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Archive - Aug 7, 2014

White Fat, Brown Fat, Beige Fat, Notch Signaling--Type 2 Diabetes and Obesity

A Purdue University study shows that Notch signaling (see image), a key biological pathway tied to development and cell communication, also plays an important role in the onset of obesity and Type 2 diabetes, a discovery that offers new targets for treatment. A research team led by Dr. Shihuan Kuang, associate professor of animal sciences, found that blocking Notch signaling in the fat tissue of mice caused white fat cells to transform into a "leaner" type of fat known as beige fat. The finding suggests that suppressing Notch signaling in fat cells could reduce the risk of obesity and related health problems, Dr. Kuang said. "This finding opens up a whole new avenue to understanding how fat is controlled at the molecular level," he said. "Now that we know Notch signaling and obesity are linked in this way, we can work on developing new therapeutics." The human body houses three kinds of fat: white, brown, and beige. White fat tissue stores fatty acids and is the main culprit in weight gain. Brown fat, which helps keep hibernating animals and infants warm, burns fatty acids to produce heat. Humans lose most of their brown fat as they mature, but they retain a similar kind of fat - beige fat, which also generates heat by breaking down fatty acids. Buried in white fat tissue, beige fat cells are unique in that they can become white fat cells depending on the body's metabolic needs. White fat cells can also transform into beige fat cells in a process known as browning, which raises the body's metabolism and cuts down on obesity. Dr. Kuang and his team found that the Notch signaling pathway inhibits browning of white fat by regulating expression of genes that are related to beige fat tissue. "The Notch pathway functions like a commander, telling the cell to make white fat," he said.

Team Determines Structure of a Molecular Machine That Targets Viral DNA for Destruction

With a featured online publication on August 7, 2014 in Science, Montana State University (MSU) researchers and collaborators have made a significant contribution to the understanding of a new field of DNA research, with the acronym CRISPR (an acronym that stands for Clustered Regularly Interspaced Short Palindromic Repeats.), that holds enormous promise for fighting infectious diseases and genetic disorders. The MSU-led research provides the first detailed blueprint of a multi-subunit "molecular machinery" that bacteria use to detect and destroy invading viruses. "We generally think of bacteria as making us sick, but rarely do we consider what happens when the bacteria themselves get sick. Viruses that infect bacteria are the most abundant biological agents on the planet, outnumbering their bacterial hosts 10 to 1," said Dr. Blake Wiedenheft, senior author of the paper and assistant professor in MSU's Department of Microbiology and Immunology. "Bacteria have evolved sophisticated immune systems to fend off viruses. We now have a precise molecular blueprint of a surveillance machine that is critical for viral defense," Dr. Wiedenheft said. These immune systems rely on a repetitive piece of DNA in the bacterial genome called a CRISPR. These repetitive elements maintain a molecular memory of viral infection by inserting short segments of invading viral DNA into the DNA of the "defending" bacteria. This information is then used to guide the bacteria's immune system to destroy the invading viral DNA. The molecular blueprint of the surveillance complex was determined by a team of scientists in Dr. Wiedenheft's lab at MSU using X-ray crystallography. Dr.

New Treatment Successful for Specific, Long-Lasting Motion Sickness

People who suffer from a rare illness called Mal de Debarquement Syndrome (MdDS), now have a chance for full recovery thanks to treatment developed by researchers at the Icahn School of Medicine at Mount Sinai in New York City. Their findings were published online on July 15, 2014 Frontiers in Neurology. People often feel a sensation of movement, called Mal de Debarquement, after they have finished boating, surfing, or a sea voyage. The symptoms usually disappear within hours, but in some people, and more frequently in women, symptoms can continue for months or years, causing fatigue, insomnia, headaches, poor coordination, anxiety, depression, and an inability to work. Known as the Mal de Debarquement Syndrome (MdDS), the rare condition is marked by continuous feelings of swaying, rocking, or bobbing. "Our study has provided the first effective treatment for this troublesome disorder, and we hope it provides relief to the thousands of people who may be affected worldwide," said Bernard Cohen, M.D., the Morris Bender Professor of Neurology at the Icahn School of Medicine at Mount Sinai. Until now, there has been no effective treatment for MdDS. Diagnostic tests and early research done at Mount Sinai suggested that MdDS was caused by malfunctioning of the vestibule-ocular reflex (VOR), a mechanism in the inner ear that maintains balance and stabilizes the eyes during head movements, said Dr. Cohen. The new treatment re-adapts the VOR by moving the visual surroundings as the head is slowly rolled from side to side at the same frequency as the subject's symptomatic rocking, swaying or bobbing. In the study, the head roll caused vertical eye movements (nystagmus), and subjects tended to turn to one side when marching in place. Subjects were rocked or swayed at about one cycle per five seconds.

Zone in with Zon—mtDNA, Inherited Disease, and Designer Babies

Dr. Gerald Zon’s latest “Zone in with Zon” blog post, dated August 4, 2014, and published by TriLink BioTechnologies of San Diego, discusses the topic of mitochondrial DNA (mtDNA) replacement in the context of eliminating disease and creating designer babies. Dr. Zon begins by giving some background on mtDNA and disease, together with a description of TriiLink’s connection with mtDNA. Initially, Dr. Zon notes that TriLink has recently introduced mtDNA PCR sequencing primers (mitoPrimers™) and an mtDNA amplification kit (mitoKit™) for forensic science and casework. Then, Dr. Zon notes that given the relatively small amount of mtDNA (~16,569 base pairs and 37 genes) in a human mitochondrion compared to genomic DNA (~2 billion base pairs and ~20,000 genes) in a human nucleus, the list of mtDNA diseases is quite lengthy. Dr. Zon notes that approximately one in 4,000 babies in the U.S. is born with an inherited mitochondrial disease. There is no known treatment for these diseases and few of the afflicted children grow into adulthood. Dr. Zon describes a recent New York Times article on Dr. Shoukhrat Mitalipov, of Oregon Health and Science University, who has developed a procedure to help women conceive children without passing on their mtDNA defects. Dr. Mitalipov’s procedure would allow these women with mtDNA mutations to bear children by placing the nucleus from the mother’s egg into a donor egg whose nucleus has been removed. The defective mitochondria, which float outside the nucleus in the egg’s cytoplasm, are left behind, thus eliminating the possibility of passing along defective mitochondria. Dr. Zon pointed out that while some advocate this process because it eliminates a significant problem, others are skeptical as the child would bear the genes of three parents—mother, father, and donor—posing a possible ethical dilemma.

Nature Cover Story Describes Synthesis of Structurally Pure Carbon Nanotubes

For the first time, researchers at Empa and the Max Planck Institute for Solid State Research have succeeded in "growing" single-wall carbon nanotubes (CNT) with a single predefined structure - and hence with identical electronic properties. The success is featured on the cover of today’s (August 7, 2014) issue of Nature. And here is how the scientists pulled it off: the CNTs "assembled themselves," as it were, out of tailor-made organic precursor molecules on a platinum surface, as reported by the researchers in the Nature article. In the future, CNTs of this kind may be used in ultra-sensitive light detectors and ultra-small transistors. For 20 years, carbon nanotubes (CNTs) have been the subject of intensive fundamental, as well as applied research. With their extraordinary mechanical, thermal, and electronic properties, these tiny tubes with their graphitic honeycomb lattice have become the paragon of nanomaterials. They could help to create next-generation electronic and electro-optical components that are smaller than ever before, and thus can achieve even faster switching times. With a diameter of roughly one nanometer, single-wall CNTs (or SWCNTs) need to be considered as quantum structures; the slightest structural changes, such as differences in diameter or in the alignment of the atomic lattice, may result in dramatic changes to the electronic properties: one SWCNT may be metallic, whilst another one with a slightly different structure is a semiconductor. Hence, there is a great deal of interest in reliable methods of making SWCNTs as structurally uniform as possible. In fact, corresponding synthesis concepts were formulated about 15 years ago.

Mutations in Gene Essential for Cell Regulation Can Cause Wilms Tumor Kidney Cancer in Children

Mutations in a gene that helps regulate when genes are switched on and off in cells have been found to cause rare cases of Wilms tumor, the most common kidney cancer occurring in children. A study led by scientists at The Institute of Cancer Research, London, identified mutations in the CTR9 gene in six children with Wilms tumor. Wilms tumor affects approximately one in 10,000 children and usually develops before the age of five years. Treatment of Wilms tumor is very successful, with 90 per cent of children being cured. Usually Wilms tumor only affects one child in a family, but very occasionally more than one child in a family develops the cancer. When this happens it indicates that hereditary genetic factors are likely to be involved. The researchers studied the genes of 35 families with more than one case of Wilms tumor, recruited to the study through a network of collaborators from across the world. In six children, from three different families, the researchers found CTR9 mutations that stopped the gene from working properly. No similar mutations were present in 1,000 individuals without Wilms tumor. The research is published today (Thursday, August 7, 2014) in an open-access article in Nature Communications and is part of the Factors Associated with Childhood Tumours Study, which is funded by the Wellcome Trust, and aims to identify genetic causes of childhood cancers. The study was also supported by Cancer Research UK. CTR9 is part of a multi-protein complex, known as PAF1 (image shows example), which regulates when genes are switched on and off. The PAF1 complex has many essential diverse roles in controlling cellular processes and organ development in the embryo.

Recurrent ESR1-CCDC170 Rearrangements Seen in Aggressive Subset of Estrogen Receptor-Positive Breast Cancers

Researchers from the Lester and Sue Smith Breast Center at Baylor College of Medicine have uncovered new information about the genetic alterations that may contribute to the development of a subtype breast cancer typically associated with more aggressive forms of the disease and higher recurrence rates. The study, led by Dr. Xiaosong Wang, assistant professor of medicine – hematology and oncology and of molecular and cellular biology at Baylor, was published today August 7, 2014 online in Nature Communications and focused on the more aggressive molecular subtype of the estrogen-receptor positive breast cancer known as luminal B breast cancer. "While expressing the estrogen receptor, the luminal B breast cancers usually have higher tumor grade, larger tumor size, and poor prognosis, with most cases difficult to treat by endocrine therapy," said Dr. Wang, the lead and corresponding author on the report. "We wanted to gain a deeper understanding about the genetic alterations underlying this particular form of breast cancer, because we do not know about what malfunctions potentially cause this form to be more aggressive." In the study, Dr. Wang and colleagues identified a particular gene fusion on the estrogen receptor itself (hybrid gene formed from two previously separate genes) that was preferentially present in a subset of samples of tumors that were luminal B and ER-positive. The fusion was a result of rearrangements in the estrogen receptor gene called ESR1 (image depicts ESR1 protein) and another neighboring gene called CCDC170, Dr. Wang said. The findings were based in part on data available through the National Human Genome Research Initiative's Cancer Genome Atlas project. Rearrangement in the genes causes the disruption of the transfer of information.