Researchers have caught a protein they previously implicated in a variety of cancer-promoting roles performing a vital function in cell division, survival, and development of brain tumors. In a paper published online on December 5, 2013 in Molecular Cell, Zhimin Lu, Ph.D., professor of Neuro-Oncology at The University of Texas MD Anderson Cancer Center and colleagues report how a tumor-specific protein flips a crucial switch in an irregular mechanism for mitosis that allows cancer cells to safely divide. "Our research shows that tumor cells rely heavily on a distinct mechanism for orderly cell division that's driven by oncogene-induced pyruvate kinase M2 (PKM2)," Dr. Lu said. After a cell begins division by replicating all of its chromosomes, mitosis separates them into two identical sets of chromosomes for both cells. After mitosis, cytokinesis completes cell divison. "Without PKM2 regulating a checkpoint in mitosis, the tumor cell would not successfully divide," Dr. Lu said. "Depleting PKM2 led to an uneven distribution of DNA to the two new cells, triggering programmed cell death, or apoptosis, of those cells after division. This new, additional role for PKM2 in cancer development and survival may provide a molecular basis for diagnosing and treating tumors with upregulated PKM2," Dr. Lu said. He and his colleagues have now identified four specific mechanisms by which PKM2 promotes cancer development. The key relationship between PKM2 activity and mitosis uncovered by the researchers led to rapid brain tumor growth when activated in mice, while blocking it reduced tumor volume by 83 percent and more than doubled survival from about 20 days to beyond 40 days.
Researchers at the University of Colorado School of Medicine may have determined what causes Meniere's disease and how to attack it. According to Carol Foster, M.D., from the department of otolaryngology and Robert Breeze, M.D., a neurosurgeon, there is a strong association between Meniere's disease and conditions involving temporary low blood flow in the brain such as migraine headaches. Meniere's disease affects approximately 3 to 5 million people in the United States. It is a disabling disorder resulting in repeated violent attacks of dizziness, ringing in the ear, and hearing loss that can last for hours and can ultimately cause permanent deafness in the affected ear. Up until now, the cause of the attacks has been unknown, with no theory fully explaining the many symptoms and signs of the disorder. "If our hypothesis is confirmed, treatment of vascular risk factors may allow control of symptoms and result in a decreased need for surgeries that destroy the balance function in order to control the spell" said Dr. Foster. "If attacks are controlled, the previously inevitable progression to severe hearing loss may be preventable in some cases." Dr. Foster explains that these attacks can be caused by a combination of two factors: 1) a malformation of the inner ear, endolymphatic hydrops (the inner ear dilated with fluid) and 2) risk factors for vascular disease in the brain, such as migraine, sleep apnea, smoking and atherosclerosis. The researchers propose that a fluid buildup in part of the inner ear, which is strongly associated with Meniere attacks, indicates the presence of a pressure-regulation problem that acts to cause mild, intermittent decreases of blood flow within the ear.
Hummingbird metabolism is a marvel of evolutionary engineering. These tiny birds can power all of their energetic hovering flight by burning the sugar contained in the floral nectar of their diet. Now new research from the University of Toronto Scarborough (UTSC) shows these tiny birds are equally adept at burning both glucose and fructose, which are the individual components of sucrose; a unique trait other vertebrates cannot achieve. "Hummingbirds have an optimal fuel-use strategy that powers their high-energy lifestyle, maximizes fat storage, and minimizes unnecessary weight gain all at the same time," says Dr. Kenneth Welch, assistant professor of biological sciences at UTSC and an expert on hummingbirds. Dr. Welch and his graduate student Chris Chen, who is co-author of the research article, fed hummingbirds separate enriched solutions of glucose and fructose while collecting exhaled breath samples. The researchers found that the birds were able to switch from burning glucose to fructose with equal facility. "What's very surprising is that, unlike mammals such as humans, who can't rely on fructose to power much of their exercise metabolism, hummingbirds use it very well. In fact, they are very happy using it and can use it just as well as glucose," says Dr. Welch. Hummingbirds require an incredible amount of energy to flap their wings 50 times or more per second in order to maintain hovering flight. In fact, if a hummingbird were the size of a human, it would consume energy at a rate more than 10 times that of an Olympic marathon runner. They are able to accomplish this by burning only the most recently ingested sugar in their muscles while avoiding the energetic expenditure of first converting sugar into fat.
Dr. Gerald Zon’s latest “Zone in with Zon” blog post, dated December 2, 2013, and published by TriLink BioTechnologies of San Diego, provides a fascinating discussion of the developing use of modified mRNAs in a wide variety of key applications, including gene therapy, nucleic acid vaccines, and cellular reprogramming, as well as the possibly tremendous commercial potential of modified mRNA technology in these and other areas. Dr. Zon begins by discussing the intellectual simplicity of gene therapy, i.e., to simply replace a broken gene with the DNA of the normal gene and thus ultimately generate the normal version of the missing or altered protein. Unfortunately, it has proven remarkably difficult over three decades of work to achieve this effectively and safely. Dr. Zon attributes this in part to the challenges for cell- or tissue-specific delivery, as well as concern for adverse events generally ascribed to unintended vector integration leading to neoplasias. Nevertheless, there are presently more than 1700 clinical trials of gene therapy taking place around the world. However, as a consequence of the slow progress of DNA-based gene therapy, a number of researchers have recently turned to the study of modified mRNAs that might be used to produce the missing protein directly by translation. This field is called “mRNA therapeutics.” Another application is in the use of mRNAs as cancer vacccines. Here the idea is to use mRNAs coding for tumor-associated antigens to induce specific immune responses to the tumor. Dr. Zon notes that a 2013 review from Novartis Vaccines & Diagnostics, and entitled “RNA: the New Revolution in Nucleic Acid Vaccines,” claims that the “prospects for success are bright.” The reasons for this, Dr.
A study published in the September 18, 2013 issue of the Journal of Neuroscience points, for the first time, to the gene NTRK3 (neurotrophic tyrosine kinase receptor type 3) (also known as trkC) as a factor in susceptibility to the disease. The researchers define the specific mechanism for the formation of fear memories which will help in the development of new pharmacological and cognitive treatments. An estimated five out of every 100 people in Spain suffer from panic disorder, one of the diseases included within the anxiety disorders, and those affected experience frequent and sudden attacks of fear that may influence their everyday lives, sometimes even rendering them incapable of things like going to the shops, driving the car, or holding down a job. It was known that this disease had a neurobiological and genetic basis and for some time the search had been on to discover which genes were involved in its development, with certain genes being implicated without their physiopathological contribution being understood. Now, for the first time, researchers from the Centre for Genomic Regulation (CRG) have revealed that the gene NTRK3, responsible for encoding a protein essential for the formation of the brain, the survival of neurones and establishing connections between them, is a factor in genetic susceptibility to panic disorder. "We have observed that deregulation of NTRK3 produces changes in brain development that lead to malfunctions in the fear-related memory system," explains Dr. Mara Dierssen, head of the Cellular and Systems Neurobiology group at the CRG.
A multidisciplinary team of scientists from Spanish universities and research centers, including the University of Valencia, has managed to design small synthetic molecules capable of joining to the genetic material of the AIDS virus and blocking its replication. This achievement has been made for the first time in the world by a group of researcher led by Dr. José Gallego from Universidad Católica de Valencia "San Vicente Mártir." The University of Valencia, the Príncipe Felipe Research Centre, and the Instituto de Salud Carlos III have participated. The work was published November 25, 2013 by Angewandte Chemie International Edition, one of the most prestigious scientific journals in the world in the area of chemistry. The newly designed synthetic molecules inhibit the output of genetic material of the virus from the infected cell nucleus to the cytoplasm, thus the virus replication is blocked and avoids the infection of other cells. The genetic material of the AIDS virus, or HIV-1, is formed by ribonucleic acid (RNA), and encodes several proteins that allow it to penetrate the human cells and reproduce within them. The new virus inhibitors, called terphenyls, developed by this group of scientists, were designed by computer to reproduce the interactions of one of the proteins encoded by the virus, the viral protein Rev. In this way, the terphenyls join Rev’s receptor in the viral RNA, preventing the interaction between the protein and its RNA receptor. This interaction is necessary for the virus genetic material to leave the infected cell nucleus and, thus, it is essential for the survival of HIV-1. The fact that the terphenyls block the virus genetic material output of the cell prevents the infection of other cells.
Scientists have long suspected that corvids – the family of birds including ravens, crows, and magpies – are highly intelligent. Now, Tübingen neurobiologists Dr. Lena Veit and Professor Andreas Nieder have demonstrated how the brains of crows produce intelligent behavior when the birds have to make strategic decisions. Their results are published in the latest edition of Nature Communications. Crows are no bird-brains. Behavioral biologists have even called them “feathered primates” because the birds make and use tools, are able to remember large numbers of feeding sites, and plan their social behavior according to what other members of their group do. This high level of intelligence might seem surprising because birds’ brains are constructed in a fundamentally different way from those of mammals, including primates – which are usually used to investigate these behaviors. The Tübingen researchers are the first to investigate the brain physiology of crows’ intelligent behavior. They trained crows to carry out memory tests on a computer. The crows were shown an image and had to remember it. Shortly afterwards, they had to select one of two test images on a touchscreen with their beaks based on a switching behavioral rules. One of the test images was identical to the first image, the other different. Sometimes the rule of the game was to select the same image, and sometimes it was to select the different one. The crows were able to carry out both tasks and to switch between them as appropriate. That demonstrates a high level of concentration and mental flexibility which few animal species can manage – and which is an effort even for humans. The crows were quickly able to carry out these tasks even when given new sets of images.
Research jointly conducted by investigators at Institut Gustave Roussy, Inserm, Institut Pasteur and the INRA (French National Agronomic Research Institute) has led to a rather surprising discovery on the manner in which cancer chemotherapy treatments act more effectively with the help of the intestinal flora (also known as the intestinal microbiota). Indeed, the researchers have just shown that the efficacy of one of the molecules most often used in chemotherapy relies to an extent on its capacity to mobilize certain bacteria from the intestinal flora toward the bloodstream and lymph nodes. Once inside the lymph nodes, these bacteria stimulate fresh immune defenses which then enhance the body’s ability to fight the malignant tumor. Results of this work were published in the November 22, 2013 issue of Science. The intestinal microbiota is made up of 100,000 billion bacteria. It is a genuine organ, because the bacterial species that comprise it carry out functions crucial to our health, such as the elimination of substances that are foreign to the body (and potentially toxic), or keeping the pathogens that contaminate us at bay. They also ensure the degradation of ingested food, for better intestinal absorption and optimal metabolism. These millions of bacteria colonize the intestine from birth, and play a key role in the maturation of the immune defenses. However, the bacterial species that make up the intestinal microbiota vary from one individual to another, and the presence or absence of one or another bacterial species seems to influence the occurrence of some diseases, or, conversely, may protect us.
In the developing world, Cryptosporidium parvum has long been the scourge of freshwater. A decade ago, it announced its presence in the United States, infecting over 400,000 people – the largest waterborne-disease outbreak in the county's history. Its rapid ability to spread, combined with an incredible resilience to water decontamination techniques, such as chlorination, led the National Institutes of Health (NIH) in the United Sates to add C. parvum to its list of public bioterrorism agents. Currently, there are no reliable treatments for cryptosporidiosis, the disease caused by C. parvum, but that may be about to change with the identification of a target molecule by investigators at the Research Institute of the McGill University Health Centre (RI-MUHC). The findings of this study were published online on September 23, 2013 in the Antimicrobial Agents and Chemotherapy (AAC) journal. "In the young, the elderly, and immunocompromised people such as people infected with HIV/AIDS, C. parvum is a very dangerous pathogen. Cryptosporidiosis is potentially life-threatening and can result in diarrhea, malnutrition, dehydration, and weight loss," says first author of the study, Dr. Momar Ndao, Director of the National Reference Centre of Parasitology (NRCP) at the MUHC and an Assistant Professor of the Departments of Medicine, Immunology, and Parasitology (Division of Infectious Diseases) at McGill University. The oocysts of C. parvum, which are shed during the infectious stage, are protected by a thick wall that allows them to survive for long periods outside the body as they spread to a new host. C. parvum is a microscopic parasite that lives in the intestinal tract of humans and many other mammals.
How is the bond between people in love maintained? Scientists at the Bonn University Medical Center have discovered a biological mechanism that could explain the attraction between loving couples: if oxytocin is administered to men and if they are shown pictures of their partner, the bonding hormone stimulates the reward center in the brain, increasing the attractiveness of the partner, and strengthening monogamy. The results were published online on November 25, 2013 in PNAS. Monogamy is not very widespread among mammals; human beings represent an exception. Comparatively many couples of the species Homo sapiens have no other partners in a love relationship. For a long time, science has therefore been trying to discover the unknown forces that cause loving couples to be faithful. "An important role in partner bonding is played by the hormone oxytocin, which is secreted in the brain," says Professor Dr. René Hurlemann, Executive Senior Physician at the Inpatient and Outpatient Department of Psychiatry and Psychotherapy of the Bonn University Medical Center. A team of scientists at the University of Bonn under the direction of Professor Hurlemann and with participation by researchers at the Ruhr University of Bochum and the University of Chengdu (China) examined the effect of the "bonding hormone" more precisely. The researchers showed pictures of their female partners to a total of 40 heterosexual men who were in a permanent relationship – and pictures of other women for comparison. First a dose of oxytocin was administered to the subjects in a nasal spray; and then a placebo at a later date. Furthermore, the scientists also studied the brain activity of the subjects with the help of functional magnetic resonance tomography.