CNIO researchers discover new genetic errors that could cause 1 of the most deadly leukaemias The sequencing of the acute dendritic cell leukaemia exome shows that more than half of patients display ‘epigenetic’ gene alterations

Juan Cruz Cigudosa from the Spanish National Cancer Research Centre’s (CNIO)

Acute dendritic leukaemia is a rare type of leukaemia, but one with the worst prognosis—the average patient survival rate is just 12-14 months—that is difficult to treat. Juan Cruz Cigudosa’s team, from the Spanish National Cancer Research Centre’s (CNIO) Molecular Cytogenetics Group, has for the first time sequenced the exome –the coding, or protein-generating, regions of the genome— of dendritic cell leukaemia.

The analyses, published in Leukemia, the world’s leading journal in onco- haematology, uncover new genetic pathways that could revolutionise treatment guidelines for these patients.

‘EPIGENETIC’ GENES ARE ALTERED IN MOST CASES

For the first time in human leukaemias, scientists have described mutations in four genes (IKZF3, HOXB9, UBE2G2 and ZEB2) that have important cellular functions, such as gene regulation and cellular differentiation.

“In addition to these genes, we have found that more than half of the cases harbour mutations in epigenetic genes at diagnosis —those genes that introduce chemical modifications in the DNA— something that had never been observed in this type of leukaemia”, says Cigudosa. “Therapies directed against these epigenetic genes already exist, so these patients could also benefit from them”.

In summary, the genetic profile of acute dendritic cell leukaemia, currently treated as a lymphoid leukaemia, is similar to that of myeloid leukaemia. “These results suggests a change in the treatment guidelines for these patients, who were completely misplaced”, says Juliane Menezes, the first author of the study.

According to Cigudosa, “this study is a clear example of the role of genomics in translational research being carried out by Spanish scientists, in general, and more specifically at CNIO”.

Use light instead of electricity to carry information in computer circuits, potentially leading to vast improvements in efficiency

False-color scanning electron microscope image, the arrow shows the path light takes as it hops between silicon rings along the edge of the chip, successfully avoiding defects — in this case a missing ring.
Credit: NIST

Scientists have a new way to edge around a difficult problem in quantum physics, now that a research team from the National Institute of Standards and Technology (NIST) and University of Maryland’s Joint Quantum Institute (JQI) have proved* their recent theory about how particles of light flow within a novel device they built.

While the problem itself—how to find an easier way to study the quantum Hall effect—may be unfamiliar to many, the team’s solution could help computer designers use light instead of electricity to carry information in computer circuits, potentially leading to vast improvements in efficiency.

The quantum Hall effect is observed when there is a magnetic field perpendicular to a flat wire that has electrons flowing through it. The field pushes the electrons over to one side of the wire, so their flow is concentrated along its edge. Although a fairly exotic piece of physics, the quantum Hall effect already has been applied to make better standards for electrical conductance. But the effect is hard to study because measuring it requires stringent lab conditions, including extremely low temperatures and samples of exceptional purity.

The team looked for a way around these issues, and in 2011 they found** a potential, albeit theoretical, answer: Build a model system in which particles of light behave exactly like electrons do when subjected to the quantum Hall effect, and study that system instead.

“We knew building an analogous system that uses photons would have additional advantages,” says NIST physicist Mohammad Hafezi. “Light can carry much more information than electricity, so working with a photon-based system also could help us design computer components that use light.”

Dolphins inspire new radar system to detect hidden surveillance and explosive devices

This is an image of Professor Tim Leighton.
Credit: University of Southampton

Inspired by the way dolphins hunt using bubble nets, scientists at the University of Southampton, in collaboration with University College London and Cobham Technical Services, have developed a new kind of radar that can detect hidden surveillance equipment and explosives.

The twin inverted pulse radar (TWIPR) is able to distinguish true ‘targets’, such as certain types of electronic circuits that may be used in explosive or espionage devices, from ‘clutter’ (other metallic items like pipes, drinks cans, nails for example) that may be mistaken for a genuine target by traditional radar and metal detectors.

The new system has been developed by a team led by Professor Tim Leighton from the University’s Institute of Sound and Vibration Research and is based on his unique sonar concept called twin inverted pulse sonar (TWIPS). TWIPS exploits the natural abilities of dolphins to process their sonar signals to distinguish between targets and clutter in bubbly water. Some dolphins have been observed to blow ‘bubble nets’ around schools of fish, which force the fish to cluster together, and their sonar would not work if they could not distinguish the fish from the bubbles.

Adalimumab reduces inflammation in refractory pediatric uveitis Biologic agent offers new option for steroid-resistant patients, according to study published in the Journal of AAPOS

Uveitis is inflammation of the uvea, which is a tissue inside the eye. The uvea is made up of three parts:
the iris (the colored part of the eye that surrounds the pupil)
the ciliary body (a muscle that helps the eye focus and makes the fluid that fills the front of the eye)
the choroid (the layer of tissue in the back of the eye, behind the retina)
Inflammation can affect any or all of these parts. Symptoms, treatment, and effects are different depending on which parts of the eye are affected.
What is the cause?
Most of the time, the cause of uveitis is not known. It can be related to autoimmune diseases that affect other parts of the body, such as sarcoidosis and some types of arthritis. Less often, infections like herpes, syphilis, or Lyme disease can cause uveitis.

A new study published in the current issue of the Journal of the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) suggests that the biologic agent adalimumab may be a viable treatment option for patients with steroid-resistant refractory pediatric uveitis. In a study of fifteen children with the disease 85.7% showed initial improvement of anterior/posterior chamber inflammatory activity after almost three months of treatment.

Uveitis in children is relatively rare but left unchecked it can impair vision and even lead to blindness or other serious complications. Frequently occurring in conjunction with other conditions such as juvenile idiopathic arthritis (JIA), pediatric uveitis is a chronic condition requiring long-term therapy. While corticosteroids are the first line of treatment, children may become resistant to the medications, develop significant side effects, or resist periocular administration. Studies show that about one third of children with uveitis develop one or more complications. Children with JIA-associated uveitis are especially prone to cataracts, band keratopathy, glaucoma, and phthisis. When complications threaten vision, urgent surgery may be necessary.

The goal of the study was to evaluate the effect of adalimumab on eye inflammation in children with refractory pediatric uveitis. Adalimumab is a recombinant human IgG1 monoclonal antibody to TNF-α that also affects TNF-α bound to receptors. Fifteen patients (12 female, average age 12 years) with either JIA-associated, idiopathic, or familial juvenile systemic granulomatosis (Blau syndrome) participated in the study. All children had previously been treated with systemic steroids and methotrexate, and a few of them had also failed to respond to immunosuppressive therapies such as cyclosporine and azathioprine, as well as the biologics etanercept and infliximab.

After subcutaneous injection with adalimumab (the dosage depended on weight) every two weeks for an average of 32 months, 85.7% of patients showed improvement of anterior/posterior chamber inflammatory activity, usually after six weeks of treatment. Adalimumab treatment was considered effective according to Standardization of Uveitis Nomenclature (SUN) Working Group grading criteria in 60% of patients although four patients failed to respond at all. Efficacy tended to ebb over time.

“The results of the present study suggest that adalimumab is a reasonable first biological agent in cases of refractory noninfectious uveitis in children with good results and a reasonable side effect profile,” said lead investigator Luciano Bravo Ljubetic, MD, of the Ophthalmology Service of the Instituto de Investigacion Hospital Universitario La Paz (Spain). Only minor injection-site side effects were observed.

Sequential GO and standard chemotherapy provides no benefit for older patients with AML according to EORTC/GIMEMA trial

Immunohistochemical diagnosis of acute myelogenous leukemia. A, Bone marrow aspirate shows increased blasts from patient with acute myeloid leukemia with inv(16) (Wright-Giemsa stain, ×50). B, Bone marrow biopsy from the same patient shows 100% cellularity with sheets of blasts (hematoxylin-eosin stain, ×40).

Results of the randomized, phase III, EORTC/GIMEMA 06012 intergroup trial (AML-17) reported in the Journal of Clinical Oncology show that sequential combination of gemtuzumab ozogamicin (GO) and standard chemotherapy provides no benefit for older patients with acute myeloid leukemia (AML) and is too toxic for patients 70 years of age or more. GO is an antibody-drug conjugate comprised of an anti-CD33 monoclonal antibody linked to a cytotoxic agent.

Patients younger than 70 years with secondary acute myeloid leukemia might possibly benefit from such treatment. However, outcomes were significantly worse in the oldest age subgroup due to a higher risk of early mortality.

Prof. Sergio Amadori of the Tor Vergata University Hospital in Rome and Coordinator of this study says, “This large trial in older patients with AML is the third randomized study to assess the addition of GO to chemotherapy in elderly patients with AML. So, it is an important addition to the literature. Unlike the two trials published so far (French ALFA-0701, and UK NCRI AML16), a higher dose of GO was used, and the GO in induction was given before standard induction chemotherapy. This turns out to be an important difference. While, as shown by the former trials, the addition of low doses of GO to chemotherapy resulted in a survival benefit for older patients with better-risk disease, our study clearly indicates that an intensification strategy combining two upfront higher doses of GO with sequential induction chemotherapy is highly myelosuppressive and not beneficial in older patients, particularly in the oldest age cohort where induction response and survival rates are significantly compromised due to excess early mortality. On the basis of the available studies, there is plausible evidence that lower doses of GO as an adjunct to standard chemotherapy may offer better outcomes for these patients with limited alternatives.”

A fresh solution for the problem lindane in the soil

At the UPV/EHU’s Department of Analytical Chemistry Itxaso San Román has studied whether iron nanoparticles can be applied to eliminate lindane, and how far they are capable of achieving this.

For many years two companies located in Bizkaia, Bilbao Chemicals (Barakaldo 1947-1987) and Nexana (Erandio 1952-1982), had been manufacturing lindane and dumping it into the environment with no control whatsoever. Today we have become aware of the need to solve the problems caused by this dumping and the difficulty in achieving this since there is no viable process that will safely destroy the lindane mixed with the soil. A study by the UPV/EHU’s Department of Physical Chemistry and Analytical Chemistry in collaboration with Tecnalia has confirmed the hypothesis of the high reactive capacity of iron nanoparticles to degrade lindane. The study has been published in the prestigious journal Chemosphere.

Lindane has been routinely used among farmers as an insecticide and pesticide, and although its use has now been banned, the consequences of lindane manufacture and use have not disappeared. The risk posed by lindane lies in the fact that it is not only toxic, it can be accumulated in living organisms. From an environmental point of view, it has low solubility, high stability and high persistence and resistance to degradation in the environment.

Although there is as yet no viable process for safely destroying lindane, an innovative, efficient alternative is to use iron nanoparticles. Iron nanoparticles have shown themselves to be very effective as a decontaminating agent when it comes to handling various families of highly toxic compounds like lindane. However, they have a number of drawbacks that limit and hamper their application, since they oxidize easily in the presence of air and their tendency to agglomerate limits their mobility in the medium in which one is seeking to apply them. So the need to protect them is done by using Carboxymethyl cellulose (CMC), polyaspartate (PAP) and poly (acrylic acid) (PAA) as biodegradable polymer coatings.

From the laboratory to the land

“The main aim of our study was to validate on a laboratory scale whether these iron nanoparticles can be applied and whether they have the capacity to eliminate the lindane,” explained Itxaso San Román, member of the UPV/EHU’s Department of Analytical Chemistry. This requires advanced analytical techniques capable of monitoring the degradation process, which will take place in the presence of the various nanoparticles, determining the speed of the reaction and likewise detecting the possible by-products that are formed in the course of that reaction.

The mysterious scarab beetles: 2 new species of the endangered ancient genus Gyronotus

This image shows a living G. Perissinottoi in its natural habitat.

Famous as the sacred beetles of ancient Egypt the scarab beetle group in fact represents much greater diversity around the globe. Some of the most vulnerable representatives are contained in the flightless genus Gyronotus, which currently includes six known species. A recent study published in the open access journal Zookeys describes two new species with unusual distribution from southern Africa. The two new species G. perissinottoi and G. schuelei both dwell in grasslands/savannas, while most of the other known species in the genus exhibit a preference for forest habitats. G. perissinottoi occurs in a small but biodiversity unique area in southern KwaZulu-Natal, in the beautiful Umthamvuna Nature Reserve. The second species, G. schuelei originates from western Swaziland and is currently known only from two specimens.

The representatives of the genus Gyronotus as well as several other genera of the tribe Canthonini, are regarded among the most endangered of the African Scarabaeinae because of their sensitivity to disturbance. Apart from G. glabrosus and the two newly described beetles, Gyronotus species are linked to coastal and low-lying forest habitats, which have undergone massive transformation during the past 50 years, through clearance, degradation and fragmentation.

Newly discovered plant structure may lead to improved biofuel processing

Debra Mohnen, left, is a professor of biochemistry and molecular biology and a member of UGA’s Complex Carbohydrate Research Center. Li Tan is an assistant research scientist with the CCRC.

Athens, Ga. – When Li Tan approached his colleagues at the University of Georgia with some unusual data he had collected, they initially seemed convinced that his experiment had become contaminated; what he was seeing simply didn’t make any sense.

Tan was examining some of the sugars, proteins and polymers that make up plant cell walls, which provide the structural support and protection that allow plants to grow. Yet his samples contained a mixture of sugars that should not be present in the same structure.

However, Tan was convinced that his samples were pure so he and Debra Mohnen, who heads the lab, met again to pore over the data. They came to realize that there were hints in the data of a connection between two different types of cell wall glycans (sugars) and a specific cell wall protein known as arabinogalactan protein. This connection is not known to exist and does not conform to the commonly held scientific definitions of plant cell wall structure.

But Tan and Mohnen, who both work as part of the BioEnergy Science Center, one of three U.S. Department of Energy-funded research centers, were persistent, and they, along with an interdisciplinary team of chemists, molecular biologists and plant experts at UGA, began searching for answers. What they found could redefine our understanding of basic plant biology, and it may lead to significant improvements in the growth and processing of biofuel crops.

Exposure to pesticides in food, air and water increases risk of type 2 diabetes

From left to right, some of the researchers at the University of Granada laboratory: Juan Pedro Arrebola, Francisco Artacho and María Fernández

A study led by the University of Granada reveals that there is a direct relationship between the presence of Persistent Organic Pollutants in the body and the development of type 2 diabetes, regardless of the patient’s age, gender or body mass index.

A study conducted at the University of Granada has revealed that there is a direct relationship between exposure to pesticides (Persistent Organic Pollutants, CPOs) in food, air and water and prevalence of type 2 diabetes in adults, regardless of age, gender and body mass index. These substances tend to concentrate in body fat, and they might be one of the reasons why obese people are more likely to develop diabetes, since the more fat the higher the COP concentrations in the body.

In a paper recently published in the journal Environmental Research, researchers demonstrate that people with higher concentrations of DDE –the main metabolite in the pesticide DDT– are four times more likely to develop type 2 diabetes than other people. In addition, the risk of type 2 diabetes is also associated with exposure to β-HCH (beta-Hexachlorocyclohexane), which is present in the formula of the pesticide Lindano.

University of Pittsburgh Cancer Institute (UPCI) researchers reveal mechanism to halt cancer cell growth, discover potential therapy

Dr. Bennett Van Houten

University of Pittsburgh Cancer Institute (UPCI) researchers have uncovered a technique to halt the growth of cancer cells, a discovery that led them to a potential new anti-cancer therapy.

When deprived of a key protein, some cancer cells are unable to properly divide, a finding described in the cover story of the February issue of the Journal of Cell Science. This research is supported in part by a grant from the National Institutes of Health.

“This is the first time anyone has explained how altering this protein at a key stage in cell reproduction can stop cancer growth,” said Bennett Van Houten, Ph.D., the Richard M. Cyert Professor of Molecular Pharmacology at UPCI and senior author of the research paper. “Our hope is that this discovery will spur the development of a new type of cancer drug that targets this process and could work synergistically with existing drugs.”

All cells have a network of mitochondria, which are tiny structures inside cells that are essential for energy production and metabolism. Dynamin-related protein 1 (Drp1) helps mitochondria undergo fission, a process by which they split themselves into two new mitochondria.

In breast or lung cancer cells made to be deficient in Drp1, the researchers observed a huge network of highly fused mitochondria. These cancer cells appear to have stalled during a stage in cell division called G2/M. Unable to divide into new cells, the cancer growth stops. Those cells that do try to divide literally tear their chromosomes apart, causing more stress for the cell.

The cover of the Journal of Cell Science includes a colorful image of a breast cancer cell deficient in Drp1 that is stuck during the process of separating its chromosomes into two identical sets to be divided among two new cells. Lead author Wei Qian, Ph.D., a postdoctoral fellow in Dr. Van Houten’s laboratory, captured the image using a confocal microscope at Pitt’s Center for Biologic Imaging run by Simon Watkins, Ph.D., a co-author of this study.

Scientists at the Monell Center have identified the location and certain genetic characteristics of taste stem cells on the tongue. Identification of progenitors may someday help treat clinical taste dysfunction

Scanning electron microscopy image illustrates the dorsal view of an E15.5 embryonic tongue and papilla types. Black arrowheads point to fungiform papillae on the anterior oral tongue; black arrow points to the single circumvallate papilla in the back. White arrowhead at the tip points to the median furrow. The straight line marks the orientation for sectioning in the sagittal plane. B: H and E stained sagittal section of an E15.5 tongue to illustrate the orientation for all images of tongue sections. Black arrowheads point to fungiform papillae. Scale bars: 250 μm.

Scientists at the Monell Center have identified the location and certain genetic characteristics of taste stem cells on the tongue. The findings will facilitate techniques to grow and manipulate new functional taste cells for both clinical and research purposes.

“Cancer patients who have taste loss following radiation to the head and neck and elderly individuals with diminished taste function are just two populations who could benefit from the ability to activate adult taste stem cells,” said Robert Margolskee, M.D., Ph.D., a molecular neurobiologist at Monell who is one of the study’s authors.

Taste cells are located in clusters called taste buds, which in turn are found in papillae, the raised bumps visible on the tongue’s surface.

Two types of taste cells contain chemical receptors that initiate perception of sweet, bitter, umami, salty, and sour taste qualities. A third type appears to serve as a supporting cell.

A remarkable characteristic of these sensory cells is that they regularly regenerate. All three taste cell types undergo frequent turnover, with an average lifespan of 10-16 days. As such, new taste cells must constantly be regenerated to replace cells that have died.

For decades, taste scientists have attempted to identify the stem or progenitor cells that spawn the different taste receptor cells. The elusive challenge also sought to establish whether one or several progenitors are involved and where they are located, whether in or near the taste bud.

UGA researchers invent new material for warm-white LEDs. Discovery brings hope to the widespread use of LEDs for indoor lighting

Light emitting diodes, more commonly called LEDs, are known for their energy efficiency and durability, but the bluish, cold light of current white LEDs has precluded their widespread use for indoor lighting.

Now, University of Georgia scientists have fabricated what is thought to be the world’s first LED that emits a warm white light using a single light emitting material, or phosphor, with a single emitting center for illumination. The material is described in detail in the current edition of the Nature Publishing Group journal “Light: Science and Applications.”

“Right now, white LEDs are mainly used in flashlights and in automotive lamps, but they give off a bluish, cool light that people tend to dislike, especially in indoor lighting,” said senior author Zhengwei Pan, an associate professor in the department of physics in the UGA Franklin College of Arts and Sciences and in the College of Engineering. “Our material achieves a warm color temperature while at the same time giving highly accurate color rendition, which is something no single-phosphor-converted LED has ever been shown to do.”

Severity of emphysema predicts mortality

HRCT scan imaging of a patient with IPF and emphysema. Upper zones of the lungs showing paraseptal emphysema and mild patchy peripheral reticular lesions (A). Lower zones of the lungs showing patchy peripheral reticular and honeycombing lesions (B).

Severity of emphysema, as measured by computed tomography (CT), is a strong independent predictor of all-cause, cardiovascular, and respiratory mortality in ever-smokers with or without chronic obstructive pulmonary disease (COPD), according to a study from researchers in Norway. In patients with severe emphysema, airway wall thickness is also associated with mortality from respiratory causes.

“Ours is the first study to examine the relationship between degree of emphysema and mortality in a community-based sample and between airway wall thickness and mortality,” said lead author Ane Johannessen, PhD, post-doctoral researcher at Haukeland University Hospital in Bergen, Norway. “Given the wide use of chest CT scans around the world, the predictive value of these measures on mortality risk is of substantial clinical importance.”

Researchers find that simple blood test can help identify trauma patients at greatest risk of death. Study of more than 9,500 patients discovered that some trauma patients are up to 58 times more likely to die than others, regardless of the severity of their original injuries

A simple, inexpensive blood test performed on trauma patients upon admission can help doctors easily identify patients at greatest risk of death, according to a new study by researchers at Intermountain Medical Center in Salt Lake City.

The Intermountain Medical Center research study of more than 9,500 patients discovered that some trauma patients are up to 58 times more likely to die than others, regardless of the severity of their original injuries.

Researchers say the study findings provide important insight into the long-term prognosis of trauma patients, something not previously well understood.

“The results were very surprising,” said Sarah Majercik, MD, an Intermountain Medical Center surgeon and trauma researcher, whose team discovered that a tool developed at Intermountain Medical Center, called the Intermountain Risk Score, can predict mortality among trauma patients.

Dr. Majercik will present the findings from the study Friday at the 27th annual Scientific Session of the Eastern Association for the Surgery of Trauma in Phoenix.

A quantum leap in gene therapy of Duchenne muscular dystrophy

Dongsheng Duan, University of Missouri, and his research team have been able to reduce muscle disease and improve muscle strength in a dystrophic dog.
Credit: Christian Basi/University of Missouri

Usually, results from a new study help scientists inch their way toward an answer whether they are battling a health problem or are on the verge of a technological breakthrough. Once in a while, those results give them a giant leap forward. In a preliminary study in a canine model of Duchenne muscular dystrophy (DMD), University of Missouri scientists showed exactly such a leap using gene therapy to treat muscular dystrophy. The results of the study will be published in the journal Molecular Therapy on Jan. 15, 2013.

Muscular dystrophy occurs when damaged muscle tissue is replaced with fibrous, bony or fatty tissue and loses function. Duchenne muscular dystrophy is the most common type of muscular dystrophy predominantly affecting boys. Patients with DMD have a gene mutation that disrupts the production of dystrophin, a protein essential for muscle cell survival and function. Absence of dystrophin starts a chain reaction that eventually leads to muscle cell degeneration and death. For years, scientists have been working to find the key to restoring dystrophin, but they have faced many challenges.

Kaiser Permanente study: Change in PSA levels over time can help predict aggressive prostate cancer

Measurements taken over time of prostate specific antigen, the most commonly used screening test for prostate cancer in men, improve the accuracy of aggressive prostate cancer detection when compared to a single measurement of PSA, according to a Kaiser Permanente study published today in the British Journal of Urology International.

The retrospective study examined the electronic health records of nearly 220,000 men ages 45 and older over a 10-year period who had at least one PSA measurement and no previous diagnosis of prostate cancer. The study found that annual percent changes in PSA more accurately predicted the presence of aggressive prostate cancer when compared to single measurements of PSA alone, but only marginally improved the prediction of prostate cancer overall.

“The use of a single, elevated PSA level to screen for prostate cancer is considered controversial given the questionable benefits of PSA screening on prostate cancer mortality. The screening may also result in unnecessary prostate biopsies and subsequent treatments for localized prostate cancer, as it does not distinguish well between slow-growing and aggressive disease,” said Lauren P. Wallner, PhD, MPH, study lead author and post-doctoral research fellow at Kaiser Permanente Southern California’s Department of Research & Evaluation. “Our study demonstrates that repeated measurements of PSA over time could provide a more accurate – and much needed – detection strategy for aggressive forms of prostate cancer.”