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Archive - Mar 19, 2015

Antihypertensive Drug (Spirolactone) Blocks Mineralocorticoid Receptors and Reduces Side Effects of Corticosteroid-Based Creams Used to Treat Certain Skin Diseases

Basic research on blood pressure has led researchers from Inserm (Inserm Unit 1138, "Cordeliers Research Centre") in France to obtain unexpected results: drugs used to treat hypertension (high blood pressure) reduce side effects from corticosteroid-based creams used to treat certain skin diseases. This work was published online on February 10, 2015 in the Journal of Investigative Dermatology and the article is titled “Topical Mineralocorticoid Receptor Blockade Limits Glucocorticoid-Induced Epidermal Atrophy in Human Skin.” Corticosteroid-based dermatological creams are indicated for the symptomatic treatment of inflammatory skin conditions, such as atopic dermatitis and psoriasis, for example. However, they have frequent side effects, such as a slight burning sensation, and very often end by inducing skin atrophy (thinning of the skin, which becomes fragile), which is inconvenient for the patient, and for which there is presently no treatment. The researchers from Inserm formulated a hypothesis whereby this harmful effect might be related to the inappropriate activation by these creams of mineralocorticoid receptors located in the epidermis. These receptors, which are present in the kidney, heart, eye, and certain neurons in particular, reacted with aldosterone, a hormone that regulates the blood pressure. Moreover, previous studies also showed them to be highly sensitive to corticosteroids. Application of corticosteroids to cultured skin causes it to become thinner: in six days, the thickness of the epidermis was reduced by one-third. The researchers then induced a pharmacological blockade of the receptors by adding specific antagonists to the corticosteroid treatment.

Protein Sequencing Helps Resolve Evolutionary Mystery of What Darwin Called the “Strangest Animals Ever Discovered”

Scientists have resolved pieces of a nearly 200-year-old evolutionary puzzle surrounding the group of mammals that Charles Darwin called the "strangest animals ever discovered." New research, led by the American Museum of Natural History, the Natural History Museum in London, and the University of York, shows that South America's so-called "native ungulates"--the last of which disappeared only 10,000 years ago--are actually related to mammals like horses rather than to elephants and other species with ancient evolutionary ties to Africa as some taxonomists have long maintained. Published online on March 18, 2015 in Nature, the findings are based on fossil protein sequences, which allow researchers to peek back in time up to 10 times farther than they can with DNA. "Fitting South American ungulates to the mammalian family tree has always been a major challenge for paleontologists, because anatomically they were these weird mosaics, exhibiting features found in a huge variety of quite unrelated species living all over the place," said Dr. Ross MacPhee, one of the paper's authors and a curator in the American Museum of Natural History's Department of Mammalogy. "This is what puzzled Darwin and his collaborator Richard Owen so much in the early 19th century. With all of these conflicting signals, they couldn't say whether these ungulates were related to giant rodents, or elephants, or camels--or what have you." Dr. Ian Barnes, research leader at the Natural History Museum in London and another of the paper's authors, explained, "Although the bones of these animals had been studied for over 180 years, no clear picture of their origins had been reached.

Robot Model for Infant Learning Shows Bodily Posture May Affect Memory and Learning

An Indiana University (IU) cognitive scientist and collaborators have found that posture is critical in the early stages of acquiring new knowledge. The study, conducted by Dr. Linda Smith, a professor in the IU Bloomington College of Arts and Sciences' Department of Psychological and Brain Sciences, in collaboration with Dr. Anthony Morse, a roboticist from England, and Dr. Viridian Benitez, a developmental psychologist from the University of Wisconsin-Madison, and others, offers a new approach to studying the way "objects of cognition," such as words or memories of physical objects, are tied to the position of the body. "This study shows that the body plays a role in early object name learning, and how toddlers use the body's position in space to connect ideas," Dr. Smith said. "The creation of a robot model for infant learning has far-reaching implications for how the brains of young people work." The research article, titled "Posture Affects How Robots and Infants Map Words to Objects," was published on March 18, 2015 in PLOS ONE, an open-access, peer-reviewed online journal. Using both robots and infants, researchers examined the role that bodily position played in the brain's ability to "map" names to objects. They found that consistency of the body's posture and spatial relationship to an object as an object's name was shown and spoken aloud were critical to successfully connecting the name to the object. The new insights stem from the field of epigenetic robotics, in which researchers are working to create robots that learn and develop like children, through interaction with their environment. Dr. Morse applied Dr. Smith's earlier research to creating a learning robot in which cognitive processes emerge from the physical constraints and capacities of its body.

Scientists Study Gut Bacteria Communication Via Quorum-Sensing Signal AI-2

A research team led by Dr. Karina Xavier at the Instituto Gulbenkian de Ciência (IGC, Portugal) has shown that bacteria living in the intestine both talk and listen to each other. Using small molecules in place of words, these microbial conversations changed the numbers of certain species of bacteria in the gut and started to repair the huge damage caused by lasting antibiotic treatment. These findings were published online on March 18, 2015 in an open-access article in Cell Reports. The same article will be published in the next print issue of Cell Reports and, because of its significance, will be highlighted on the journal's cover. The articles highlights the potential of using bacteria’s own language to communicate with, control, and exploit the multitude of microbes that live inside of the human gut. The article is titled “Manipulation of the Quorum-Sensing Signal AI-2 Affects the Antibiotic-Treated Gut Microbiota.” Bacteria were long seen as predominantly harmful organisms, responsible for many illnesses across the world. This picture has been changing over the last ten years. Scientists are now reporting many beneficial characteristics of certain bacterial species, particularly those living inside human bodies, in particular in the intestine. These microbes can be seen as tiny lodgers in the gut, helping the body to get the most out of ingested food and protecting from opportunistic invaders that cause disease. "When we lose some of these lodgers: by taking antibiotics or changing our diet, for example, the resulting imbalance in the community of bacteria can leave us at risk of infection, inflammatory bowel disease, obesity, or cancer," explains Dr. Xavier. Therefore, scientists like herself are keen to understand how these bacteria interact, and then use this knowledge to benefit human health.

Possible Key to Alleviating Chronic Pain & Itch Discovered; Targeted Therapy Not Yet Possible; Results Support 50-Year-Old “Gate Control Theory” of Pain

Sensing pain is extremely unpleasant and sometimes hard to bear, and pain can even become chronic. The perception of pain varies significantly depending on the context in which it is experienced. 50 years ago, neurobiologist Dr. Patrick Wall and psychologist Dr. Ronald Melzack formulated the so-called "Gate Control Theory" of pain. The two researchers proposed that inhibitory nerve cells in the spinal cord determine whether a pain impulse coming from the periphery, such as the foot, is relayed to the brain or not. A team headed by Dr. Hanns Ulrich Zeilhofer from the Institute of Pharmacology and Toxicology at the University of Zurich (UZH) has now discovered which inhibitory neurons in the spinal cord are responsible for this control function: As the study published online on March 18, 2015 in an open-access article in Neuron shows, the control cells are located in the spinal dorsal horn and use the amino acid glycine as an inhibitory messenger. The Neuron article is titled “Targeted Ablation, Silencing, and Activation Establish Glycinergic Dorsal Horn Neurons As Key Components of a Spinal Gate for Pain and Itch.” With the aid of genetically modified viruses, the research group from UZH managed to specifically interfere with the function of these neurons in mice. They discovered that disabling the glycine-releasing neurons leads to an increased sensitivity to pain and signs of spontaneous pain. Moreover, Dr. Zeilhofer's team developed viruses that enable these specific pain-control cells to be activated pharmacologically. Mice treated with these viruses were less sensitive to painful stimuli than their untreated counterparts. Activating these nerve cells also alleviated chronic pain. And the surprising additional result: "Evidently, the neurons don't just control pain, but also various forms of itch," explains Dr. Zeilhofer.

Prolonged Breastfeeding Associated with Increased Intelligence, Longer Schooling, and Higher Earnings in Adults, 30-Year Study Finds; Role for DHAs Suggested

Longer duration of breastfeeding is linked with increased intelligence in adulthood, longer schooling, and higher adult earnings, according to results of a study following a group of almost 3500 newborns for 30 years and published in an open-access article in the April 2015 issue The Lancet Global Health. [Note that there is an audio description of this research and the link to this audio is provided in the article, for which a link is provided below. There is also a commentary on the article, which you can also find in the article at the link below. Note, in particular, that the commentary suggests an alternative explanation for the results obtained. ] "The effect of breastfeeding on brain development and child intelligence is well established, but whether these effects persist into adulthood is less clear,"* explains lead author Dr. Bernardo Lessa Horta from the Federal University of Pelotas in Brazil. "Our study provides the first evidence that prolonged breastfeeding not only increases intelligence until at least the age of 30 years but also has an impact both at an individual and societal level by improving educational attainment and earning ability. What is unique about this study is the fact that, in the population we studied, breastfeeding was not more common among highly educated, high-income women, but was evenly distributed by social class. Previous studies from developed countries have been criticized for failing to disentangle the effect of breastfeeding from that of socioeconomic advantage, but our work addresses this issue for the first time." Dr. Horta and colleagues analyzed data from a prospective study of nearly 6,000 infants born in Pelotas, Brazil in 1982. Information on breastfeeding was collected in early childhood.

Targeted Drug (BV) Doubles Progression-Free Survival in Difficult-to-Treat Cases of Hodgkin Lymphoma

A phase 3 trial of brentuximab vedotin (BV), the first new drug for Hodgkin lymphoma in over 30 years, shows that adults with hard-to-treat Hodgkin lymphoma who are given BV immediately after stem cell transplant survived without the disease progressing for almost twice as long as those given placebo (43 months versus 24 months). The findings, published online on March 18, 2015 in The Lancet, are potentially practice-changing for this young cancer population that has exhausted other treatment options and for which prognosis is poor. "No medication available today has had such dramatic results in patients with hard-to-treat Hodgkin lymphoma," says lead author Dr. Craig Moskowitz, a Professor of Medicine at Memorial Sloan Kettering Cancer Center, New York, USA. Hodgkin lymphoma is the most common blood cancer in young adults aged between 15 and 35 years. Most patients are cured with chemotherapy or radiotherapy. However, for patients who relapse, or do not respond to initial therapy, the treatment of choice is usually a combination of high-dose chemotherapy and autologous stem cell transplant (ASCT)--a procedure that uses healthy stem cells from the patient to replace those lost to disease or chemotherapy. While about 50% of patients who undergo this procedure are cured, for the other half, treatment is only palliative.