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Tracking the Ebola outbreak in near real-time: HealthMap, ProMED and other tools

Tracking the Ebola outbreak in near real-time: HealthMap, ProMED and other tools | Amazing Science |

Sobering news keeps coming out of the West African Ebola outbreak. According to numbers released on August 6, the virus has sickened 1,711 and claimed 932 lives across four nations. The outbreak continues to grow, with a high risk of continued regional spread, according to a threat analysis released byHealthMap (an outbreak tracking system operated out of Boston Children’s Hospital) and Bio.Diaspora (a Canadian project that monitors communicable disease spread via international travel).

“What we’ve seen here—because of inadequate public health measures, because of general fear—is [an outbreak that] truly hasn’t been kept under control,”John Brownstein, PhD, co-founder of HealthMap and a computational epidemiologist at Boston Children’s Hospital, told ABC News. “The event started, calmed down and jumped up again. Now, we’re seeing movement into densely populated areas, which is highly concerning.”

If you’re interested in keeping tabs on the outbreak yourself, there are several tools that can help:

  • HealthMap’s Ebola map. The HealthMap team is maintaining a dedicated, interactive map and timeline of the epidemic (embedded at the top of this post). Both map and timeline are regularly updated as new information becomes available, as is the HealthMap Twitter account.
  • ProMED. The International Society for Infectious Disease, a non-profit organization for infectious and emerging disease research, operatesProMED, a disease news monitoring service that tracks outbreaks of human and veterinary infectious diseases. ProMED (short for Program for Monitoring Emerging Diseases) has been sending out regular email and Twitter alerts about the Ebola outbreak since it was first noticed in March.
  • US Centers for Disease Control and Prevention (CDC). The CDC is regularly posting updated news and patient counts—as well as travel and preparedness guidance and other information about the virus—on both their website and Twitter.
  • World Health Organization (WHO). The WHO’s Global Alert and Response system is providing regular updates on disease spread and control efforts. The organization is also distributing updates via its Twitter feed.
Biodefense News's curator insight, August 14, 10:20 PM

One glaring omission from this list is, which is supplying CDC/GDD with outbreak information and forecasting.  Ascel Bio was also in constant contact with Samaritan's Purse and asked to help respond to evacuate.

M. Philip Oliver's curator insight, August 15, 12:33 PM

Thanks To Dr. Stefan

Luigi Cappel's curator insight, August 16, 5:53 PM

Not only is this a great site, but when I went in, it automatically identified that I live in New Zealand and showed me areas close to me where there are notifiable diseases. It showed that currently measles is growing around our country. This is a great site to check out, whether you are traveling overseas and want to see if there are things you want to be forewarned about, perhaps be inoculated against, or in the case of something like Ebola, places you might be better off staying well away from at least in the short to medium term. 


I recommend checking it out, whether you are traveling, or simply want to see great use of maps to show real time data. The time-lapse video showing the expansion of Ebola is fascinating. This is the sort of thing we usually just see on movies showing the CDC, like one of my favorite TV shows 24. Where's Jack Bauer when you need him? Oh, I here a rumor he may be coming back:)

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Blood-brain-barrier disruption with high-frequency pulsed electric fields

Blood-brain-barrier disruption with high-frequency pulsed electric fields | Amazing Science |

A team of researchers from Virginia Tech and Wake Forest University School of Biomedical Engineering and Sciences have developed a new technique for using pulsed electric energy to open the blood-brain-barrier (BBB) for treating brain cancer and neurological disorders.

Their Vascular Enabled Integrated Nanosecond pulse (VEIN pulse) procedure consists of inserting minimally invasive needle electrodes into the diseased tissue and applying multiple bursts of 850-nanosecond pulsed electric energy with alternating polarity.

The researchers think the bursts disrupt tight junction proteins responsible for maintaining the integrity of the BBB, but without causing damage to the surrounding tissue. This technique will be described in the upcoming issue of the journal TECHNOLOGY.

For the treatment of brain cancer, “VEIN pulses could be applied at the same time as biopsy or through the same track as the biopsy probe in order to mitigate damage to the healthy tissue by limiting the number of needle insertions,” saysRafael V. Davalos, Ph.D, director of the Bioelectromechanical Systems Laboratory at Virginia Tech.

The BBB is a network of tight junctions that normally acts to protect the brain from foreign substances by preventing them from leaking from blood vessels into neural structures. But that also limits the effectiveness of drugs to treat brain disease. Temporarily opening the BBB is a way to ensure that drugs can still be effective.

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Bert Vogelstein’s Liquid Biopsy Blood Test for DNA Could Stop Cancer in its Tracks

Bert Vogelstein’s Liquid Biopsy Blood Test for DNA Could Stop Cancer in its Tracks | Amazing Science |

He watched his brother die from a cancer that no drug could cure. Globally, eight million people died of cancer in 2012. Now one of the world’s most renowned cancer researchers says it’s time for Plan B. The answers Bert Vogelstein needed and feared were in the blood sample.

Vogelstein is among the most highly cited scientists in the world. He was described, in the 1980s, as having broken into “the cockpit of cancer” after he and coworkers at Johns Hopkins University showed for the first time exactly how a series of DNA mutations, adding up silently over decades, turn cells cancerous. Damaged DNA, he helped prove, is the cause of cancer.

Now imagine you could see these mutations—see cancer itself—in a vial of blood. Nearly every type of cancer sheds DNA into the bloodstream, and Vogelstein’s laboratory at Johns ­Hopkins has developed a technique, called a “liquid biopsy,” that can find the telltale genetic material.

The technology is made possible by instruments that speedily sequence DNA in a blood sample so researchers can spot tumor DNA even when it’s present in trace amounts. The ­Hopkins scientists, working alongside doctors who treat patients in Baltimore’s largest oncology center, have now studied blood from more than a thousand people. They say liquid biopsies can find cancer long before symptoms of the disease arise.

This particular blood sample, though, was personal. It was from Vogelstein’s brother, an orthopedic surgeon one year younger. He was fighting skin cancer, and the disease was already spreading. There was hope he’d respond to a new type of drug, but the treatment causes swelling, and it’s difficult to tell from an x-ray or CT scan whether the cancer is melting away or not. So Vogelstein used his lab’s new technology. If the cancer DNA had disappeared from the blood, they might celebrate. If it was still there, maybe he could steer his brother to some last-ditch drug.

“We tried to guide the treatment. That was the hope, anyway,” says Vogelstein. His voice tightens. He doesn’t say what happened next.

The obituary of Barry Vogelstein, born in Baltimore, appeared on July 3, 2013.

We’re not winning the war on cancer, and the death of ­Vogelstein’s brother shows why. Too many cancers are caught when they have become incurable. Each year, $91 billion is spent on cancer drugs worldwide, but most of those medicines are given to patients when it’s too late. The newest treatments, created at staggering expense, cost $10,000 a month and often extend life by only a few weeks. Pharmaceutical firms develop and test more drugs for late-stage cancer than for any other kind of disease.

“We as the public and as scientists have been entranced by this idea of curing advanced cancers,” says Vogelstein. “That is society’s Plan A. I don’t think that has to be the case.” There are other ways to reduce cancer deaths: wearing sunscreen, not smoking, and getting screened to catch cancer early. To ­Vogelstein, all these preventive steps represent “Plan B” because they receive so much less attention and funding. Yet when prevention works, it has better results than any drug. In the United States, the chance of dying from colorectal cancer is 40 percent lower than it was in 1975, a decrease mostly due to colonoscopy screening. Melanoma skin cancer, too, is treatable with surgery if caught early. “We think Plan B needs to be Plan A,” says Vogelstein.

The new blood tests could make that possible. For the first time, Hopkins researchers say, they are within reach of a general screening tool that could be used to scan broadly—perhaps at an annual physical—for molecular traces of cancer in people with no symptoms. “We think we’ve solved early detection,” says Victor Velculescu, a Hopkins researcher who runs a lab in the building next to Vogelstein’s.

Making such screening a routine practice in medicine will be challenging. One difficulty is that while the test may detect the presence of cancer DNA in the body, physicians might not know where the tumor is, how dangerous it is, or even whether it is worth treating. “We have to be cautious about how we talk about that,” says Daniel Haber, director of the Massachusetts General Hospital Cancer Center. He believes the DNA blood tests are “far from ready” and says very large studies will be needed to prove that they are useful. “There is a huge bar to get over,” he says.

Despite such skepticism, the technology is gaining attention. Tony Dickherber, head of the Innovative Molecular Analysis Technologies Program at the National Cancer Institute, says the idea of scanning blood for tumor DNA was “fringe at best” only three years ago. But now labs and companies from California to London are jumping in, producing a stream of improvements to the blood screening technology and new data supporting it. “People are starting to think that Vogelstein is right—this could be the best way to do early diagnosis,” he says. “[It] could be done much more widely than other screening technology we have, and you could screen for an incredible range of cancers.”

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AACR: Cancer Immunotherapy On Its Way To The Clinic

AACR: Cancer Immunotherapy On Its Way To The Clinic | Amazing Science |
Cancer immunotherapy refers to treatments that can unleash the power of a patient’s immune system to fight his or her cancer.

It seems that hardly a week goes by without there being a report of new breakthroughs in cancer immunotherapy. At the start of 2014, the focus was on the decision of the editors of Science to choose cancer immunotherapy as Breakthrough of the Year for 2013. In February, researchers at Memorial Sloan Kettering Cancer Center in New York published a study showing that 14 of 16 adults with relapsed or refractory acute lymphoblastic leukemia (ALL) had a complete response after treatment with an investigational cancer immunotherapy. And so it has gone on. Most recently, the U.S. Food and Drug Administration (FDA) granted breakthrough therapy designation to another investigational cancer immunotherapy, CTL019, for the treatment of pediatric and adult patients with relapsed/refractory ALL.

The excitement surrounding cancer immunotherapy was evident June 18, when a Twitter chat titled “The Promise of Immunotherapy,” organized by the American Association for Cancer Research (AACR) in partnership with Time magazine, the Mayo Clinic Cancer Center, and the Cancer Research Institute, reached an estimated 1.3 million individuals. But what is cancer immunotherapy, how does it work, and why are people so excited about it?

Cancer immunotherapy, which was featured as a key advance in patient care in the AACR Cancer Progress Report 2013, refers to treatments that can unleash the power of a patient’s immune system to fight his or her cancer. Decades of research have provided us with immense scientific insight into the immune system and how it interacts with cancer cells. This is what is allowing us to design increasing numbers of anticancer therapies that harness the immune system in different ways. It is also what is underpinning the groundswell of clinical trials testing cancer immunotherapies that we have seen in the past few years.

One of the reasons cancer immunotherapies have generated such excitement is that some have yielded dramatic and long-lasting responses in a number of patients. For example, Andrew Messinger (a cancer survivor featured in the AACR Cancer Progress Report 2013), who has metastatic melanoma – a disease that has an overall five-year survival rate of just 16 percent – is continuing to benefit from the cancer immunotherapy ipilimumab (Yervoy) five years after his first dose.

Ipilimumab is an example of a type of cancer immunotherapy known as a checkpoint inhibitor. These cancer immunotherapies work by releasing the ‘brakes’ on immune cells called T cells, which are naturally capable of destroying cancer cells. The brake released by ipilimumab is called CTLA4.

As highlighted in the AACR Cancer Progress Report 2014, which will be released in mid-September, a number of investigational cancer immunotherapies target a second T-cell brake called PD-1. One of these, pembrolizumab, is under review at the FDA as a potential treatment for metastatic melanoma. Another, nivolumab, received regulatory approval as a treatment for unresectable melanoma in Japan in July. Promising early results among patients with a number of other types of cancer, including non-small cell lung cancer and non-Hodgkin lymphoma, have been reported for PD-1-targeted cancer immunotherapies, but the data need to be confirmed in larger cohorts.

Despite all the excitement surrounding cancer immunotherapies, ipilimumab is one of the few currently approved by the FDA - it was approved for the treatment of metastatic melanoma in March 2011. As a result, most cancer immunotherapies remain investigational treatments, meaning that they have not yet been approved by the FDA and are still in development.

Fortunately, researchers are continuing to uncover new information about how the immune system functions. Thus, we can expect to see novel immunotherapies and new ways to use those that we already have in the future. Some of the most promising research in this area will be discussed at the AACR special conference Tumor Immunology and Immunotherapy: A New Chapter, which is being held in Orlando, Florida, Dec. 1-4. This conference is being put together in part by the AACR’s Cancer Immunology Working Group, which helps provide a forum for immunologists and non-immunologists to meet, exchange knowledge and ideas, and discuss the present status and future promise of cancer immunology.

Via Stefanie Greene
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Electron spin changes as a general mechanism for general anesthesia?

Electron spin changes as a general mechanism for general anesthesia? | Amazing Science |

How does consciousness work? Few questions if any could be more profound. Lipid solubility appears to be one key clue to anesthesia. The empirical cornerstone of anesthesiology is a 100 year old rule of thumb known as the Meyer-Overton relationship. It provides that the potency of general anesthetics (GAs), regardless of their size or structure, is approximately proportional to how soluble they are in lipids. Since that time, studies have suggested that GAs can also bind to lipid-like parts of proteins, presumably those near or embedded within cell membranes.

The first real stab at explaining the "how" of anesthetics, as opposed to just the "where", has now been taken by Turin and his colleagues Efthimios Skoulakis and Andrew Horsfield. Their new work, just published in PNAS, suggests that volatile anesthetics operate by perturbing the internal electronic structure of proteins. This would lead to changes in electron currents in those proteins, in cells, and in the organism. They don't just theorize about these effects, they actually measure the electron currents in anesthetized flies using a technique known as electron spin resonance (often called electron paramagnetic resonance).

ESR is similar to nuclear magnetic resonance, the techno-phenomenon at heart of the modern MRI machine. The main difference is that in ESR excited electron spins are measured instead of proton resonance. Typically, microwaves are applied in the presence of a magnetic field to a sample (or whole organism) inside the resonator cavity of an ESR spectrometer.What Turin and colleagues have shown is that the total amount of free electron spins in fruit flies increases when they are exposed to general anesthetics. The amount of free spins generated during anesthesia is independent of melanin content and far larger than any signal previously measured from free radicals which are the other source of spin.

To account for the fact that a very broad class of compounds act as volatile anesthetics the researchers propose a unitary mechanism for their action involving electrons. They note that the smallest among them, Xenon (Xe), presents a puzzle to chemical theories of anesthetic action. Xe is a wonderful (if expensive) anesthetic but it has no biologically relevant chemistry to speak of— it is completely inert. Furthermore, it persists as a perfect sphere of electron density and so is devoid of any possibly interesting shape. However, as Turin and colleagues point out, "Xe has physics". In particular, it can conduct electrons, as the IBM researchers who first used a scanning tunneling microscope to write the company's logo in Xe atoms found out.

To see whether this property would apply to all anesthetics, and not just Xe, Turin used a modeling technique called density functional theory to show that Xe and other anesthetics effect the highest occupied molecular orbit (HOMO) of the alpha helices common to membrane proteins. The HOMO level for organic molecules or semiconductors is analogous to what the valence band maximum is to inorganic semiconductors. Intriguingly, while all the anesthetics were found to extend the alpha helix HOMO level, similar molecules with strong convulsant effects on the brain, but no anesthetic effects, had the smallest HOMO effect.

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Stem cell stroke therapy shows promise after first human trial

Stem cell stroke therapy shows promise after first human trial | Amazing Science |

Treatment with CD34+ hematopoietic stem/progenitor cells has been shown before to improve functional recovery in nonhuman models of ischemic stroke via promotion of angiogenesis and neurogenesis. A pilot study undertaken by researchers from Imperial College Healthcare NHS Trust and Imperial College London has now shown promise in rapid treatment of serious strokes. The study, the first of its kind published in the UK, treated patients using stem cells from bone marrow.

According to the Stroke Association, about 152,000 people suffer a stroke in the UK alone each year. However, the five patients treated in the recent Imperial College pilot study all showed improvements. According to doctors, four of those had suffered the most severe kind of stroke, which leaves only four percent of people alive or able to live independently six months after the event. All four of the patients were alive after six months.

A particular set of CD34+ stem cells was used, as they help with the production of blood cells and blood vessels’ lining cells. These same cells have been found to improve the effects of stroke in animals, and they assist in brain tissue and blood growth in the affected areas of the brain. The CD34+ cells were isolated from samples taken from patients’ bone marrow and then infused into the affected area via an artery that leads to the brain, using keyhole surgery.

The innovative stem cell treatment differs from others in one important way: patients are treated within seven days of their stroke, rather than six months hence. The stroke sufferers all recorded improvements in terms of clinical measures of disability, despite four of the five having suffered the most severe kind of stroke.

Autologous CD34+ selected stem/progenitor cell therapy delivered intra-arterially into the infarct territory can be achieved safely in patients with acute ischemic stroke. Future studies that address eligibility criteria, dosage, delivery site, and timing and that use surrogate imaging markers of outcome are desirable before larger scale clinical trials.

Eric Chan Wei Chiang's curator insight, August 12, 10:54 PM

A groundbreaking therapy in regenerative medicine. A stroke can cause permanent neurological damage or death and is in some ways it is more debilitating than a heart attack.


Any therapy which can repair some of the neurological damage is significant. The major challenge in preventing neurological damage is early detection, which can be difficult because there is often little discomfort and suffers may not know they are experiencing a stroke.


Recently, researchers have also mapped the functions of different regions of the brain. This forms part of the evidence against the "10% myth". Read more here:

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DCC-Netrin1: Mystery of brain cell growth unraveled by scientists

DCC-Netrin1: Mystery of brain cell growth unraveled by scientists | Amazing Science |
Scientists have discovered how a single protein can exert both a push and a pull force to nudge a neuron in the desired direction, helping neurons navigate to their assigned places in the developing brain.

Jia-huai Wang, PhD, who led the work at Dana-Farber and Peking University in Beijing, is a corresponding author of a report published in the August 7 online edition of Neuron that explains how one guidance protein, netrin-1, can either attract or repel a brain cell to steer it along its course. Wang and co-authors at the European Molecular Biology Laboratory (EMBL) in Hamburg, Germany, used X-ray crystallography to reveal the three-dimensional atomic structure of netrin-1 as it bound to a docking molecule, called DCC (Deleted in Colorectal Carcinoma), on the axon of a neuron. The axon is the long, thin extension of a neuron that connects to other neurons or to muscle cells.

DCC in a receptor for netrin-1 and is currently believed by some to be a conditional tumour suppressor gene, meaning that it normally prevents cell growth when in the absence of netrin-1. DCC elimination is not believed to be a key genetic change in tumour formation, but one of many alterations that can promote existing tumour growth. DCC's possible role in migration of cancerous cells is in the process of being characterized. While recent results make it fairly likely that DCC is involved in the biology of several cancers, the extent of its involvement and the details of how it works are still being studied.

As connections between neurons are established -- in the developing brain and throughout life -- axons grow out from a neuron and extend through the brain until they reach the neuron they are connecting to. To choose its path, a growing axon senses and reacts to different molecules it encounters along the way. One of these molecules, netrin-1, posed an interesting puzzle: an axon can be both attracted to and repelled from this cue. The axon's behavior is determined by two types of receptors on its tip: DCC drives attraction, while UNC5 in combination with DCC drives repulsion.

"How netrin works at the molecular level has long been a puzzle in neuroscience field," said Wang, "We now provide structure evidences that reveal a novel mechanism of this important guidance cue molecule." The structure showed that netrin-1 binds not to one, but to two DCC molecules. And most surprisingly, it binds those two molecules in different ways.

"Normally a receptor and a signal are like lock-and-key, they have evolved to bind each other and are highly specific -- and that's what we see in one netrin site," said Meijers. "But the second binding site is a very unusual one, which is not specific for DCC."

Not all of the second binding site connects directly to a receptor. Instead, in a large portion of the binding interface, it requires small molecules that act as middle-men. These intermediary molecules seem to have a preference for UNC5, so if the axon has both UNC5 and DCC receptors, netrin-1 will bind to one copy of UNC5 via those molecules and the other copy of DCC at the DCC-specific site. This triggers a cascade of events inside the cell that ultimately drives the axon away from the source of netrin-1, author Yan Zhang's lab at Peking University found. The researchers surmised that, if an axon has only DCC receptors, each netrin-1 molecule binds two DCC molecules, which results in the axon being attracted to netrin-1. "By controlling whether or not UNC5 is present on its tip, an axon can switch from moving toward netrin to moving away from it, weaving through the brain to establish the right connection," said Zhang.

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IVF technique that tests embryos for genetic disorders has first success

IVF technique that tests embryos for genetic disorders has first success | Amazing Science |

Doctors in London have reported the first pregnancy in Europe from a new IVF procedure that checks embryos for genetic disorders before they are implanted. The technique allows doctors to select embryos that are free of dangerous mutations carried by one or both parents even if the precise nature of the genetic defect is unknown.

Fertility specialists at the Centre for Reproductive and Genetic Health (CRGH) said the couple, Carmen Meagu, 26, and her husband Gabriel, had a high risk of passing on a lethal disease to their children. They are now 17 weeks into the pregnancy. Common embryo testing procedures require months of laboratory work, but the latest tool, known as karyomapping, can be completed within two weeks, meaning a couple can undergo tests without breaking from their IVF treatment cycle.

Meagu's father was badly affected by a condition called Charcot-Marie-Tooth disease, a form of muscular dystrophy, and died in his 50s. She inherited the condition but only has it very mildly. She had a 50% chance of passing it on to her children before the new procedure.

Paul Serhal, the centre's medical director, said the technique, which will be available on the NHS, was likely to replace more traditional ways of testing embryos because it was faster, more powerful and no more expensive. A second couple are 10 weeks into a pregnancy after receiving the same treatment at the clinic.

"Parents at risk of passing on a genetic disorder are faced with heartbreaking implications of potentially creating a life with an inherited illness," Serhal said. "The breakthrough we have achieved means that parents affected may be able to pursue treatment confident that their condition wouldn't be handed down." The couple have standard IVF treatment to create a set of embryos which are then biopsied. Usually, a few cells are taken when the embryo is a ball of 100 or so cells, though single cells can be plucked from younger, three-day-old embryos.

To perform the karyomapping, doctors first obtain DNA from cheek swabs of the parents and a family member affected by the disorder. The gene sequences are then compared and used to work up a genetic fingerprint for the mutation that causes the disease. Doctors can then check the cells removed from the embryos and work out which will be affected or not by the disorder, or will be carriers that could pass it on.

The test also checks embryos have the right number of chromosomes, a common cause of miscarriage and developmental disorders such as Down's syndrome. "The short workup time is critical because a woman's fertility may decline rapidly with time. Also, by identifying abnormal sets of chromosomes we can reduce miscarriage rates and increase the number of healthy IVF pregnancies," Serhal said.

"In more than two decades of working this field, this is the single biggest technological leap I have seen. Karyomapping is already making a significant difference to patients," said Dagan Wells at Reprogenetics UK, an Oxford-based company that tested the embryos.

"We believe the CRGH patient is one of the first, if not the first, in the world to receive karyomapping as a frontline clinical test," Wells said. Ten UK fertility clinics offer it to parents.

The procedure could have a big impact on couples who want to have children but are worried about passing on serious genetic disorders that run in their families. Because embryos are tested before they are implanted, the parents do not face decisions about terminating the pregnancy later on. In the UK the procedure can only be used to prevent severe diseases.

"The only embryos transferred to the mother are those that have the correct number of chromosomes and are free of the family's inherited condition," Wells said. "This all but eliminates the inherited disorder from the family and greatly reduces the risk of miscarriage.

"We are entering a golden age of genetics applied to the understanding of infertility, early human development and the diagnosis of inherited disease. Several other major technical advances are now on the verge of routine clinical application and the landscape of IVF is likely to be radically altered in the coming months and years."

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Self-assembling anti-cancer molecules created in minutes

Self-assembling anti-cancer molecules created in minutes | Amazing Science |

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavorable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens.

Scientists now report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli.

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Comprehensive molecular characterization of gastric cancer shows 4 major types

Comprehensive molecular characterization of gastric cancer shows 4 major types | Amazing Science |

Gastric cancer was the world’s third leading cause of cancer mortality in 2012, responsible for 723,000 deaths1. The vast majority of gastric cancers are adenocarcinomas, which can be further subdivided into intestinal and diffuse types according to the Lauren classification2. An alternative system, proposed by the World Health Organization, divides gastric cancer into papillary, tubular, mucinous (colloid) and poorly cohesive carcinomas3. These classification systems have little clinical utility, making the development of robust classifiers that can guide patient therapy an urgent priority.

Molecular analysis of its molecular and clinical characteristics has been complicated by histological and etiological heterogeneity. A team of scientists now describes in Nature a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. They propose a molecular classification dividing gastric cancer into four subtypes: (i) tumors positive for Epstein–Barr virus, which display recurrentPIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); (ii) microsatellite unstable tumors, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signaling proteins; (iii) genomically stable tumors, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and (iv) tumors with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.

The majority of gastric cancers are associated with infectious agents, including the bacterium Helicobacter pylori4 and Epstein–Barr virus (EBV). The distribution of histological subtypes of gastric cancer and the frequencies of H. pylori and EBV associated gastric cancer vary across the globe5. A small minority of gastric cancer cases are associated with germline mutation in E-cadherin (CDH1)6 or mismatch repair genes7 (Lynch syndrome), whereas sporadic mismatch repair-deficient gastric cancers have epigenetic silencing of MLH1 in the context of a CpG island methylator phenotype (CIMP)8. Molecular profiling of gastric cancer has been performed using gene expression or DNA sequencing9101112, but has not led to a clear biologic classification scheme. The goals of this study by The Cancer Genome Atlas (TCGA) were to develop a robust molecular classification of gastric cancer and to identify dysregulated pathways and candidate drivers of distinct classes of gastric cancer.

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Diet Affects Men’s and Women’s Intestinal Microbes Differently

Diet Affects Men’s and Women’s Intestinal Microbes Differently | Amazing Science |

 The microbes living in the guts of males and females react differently to diet, even when the diets are identical, according to a study by scientists from The University of Texas at Austin and six other institutions published this week in the journal Nature CommunicationsThese results suggest that therapies designed to improve human health and treat diseases through nutrition might need to be tailored for each sex.

The researchers studied the gut microbes in two species of fish and in mice, and also conducted an in-depth analysis of data that other researchers collected on humans. They found that in fish and humans diet affected the microbiota of males and females differently. In some cases, different species of microbes would dominate, while in others, the diversity of bacteria would be higher in one sex than the other.

These results suggest that any therapies designed to improve human health through diet should take into account whether the patient is male or female.

Only in recent years has science begun to completely appreciate the importance of the human microbiome, which consists of all the bacteria that live in and on people’s bodies. There are hundreds or even thousands of species of microbes in the human digestive system alone, each varying in abundance.

Genetics and diet can affect the variety and number of these microbes in the human gut, which can in turn have a profound influence on human health. Obesity, diabetes, and inflammatory bowel disease have all been linked to low diversity of bacteria in the human gut.

One concept for treating such diseases is to manipulate the microbes within a person’s gut through diet. The idea is gaining in popularity because dietary changes would make for a relatively cheap and simple treatment.

Much has to be learned about which species, or combination of microbial species, is best for human health. In order to accomplish this, research has to illuminate how these microbes react to various combinations of diet, genetics and environment. Unfortunately, to date most such studies only examine one factor at a time and do not take into account how these variables interact.

“Our study asks not just how diet influences the microbiome, but it splits the hosts into males and females and asks, do males show the same diet effects as females?” said Daniel Bolnick, professor in The University of Texas at Austin's College of Natural Sciences and lead author of the study.

Eric Chan Wei Chiang's curator insight, August 2, 11:36 PM

Previously, it was assumed that men and women have mostly similar biological functions. This is an interesting paradigm shift indeed. 


This has future implication with our diet and how we treat diseases.

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Designing nanoparticles that can deliver drugs more easily

Designing nanoparticles that can deliver drugs more easily | Amazing Science |

A new study led by MIT materials scientists reveals the reason why gold nanoparticles  can easily slip through cell membranes to deliver drugs directly to target cells. The 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.”

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. But in 2008, MIT researchers found that a special class of gold nanoparticles coated with a mix of molecules could enter cells without any disruption.

Last year, they 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.


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Noninvasive retinal imaging device detects Alzheimer’s up to 20 years in advance

Noninvasive retinal imaging device detects Alzheimer’s up to 20 years in advance | Amazing Science |

Cedars-SinaI Medical Center researchers have developed a noninvasive retinal imaging device that can provide early detection of changes indicating Alzheimer’s disease 15 to 20 years before clinical diagnosis.

“In preliminary results in 40 patients, the test could differentiate between Alzheimer’s disease and non-Alzheimer’s disease with 100 percent sensitivity and 80.6 percent specificity, meaning that all people with the disease tested positive and most of the people without the disease tested negative,” said Shaun Frost, a biomedical scientist and the study manager at the Commonwealth Scientific and Industrial Research Organisation (CSIRO), Australia’s national science agency.

Keith Black, MD, professor and chair of Cedars-Sinai’s Department of Neurosurgery and director of the Maxine Dunitz Neurosurgical Institute and the Ruth and Lawrence Harvey Chair in Neuroscience, said the accumulation of beta-amyloid plaque in the brain is a hallmark sign of Alzheimer’s, but current tests detect changes only after the disease has advanced to late stages.

Researchers believe that as treatment options improve, early detection will be critical, but existing diagnostic methods are inconvenient, costly and impractical for routine screening.

“PET scans require the use of radioactive tracers, and cerebrospinal fluid analysis requires that patients undergo invasive and often painful lumbar punctures, but neither approach is quite feasible, especially for patients in the earlier stages of disease,” he said. Positron emission tomography, or PET, is the current diagnostic standard.

“The retina, unlike other structures of the eye, is part of the central nervous system, sharing many characteristics of the brain. A few years ago, we discovered at Cedars-Sinai that the plaques associated with Alzheimer’s disease occur not only in the brain but also in the retina.

Krishan Maggon 's curator insight, July 22, 5:43 PM

The test has to be validated in a large number of AD patients at various stages of AD with an elderly control group with normal cognition function.

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Gene that controls nerve conduction velocity linked to multiple sclerosis.

Gene that controls nerve conduction velocity linked to multiple sclerosis. | Amazing Science |

A new study from the University of Lubeck identifies a novel gene that controls nerve conduction velocity. Investigators report that even minor reductions in conduction velocity may aggravate disease in multiple sclerosis (MS) patients and in mice bred for the MS-like condition experimental autoimmune encephalomyelitis (EAE).

A strong tool for investigating the pathophysiology of a complex disease is the identification of underlying genetic controls. Multiple genes have been implicated as contributing to the risk of developing MS. Unlike studies that have focused on genetic regulators of inflammation, autoimmunity, demyelination, and neurodegeneration in MS, this study focused on nerve conduction velocity. Investigators found that polymorphisms of the inositol polyphosphate-4-phosphatase, type II (Inpp4b) gene affect the speed of nerve conduction in both mice with EAE and humans with MS.

Impairment of nerve conduction is a common feature in neurodegenerative and neuroinflammatory diseases such as MS. Measurement of evoked potentials (whether visual, motor, or sensory) is widely used for diagnosis and recently also as a prognostic marker for MS.

Using several genomic approaches, the investigators narrowed their search to the genetic region controlling the enzyme inositol-polyphosphate-4-phosphatase II (INPP4B), the product of which helps to regulate the phosphatidyl inositol signaling pathway. Enzymes in this family are involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival, and intracellular communication.

In one series of experiments, the researchers analyzed the genetic locus EAE31, which previously had been shown to control the latency of motor evoked potentials and clinical onset of EAE in mice. Using advanced techniques including congenic mapping, in silico haplotype analyses (computer simulations), and comparative genomics (from rats, mice and humans), they were able to ‘finemap’ the focus to Inpp4b as the quantitative trait gene for EAE31.

When the investigators analyzed this region in eight different strains of mice, they found they could divide the strains into two groups based on differences in amino acid sequences. The strains with the longer-latency SJL/J allele had the two amino acids (arginine and proline), whereas those with the shorter-latency C57BL/10S allele had others (serine and histidine).  These data suggest that Inpp4b structural polymorphism is associated with the speed of neuronal conduction.

In another experiment, the scientists compared motor conduction velocity in genetically modified mice with a mutant Inpp4b gene to that of control mice. The nerve conduction in this group was slower than in the control group.

Finally, the investigators studied INPP4B polymorphisms in MS patients. They looked at two cohorts: one from Spain (349 cases and 362 controls) and a second from Germany (562 cases and 3,314 controls). The association between the INPP4B polymorphisms and susceptibility to MS was statistically significant when the cohorts were pooled.

However, although the Spanish cohort showed a strong association between INPP4B and MS, the association was weaker in the German cohort. The exact reason for the diverging effect across these populations remains unresolved.

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Deadly Ebola Virus And The Development Of Designer Drugs To Fight The Disease

Deadly Ebola Virus And The Development Of Designer Drugs To Fight The Disease | Amazing Science |

The Ebola virus has sickened 1,711 people in West Africa and killed 932 in the latest outbreak, according to the World Health Organization. The virus has historically killed as many as 90 percent of those who contract it. The current outbreak has claimed the lives of about 60 percent of its victims.

On a small plot of land incongruously tucked amid a Kentucky industrial park sit five weather-beaten greenhouses. At the site, tobacco plants contain one of the most promising hopes for developing an effective treatment for the deadly Ebola virus.

The plants contain designer antibodies developed by San Diego-based Mapp Biopharmaceutical Inc. and are grown in Kentucky by a unit of Reynolds American Inc. Two stricken U.S. health workers received an experimental treatment containing the antibodies in Liberia last week. Since receiving doses of the drug, both patients’ conditions have improved.

Tobacco plant-derived medicines, which are also being developed by a company whose investors include Philip Morris International Inc., are part of a handful of cutting edge plant-based treatments that are in the works for everything from pandemic flu to rabies using plants such as lettuce, carrots and even duckweed. While the technique has existed for years, the treatments have only recently begun to reach the marketplace.

“Producing antibodies in plants is faster and less expensive than traditional manufacturing,” said Mary Kate Hart, an immunology researcher who did pioneering research on Ebola antibodies for the U.S. Army. She now is chief scientific officer for DynPort Vaccine Co.

Few modified-plant derived drugs have made it to market. Pfizer Inc. and Protalix Biotherapeutics Inc.’s enzyme Elelyso, produced in modified carrot cells was approved by U.S. regulators in 2012 to treat Gaucher’s disease. Locteron, an interferon-based hepatitis C drug candidate derived from duckweed, went through Phase 2 trials before its maker, Biolex Therapeutics Inc., declared bankruptcy. Neither drug is a monoclonal antibody and so far there has not been a vegetable-grown antibody approved by regulators, Chen said.

“Tobacco has always had negative press,” said Ebelhar, 66. “But now it may come back to be a benefit to mankind.’ Another tobacco giant-backed company working on biotech drugs grown in tobacco plants is Medicago Inc. in Quebec City, which is owned by Mitsubishi Tanabe Pharma Corp. and Philip Morris. Medicago is working on testing a vaccine for pandemic influenza and has a production greenhouse facility in North Carolina, said Jean-Luc Martre, senior director for government affairs at Medicago. Medicago is planning a final stage trial of the pandemic flu vaccine for next year, he said in a telephone interview. The plant method is flexible and capable of making antibodies and vaccines for numerous types of viruses, said Martre. In addition to influenza, the company’s website says it is in early stages of testing products for rabies and rotavirus.

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Mouse Avatars: Personalized Cancer Grafting Offers Clues to Individualized Treatment

Mouse Avatars: Personalized Cancer Grafting Offers Clues to Individualized Treatment | Amazing Science |

For $12,000, a company grafts a patient’s cancer into rodents and tests drugs on them. At a laboratory in Baltimore, hairless mice kept in racks of plastic crates are labelled with yellow cards, each identifying a person fighting cancer. These mice are cancer “avatars”—the lumpy tumors visible under their skin come from actual patients.

The technology is a twist on personalized medicine that’s being developed by Champions Oncology. The company, based in New Jersey and Maryland, has started offering mouse avatars directly to patients, at a cost of $10,000 to $12,000. Insurance companies don’t yet pay for the technology, which remains experimental.

In the service Champions is selling, doctors first remove a piece of a patient’s tumor during a surgery or biopsy. Then they ship it to the company, where it gets grafted under the skin of an immune-deficient mouse. Because the rodents have impaired defenses, the human tumor is able to grow. Parts of it can be removed and implanted in additional mice.

The data from the avatars is potentially life-saving, since the choice of what drug to give a cancer patient is often made by guesswork or trial and error. “Generally, the drugs we give to patients are more likely to not work than to work,” says Justin Stebbing, an oncologist at the Imperial College London, who has been involved in medical studies of Champions’s technology. The results from the personalized mice, he says, “give patients an additional layer of confidence.”

Cancer avatars are part of a wider effort to carry out experiments on people’s tumors outside their bodies. Some researchers have created fruit flies that share the same gene mutations patients have. Another technology, still in development, looks to capture floating tumor cells from a person’s bloodstream, then grow and test them in culture dishes (see “A Laboratory for Rare Cells Sheds Light on Cancer”). Still further out, scientists have plans to grow mini-organs, complete with an immune system that matches the patient’s (see “Building an Organ on a Chip”).

Over the last few decades, study of cancer in mouse models has gained popularity. Sophisticated genetic manipulation technologies and commercialization of these murine systems have made it possible to generate mice to study human disease. Given the large socio-economic burden of cancer, both on academic research and the health care industry, there is a need for in vivo animal cancer models that can provide a rationale that is translatable to the clinic. Such a bench-to-bedside transition will facilitate a long term robust strategy that is economically feasible and clinically effective to manage cancer. The major hurdles in considering mouse models as a translational platform are the lack of tumor heterogeneity and genetic diversity, which are a hallmark of human cancers. The present review, while critical of these pitfalls, discusses two newly emerging concepts of personalized mouse models called “Mouse Avatars” and Co-clinical Trials. Development of “Mouse Avatars” entails implantation of patient tumor samples in mice for subsequent use in drug efficacy studies. These avatars allow for each patient to have their own tumor growing in an in vivo system, thereby allowing the identification of a personalized therapeutic regimen, eliminating the cost and toxicity associated with non-targeted chemotherapeutic measures. In Co-clinical Trials, genetically engineered mouse models (GEMMs) are used to guide therapy in an ongoing human patient trial. Murine and patient trials are conducted concurrently, and information obtained from the murine system is applied towards future clinical management of the patient’s tumor. The concurrent trials allow for a real-time integration of the murine and human tumor data. In combination with several molecular profiling techniques, the “Mouse Avatar” and Co-clinical Trial concepts have the potential to revolutionize the drug development and health care process.

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‘Nanodaisies’ deliver a more powerful drug cocktail to cancer cells

‘Nanodaisies’ deliver a more powerful drug cocktail to cancer cells | Amazing Science |

Nanoscale flower-like structures that can introduce a “cocktail” of multiple drugs into cancer cells have been developed by biomedical engineering researchers at North Carolina State University and the University of North Carolina at Chapel Hill.

“We found that this technique was much better than conventional drug-delivery techniques at inhibiting the growth of lung cancer tumors in mice,” says Dr. Zhen Gu, senior author of the paper and an assistant professor in the joint biomedical engineering program.

“And based on in vitro (lab) tests in nine different cell lines, the technique is also promising for use against leukemia, breast, prostate, liver, ovarian and brain cancers.”

To make the “nanodaisies,” the researchers begin with a solution that contains a polymer called polyethylene glycol (PEG). The PEG forms long strands that have much shorter strands branching off to either side. Researchers directly link the anti-cancer drug camptothecin (CPT) onto the shorter strands and introduce the anti-cancer drug doxorubicin (Dox) into the solution.

PEG is hydrophilic, meaning it likes water. CPT and Dox are hydrophobic, meaning they don’t like water. As a result, the CPT and Dox cluster together in the solution, wrapping the PEG around themselves. This results in a daisy-shaped drug cocktail, only 50 nanometers in diameter, which can be injected into a cancer patient.

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Researchers Combine Ideas of 3D Printing With Molecular Self-assembly – Is Molecular Manufacturing Next?

Researchers Combine Ideas of 3D Printing With Molecular Self-assembly – Is Molecular Manufacturing Next? | Amazing Science |

What’s the ultimate extension of 3D printing technology? Where could 3D printing take us in the future? Eventually, we will have nano-factories, 3D printing at the molecular level. We will be able to turn our garbage into just about anything we want, via a sophisticated computer system, along with hardware capable of breaking any mass down to its molecular level, before using those molecules to construct a brand new object.

The two men have now combined the ideas of 3D printing with that of molecular self assembly to create a process which they call ‘genetic 3D printing’. For those who are not biologists, molecular self assembly is simply the process in which molecules arrange themselves in a particular order without guidance from an outside source. Molecular self assembly is a bottom-up approach like that of 3D printing. The discovery, which was accidental, allowed the researchers to create proteins which have the ability to self assemble into fibers. The discovery was made while they were simply trying to produce gluten adhesives, by cutting out a section of the gluten protein. What happened next surprised them. When the section of the protein was removed, fibers self assembled themselves in the beaker.

The quality of the fibers were on par with those produced by silk spiders, something which researchers have been trying to produce for years. Spider silk has a strength-to-weight ratio which is five times that of steel, making it an ideal material for all sorts of applications. The researchers went back and realized that they can manipulate the protein structures of the fibers to change their colors, but this wasn’t all. By combining the gluten protein with other proteins, they are able to molecularly print fibers with varying electrical properties, strengths and colors. In ordinary 3D printing, individuals use a software to translate a computer code and raw material into a physical object. In this case the researchers found that they were able to use a genetic blueprint as their computer code and back-calculate the DNA, which was inserted into a host bacterium, in this case e-coli. From there, the protein (raw material) grew, left the cell, and interacted with one another to build the fibers which the researchers had predetermined.

If this seems amazing, both Barone and Senger believe that they could eventually utilize this method as a way to molecularly manufacture all sorts of objects. Because the protein fibers are natural building blocks, once a method is figured out in which they are able to get the fibers to organize into larger structures, anything could be possible. From a coffee pot, to human bone, or even muscle, the researchers believe that one day this method of 3D printing fibers could manufacture it all. The researchers are currently working to further their discovery, and produce the silk-like fibers in large quantity for a variety of uses.  Additionally they are looking for ways to increase the size of each fiber, eventually enabling the manufacturing of larger objects.

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Nanoparticles open a new window into the brain

Nanoparticles open a new window into the brain | Amazing Science |

New imaging technique could help treat strokes, cancer and dementia.

Researchers at Stanford University in the US have developed the first non-invasive imaging technique that can detect micron-sized structures within blood vessels in the brains of mice. The method involves detecting near-infrared fluorescent light from single-walled carbon nanotubes (SWCNTs) that are injected into the mice. The ability to monitor the structure of blood vessels – and the blood flow within them – is extremely important for treating conditions such as strokes, dementia and brain tumors.

Today, brain imaging mainly relies on techniques such as X-ray computed tomography and magnetic resonance angiography. However, these methods cannot image structures several microns in size. In addition, with these approaches it can take several minutes to acquire an image, which means that it is not possible to use them to monitor blood flow in real time.

Fluorescence-based brain imaging in the visible and near-infrared (NIR) regions of the electromagnetic spectrum (400–900 nm) is a good alternative but at the moment it requires skull-thinning or, worse still, craniotomy – where sections of the skull are removed and replaced with a transparent "window" – to work properly. This is because light at these wavelengths can only travel about 1 mm through the skull.

Now, a team led by Hongjie Dai and Calvin Kuo at Stanford has developed a new through-scalp and through-skull fluorescence imaging technique that goes a long way in overcoming these problems. The method makes use of the intrinsic fluorescence of SWCNTs in the 1.3–1.4 µm range. "We define this wavelength as the NIR-IIa window, and it represents just about the longest wavelengths for fluorescence imaging reported thus far," explains Dai.

"Photons at these wavelengths are much less scattered than those in the 400–900 nm window when traversing biological tissues and are not absorbed significantly by water either," says Dai. "All in all, this allows us to see deeper into the brain through intact scalp skin and bone than is possible with traditional fluorescence imaging, which is mostly done with <800 nm wavelength photons."

"Compared with all other techniques for in vivo brain imaging (including MRI and CT), our technique affords higher spatial resolution", he says. "It allows us to image single capillary blood vessels that are just microns across and as deep as 3 mm inside the brain."

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New ovarian cancer biomarker discovered

New ovarian cancer biomarker discovered | Amazing Science |
New clues to early detection and personalized treatment of ovarian cancer have been made by researchers. Ovarian cancer is currently one of the most difficult cancers to diagnose early due to the lack of symptoms that are unique to the illness. Successful treatment is difficult at this late stage, resulting in high mortality rates.

There are three predominant cancers that affect women -- breast, ovarian and womb cancer. Of the three, ovarian cancer is of the greatest concern as it is usually diagnosed only at an advanced stage due to the absence of clear early warning symptoms. Successful treatment is difficult at this late stage, resulting in high mortality rates. Ovarian cancer has increased in prevalence in Singapore as well as other developed countries recently. It is now the fifth most common cancer in Singapore amongst women, with about 280 cases diagnosed annually and 90 deaths per year.

Scientists have now successfully identified a biomarker of ovarian stem cells, which may allow for earlier detection of ovarian cancer and thus allow treatment at an early stage of the illness.

The team has identified a molecule, known as Lgr5, on a subset of cells in the ovarian surface epithelium. Lgr5 has been previously used to identify stem cells in other tissues including the intestine and stomach, but this is the first time that scientists have successfully located this important biomarker in the ovary. In doing so, they have unearthed a new population of epithelial stem cells in the ovary which produce Lgr5 and control the development of the ovary. Using Lgr5 as a biomarker of ovarian stem cells, ovarian cancer can potentially be detected earlier, allowing for more effective treatment at an early stage of the illness (see Annex A). These findings were published online in Nature Cell Biology in July 2014.

Of the different types of ovarian cancers detected, high-grade serous ovarian carcinoma (HG-SOC) is the most prevalent of epithelial ovarian cancers. It has also proven to be one of the most lethal ovarian cancers, with only 30 per cent of such patients surviving more than five years after diagnosis. HG-SOC remains poorly understood, with a lack of biomarkers identified for clinical use, from diagnosis to prognosis of patient survival rates.

By applying bioinformatics analysis on big cancer genomics data, BII scientists were able to identify genes whose mutation status could be used for prognosis and development of personalized treatment for HG-SOC. The gene, Checkpoint Kinase 2 (CHEK2), has been identified as an effective prognostic marker of patient survival. HG-SOC patients with mutations in this gene succumbed to the disease within five years of diagnosis, possibly because CHEK2 mutations were associated with poor response to existing cancer therapies (see Annex B). These findings were published in Cell Cycle in July 2014.

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Monoclonal antibodies from mice, made look human, then produced in tobacco: Bio-high-tech treatment for Ebola is saving lives

Monoclonal antibodies from mice, made look human, then produced in tobacco: Bio-high-tech treatment for Ebola is saving lives | Amazing Science |

CNN reported recently that the two US citizens who were flown back to the states after contracting the Ebola virus were given an extremely experimental treatment, one that's still undergoing animal testing. While the treatment involves antibodies, it's not a vaccine, and it can work effectively even after an infection has started. The process that produced it is a testament to the impressive capabilities developed in the field of biotechnology.

The Ebola virus, known for its horrific symptoms and high fatality rate, currently has no established treatment. The health care workers who are fighting the disease—and are thus at high risk for becoming infected themselves—can do little more than put themselves in isolation and try to compensate for the damage the virus causes. That situation was apparently the case for two Americans who contracted the virus while working in Liberia.

In this case, however, both people were apparently given an experimental treatment developed in part by a company called Mapp Biopharmaceutical. Complicating matters, Mapp licenses its developments to a company called LeafBio for production and distribution. But LeafBio has also licensed an Ebola treatment from a second company, called Defyrus, and it plans on combining the two. It's unclear whether the Americans received the original or combined therapy. In either case, both therapies were based on the same developmental process outlined below.

Fortunately, Mapp has been publishing papers describing its progress on an Ebola treatment as it went along, so it's possible to understand how the therapy was developed and how it operates. Despite its fearsome behavior, Ebola is a fairly simple virus, with only seven genes. The gene that is essential for the virus to attach to human cells, called Ebola glycoprotein, has been identified previously. Antibodies that stick to this protein would be expected to block infection of new cells and target any virus circulating in the blood stream for destruction. The problem appears to be that an effective antibody response comes too late for the patients. The virus also takes steps to tone down the immune response.

Mapp decided to do the immune system's job for it by making antibodies that can then be injected into infected individuals to perform the same function. The challenges are making the right ones and making enough of them. To get the material they needed, the researchers turned to a well established technology called monoclonal antibody production. They injected mice with the Ebola glycoprotein and then fused individual antibody-producing cells with a cancer cell. This process produced a cell that continued to divide in culture, making a single type of antibody. Some of the antibodies probably recognized cold and flu viruses, so the researchers had to screen for cells that made Ebola-specific antibodies. They identified three that stuck to different parts of the Ebola glycoprotein.

The problem at this point was that the antibodies were from mice. If injected into humans, the human immune system would recognize the antibodies as foreign and start an immune response against the treatment. So Mapp cloned the genes for these antibodies and then swapped out parts, replacing parts of the mouse version with the human portion of the same gene and carefully avoiding alterations in the parts that recognize the Ebola protein.

The researchers then needed to produce the antibodies in large quantities. So they managed to insert the genes into cells from a tobacco plant, which can be grown in large numbers with little fuss. The potential therapy was ready for testing.

Mapp has been pursing that testing, starting in mice and working its way up to primates. The company has also been shifting steadily later into the infection process. Its first tests showed that the treatment could be used prophylactically, given to monkeys prior to infection. In the researchers' most recent published work, from about a year ago, they used it on macaques that were already developing fevers as a result of the infection. Nearly half of the animals survived, while the infection was completely fatal in the control group.

Notably, that paper had members of the US Army Medical Research Institute of Infectious Diseases among its authors, suggesting that further development had a party with deep pockets willing to back the research through human trials. But it's not clear whether those trials had even started when, according to CNN, vials of the treatment were rushed to Liberia. And there's no way of telling how much, if at all, the antibodies helped the two people they were given to. We'll have to wait for larger clinical trials.

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End of chemotherapy within 20 years as pioneering DNA sequencing project is launched in the UK

End of chemotherapy within 20 years as pioneering DNA sequencing project is launched in the UK | Amazing Science |

Cancer patients will no longer have to put up with the debilitating side-effects of chemotherapy after David Cameron launched a new landmark project to map the genetic causes of the disease.

David Cameron, the prime minister, said the venture would ‘unlock the power of DNA’ to deliver ‘better tests, better drugs and better care for patients.’ "As our plan becomes a reality, I believe we will be able to transform how devastating diseases are diagnosed and treated in the NHS and across the world,” he said.

The first few hundred pilot participants in London, Cambridge and Newcastle have already donated DNA samples and the project is expected to be completed 2018. "20 years from now there will be therapies, instead of chemo, that will be a much more targeted approach to treatment,” said Prof Jeremy Farrer, head of the Wellcome Trust.

“We will look back in 20 years time and the blockbuster chemotherapy drugs that gave you all those nasty side effects will be a thing of the past and we will think ‘gosh what an era that was’. “Understanding humanity’s genetic code is not only going to be fundamental to the medicine of the future. It is essential part of medicine today. In rare congenital disease, in cancer and in infections, genomic insights are already transforming diagnosis and treatment.” Prof Farrer also predicted that genome sequencing to find the causes of the disease will become standard within our lifetime.

The first human genome was sequenced in 2003 following 13 years of work at a cost of £2 billion. Now it takes around two days and costs just £1,000.

A genome consists of a person’s 20,000 or so genes and the DNA in between. Each genome consists of a code of 3 billion letters. Over the next four years, about 75,000 patients with cancer and rare diseases, plus their close relatives, will have their whole genetic codes, or genomes, sequenced.

Cancer patients will have the DNA of both healthy and tumour cells mapped, making up the 100,000 total. Scientists expect the project to be pivotal to the development of future personalised treatments based on genetics, with the potential to revolutionise medicine.

A £78 million partnership between Genomics England, the body set up by the Department of Health to oversee the project, and the Californian DNA sequencing technology company Illumina was unveiled by Mr Cameron today.

Illumina, originally "spun out" by Cambridge University scientists, will invest around £162 million into the project over its lifetime. By the end of next year that figure is expected to have risen to about 10,000.

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Largest ever Ebola outbreak is NOT a global threat

Largest ever Ebola outbreak is NOT a global threat | Amazing Science |
Although the virus is exerting a heavy toll in West Africa, it does not spread easily.

Can Ebola spread on planes?

Deadly Ebola probably touched down in Lagos, Nigeria, the largest city in Africa, on 20 July. A man who was thought to be infected with the virus had arrived there on a flight from Liberia, where, along with Guinea and Sierra Leone, the largest recorded Ebola outbreak is currently raging. The Lagos case is the first to be internationally exported by air travel and today the UK foreign secretary announced that he would chair a government meeting on Ebola. As long as the virus continues to infect people in Liberia, Guinea and Sierra Leone, there is a small risk of more long-distance exports of the disease. But, Ebola does not pose a global threat.

The World Health Organization still considers the Lagos case a “probable” infection because it has not yet confirmed that the 40-year-old Liberian man had Ebola. He was quarantined upon arrival at the airport and taken to hospital, where he died on 25 July. Assuming he had Ebola, if proper control measures were taken at the airport and at the hospital, the risk that health-care workers or others will become infected as a result of contact with him is low. The European Centre for Disease Prevention and Control classifies people sharing public transport with someone infected as having a “very low” risk of catching the virus. Healthcare workers and doctors, several of whom have now been infected and died as a result of caring for people in the current outbreak, are at much higher risk and the WHO advises that they take strict precautions, which greatly lowers the risk.

The ECDC also says the probability of an infected person getting on a flight in the first place is low,given the small overall number of Ebola cases. Moreover, functional health systems should be able to prevent onward spread from any exported cases. Overall, the World Health Organisation estimates that there is a high risk of spread to countries bordering those with existing outbreaks, a moderate risk to countries further afield in the sub-region, but that there is little chance of spread overseas. There is no reason to assume that an exported case — be it to Lagos, a city of 17 million people, or any other place — will spark new outbreaks, because Ebola is not highly contagious.

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Nonablative Laser Light Increases Influenza Vaccine Response 4 to 7-fold - Neomatica

Nonablative Laser Light Increases Influenza Vaccine Response 4 to 7-fold - Neomatica | Amazing Science |

Influenza imposes a heavy annual public health burden, and lies historically at the heart of a number of global pandemics that killed tens of millions.  To overcome the challenges of manufacturing enough vaccines such that we may stave off the next epidemic, medical researchers are searching for ways to strengthen or extend the power of existing and stockpiled vaccines.  Now a team of scientists in Boston has just developed a new method of using laser light to stimulate and enhance the immune response to a vaccine by a remarkable 4 to 7-fold against disease agents. Such treatments that assist vaccines but are not vaccines themselves are known as adjuvants.

Interestingly, the improved 4 to 7-fold laser adjuvant could not be matched even when compared against increasing the vaccine dosage 10-fold.  Efficacy of the vaccine was measured by the level of influenza-specific antibodies generated in an inoculated person.  The new method improves on an existing adjuvant hampered by harmful side effects which thus far has prevented its usage broadly.  Although the results were obtained in the context of two animal models, adult and aged mice, as well as pigs, its fairly general immunological basis is expected to translate to humans.

Before inoculation, the injection site is exposed to laser light for a short time. The light does not perforate the outer layers of the skin, but rather injures the dermis.  Because of the way the laser light is arranged, this creates a number of “microthermal zones.”  In each zone, dermal cells that are damaged stimulate inflammation, signaling danger to the immune system, which in turn attracts antigen-presenting cells (APCs) to the damaged area. APCs are cells that occur naturally in the body that bind antigens of harmful disease agents so as to prepare the rest of the immune system to recognize and neutralize the threat.

The damaged area is so small such that that self-healing occurs within 72 hours. The inspiration for the adjuvant comes from a type of skin treatment used in cosmetic dermatology.  In the cosmetic context, the laser light is used to stimulate lightly skin with aged appearance.  Post-damage, epithelial cells quickly grow to surround the microthermal zone to give rise to more youthful looking skin.  The same class of non-ablative lasers were used in this study.

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Study suggests probiotics could prevent obesity and insulin resistance

Study suggests probiotics could prevent obesity and insulin resistance | Amazing Science |

Vanderbilt University researchers have discovered that engineered probiotic bacteria (“friendly” bacteria like those in yogurt) in the gut produce a therapeutic compound that inhibits weight gain, insulin resistance, and other adverse effects of a high-fat diet in mice.

“Of course it’s hard to speculate from mouse to human,” said senior investigator Sean Davies, Ph.D., assistant professor of Pharmacology. “But essentially, we’ve prevented most of the negative consequences of obesity in mice, even though they’re eating a high-fat diet.”

The findings published in the August issue of the Journal of Clinical Investigation (open access) suggest that it may be possible to manipulate the bacterial residents of the gut — the gut microbiota — to treat obesity and other chronic diseases.

Davies has a long-standing interest in using probiotic bacteria to deliver drugs to the gut in a sustained manner, in order to eliminate the daily drug regimens associated with chronic diseases. In 2007, he received a National Institutes of Health Director’s New Innovator Award to develop and test the idea.

Other studies have demonstrated that the natural gut microbiota plays a role in obesity, diabetes and cardiovascular disease. “The types of bacteria you have in your gut influence your risk for chronic diseases,” Davies said. “We wondered if we could manipulate the gut microbiota in a way that would promote health.”

To start, the team needed a safe bacterial strain that colonizes the human gut. They selected E. coli Nissle 1917, which has been used as a probiotic treatment for diarrhea since its discovery nearly 100 years ago.

They genetically modified the E. coli Nissle strain to produce a lipid compound called N-acyl phosphatidylethanolamine (NAPE)*, which is normally synthesized in the small intestine in response to feeding. NAPE is rapidly converted to NAE, a compound that reduces both food intake and weight gain. Some evidence suggests that NAPE production may be reduced in individuals eating a high-fat diet.

“NAPE seemed like a great compound to try — since it’s something that the host normally produces,” Davies said.

The investigators added the NAPE-producing bacteria to the drinking water of mice eating a high-fat diet for eight weeks. Mice that received the modified bacteria had dramatically lower food intake, body fat, insulin resistance and fatty liver compared to mice receiving control bacteria.

They found that these protective effects persisted for at least four weeks after the NAPE-producing bacteria were removed from the drinking water. And even 12 weeks after the modified bacteria were removed, the treated mice still had much lower body weight and body fat compared to the control mice. Active bacteria no longer persisted after about six weeks.

Deborah Verran's comment, July 26, 10:31 AM
NB This research was performed in mice. The value of probiotics as for eg in some manufactured brands of yoghurt remains to be seen.
Eric Chan Wei Chiang's curator insight, July 27, 7:39 AM

The term biofortification is often applied to the nutritional enhancement of crops via selective breeding or genetic modification. I felt that term was suitable for describing the genetic enhancement of probiotics as these bacteria confer nutritional benefits and are often incorporated into functional foods.


I also find this technology fascinating because it much simpler and than other comparable therapies such as a bionic pancrease


Functional foods are another topic which interest me and more scoops on the topic can be read here:


Pierre-André Marechal's curator insight, July 28, 12:23 PM

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