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Schizophrenia is not a single disease but rather consists of eight different genetically distinct classes

Schizophrenia is not a single disease but rather consists of eight different genetically distinct classes | Amazing Science |

New research shows that schizophrenia isn’t a single disease but a group of eight genetically distinct disorders, each with its own set of symptoms. The finding could be a first step toward improved diagnosis and treatment for the debilitating psychiatric illness.

The research at Washington University School of Medicine in St. Louis is reported online Sept. 15 in The American Journal of Psychiatry. About 80 percent of the risk for schizophrenia is known to be inherited, but scientists have struggled to identify specific genes for the condition.

Now, in a novel approach analyzing genetic influences on more than 4,000 people with schizophrenia, the research team has identified distinct gene clusters that contribute to eight different classes of schizophrenia.

“Genes don’t operate by themselves,” said C. Robert Cloninger, MD, PhD, one of the study’s senior investigators. “They function in concert much like an orchestra, and to understand how they’re working, you have to know not just who the members of the orchestra are but how they interact.” 

Cloninger, the Wallace Renard Professor of Psychiatry and Genetics, and his colleagues matched precise DNA variations in people with and without schizophrenia to symptoms in individual patients. In all, the researchers analyzed nearly 700,000 sites within the genome where a single unit of DNA is changed, often referred to as a single nucleotide polymorphism (SNP). They looked at SNPs in 4,200 people with schizophrenia and 3,800 healthy controls, learning how individual genetic variations interacted with each other to produce the illness. 

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Japanese woman is first recipient of next-generation stem cells

Japanese woman is first recipient of next-generation stem cells | Amazing Science |

A Japanese woman in her 70s is the world's first recipient of cells derived from induced pluripotent stem cells, a technology that has created great expectations since it could offer the same advantages as embryo-derived cells but without some of the controversial aspects and safety concerns.

In a two-hour procedure, a team of three eye specialists lead by Yasuo Kurimoto of the Kobe City Medical Center General Hospital, transplanted a 1.3 by 3.0 millimeter sheet of retinal pigment epithelium cells into an eye of the Hyogo prefecture resident, who suffers from age-related macular degeneration.

The procedure took place at the Institute of Biomedical Research and Innovation Hospital, next to the RIKEN Center for Developmental Biology (CDB) where ophthalmologist Masayo Takahashi had developed and tested the epithelium sheets. She derived them from the patient's skin cells, after producing induced pluripotent stem (iPS) cells and then getting them to differentiate into retinal cells. Afterwards, the patient experienced no effusive bleeding or other serious problems, RIKEN has reported.

The patient “took on all the risk that go with the treatment as well as the surgery”, Kurimoto said in a statement released by RIKEN. “I have deep respect for bravery she showed in resolving to go through with it.”

He hit a somber note in thanking Yoshiki Sasai, a CDB researcher who recenty committed suicide. “This project could not have existed without the late Yoshiki Sasai’s research, which led the way to differentiating retinal tissue from stem cells.”

Kurimoto also thanked Shinya Yamanaka, a stem-cell scientist at Kyoto University “without whose discovery of iPS cells, this clinical research would not be possible.” Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine for that work.

Kurimoto performed the procedure a mere four days after a health-ministry committee gave Takahashi clearance for the human trials (see 'Next-generation stem cells cleared for human trial').

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Woman of 24 found to have no cerebellum in her brain

Woman of 24 found to have no cerebellum in her brain | Amazing Science |

A 24-year-old woman has discovered that her cerebellum is completely missing, explaining some of the unusual problems she has had with movement and speech. The case highlights just how adaptable the organ is.

The discovery was made when the woman was admitted to the Chinese PLA General Hospital of Jinan Military Area Command in Shandong Province complaining of dizziness and nausea. She told doctors she'd had problems walking steadily for most of her life, and her mother reported that she hadn't walked until she was 7 and that her speech only became intelligible at the age of 6.

Doctors did a CAT scan and immediately identified the source of the problem – her entire cerebellum was missing (see scan, below left). The space where it should be was empty of tissue. Instead it was filled with cerebrospinal fluid, which cushions the brain and provides defence against disease.

The cerebellum – sometimes known as the "little brain" – is located underneath the two hemispheres. It looks different from the rest of the brain because it consists of much smaller and more compact folds of tissue. It represents about 10 per cent of the brain's total volume but contains 50 per cent of its neurons.

Although it is not unheard of to have part of your brain missing, either congenitally or from surgery, the woman joins an elite club of just nine people who are known to have lived without their entire cerebellum. A detailed description of how the disorder affects a living adult is almost non-existent, say doctors from the Chinese hospital, because most people with the condition die at a young age and the problem is only discovered on autopsy (Brain,

The cerebellum's main job is to control voluntary movements and balance, and it is also thought to be involved in our ability to learn specific motor actions and speak. Problems in the cerebellum can lead to severe mental impairment, movement disorders, epilepsy or a potentially fatal build-up of fluid in the brain. However, in this woman, the missing cerebellum resulted in only mild to moderate motor deficiency, and mild speech problems such as slightly slurred pronunciation. Her doctors describe these effects as "less than would be expected", and say her case highlights the remarkable plasticity of the brain.

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Estimating the fatality of the 2014 West African Ebola Outbreak

Estimating the fatality of the 2014 West African Ebola Outbreak | Amazing Science |

Case fatality rate" - or CFR - is a term that's been tossed around a lot lately in the context of the 2014 West African Ebola outbreak… But what does it really mean?

The CFR – which is calculated by dividing the number of deaths that have occurred due to a certain condition by the total number of cases – is actually a measure of risk. For infectious disease, CFR is a very important epidemiological measure to estimate because it tells us the probability of dying after infection. If estimated properly in the middle of an outbreak, it can even help us examine the efficacy of interventions as they take place.

Because different outbreaks of the same disease can demonstrate different CFRs, there’s usually a range of possible CFRs for a given disease. In the past, outbreaks caused by Zaire ebolavirus have demonstrated a mean end-of-outbreak CFR of 80% . But based off of the WHO's most recent report, it seems that only about 53% of reported Ebola cases thus far have ended in death since the 2014 outbreak began.

However, if we want to be particular, that 53% isn't really a CFR; it's actually the proportion of fatal cases - or PFC. This is a critical distinction. Because the outbreak in West Africa is still ongoing, we can't calculate end-of-outbreak CFR yet. We don’t know how many people will die from Ebola in the weeks ahead or how many total cases will ultimately accumulate by the end of the outbreak. So, for the time being, we have to make do with the PFC, which is essentially the number of deaths thus far divided by the number of cases to date.

When the WHO releases a report on the current situation in West Africa, it tells us two things: the number of people who've died and the number of reported cases at some specified point in time. For instance, in the most recent report, the WHO cited 4293 total cases and 2296 deaths as of September 8th. Dividing 2296 by 4293 gives us our previously stated PFC of 53%.

At first glance, it might seem then that only 53% of Ebola cases have been dying during this outbreak - a good deal less than the 80% we've seen prior... But what it really means is that only 53% of Ebola cases have died as of September 8th. We have no way of knowing whether all the people who were still hospitalized as of September 8th will survive the disease. Because of this, mid-outbreak PFC - as we've defined it thus far - doesn't tell us much about the likelihood of dying.

Despite Ebola’s frightening reputation, not all Ebola fatalities happen quickly. Without a little fine-tuning, PFC doesn't account for the lag between when a case is reported and when a case dies - approximately 16 days for this outbreak [3]. What this means is that the 2296 deaths reported as of September 8th were all likely reported as cases by August 23rd. Adjusting PFC for this lag-time gives us a much better approximation of CFR well before the outbreak ends.

Below is a chart that shows both unadjusted and lag-adjusted PFC over time for Ebola in West Africa [5]. The lag-adjusted PFC - about 80-85% - is significantly higher than the unadjusted PFC but is consistent with recent fatality estimates by Médecins Sans Frontières.

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Ultraviolet light-induced mutation drives many skin cancers and over 330 genes seem to be involved in the process

Ultraviolet light-induced mutation drives many skin cancers and over 330 genes seem to be involved in the process | Amazing Science |
Genes that cause cancer when mutated are known as oncogenes. Although KNSTRN hasn't been previously implicated as a cause of human cancers, the research suggests it may be one of the most commonly mutated oncogenes in the world.

"This previously unknown oncogene is activated by sunlight and drives the development of cutaneous squamous cell carcinomas," said Paul Khavari, MD, PhD, the Carl J. Herzog Professor in Dermatology in the School of Medicine and chair of the Department of Dermatology. "Our research shows that skin cancers arise differently from other cancers, and that a single mutation can cause genomic catastrophe."

Cutaneous squamous cell carcinoma is the second most common cancer in humans. More than 1 million new cases are diagnosed globally each year. The researchers found that a particular region of KNSTRN is mutated in about 20 percent of cutaneous squamous cell carcinomas and in about 5 percent of melanomas.

A paper describing the research will be published online Sept. 7, 2014 in Nature Genetics. Khavari, who is also a member of the Stanford Cancer Institute and chief of the dermatology service at the Veterans Affairs Palo Alto Health Care System, is the senior author of the paper. Postdoctoral scholar Carolyn Lee, MD, PhD, is the lead author.

Lee and Khavari made the discovery while investigating the genetic causes of cutaneous squamous cell carcinoma. They compared the DNA sequences of genes from the tumor cells with those of normal skin and looked for mutations that occurred only in the tumors. They found 336 candidate genes for further study, including some familiar culprits. The top two most commonly mutated genes were CDKN2A and TP53, which were already known to be associated with squamous cell carcinoma.

The third most commonly mutated gene, KNSTRN, was a surprise. It encodes a protein that helps to form the kinetochore -- a structure that serves as a kind of handle used to pull pairs of newly replicated chromosomes to either end of the cell during cell division. Sequestering the DNA at either end of the cell allows the cell to split along the middle to form two daughter cells, each with the proper complement of chromosomes.

If the chromosomes don't separate correctly, the daughter cells will have abnormal amounts of DNA. These cells with extra or missing chromosomes are known as aneuploid, and they are often severely dysfunctional. They tend to misread cellular cues and to behave erratically. Aneuploidy is a critical early step toward the development of many types of cancer.

The mutation in the KNSTRN gene was caused by the replacement of a single nucleotide, called a cytosine, with another, called a thymine, within a specific, short stretch of DNA. The swap is indicative of a cell's attempt to repair damage from high-energy ultraviolet rays, such as those found in sunlight.

"Mutations at this UV hotspot are not found in any of the other cancers we investigated," said Khavari. "They occur only in skin cancers." The researchers found the UV-induced KNSTRN mutation in about 20 percent of actinic keratoses -- a premalignant skin condition that often progresses to squamous cell carcinoma -- but never in 122 samples of normal skin, indicating the mutation is likely to be an early event in the development of squamous cell carcinomas.
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FDA-Approved 3D Printed Face Implant is a First

FDA-Approved 3D Printed Face Implant is a First | Amazing Science |

3D printed organsskulls and vertebrae are just a few of the ways 3D printing can literally be a part of us. On Tuesday, biomedical devices company Oxford Performance Materials (OPM) announced the latest addition to 3D printed body parts: a 3D printed face.

OPM has received official FDA approval for a 3D printed facial device that can be used on patients in need of facial reconstructive surgery. The 3D printed OsteoFab® Patient-Specific Facial Device (OPSFD), which is the first and only FDA cleared 3D printed polymeric facial implant, is entirely customizable. It is made of different 3D printed parts that are made to fit each individual patient’s anatomical features.

What is equally revolutionary about the 3D printed facial implant is the drastic reduction in price it brings to facial reconstructive surgery. As it is tailor-made to each patient, the OPSFD reduces overall cost of ownership of a facial implant by reducing operating time, hospital stay duration and the chance of procedure complications. It also minimizes time before surgery as the implant can be 3D printed quickly.

Scott DeFelice, the CEO of OPM, referred to the FDA’s approval of the OPSFD as a paradigm shift:

“There has been a substantial unmet need in personalized medicine for truly individualized – yet economical – solutions for facial reconstruction, and the FDA’s clearance of OPM’s latest orthopedic implant marks a new era in the standard of care for facial reconstruction. Until now, a technology did not exist that could treat the highly complex anatomy of these demanding cases.

With the clearance of our 3D printed facial device, we now have the ability to treat these extremely complex cases in a highly effective and economical way, printing patient-specific maxillofacial implants from individualized MRI or CT digital image files from the surgeon. This is a classic example of a paradigm shift in which technology advances to meet both the patient’s needs and the cost realities of the overall healthcare system.”

Oxford Performance Materials also developed the first and only 3D printed customizable skull implant, which was approved by the FDA in February 2013 and later used to replace 75% of a patient’s skull. According to the president of OPM’s biomedical division, the two implants can now be used together for more complex cases.

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The Gut Microbe That Protects Against Peanut Allergy

The Gut Microbe That Protects Against Peanut Allergy | Amazing Science |

The presence of a common gut microbe called Clostridia protects mice against peanut sensitization by keeping the allergens from entering their bloodstream, according to findings published in Proceedings of the National Academy of Sciences.

In the U.S., food allergy rates among children rose about 50 percent between 1997 and 2011. We don’t know what causes food allergies, though numerous studies hint that recent changes in diet and hygiene (and the use of antibiotics and antimicrobial this and that) have altered the natural community of microorganisms in our gastrointestinal tracts -- increasing our susceptibility to food allergies.

To see how altered microbiota affect immune responses to food, a team led by Cathryn Nagler from the University of Chicago exposed three groups of mice to peanut allergens: germ-free mice without any resident bacteria, mice given antibiotics as newborns to reduce their GI bacteria, and control mice with a normal cohort of GI bacteria.

Germ-free and antibiotic-treated mice showed strong immunological responses, producing higher levels of antibodies against peanuts allergens -- compared to mice with normal gut bacteria, which seem to provide some degree of protection against food allergies.

This peanut sensitization (the rodent model of human allergy) can be reversed. WhenClostridia bacteria were reintroduced into the intestines of germ-free and antibiotic-treated mice, they were no longer sensitive to peanuts. Introducing another type of common GI bacteria, called Bacteroides, failed to alleviate sensitization, further suggesting thatClostridia bacteria are the ones mediating the protection.

To identify the protective mechanism, the team looked at the immune responses on a cellular and molecular level. A gene expression analysis revealed that Clostridia induced an immune response -- the production of molecules called cytokine interleukin-22 (IL-22) -- which reduces the permeability of the lining of mouse intestines. This results in less allergen reaching the bloodstream. “The bacteria are maintaining the integrity of the [intestinal] barrier,” Nagler tells Science.

Finally, the team gave antibiotic-treated mice either IL-22 or Clostridia. When exposed to peanut allergens, mice in both conditions showed reduced allergen levels in their blood, compared to controls. Accordingly, allergen levels increased when mice were given antibodies that neutralized IL-22.

“The first step in getting sensitized to a food allergen is for it to get into your blood and be presented to your immune system,” Nagler says in a news release. “The presence of these bacteria regulates that process." Her team is working to develop and test compositions that could be used for probiotic therapy.

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F.D.A. Allows First Use of Cancer Drug Against Novel Target Class

F.D.A. Allows First Use of Cancer Drug Against Novel Target Class | Amazing Science |

The Food and Drug Administration on Thursday approved the first of an eagerly awaited new class of cancer drugs that unleashes the body’s immune system to fight tumors. The drug, which Merck will sell under the name Keytruda, was approved for patients with advanced melanoma who have exhausted other therapies.

Cancer researchers have been almost giddy in the last couple of years about the potential of drugs like Keytruda, which seem to solve a century-old mystery of how cancerous cells manage to evade the body’s immune system.

The answer is that tumors activate brakes on the immune system, preventing it from attacking them. Keytruda is the first drug approved that inhibits the action of one of those brakes, a protein known as PD-1, or programmed death receptor 1.

“This is really opening up a whole new avenue of effective therapies previously not available,” said Dr. Louis M. Weiner, director of the Georgetown Lombardi Comprehensive Cancer Center in Washington and a spokesman for the American Association for Cancer Research. “It allows us to see a time when we can treat many dreaded cancers without resorting to cytotoxic chemotherapy.”

This general approach might work for many types of cancer, though so far the main successes in clinical trials have come against the deadly skin cancer melanoma, lung cancer and kidney cancer.

But the treatments will not be inexpensive. Merck said Thursday that the drug, known generically as pembrolizumab, would cost about $12,500 a month, or about $150,000 a year.

Merck said the price was in line with that of other cancer drugs, though it seemed to be a bit higher than some. Many cancer doctors have already complained about the rapidly escalating prices of cancer drugs, which they said could put treatments out of reach for some patients.

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CRISPR-CAS shows promising results for correcting muscular dystrophy in mice

CRISPR-CAS shows promising results for correcting muscular dystrophy in mice | Amazing Science |

Researchers used a technique called CRISPR/Cas9-mediated genome editing, which can precisely remove a mutation in DNA, allowing the body’s DNA repair mechanisms to replace it with a normal copy of the gene. The benefit of this over other gene therapy techniques is that it can permanently correct the “defect” in a gene rather than just transiently adding a “functional” one, said Dr. Eric Olson, Director of the Hamon Center for Regenerative Science and Medicine at UT Southwestern and Chairman ofMolecular Biology.

Using CRISPR/Cas9, the Hamon Center team was able to correct the genetic defect in the mouse model of DMD and prevent the development of features of the disease in boys, which causes progressive muscle weakness and degeneration, often along with breathing and heart complications.

“Our findings show that CRISPR/Cas9 can correct the genetic mutation that leads to DMD, at least in mice,” said Dr. Olson, holder of the Pogue Distinguished Chair in Research on Cardiac Birth Defects, the Robert A. Welch Distinguished Chair in Science, and the Annie and Willie Nelson Professorship in Stem Cell Research. “Even in mice with only a subset of corrected cells, we saw widespread and progressive improvement of the condition over time, likely reflecting an advantage of the corrected cells and their contribution to regenerating muscle.”

He also pointed out “this is very important for possible clinical application of this approach in the future. Skeletal muscle is the largest tissue in the human body and current gene therapy methods are only able to affect a portion of the muscle. If the corrected tissue can replace the diseased muscle, patients may get greater clinical benefit.”

Although the genetic cause of DMD has been known for nearly 30 years, there are no treatments that can cure the condition. Duchenne muscular dystrophy breaks down muscle fibers and replaces them with fibrous and/or fatty tissue causing the muscle to gradually weaken.

DMD affects an estimated 1 in 3,600–6,000 male births in the United States, according to the Centers for Disease Control (CDC). Left untreated, those with DMD eventually require use of a wheelchair between age 8 and 11, and have a life expectancy of 25 years. Initial symptoms include difficulty running and jumping, and delays in speech development. DMD can be detected through high levels of a protein called creatine kinase as it leaks into the blood stream, and is confirmed by genetic testing.

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An end to drug errors? Eliminate medication errors with intelligent scanning system

An end to drug errors? Eliminate medication errors with intelligent scanning system | Amazing Science |
Mint Solutions tackles medication errors with scanning system that ensures patients get the right pills.

MIT alumni entrepreneurs Gauti Reynisson MBA ’10 and Ívar Helgason HS ’08 spent the early 2000s working for companies that implemented medication-safety technologies — such as electronic-prescription and pill-barcoding systems — at hospitals in their native Iceland and other European countries.

But all that time spent in hospitals soon opened their eyes to a major health care issue: Surprisingly often, patients receive the wrong medications. Indeed, a 2006 report from the Institute of Medicine found that 1.5 million hospitalized patients in the United States experience medication errors every year due, in part, to drug-administration mistakes. Some cases have adverse or fatal results.

Frustrated and seeking a solution, the Icelandic duo quit their careers and traveled to MIT for inspiration. There, they teamed up with María Rúnarsdóttir MBA ’08 and devised MedEye, a bedside medication-scanning system that uses computer vision to identify pills and check them against medication records, to ensure that a patient gets the right drug and dosage.

Commercialized through startup Mint Solutions, MedEye has now been used for a year in hospitals in the Netherlands (where the startup is based), garnering significant attention from the medical community. Through this Dutch use, the co-founders have determined that roughly 10 percent of MedEye’s scans catch medication errors.

“Medication verification is a pinnacle point of medical safety,” says Helgason, a physician and product developer. “It’s a complicated chain of events that leads up to medication mistakes. But the bedside is the last possible place to stop these mistakes.”

Mint Solutions’ aim, Reynisson says, is to aid nurses in rapidly, efficiently, and correctly administering medication. “We want the device to be the nurse’s best friend,” says Reynisson, now Mint’s CEO. The device, he adds, could yield savings by averting medication mishaps, which can cost hundreds of millions of dollars.

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Chromatophagy, A New Cancer Therapy: Starve The Diseased Cell Until It Eats Its Own DNA

Chromatophagy, A New Cancer Therapy: Starve The Diseased Cell Until It Eats Its Own DNA | Amazing Science |

Nutritional starvation therapy is under intensive investigation because it provides a potentially lower toxicity with higher specificity than conventional cancer therapy. Autophagy, often triggered by starvation, represents an energy-saving, pro-survival cellular function; however, dysregulated autophagy could also lead to cell death, a process distinct from the classic caspase-dependent apoptosis.

A recent study shows how arginine starvation specifically kills tumor cells by a novel mechanism involving mitochondria dysfunction, reactive oxygen species generation, DNA leakage, and chromatin autophagy, where leaked DNA is captured by giant autophagosomes. 

Cells when stressed, whether cancerous or not, undergo a process of cellular suicide that involves controlled dismantling of its interior components such as proteins, DNA, and various compartments.  By far the most famous of such processes is “apoptosis”.  The authors in this study have found another, distinct process involving mitochondria dysfunction, reactive oxygen species (ROS) generation, DNA leakage, and chromatin autophagy.

The senior author, Professor Hsing-Jien Kung, both a cancer biology at UC Davis and  the Director of the National Health Research Institutes in Taipei, Taiwan, first discovered in 2009 the basic mechanism by which arginine shortage kills cancer cells.

“Traditional cancer therapies involve ‘poisoning‘ by toxic chemicals or ‘burning‘ by radiation cancer cells to death, which often have side effects,” according to Professor Kung. “An emerging strategy is to ‘starve’ cancer cells to death, taking advantage of the different metabolic requirements of normal and cancer cells. This approach is generally milder, but as this study illustrates, it also utilizes a different death mechanism, which may complement the killing effects of the conventional therapy.”

AdnanD's curator insight, August 29, 2014 12:29 PM

The perseverance of man kind ! 

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Whole functional organ has been grown from scratch inside an animal for the first time

Whole functional organ has been grown from scratch inside an animal for the first time | Amazing Science |

A group of cells developed into a thymus - a critical part of the immune system - when transplanted into mice. The findings, published in Nature Cell Biology, could pave the way to alternatives to organ transplantation.

Experts said the research was promising, but still years away from human therapies.

The thymus is found near the heart and produces a component of the immune system, called T-cells, which fight infection. Scientists at the Medical Research Council centre for regenerative medicine at the University of Edinburgh started with cells from a mouse embryo.

These cells were genetically "reprogrammed" and started to transform into a type of cell found in the thymus. These were mixed with other support-role cells and placed inside mice.

Once inside, the bunch of cells developed into a functional thymus.

It is similar to a feat last year, when lab-grown human brains reached the same level of development as a nine-week-old fetus.

The thymus is a much simpler organ and in these experiments became fully functional. Structurally it contained the two main regions - the cortex and medulla - and it also produced T-cells.

Prof. Clare Blackburn, part of the research team, said it was "tremendously exciting" when the team realized what they had achieved. "This was a complete surprise to us, that we were really being able to generate a fully functional and fully organized organ starting with reprogrammed cells in really a very straightforward way. This is a very exciting advance and it's also very tantalising in terms of the wider field of regenerative medicine."

Patients who need a bone marrow transplant and children who are born without a functioning thymus could all benefit. Ways of boosting the thymus could also help elderly people. The organ shrinks with age and leads to a weaker immune system. However, there are a number of obstacles to overcome before this research moves from animal studies to hospital therapies. The current technique uses embryos. This means the developing thymus would not be a tissue match for the patient.

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An MRI-guided brain surgery technology goes global

An MRI-guided brain surgery technology goes global | Amazing Science |

An MRI-guided laser system that allows surgeons to perform brain surgery on tumors and epileptic lesions in the brain is expected to become widely available to patients in need now that the technology has been acquired from Visualase Inc. by the global medical device company Medtronic, Inc., says a biomedical engineering professor from Texas A&M University who co-founded the company responsible for the technology.

The technology, says Gerard Coté, professor in the university’s Department of Biomedical Engineering and director of the Center for Remote Healthcare Technology, enables surgeons to pinpoint and destroy brain tumors and lesions with extreme precision and is a much less-invasive alternative to conventional surgery.

The advantage of this approach over other approaches for brain surgery, Coté explains, is that it can be performed while the patient is awake, requires no radiation and no skull flap (the large opening in traditional craniotomies), and is often performed in otherwise inoperable areas of the brain.

Traditional brain surgery, he explains, is usually a daylong operation that involves removing part of the skull, cutting through healthy brain matter and physically removing the problematic tissue. That procedure, he adds, can be followed by a weeklong hospital stay and prolonged recovery period. 

The technology developed by former Texas A&M students Ashok Gowda and the late Roger McNichols, conversely, can be completed in about four hours, and most patients can return home the following day, Coté says. 

Known as “Visualase,” the technology is already used in more than 45 hospitals, nationwide, including 15 pediatric hospitals. Before the surgical procedure, computer software first helps identify the targeted tissue so that it may be treated and the surrounding healthy tissue can be avoided, Coté explains. During the procedure, a small entry is made in the skull that allows a laser applicator (about the size of a pencil lead) to be inserted into the tissue. The patient is placed in the MRI, and a physician receives and reviews images to verify proper positioning of the laser applicator in the skull. The clinician then uses a laser to heat and destroy the problematic tissue while imaging the tissue being damaged in real time to ensure destruction of the problematic tissue and to avoid damaging healthy tissue. The laser applicator is then removed, and the scalp is closed with one stitch, Coté notes.

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Artificial spleen cleans up blood: Device improves survival in rats after severe infections

Artificial spleen cleans up blood: Device improves survival in rats after severe infections | Amazing Science |

Researchers have developed a high-tech method to rid the body of infections — even those caused by unknown pathogens. A device inspired by the spleen can quickly clean blood of everything from Escherichia coli to Ebola, researchers report on 14 September in Nature Medicine1.

The device uses a modified version of mannose-binding lectin (MBL), a protein found in humans that binds to sugar molecules on the surfaces of more than 90 different bacteria, viruses and fungi, as well as to the toxins released by dead bacteria that trigger the immune overreaction in sepsis.

The researchers coated magnetic nanobeads with MBL. As blood enters the biospleen device, passes by the MBL-equipped nanobeads, which bind to most pathogens. A magnet on the biospleen device then pulls the beads and their quarry out of the blood, which can then be routed back into the patient.

To test the device, Ingber and his team infected rats with either E. coli or Staphylococcus aureus and filtered blood from some of the animals through the biospleen. Five hours after infection, 89% of the rats whose blood had been filtered were still alive, compared with only 14% of those that were infected but not treated. The researchers found that the device had removed more than 90% of the bacteria from the rats' blood. The rats whose blood had been filtered also had less inflammation in their lungs and other organs, suggesting they would be less prone to sepsis.

The researchers then tested whether the biospleen could handle the volume of blood in an average adult human — about 5 liters. They ran human blood containing a mixture of bacteria and fungi through the biospleen at a rate of 1 liter per hour, and found that the device removed most of the pathogens within five hours.

Anne Pascucci, MPA, CRA's curator insight, September 15, 2014 1:54 PM

"Inspired by the spleen" Gotta be the first time in history those words were put together!

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Scientists reset human stem cells to earliest developmental state equivalent to 7-9 days old embryo

Scientists reset human stem cells to earliest developmental state equivalent to 7-9 days old embryo | Amazing Science |

Scientists have successfully ‘reset’ human pluripotent stem cells to the earliest developmental state – equivalent to cells found in an embryo before it implants in the womb (7-9 days old). These ‘pristine’ stem cells may mark the true starting point for human development, but have until now been impossible to replicate in the lab. fThe discovery, published in Cell, will lead to a better understanding of human development and could in future allow the production of safe and more reproducible starting materials for a wide range of applications including cell therapies.

Human pluripotent stem cells, which have the potential to become any of the cells and tissues in the body, can be made in the lab either from cells extracted from a very early stage embryo or from adult cells that have been induced into a pluripotent state.

However, scientists have struggled to generate human pluripotent stem cells that are truly pristine (also known as naïve). Instead, researchers have only been able to derive cells which have advanced slightly further down the developmental pathway. These bear some of the early hallmarks of differentiation into distinct cell types – they’re not a truly ‘blank slate’. This may explain why existing human pluripotent stem cell lines often exhibit a bias towards producing certain tissue types in the laboratory.

Now researchers led by the Wellcome Trust-Medical Research Council (MRC) Cambridge Stem Cell Institute at the University of Cambridge, have managed to induce a ground state by rewiring the genetic circuitry in human embryonic and induced pluripotent stem cells. Their ‘reset cells’ share many of the characteristics of authentic naïve embryonic stem cells isolated from mice, suggesting that they represent the earliest stage of development.

“Capturing embryonic stem cells is like stopping the developmental clock at the precise moment before they begin to turn into distinct cells and tissues,” explains Professor Austin Smith, Director of the Stem Cell Institute, who co-authored the paper. “Scientists have perfected a reliable way of doing this with mouse cells, but human cells have proved more difficult to arrest and show subtle differences between the individual cells. It’s as if the developmental clock has not stopped at the same time and some cells are a few minutes ahead of others.”

The process of generating stem cells in the lab is much easier to control in mouse cells, which can be frozen in a state of naïve pluripotency using a protein called LIF. Human cells are not as responsive to LIF, so they must be controlled in a different way that involves switching key genes on and off. For this reason scientists have been unable to generate human pluripotent cells that are as primitive or as consistent as mouse embryonic stem cells.

The researchers overcame this problem by introducing two genes – NANOG and KLF2 – causing the network of genes that control the cell to reboot and induce the naïve pluripotent state. Importantly, the introduced genes only need to be present for a short time. Then, like other stem cells, reset cells can self-renew indefinitely to produce large numbers, are stable and can differentiate into other cell types, including nerve and heart cells.

By studying the reset cells, scientists will be able to learn more about how normal embryo development progresses and also how it can go wrong, leading to miscarriage and developmental disorders. The naïve state of the reset stem cells may also make it easier and more reliable to grow and manipulate them in the laboratory and may allow them to serve as a blank canvas for creating specialised cells and tissues for use in regenerative medicine.

Professor Smith adds: “Our findings suggest that it is possible to rewind the clock to achieve true ground state pluripotency in human cells. These cells may represent the real starting point for formation of tissues in the human embryo. We hope that in time they will allow us to unlock the fundamental biology of early development, which is impossible to study directly in people.” 

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Malaria parasites found to hide out in the bone marrow

Malaria parasites found to hide out in the bone marrow | Amazing Science |

Malaria is an infectious disease which claims the lives of more children worldwide than any other; it is caused by parasitic micro-organisms, plasmodiums. These parasites are transmitted to their hosts via mosquito bites, where they induce a range of symptoms, including vomiting, fever, headaches, and, in severe cases, death. Incidence of malaria is prevalent in poverty stricken areas around the equator, with an estimated 207 million cases in 2012.  The most life threatening form of the disease is caused by Plasmodium falciparum

Within humans, P. falciparum undergoes two distinct stages, asexual replication, and differentiation into what are called gametocytes. Asexual replication occurs within red blood cells, with pathological symptoms arising from the inevitable red blood cell rupturing. Released parasites generally invade additional red blood cells for subsequent rounds of asexual replication; however, a small subset of parasites instead differentiate into the male and female forms that are refered to as gametocytes. Once taken up by a female Anopheles mosquito, these gametocytes are able to undergo sexual replication. Thus, the differentiation of P. falciparum into gametocytes represents an attractive target for intervention strategies. However, within the blood only mature gametocytes are found, and until recently, relatively little was known about immature gametocyte sequestration within tissues.

recent study carried out a systematic organ survey of children who died from malaria, successfully identifying sites of immature gametocyte accumulation using a combination of immunohistochemical labelling, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The study provides strong evidence that gametocyte development occurs within the haematopoietic system present in the bone marrow, where they may form and develop within red blood cell precursors. Furthermore, binding interactions with red blood cell precursors seem to support the retention of developing gametocytes within the bone marrow’s extravascular space, where they are able to avoid immune detection until they are mature enough to be released back into the blood. The observation of gametocytes adopting a specialised niche within the haematopoietic system of the bone marrow is supported by an independent study, which earlier this year used qRT-PCR to demonstrate that the bone marrow of infected children is enriched for immature gametocytes.

The recently characterized locations and mechanisms of gametocyte sequestration within the bone marrow, provide novel targets through which malaria transmission could be blocked, advancing both prevention and treatment efforts.

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Vaccinated monkeys show "long-term" immunity to the Ebola virus, raising a prospect of successful human trials

Vaccinated monkeys show "long-term" immunity to the Ebola virus, raising a prospect of successful human trials | Amazing Science |

The experiments by the US National Institutes of Health showed immunity could last at least 10 months. Human trials of the vaccine started this week in the US and will extend to the UK and Africa.

The World Health Organization says more than 2,000 people have now died in the outbreak in West Africa. Several experimental treatments are now being considered to help contain the spread of Ebola.

This includes a vaccine being developed by the US National Institute of Allergy and Infectious Diseases and pharmaceutical company GlaxoSmithKline. It uses a genetically modified chimp virus containing components of two species of Ebola - Zaire, which is currently circulating in West Africa, and the common Sudan species.

The viral vaccine does not replicate inside the body, but it is hoped the immune system will react to the Ebola component of the vaccine and develop immunity.

The first patient, a 39-year-old woman, was given the vaccine last week as human trials got under way. There will also be separate trials of the vaccine against just the Zaire Ebola species.

These will take place in the US, the University of Oxford in the UK as well as in Mali and Gambia. People will be given just the initial jab, not a follow-up booster, in the trials.

The WHO said safety data would be ready by November 2014 and, if the vaccine proved safe, it would be used in West Africa immediately.

Healthcare workers and other frontline staff would be prioritised for vaccination.

The number of doses currently available is between 400 - if a lot of vaccine is needed for immunity - and 4,000 if smaller amounts are sufficient. As with all experimental therapies, the WHO has warned hopes of a vaccine must not detract from the proven methods of infection control which have defeated all previous outbreaks.

Prof Jonathan Ball, a virologist at the University of Nottingham, said: "This is really encouraging data.

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Lactic acid bacteria from the honey bees could be the source for efficient treatment of MRSA

Lactic acid bacteria from the honey bees could be the source for efficient treatment of MRSA | Amazing Science |

Could honeybees' most valuable contribution to mankind besides pollination services be alternative tools against infections? Today, due to the emerging antibiotic-resistant pathogens, we are facing a new era of searching for alternative tools against infections. Natural products such as honey have been applied against human's infections for millennia without sufficient scientific evidence. A unique lactic acid bacterial (LAB) microbiota was discovered by us, which is in symbiosis with honeybees and present in large amounts in fresh honey across the world. This work investigates if the LAB symbionts are the source to the unknown factors contributing to honey's properties.

Hence, a group of researchers at Lund University have tested the LAB against severe wound pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and vancomycin-resistant Enterococcus (VRE) among others. They were able to demonstrate a strong antimicrobial activity from each symbiont and a synergistic effect, which counteracted all the tested pathogens. The mechanisms of action are partly shown by elucidating the production of active compounds such as proteins, fatty acids, anaesthetics, organic acids, volatiles and hydrogen peroxide. The team showed that the symbionts produce a myriad of active compounds that remain in variable amounts in mature honey. Further studies are now required to investigate if these symbionts have a potential in clinical applications as alternative tools against topical human and animal infections.

"Antibiotics are mostly one active substance, effective against only a narrow spectrum of bacteria. When used alive, these 13 lactic acid bacteria produce the right kind of antimicrobial compounds as needed, depending on the threat. It seems to have worked well for millions of years of protecting bees' health and honey against other harmful microorganisms. However, since store-bought honey doesn't contain the living lactic acid bacteria, many of its unique properties have been lost in recent times", explains Tobias Olofsson.

The next step is further studies to investigate wider clinical use against topical human infections as well as on animals. The findings have implications for developing countries, where fresh honey is easily available, but also for Western countries where antibiotic resistance is seriously increasing.

Reference: Lactic acid bacterial symbionts in honeybees – an unknown key to honey's antimicrobial and therapeutic activities

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Membrane of banked red blood cells grows stiffer with age, study finds

Membrane of banked red blood cells grows stiffer with age, study finds | Amazing Science |

It may look like fresh blood and flow like fresh blood, but the longer blood is stored, the less it can carry oxygen into the tiny microcapillaries of the body, says a new study from University of Illinois researchers.

Using advanced SLIM topography, the researchers measured the stiffness of the membrane surrounding red blood cells over time. They found that, even though the cells retain their shape and hemoglobin content, the membranes get stiffer, which steadily decreases the cells’ functionality. 

Led by electrical and computer engineering professor Gabriel Popescu, the team published its results in the journal Scientific Reports.

“Our results show some surprising facts: Even though the blood looks good on the surface, its functionality is degrading steadily with time,” said Popescu, who is also part of the Beckman Institute for Advanced Science and Technology at the U. of I. 

Nearly 14 million units of blood are banked annually in the U.S. The established “shelf life” for blood in blood banks is 42 days. During that time, a lot of changes can happen to the blood cells – they can become damaged or rupture. But much of the blood keeps its shape and, by all appearances, looks like it did the day it was donated.  

Popescu and his colleagues wanted to quantitatively measure blood cells over time to see what changed and what stayed the same, to help determine what effect older blood could have on a patient. They used a special optical technique called spatial light interference microscopy (SLIM), a method developed in Popescu’s lab at Illinois in 2011. It uses light to noninvasively measure cell mass and topology with nanoscale accuracy. Through software and hardware advances, the SLIM system today acquires images almost 100 times faster than just three years ago.

The researchers took time-lapse images of the cells, measuring and charting the cell’s properties. In particular, they were able to measure nanometer scale motions of the cell membrane, which are indicative of the cell’s stiffness and function. The fainter the membrane motion, the less functional the cell, much like how a fainter pulse indicates problems with a patient.

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Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature

Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature | Amazing Science |

Current evidence suggests that the inflammatory bowel diseases (IBDs) Crohn disease (CD) and ulcerative colitis (UC) are caused by a complex interaction among host genetic background, microbial shifts, and environmental cues, leading to inappropriate chronic activation of the mucosal immune system (13). While it is difficult to establish causality in patient-based studies, it is reasonable to suggest that large inception cohorts that include clinical, genetic, mucosal, and microbial profiling might be the optimal way to address the diversity associated with IBD pathogenesis with adequate power.

A recent meta-analysis of IBD genetic studies identified 163 IBD risk loci (4), and many of these risk alleles exhibit infection-related balancing natural selection. Consistent with this finding, an overall dysfunction in the human gut microbial community has been described in both long-standing adult-onset IBD (5) and treatment-naive pediatric-onset IBD (6), and patients exhibit altered responses to bacterial DNA (7). Animal models have conclusively shown causality in the requirement for bacterial colonization in the development of intestinal inflammation in genetically susceptible hosts (3). However, characterization of host/microbial profiles in the affected and unaffected mucosa at the onset of disease in large patient-based cohorts has been lacking.

Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. A team of scientists now identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was down-regulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury.

A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches.

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Assessing the International Spreading Risk Associated with the 2014 West African Ebola Outbreak

Assessing the International Spreading Risk Associated with the 2014 West African Ebola Outbreak | Amazing Science |

The outbreak of Ebola virus disease (EVD) that started in December 2013 has defied several months of mitigation and containment efforts. In July 2014 it was still evolving in Guinea, Liberia and Sierra Leone. As of 20 August, the toll in those countries had reached 844 EVD confirmed deaths 1. On 20 July, the outbreak reached Nigeria through an infected traveler coming from Liberia. The Nigerian official reports list 12 probable cases, and it is not clear if the outbreak has been contained.

EVD is caused by infection with a virus of the family Filoviridae, genus Ebolavirus 2. EVD transmission during the incubation period is very unlikely and occurs via direct contact with blood, secretions, and/or other bodily fluids of dead or living infected persons. Gene sequencing of the virus causing the 2014 West African (2014WA) outbreak has demonstrated 98% homology with the Zaire Ebola virus, with a 55% case fatality ratio (CFR) across the affected countries 3. Unfortunately there are no licensed treatments available for EVD, and severely ill patients can only be cared for with intensive supportive care.

The 2014WA outbreak is the largest ever observed, both by number of cases and geographical extension. For this reason, on 6-7 August, an Emergency Committee of the WHO 4 advised the 2014WA outbreak constitutes an ’extraordinary event’ and a public health risk to other States. Indeed, although the outbreak started in an isolated region of Guinea, transmission has occurred in large cities (Conakry, Freetown, Monrovia and Lagos) of the four affected countries. These urban areas have major international airports, thus raising concern about a quick internationalization of the outbreak (see Fig. 1). While importation of cases should not generate large outbreaks in countries where prompt isolation of cases in appropriate health care facilities occurs, it is clear that a quantitative analysis of the risk of importation of cases (likelihood, timeline, number of cases) in countries not affected at the moment by the outbreak may provide valuable intelligence on the evolution of the 2014WA outbreak.

So far most of the analyses on the risk of international spread of the outbreak have focused on the analysis of the sheer volume of international passenger traffic across countries 5,6. These analyses however do not consider the local evolution of the outbreak in the affected countries and the specific etiology of the disease (incubation time scale, etc.). Here we provide a quantitative assessment of the international spread based on large-scale computer microsimulations of the 2014WA outbreak that generate stochastic simulations of epidemic spread worldwide, yielding, among other measures, the case importation events at a daily resolution for 3,362 subpopulations in 220 countries. We use the Global Epidemic and Mobility Model that integrates high-resolution data on human demography and mobility on a worldwide scale in a metapopulation stochastic epidemic model 7,8,9. The disease dynamics within each population consider explicitly that EVD transmissions occur in the general community, in hospital settings, and during funeral rites 10. For parameter inference, we use a Monte Carlo likelihood analysis that considers more than 1,000,000 simulations that sample the disease model space and the data on the 2014WA outbreak up to 9 August 2014. This approach selects the disease dynamic model that we use to generate numerical stochastic simulations of an epidemic’s local (within West African countries) and global progression.

We evaluate the progression of the epidemic in West Africa and its international spread under the assumption that the EVD outbreak continues to evolve at the current pace. The numerical simulation results show a steep increase of cases in the West Africa region, unless the transmissibility of the EVD is successfully mitigated. The overall basic reproductive number of the epidemic in the region is estimated to be in the range 1.− 2.0. We find that, although surveillance and containment measures have been in place for several months, the transmissibility in hospital and funeral rites are likely an appreciable component of the overall transmissibility. The probability of case exportation is extremely modest (upper bound less than 5%) for non-African countries, with the exception of the United Kingdom (UK), Belgium, France and the United States (US). As of the beginning of September, the countries with the largest probability of seeing the arrival of EVD cases are Ghana, UK and Gambia. The overall probability of international spread will increase if the Nigerian outbreak is not promptly controlled. We also show that as of the end of September, the size distribution of outbreaks due to the international spread of the EVD is contained (median value <4 cases) for countries outside of the African region. Severe travel restrictions to and from the affected areas (80% airline traffic reduction) generates only a 3-4 weeks delay in the international spreading.

The lack of detailed data on the 2014WA EVD outbreak makes any modeling approach vulnerable to the many assumptions and uncertainty about basic parameters and the quality of data. However, we hope that the characterization of the EVD 2014WA outbreak and the associated risk of international spread provided here may be useful to national and international agencies in allocating resources for interventions to contain and to mitigate the epidemic.

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Herpes simplex virus type 1 and Alzheimer’s disease: Increasing evidence for a major role of the virus

Herpes simplex virus type 1 and Alzheimer’s disease: Increasing evidence for a major role of the virus | Amazing Science |

The concept of a viral role in Alzheimer’s disease (AD), specifically of herpes simplex virus type 1 (HSV1), was first proposed several decades ago (Ball, 1982Gannicliffe et al., 1986). Legitimizing the concept clearly depended on a positive answer to a number of test questions, the first of which was whether or not HSV1 is ever present in human brain. The subsequent discovery that HSV1 DNA resides in a high proportion of brains of elderly people in latent form (Jamieson et al., 1991)—both normals and AD patients—immediately made the concept more credible, but raised associated questions such as whether or not the virus is ever active in brain or is merely a passive resident there; whether on its own it is a causative factor in AD or it acts thus only with another factor, perhaps genetic; if active, what causes its activity; whether there is any link with the characteristic abnormal features of AD brains or their components, and whether, if indeed implicated in AD, antiviral agents would be useful for treating the disease. These questions were posed in a previous review (Wozniak and Itzhaki, 2010)—and strong evidence was presented that permitted the answer to each question to be “yes” or, very likely to be “yes”. The present review briefly summarizes the earlier evidence, and provides an update, which is especially timely in view of the subsequent steady increase in number of relevant publications.

Herpes simplex virus type 1 (HSV1), when present in brain of carriers of the type 4 allele of the apolipoprotein E gene (APOE), has been implicated as a major factor in Alzheimer’s disease (AD). It is proposed that virus is normally latent in many elderly brains but reactivates periodically (as in the peripheral nervous system) under certain conditions, for example stress, immunosuppression, and peripheral infection, causing cumulative damage and eventually development of AD.

Diverse approaches have provided data that explicitly support, directly or indirectly, these concepts. Several have confirmed HSV1 DNA presence in human brains, and the HSV1-APOE-ε4 association in AD. Further, studies on HSV1-infected APOE-transgenic mice have shown that APOE-e4 animals display a greater potential for viral damage. Reactivated HSV1 can cause direct and inflammatory damage, probably involving increased formation of beta amyloid (Aβ) and of AD-like tau (P-tau)—changes found to occur in HSV1-infected cell cultures.

Implicating HSV1 further in AD is the discovery that HSV1 DNA is specifically localized in amyloid plaques in AD. Other relevant, harmful effects of infection include the following: dynamic interactions between HSV1 and amyloid precursor protein (APP), which would affect both viral and APP transport; induction of toll-like receptors (TLRs) in HSV1-infected astrocyte cultures, which has been linked to the likely effects of reactivation of the virus in brain.

Several epidemiological studies have now shown, using serological data, an association between systemic infections and cognitive decline, with HSV1 particularly implicated. Genetic studies too have linked various pathways in AD with those occurring on HSV1 infection. In relation to the potential usage of antivirals to treat AD patients, acyclovir (ACV) is effective in reducing HSV1-induced AD-like changes in cell cultures, and valacyclovir, the bioactive form of ACV, might be most effective if combined with an antiviral that acts by a different mechanism, such as intravenous immunoglobulin (IVIG).

Krishan Maggon 's curator insight, September 2, 2014 6:48 PM

Thanks Dr. Gruenwald.

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Eczema Fungus Found Everywhere Including Deep Hydrothermal Vents And Antarctic Soil

Eczema Fungus Found Everywhere Including Deep Hydrothermal Vents And Antarctic Soil | Amazing Science |

Professor Anthony Amend from the University of Hawaii at Manoa showed very recently that the fungus genus Malassezia is not only found on human skin with conditions such as dandruff and eczema, but has also been identified in marine environments such as deep-sea sediment, hydrothermal vents, corals, guts of lobster larvae, eel tissue, and Antarctica soils.

More remarkably, sequencing and tree building of species relatedness shows that the marine species and terrestrial (non-marine) species do not group together but “interdigitate”, or are spread randomly in the way they group together in their relatedness.  The evidence suggests that the marine and terrestrial forms have jumped repeatedly between habitats.

The data was obtained from a number of sources, most of them “environmental sequencing” projects around the world which aim to do simultaneous sequencing of all DNA found in a sample.  Done correctly the analysis yields in one try the identities of all organisms captured in a sample.

Prior to this analysis, it was thought that these fungus evolved to become optimally suited to mammalian skin.  But the careful analysis of environmental sequencing efforts overturned that belief.  One species could be spread out all over the globe, on land as well as in ocean.  One example is Malassezia restricta, found on human skin but also in extreme habitats such as arctic soil and hydrothermal vents. Marine animals also carry this fungus, including higher order seals and lower order fish, lobsters, and corals.

One criticism is that sequencing is bound to become contaminated especially with a fungus endemic to human skin.  However, the detection of completely novel species cannot be explained by contamination.  And moreover, RNA is a fairly unstable molecule, so in the cases where detection occurred for some of the samples in which there was sufficient time for degradation suggests that microbes were actively generating RNA.

While it is associated with many skin conditions it is unclear as of yet whether the fungus is a causal factor.  This is simply because disease etiology is a complex interplay of an individual immune system and disease agent.

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Preclinical Study Shows Microbicide Gel’s Effectiveness Against HIV and Other Viruses

Preclinical Study Shows Microbicide Gel’s Effectiveness Against HIV and Other Viruses | Amazing Science |

Results of a recent animal study offer new optimism for microbicides, biomedical products being developed to protect people against sexually transmitted infections (STIs), including HIV. Population Council scientists and their partners have found that a proprietary microbicide gel developed by the Council is safe, stable, and can prevent the transmission of HIV, herpes simplex virus 2 (HSV-2), and human papillomavirus (HPV), in both the vagina and rectum in animals. It has a window of efficacy in the vagina against all three viruses of at least eight hours prior to exposure. An in vitro study also provides the first data that the gel is effective against multiple strains of HIV.

The gel, known as MZC, contains MIV-150, zinc acetate, and carrageenan. MIV-150 and zinc acetate are potent antiviral agents that inhibit HIV via different mechanisms of action. MIV-150 is an enzyme inhibitor that blocks an early step of HIV replication in target cells, and zinc acetate is an antiviral agent with demonstrated activity against HIV and HSV-2. These compounds are mixed in a water-based solution of carrageenan, a compound derived from seaweed that has been shown to have potent activity against HPV. Infection with HSV-2 or HPV is associated with increased risk of HIV infection. Researchers believe that microbicides that target HIV, HSV-2, and HPV may more effectively limit HIV transmission than those that target HIV alone.

In this study, Council scientists and their partners used macaque and mouse models to examine whether MZC gel could prevent vaginal and rectal transmission of SHIV-RT (a virus combining genes from HIV and SIV, the monkey version of HIV), HSV-2, and HPV. 

They found that MZC:

  • protected macaques against vaginal SHIV-RT infection when applied up to 8 hours prior to challenge
  • protected macaques against rectal SHIV-RT infection when used close to the time of viral challenge
  • protected mice against HSV-2 infection when applied vaginally or anally/rectally just before a high dose of virus
  • protected mice against HSV-2 when applied between 8 hours before and 4 hours after vaginal challenge with a low dose of HSV-2
  • protected mice against HPV when applied up to 24 hours before and 2 hours after vaginal challenge and also if applied 2 hours before or after HPV inoculation of the anus/rectum.

The study was designed to establish proof of concept in monkeys and mice before taking steps to test in humans. Preclinical testing in animals is required by the FDA and is important to ensure the highest level of safety and to build the evidence base for potential efficacy in humans. Phase 1 safety trials of the gel in humans are now underway.

“In addition to the gel,” said Fernández-Romero, “we are exploring sustained-release intravaginal rings and on-demand nanofiber-based delivery systems for MZC.” He stressed that developing different delivery systems for effective medications is an important step in ensuring the ultimate success of any microbicide, adding, “There is a growing demand for microbicides that prevent multiple STIs, and we are committed to ensuring that women and men have options when choosing what works most effectively for their own protection.”

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Genetically engineered pig hearts survived more than a year in baboon abdomens

Genetically engineered pig hearts survived more than a year in baboon abdomens | Amazing Science |

The heart didn't beat for the baboon, but it did overcome the risk of organ rejection.

By breeding piglets with a few choice human genes, scientists were able to create sort-of-pig hearts that seem to be compatible with primate hosts. The organ wasn't used as a heart, but was instead grafted into the abdomen of an otherwise healthy baboon. After over a year, the best of the hearts are still living, viable organs. Next stop, the chest cavity!

Researchers at the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health will publish their results in the September issue of The Journal of Thoracic and Cardiovascular Surgery, though their findings were discussed several months ago at a conference. According to the study, the researchers experimented with different degrees of genetic modification in the pigs. They prevented all of the piglets from producing certain enzymes known to cause organ rejection in baboons (and, by extension, humans) but were given different gene alterations to keep blood from clotting, which is another common issue.

The most successful group had the human thrombomodulin gene added to their genomes. The expression of this gene prevented clotting, lead investigator Muhammad M. Mohiuddin said in a statement. While the average survival of the other groups were 70 days, 21 days and 80 days, the thrombomodulin group survived an average of 200 days in the baboon abdomen. And three of the five grafts in the group were still alive at 200 to 500 days since their grafting, when the study was submitted for review.

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