperatures, with record warmth across part of southeastern Greenland, parts of northern South America, areas in eastern and central Africa, and sections of southern and southeastern Asia. Similar to May, scattered sections across every major ocean basin were also record warm. Notably, large parts of the western equatorial and northeastern Pacific Ocean and most of the Indian Ocean were record warm or much warmer than average for the month. A few areas in North America, Far East Russia, and small parts of central and northeastern Europe were cooler or much cooler than average.

A monthly summary (http://www.ncdc.noaa.gov/sotc/global/2014/6) from NOAA's National Climatic Data Center in Asheville, NC, is part of the suite of climate services NOAA provides to government, the business sector, academia and the public to support informed decision making.

Selected significant climate anomalies and events: June 2014.
Global temperature highlights: June

• The combined average temperature over global land and ocean surfaces for June 2014 was record high for the month at 61.20°F (16.22°C), or 1.30°F (0.72°C) above the 20th century average of 59.9°F (15.5°C). This surpasses the previous record, set in 2010, by (0.05°F) 0.03°C. Nine of the ten warmest Junes on record have all occurred during the 21st century, including each of the past five years. The margin of error associated with this temperature is +/- 0.16°F (0.09°C).
• The June global land temperature was the seventh highest for June on record at 1.71°F (0.95°C) above the 20th century average of 55.9°F (13.3°C). The margin of error is +/- 0.25°F (0.14°C). The seven highest June global land surface temperatures have occurred in the past decade.
• Thirty-one countries across every continent, with the exception of Antarctica, reported at least one station with a record warm June temperature. The period of record varies by station. Some national temperature highlights include:
  • New Zealand observed its warmest June since national records began in 1909. The warmth was notable for both its intensity and coverage, with above-average temperatures from the top of the North Island to the bottom of the South Island.
  • France observed its fifth warmest June in the country's 115-year period of record at 2.3°F (1.3°C) above the 1981-2010 average. A week-long heat wave contributed to the overall warmth for the month.
  • Parts of Greenland were record warm during June. Kangerlussuaq in southwestern Greenland observed its record highest maximum June temperature of 23.2°C (73.8°F) on June 15, surpassing the previous record of 23.1°C (73.6°F) set in both 1988 and 2002. Records at this station date back to 1958.
• For the ocean, the June global sea surface temperature was 1.15°F (0.64°C) above the 20th century average of 61.5°F (16.4°C), the highest for June on record. This surpasses the previous all-time record for any month by 0.09°F (0.05°C), set in June 1998 and tied in October 2003, July 2009, and just last month in May 2014. The margin of error is +/- 0.07°F (0.04°C).
• Although neither El Niño nor La Niña conditions were present across the central and eastern equatorial Pacific Ocean during June 2014, NOAA's Climate Prediction Center estimates that there is about a 70 percent chance that El Niño conditions will develop during Northern Hemisphere summer 2014 and 80 percent chance it will develop during the fall and winter.

Polar ice highlights: June

• The average Arctic sea ice extent for June was 4.4 million square miles, 220,000 square miles (4.9 percent) below the 1981-2010 average and the sixth smallest June extent since records began in 1979, according to the National Snow and Ice Data Center. The seasonal sea ice extent decline during June was faster than average, with rapid ice loss near the end of month.
• On the opposite pole, the Antarctic sea ice extent for June was 5.9 million square miles, 510,000 square miles (9.6 percent) above the 1981-2010 average. This marked the largest June Antarctic sea ice extent since records began in 1979, surpassing the previous record large June Antarctic sea ice extent that occurred in 2010 by about 100,000 square miles. Seven of the past 12 months have had a record large Antarctic sea ice extent.
• Combining the Arctic and Antarctic sea ice, June global sea ice was 10.3 million square miles, 2.9 percent above the 1981-2010 average. This was the third largest global June sea ice extent on record and the largest since 1982.

Precipitation highlights: June

• Extreme wetness was observed during June over regions including central North America and parts of eastern and northern Europe. Extreme dryness was scattered across different parts of the globe, including much of South Asia and Australia.
• In India, the southwest monsoon onset over Kerala occurred on June 6, five days later than the normal date of June 1. For the period June 1-30, rainfall across the country was just 60 percent of the 1951-2000 average for the country as a whole. Every region experienced rainfall deficits during this period, ranging from 43 percent of average in Central India to 72 percent of average on the South Peninsula. The monsoon season lasts from early June through late September.
• Australia received 68 percent of average rainfall during June. Western Australia received just 28 percent of their average rainfall for the month, the seventh lowest for June for the state.

Global temperature highlights: Year-to-date

• The first half of 2014 (January-June) tied with 2002 as the third warmest such period on record, with a combined global land and ocean average surface temperature 1.21°F (0.67°C) above the 20th century average of 56.3°F (13.5°C). Only 2010 and 1998 were warmer. Thirteen of the past fourteen such periods have occurred during the 21st century. The margin of error is +/- 0.18°F (0.10°C).
• The January-June worldwide land surface temperature was 1.87°F (1.04°C) above the 20th century average, tying with 1998 and 2005 as the fourth warmest such period on record. The margin of error is +/- 0.41°F (0.23°C).
• The global ocean surface temperature for the year to date was 0.95°F (0.53°C) above average, the third warmest such period on record behind 1998 and 2010. The margin of error is +/-0.09°F (0.05°C).

On the Web:

• Global Climate Report for June 2014: http://www.ncdc.noaa.gov/sotc/global/2014/06/
• U.S. Climate Report for June 2014: http://www.ncdc.noaa.gov/sotc/national/2014/6/
• NOAA Climate Portal: http://www.climate.gov

Courtesy: NOAA/National Climatic Data Center. "Global temperature reaches record high in June following record warmth in May." ScienceDaily. ScienceDaily, 22 July 2014. .

Ötzi's non-human DNA: Opportunistic pathogen discovered in Iceman tissue biopsy

Otzi's human genome was decoded from a hip bone sample taken from the 5,300 year old mummy. However the tiny sample weighing no more than 0.1 g provides so much more information. A team of scientists from EURAC in Bolzano/Bozen together with colleagues from the University of Vienna successfully analysed the non-human DNA in the sample. They found evidence for the presence of Treponema denticola, an opportunistic pathogen involved in the development of periodontal disease. Thus, by just looking at the DNA, the researchers could support a CT-based diagnosis made last year which indicated that the Iceman suffered from periodontitis. The results of the current study have recently been published in the online scientific journal PLOS ONE.

 

Much of what we know about Ötzi -- for example what he looked like or that he suffered from lactose intolerance -- stems from a tiny bone sample which allowed the decoding of his genetic make-up. Now, however, the team of scientists have examined more closely the part of the sample consisting of non-human DNA. "What is new is that we did not carry out a directed DNA analysis but rather investigated the whole spectrum of DNA to better understand which organisms are in this sample and what is their potential function," is how Frank Maixner, from the EURAC Institute for Mummies and the Iceman in Bozen/Bolzano, described the new approach which the team of scientists are now pursuing.
"This 'non-human' DNA mostly derives from bacteria normally living on and within our body. Only the interplay between certain bacteria or an imbalance within this bacterial community might cause certain diseases. Therefore it is highly important to reconstruct and understand the bacterial community composition by analysing this DNA mixture," said Thomas Rattei, Professor of Bioinformatics from the Department of Microbiology and Ecosystem Science at the University of Vienna.
Unexpectedly the team of scientists, specialists in both microbiology as well as bioinformatics, detected in the DNA mixture a sizeable presence of a particular bacterium: Treponema denticola, an opportunistic pathogen involved in the development of periodontitis. Thus this finding supports the computer tomography based diagnosis that the Iceman suffered from periodontitis. Even more surprising is that the analysis of a tiny bone sample can still, after 5,300 years, provide us with the information that this opportunistic pathogen seems to have been distributed via the bloodstream from the mouth to the hip bone. Furthermore, the investigations indicate that these members of the human commensal oral microflora were old bacteria which did not colonise the body after death.
Besides the opportunistic pathogen, the team of scientists led by Albert Zink -- head of the EURAC Institute for Mummies and the Iceman -- also detected Clostridia-like bacteria in the Iceman bone sample which are at present most presumably in a kind of dormant state. Under hermetically sealed, anaerobic conditions, however, these bacteria can re-grow and degrade tissue. This discovery may well play a significant part in the future conservation of the world-famous mummy. "This finding indicates that altered conditions for preserving the glacier mummy, for example when changing to a nitrogen-based atmosphere commonly used for objects of cultural value, will require additional micro-biological monitoring," explained the team of scientists who will now look closer at the microbiome of the Iceman.

Journal Reference:

1. Frank Maixner, Anton Thomma, Giovanna Cipollini, Stefanie Widder, Thomas Rattei, Albert Zink. Metagenomic Analysis Reveals Presence of Treponema denticola in a Tissue Biopsy of the Iceman. PLoS ONE, 2014; 9 (6): e99994 DOI: 10.1371/journal.pone.0099994 

Courtesy: ScienceDaily

Protein's 'hands' enable bacteria to establish infection, research finds

Kansas State University biochemists have found the helping hand: groups of tiny protein loops on the surface of cells. These loops are similar to the fingers of a hand, and by observing seven individual loops on the surface of E. coli bacterial cells, the researchers found that the loops can open or close to grab iron in the environment.

"These structures are like small hands on the surface of bacterial cells," said Phillip Klebba, principal investigator and professor and head of biochemistry and molecular biophysics. "They make the bacteria capable of recognizing something and grabbing it from the environment. It's amazing that such a tiny molecule can do that."

Kansas State University researchers are the first to observe this process. Their experiments may lead to new ways to protect people and animals against bacterial infections by helping scientists develop targeted treatment and intervention methods.

The research is featured as the cover article for the July issue of the Journal of General Physiology.

All cells need iron to stay alive, which puts iron at the center of the microbial pathogenesis process. When bacteria invade an animal or human, they must acquire iron to establish an infection, Klebba said.

"A microbiological war is going on in the host tissue," Klebba said. "The host is trying to prevent the microbe from getting iron. The microbe is trying to get the iron using proteins that can essentially see their environment, grab iron and internalize it into the bacterial cell."

In the latest research, the scientists used site-directed spectroscopic analysis of E. coli cells to monitor the activity of the surface transport proteins. Through their experiments, they observed the seven loops on the cell surface moving as they recognized and absorbed iron in the environment for later transport into the cell.

The absorption process happens quickly and efficiently, Klebba said. Less than a second after the bacteria enter an environment with iron compounds, they recognize the molecules, grab them and start the transfer process.

"If we can understand exactly how this acquisition process works, we can design, isolate or identify small molecules that inhibit the iron uptake process," Klebba said. "Those are potentially antimicrobial agents that could protect people and animals against bacterial disease."

The scientists will continue the research to get a full understanding of how the proteins manage to transport iron from the outside to the inside of cells.

Journal Reference:

1. C. R. Smallwood, L. Jordan, V. Trinh, D. W. Schuerch, A. Gala, M. Hanson, Y. Shipelskiy, A. Majumdar, S. M. C. Newton, P. E. Klebba. Concerted loop motion triggers induced fit of FepA to ferric enterobactin. The Journal of General Physiology, 2014; DOI: 10.1085/jgp.20131115907012014c

 Courtesy: ScienceDaily

Taking B vitamins won't prevent Alzheimer's disease, researchers conclude

Taking B vitamins doesn't slow mental decline as we age, nor is it likely to prevent Alzheimer's disease, conclude Oxford University researchers who have assembled all the best clinical trial data involving 22,000 people to offer a final answer on this debate.

High levels in the blood of a compound called homocysteine have been found in people with Alzheimer's disease, and people with higher levels of homocysteine have been shown to be at increased risk of Alzheimer's disease. Taking folic acid and vitamin B-12 are known to lower levels of homocysteine in the body, so this gave rise to the 'homocysteine hypothesis' that taking B vitamins could reduce the risk of Alzheimer's disease.
The new analysis was carried out by the B-Vitamin Treatment Trialists' Collaboration, an international group of researchers led by the Clinical Trial Service Unit at the University of Oxford. The researchers brought together data from 11 randomized clinical trials involving 22,000 people which compared the effect of B vitamins on cognitive function in older people against placebo. Participants receiving B vitamins did see a reduction in the levels of homocysteine in their blood by around a quarter. However, this had no effect on their mental abilities.
When looking at measures of global cognitive function -- or scores for specific mental processes such as memory, speed or executive function -- there was no difference between those on B vitamins and those receiving placebo to a high degree of accuracy.
'It would have been very nice to have found something different,' says Dr Robert Clarke of Oxford University, who led the work. 'Our study draws a line under the debate: B vitamins don't reduce cognitive decline as we age. Taking folic acid and vitamin B-12 is sadly not going to prevent Alzheimer's disease.'
The study was funded by the British Heart Foundation, the UK Medical Research Council (MRC), Cancer Research UK, the UK Food Standards Agency and the Department of Health. The findings are published in the American Journal of Clinical Nutrition.
'Taking supplements like B vitamins doesn't prevent heart disease, stroke or cognitive decline,' says Professor Clarke. 'About 25-30% of the adult population take multi-vitamins, often with the idea that they are also good for the heart or the brain, but the evidence just isn't there. Much better is to eat more fruit and vegetables, avoid too much red meat and too many calories, and have a balanced diet.'
Maternal folic acid intake before and during early pregnancy reduces a woman's risk of having a neural tube defect birth defect and those thinking of having a baby are routinely advised to take folic acid supplements. Countries that have adopted mandatory population-wide folic acid fortification programmes have also demonstrated reductions in neural-tube defect associated pregnancies without any adverse effects.
Dr Simon Ridley, Head of Research at Alzheimer's Research UK, said:
'Although one trial in 2010 showed that for people with high homocysteine, B vitamins had some beneficial effect on the rate of brain shrinkage, this comprehensive review of several trials shows that B vitamins have not been able to slow mental decline as we age, nor are they likely to prevent Alzheimer's. While the outcome of this new and far reaching analysis is not what we hoped for, it does underline the need for larger studies to improve certainty around the effects of any treatment.
'Alzheimer's is feared by many and it's natural that people want to take action to try to prevent the disease, but people should always speak to their GP before changing their diet to include vitamin supplements. Research to understand how to prevent Alzheimer's must continue, and in the meantime evidence shows that a number of simple lifestyle changes can help reduce the risk of the disease. Eating a healthy, balanced diet, taking regular exercise and keeping blood pressure and weight in check can all help lower the risk of Alzheimer's.'
Dr James Pickett, Head of Research at Alzheimer's Society said:
'Given that many previous studies have shown that vitamin B doesn't slow the progression of dementia or reduce risk, it's not a huge surprise that a review of all of the evidence finds much the same. While taking B vitamins may not help everyone, they may have some benefits in specific groups of people with dementia. However, this study suggests that we need much more work to establish more evidence for this.
'One in three people over the age of 65 will develop dementia and yet research funding lags behind other conditions and we haven't seen a new treatment made available in a decade. We need to see significantly more investment and recruit the next generation of leaders in research in order to deliver breakthroughs that could prove so vital to those affected by the condition.'
Hugh Perry, chair of the MRC Neurosciences and Mental Health Board, said:
'Science progresses through testing and re-testing previous research and sometimes overturning existing theories. Health advice always needs to be based on the best available data from the largest possible studies and this is even more important when the findings have implications for what we do or don't eat and drink.'

Journal Reference:

1. R. Clarke, D. Bennett, S. Parish, S. Lewington, M. Skeaff, S. J. Eussen, C. Lewerin, D. J. Stott, J. Armitage, G. J. Hankey, E. Lonn, D. Spence, P. Galan, L. C. de Groot, J. Halsey, A. D. Dangour, R. Collins, F. Grodstein. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. American Journal of Clinical Nutrition, 2014; DOI: 10.3945/%u200Bajcn.113.076349

Courtesy: ScienceDaily

Herpes virus infection drives HIV infection among non-injecting drug users in New York

HIV and its transmission has long been associated with injecting drug use, where hypodermic syringes are used to administer illicit drugs. Now, a newly reported study by researchers affiliated with New York University's Center for Drug Use and HIV Research (CDUHR) in the journal PLOS ONE, shows that HIV infection among heterosexual non-injecting drug users (no hypodermic syringe is used; drugs are taken orally or nasally) in New York City (NYC) has now surpassed HIV infection among persons who inject drugs.

The study, "HSV-2 Co-Infection as a Driver of HIV Transmission among Heterosexual Non-Injecting Drug Users in New York City," was conducted among drug users entering the Mount Sinai Beth Israel drug treatment programs in NYC. The researchers found that HIV infection among non-injecting drug users doubled over the last two decades, from 7% infected in the late 1990s (n= 785) to 14% (n=1764) currently. During this same time-frame, HIV infection among persons who inject drugs fell to 10%.
The increased efficiency for transmitting HIV occurs even when persons with herpes simplex virus 2 (HSV-2) are between outbreaks, as herpes increases both susceptibility to and transmissibility of HIV. More than half of the non-injecting drug users in the study were infected with HSV-2.
"Heterosexual intercourse is usually not very efficient for transmitting HIV, but the efficiency of heterosexual transmission nearly triples in the presence of herpes simplex virus type 2," notes the study's lead author, Don Des Jarlais, PhD, Deputy Director, Research Methods and Infectious Diseases Cores, Center for Drug Use and HIV Research (CDUHR) and Professor of Psychiatry and of Preventive Medicine at Mount Sinai Beth Israel. "In New York City, we have done an excellent job of reducing HIV among persons who inject drugs and we must now put more efforts into reducing sexual transmission associated with non-injecting drug use."
The study concludes that an increase in HIV infection among these non-injecting drug users is better considered as an increase in HSV- 2/HIV co-infection rather than simply an increase in HIV prevalence. Additional interventions (such as treatment as prevention and pre-exposure prophylaxis) are needed to reduce further HIV transmission from HSV-2/HIV co-infected non-injecting drug users.
The City Department of Health and Mental Hygiene has initiated a program "treatment as prevention," in which HIV infected persons are given anti-viral medications to both protect their own health and to reduce the chances that they will transmit HIV to others. There are also new federal recommendations to provide anti-retroviral medications to HIV uninfected persons at high risk for becoming infected.
"If we can implement these programs on a large scale, we should be able to control sexual transmission of HIV in the city, and achieve the goal of an "End to the AIDS Epidemic," said Dr. Des Jarlais.
 

Journal Reference:

1. Don C. Des Jarlais, Kamyar Arasteh, Courtney McKnight, David C. Perlman, Jonathan Feelemyer, Holly Hagan, Hannah L. F. Cooper. HSV-2 Co-Infection as a Driver of HIV Transmission among Heterosexual Non-Injecting Drug Users in New York City. PLoS ONE, 2014; 9 (1): e87993 DOI: 10.1371/journal.pone.0087993 

Courtesy: ScienceDaily
 

Potential Alzheimer's drug prevents abnormal blood clots in brain

Without a steady supply of blood, neurons can't work. That's why one of the culprits behind Alzheimer's disease is believed to be the persistent blood clots that often form in the brains of Alzheimer's patients, contributing to the condition's hallmark memory loss, confusion and cognitive decline.

Treatment with the compound RU-505 improved the chronic and damaging inflammation (red) in the brains of mice exhibiting Alzheimer's (top), as compared to Alzheimer's mice that went untreated (bottom).

Credit: Strickland Lab, The Rockefeller University

New experiments in Sidney Strickland's Laboratory of Neurobiology and Genetics at Rockefeller University have identified a compound that might halt the progression of Alzheimer's by interfering with the role amyloid-β, a small protein that forms plaques in Alzheimer's brains, plays in the formation of blood clots. This work is highlighted in the July issue of Nature Reviews Drug Discovery.
For more than a decade, potential Alzheimer's drugs have targeted amyloid-β, but, in clinical trials, they have either failed to slow the progression of the disease or caused serious side effects. However, by targeting the protein's ability to bind to a clotting agent in blood, the work in the Strickland lab offers a promising new strategy, according to the highlight, which will be published in print on July 1.
This latest study builds on previous work in Strickland's lab showing amyloid-β can interact with fibrinogen, the clotting agent, to form difficult-to-break-down clots that alter blood flow, cause inflammation and choke neurons.
"Our experiments in test tubes and in mouse models of Alzheimer's showed the compound, known as RU-505, helped restore normal clotting and cerebral blood flow. But the big pay-off came with behavioral tests in which the Alzheimer's mice treated with RU-505 exhibited better memories than their untreated counterparts," Strickland says. "These results suggest we have found a new strategy with which to treat Alzheimer's disease."
RU-505 emerged from a pack of 93,716 candidates selected from libraries of compounds, the researchers write in the June issue of the Journal of Experimental Medicine. Hyung Jin Ahn, a research associate in the lab, examined these candidates with a specific goal in mind: Find one that interferes with the interaction between fibrinogen and amyloid-β. In a series of tests that began with a massive, automated screening effort at Rockefeller's High Throughput Resource Center, Ahn and colleagues winnowed the 93,000 contenders to five. Then, test tube experiments whittled the list down to one contender: RU-505, a small, synthetic compound. Because RU-505 binds to amyloid-β and only prevents abnormal blood clot formation, it does not interfere with normal clotting. It is also capable of passing through the blood-brain barrier.
"We tested RU-505 in mouse models of Alzheimer's disease that over-express amyloid- β and have a relatively early onset of disease. Because Alzheimer's disease is a long-term, progressive disease, these treatments lasted for three months," Ahn says. "Afterward, we found evidence of improvement both at the cellular and the behavioral levels."
The brains of the treated mice had less of the chronic and harmful inflammation associated with the disease, and blood flow in their brains was closer to normal than that of untreated Alzheimer's mice. The RU-505-treated mice also did better when placed in a maze. Mice naturally want to escape the maze, and are trained to recognize visual cues to find the exit quickly. Even after training, Alzheimer's mice have difficulty in exiting the maze. After these mice were treated with RU-505, they performed much better.
"While the behavior and the brains of the Alzheimer's mice did not fully recover, the three-month treatment with RU-505 prevents much of the decline associated with the disease," Strickland says.
The researchers have begun the next steps toward developing a human treatment. Refinements to the compound are being supported by the Robertson Therapeutic Development Fund and the Tri-Institutional Therapeutic Discovery Institute. As part of a goal to help bridge critical gaps in drug discovery, these initiatives support the early stages of drug development, as is being done with RU-505.
"At very high doses, RU-505 is toxic to mice and even at lower doses it caused some inflammation at the injection site, so we are hoping to find ways to reduce this toxicity, while also increasing RU-505's efficacy so smaller doses can accomplish similar results," Ahn says.
 

Journal Reference:

1. H. J. Ahn, J. F. Glickman, K. L. Poon, D. Zamolodchikov, O. C. Jno-Charles, E. H. Norris, S. Strickland. A novel A -fibrinogen interaction inhibitor rescues altered thrombosis and cognitive decline in Alzheimer's disease mice. Journal of Experimental Medicine, 2014; 211 (6): 1049 DOI: 10.1084/jem.20131751 

Courtesy: ScienceDaily