Syndicate content

Archive - 2016

January 22nd

Guardian of the Genome, Tumor Suppressor p53, Restrains Movement of Retrotransposons; Mutated p53 Permits Much-Increased Movement of Retrotransposons, Leading to Tumor Formation

The most commonly mutated gene in cancer, p53, works to prevent tumor formation by keeping mobile elements in check that otherwise lead to genomic instability, University of Texas (UT) Southwestern Medical Center researchers have found. The p53 gene has long been known to suppress tumor formation, but the mechanisms behind this function - and why disabling the gene allows tumors to form - were not fully understood. Findings from the new study, published online on December 23, 2015 in Genes & Development, answer some of these questions and could one day lead to new ways of diagnosing and treating cancer, said the study's senior author, Dr. John Abrams, Professor of Cell Biology at UT Southwestern. The investigators found that normal p53 gene action restrains transposons, mobile genetic elements called retroelements that can make copies of themselves and move to different positions on chromosomes. But, they discovered, when p53 is disabled by mutation, dramatic eruptions of these mobile elements occur. The study revealed that in mice with cancer and in human samples of two types of cancer (Wilms' tumors and colon tumors) disabled for p53, transposons became very active. In a healthy state, certain mechanisms work to keep these retroelements quiet and inactive, explained Dr. Abrams. One of those mechanisms is p53 action. Conversely, when p53 is mutated, retroelements can erupt. "If you take the gene away, transposons can wreak havoc throughout the genome by causing it to become highly dysregulated, which can lead to disease," Dr. Abrams said. "Our findings help explain why cancer genomes are so much more fluid and destabilized than normal genomes. They also provide a novel framework for understanding how normal cells become tumors." Although much more research is needed, Dr.

World’s First Liquid Biopsy Test Designed to Isolate & Analyze Exosomal RNA from Blood Is Launched by Exosome Diagnostics; New Test Detects EML4-ALK Fusion Transcripts in NSCLC

Exosome Diagnostics, Inc., the developer of a revolutionary liquid biopsy platform that enables non-invasive detection of clinical biomarkers, potentially obviating the need for tissue biopsy, today announced, on Thursday, January 21, 2016, the launch of ExoDx™ Lung(ALK), the world’s first liquid biopsy test designed to isolate and analyze exosomal RNA (exoRNA) from a blood sample. ExoDx Lung(ALK), which has been validated in Exosome Diagnostics’ CLIA-certified laboratory, is a plasma-based diagnostic that enables sensitive, accurate, and real-time detection of EML4-ALK mutations in patients with non-small cell lung cancer (NSCLC). Exosome Diagnostic’s proprietary platform for the isolation of RNA from exosomes provides a more direct and sensitive method of detecting fusions such as EML4-ALK, compared to cell-free DNA (cfDNA) alone. ExoDx Lung(ALK) detects EML4-ALK fusion transcripts with the goal of informing individualized treatment decisions for patients. ExoDx Lung(ALK) is now commercially available in the United States and can be ordered by clinicians. The test will assist oncologists in identifying patients who may benefit from ALK inhibitory therapy among the population of NSCLC patients whose tissue samples are unavailable or who are unwilling or unable to undergo repeat biopsy. “Capturing exosomal RNA for identifying ALK in a liquid biopsy is a huge advance in oncology,” said Luis Raez, M.D., Medical Director, Memorial Cancer Institute, Fort Lauderdale, Florida. “Understanding which fusion transcript is involved will be important as more targeted drugs become available. Validation results of the test, comparing tissue ALK status with matched plasma samples in patients who had progressed on a prior ALK inhibitor and prior to receiving a second generation ALK inhibitor, showed sensitivity of 88% and specificity of 100%.

Fertility Experts Identify Genetic Pattern in Womb That Is Linked to IVF Failure

Fertility experts in Southhampton, UK, and the Netherlands have identified a specific genetic pattern in the womb that could predict whether or not in vitro fertilization (IVF) treatment is likely to be successful. Study co-lead Professor Nick Macklon, Chair in Obstetrics and Gynecology at the University of Southampton, said the discovery would help clinicians understand why IVF fails repeatedly in some women. He said it could also lead to the development of a new test to help patients understand how likely they are to achieve a pregnancy before they embark on the treatment process - and to guide others on whether or not they should continue even after a number of unsuccessful cycles. "Many women undergo a number of IVF cycles without success despite having good quality embryos and, up to now, it has been unclear whether or not the lining of the womb may be the cause of that," explained Professir Macklon, Medical Director of the Complete Fertility Centre Southampton, which is based at the city's Princess Anne Hospital and is part of the NIHR Southampton Biomedical Research Centre. "We have now shown that an abnormal gene expression in the lining can be identified in many of these women and that a specific gene 'fingerprint', when present, is always associated with failure, which is very significant in aiding our understanding of IVF failure." Patients were recruited for the study, published online on January 22, 2016, in an open-access article in the journal Scientific Reports, at the University Medical Center Utrecht between 2006 and 2007 and at both Utrecht and the Academic Medical Center in Amsterdam between 2011 and 2013. The article is titled “An endometrial gene expression signature accurately predicts recurrent implantation failure after IVF..”

World's Greatest Literature Reveals Multifractals and Cascades of Consciousness; Absolute Record for Literary Multifractality Goes to Finnegan’s Wake by Irish Writer James Joyce

Regardless of the language they were working in, some of the world's greatest writers appear to be, in some respects, constructing fractals. Statistical analysis carried out at the Institute of Nuclear Physics of the Polish Academy of Sciences, however, revealed something even more intriguing. The composition of works from within a particular genre was characterized by the exceptional dynamics of a cascading (avalanche) narrative structure. This type of narrative turns out to be multifractal. That is, fractals of fractals are created. As far as many bookworms are concerned, advanced equations and graphs are the last things which would hold their interest, but there's no escape from the math. Physicists from the Institute of Nuclear Physics of the Polish Academy of Sciences (IFJ PAN) in Cracow, Poland, performed a detailed statistical analysis of more than one hundred famous works of world literature, written in several languages and representing various literary genres. The books, tested for revealing correlations in variations of sentence length, proved to be governed by the dynamics of a cascade. This means that the construction of these books is in fact a fractal. In the case of several works their mathematical complexity proved to be exceptional, comparable to the structure of complex mathematical objects considered to be multifractal. Interestingly, in the analyzed pool of all the works, one genre turned out to be exceptionally multifractal in nature. Fractals are self-similar mathematical objects: when we begin to expand one fragment or another, what eventually emerges is a structure that resembles the original object.

January 21st

CDK4/CDK6 Inhibitors Alter Metabolism of Pancreatic Cancer Cells; New Findings Reveal Biologic Vulnerability That Might Be Exploited for Therapeutic Gain in Treatment of Pancreatic Cancer

A new brain imaging study from MIT and Harvard Medical School may lead to a screen that could identify children at high risk of developing depressioUniversity of Texas (UT) Southwestern Medical Center researchers have found that cancer drugs known as CDK4/CDK6 inhibitors alter the metabolism of pancreatic cancer cells, revealing a biologic vulnerability that could be exploited for therapeutic gain. The findings were published online today (January 21, 2015) in an open-access article in Cell Reports. The article is titled “Metabolic Reprogramming of Pancreatic Cancer Mediated by CDK4/6 Inhibition Elicits Unique Vulnerabilities.” Because pancreatic cancer has one of the worst prognoses of any cancer and is the third leading cause of cancer deaths in the U.S., according to the National Cancer Institute, researchers for years have sought to find better treatment options. Last year, the FDA approved the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor for treating a certain type of advanced breast cancer. This class of drugs has been widely studied in clinical trials for many other types of cancer, including pancreatic cancer. CDK 4/6 inhibitors are cytostatic, meaning they work by preventing cancer cells from growing and dividing. “On the one hand, that’s great, because the tumor won’t grow, but on the other hand, the patient still has a tumor, which will eventually become resistant to those drugs,” said study senior author Dr. Erik Knudsen (photo), Professor of Internal Medicine in the Eugene McDermott Center for Human Growth and Development at UT Southwestern. “There’s a lot of interest in better understanding the biology behind CDK4/6 inhibitors – and in finding out whether we can use that information to kill tumors instead of simply stopping their growth,” added Dr.

Boyce Thompson Institute (BTI) Scientists ID 138 Genes Constituting Core Set of Genes for Plant-Fungus Symbiosis; New Findings May Aid Development of Fertilizer-Free Crops

A new study by researchers at Boyce Thompson Institute (BTI) has uncovered a veritable treasure trove of genes used by plants to form symbiotic relationships with fungi, vastly increasing the knowledge of the genetic basis for this agriculturally valuable interaction. Most land plants obtain a large portion of their mineral nutrients through a symbiotic relationship with soil fungi called arbuscular mycorrhizal (AM) symbiosis. But, despite decades of research, many of the genes required to form this relationship remain elusive. Now, with the advent of widely available genome sequences, BTI researchers were able to compare 50 plant genomes to identify 138 genes shared exclusively by plants capable of AM symbiosis. The findings, which appear on January 18,2016, in the journal Nature Plants, may ultimately bring us closer to developing plants that thrive without added fertilizer. "Currently, our research field has identified only a handful of genes required exclusively for AM symbiosis and we know that there are huge gaps in our knowledge," said senior author Maria Harrison,Ph.D., the William H. Crocker Professor at BTI. "These 138 genes are a valuable resource and provide new insights into the ways that plant cells host their fungal symbionts." In the past, researchers have identified genes involved in AM symbiosis through time-consuming genetic screens that could take upwards of five years to complete. Having identified a few genes from the barrel medic plant (Medicago truncatula) through this approach, the researchers noted that several of these AM symbiosis genes are missing from another plant species that does not host the fungi. This realization inspired Nathan Pumplin, a former graduate student in the Harrison laboratory to initiate a genome comparison approach in the hope of identifying more genes that fit this pattern.

MIT/Harvard fMRI Brain Study of Children at High Risk of Depression May Lead to Screen That Could ID Those at High Risk of Developing Depression As Adults & Enable Pre-Depression Intervention

A new brain imaging study from MIT and Harvard Medical School may lead to a screen that could identify children at high risk of developing depression later in life. In the study, the researchers found distinctive brain differences in children known to be at high risk because of family history of major depression. The finding suggests that this type of scan could be used to identify children whose risk was previously unknown, allowing them to undergo treatment before developing depression, says John Gabrieli, Ph.D., the Grover M. Hermann Professor in Health Sciences and Technology and a professor of brain and cognitive sciences at MIT. “We’d like to develop the tools to be able to identify people at true risk, independent of why they got there, with the ultimate goal of maybe intervening early and not waiting for depression to strike the person,” says Dr. Gabrieli, an author of the study, which was published online on December 16, 2015 in Biological Psychiatry. The article is titled “Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression.” Early intervention is important because once a person suffers from an episode of depression, they become more likely to have another. “If you can avoid that first bout, maybe it would put the person on a different trajectory,” says Dr. Gabrieli, who is a member of MIT’s McGovern Institute for Brain Research. The paper’s lead author is McGovern Institute postdoc Xiaoqian Chai, Ph.D., and the senior author is Susan Whitfield-Gabrieli, Ph.D., a research scientist at the McGovern Institute. The study also helps to answer a key question about the brain structures of depressed patients.

Ancient Origin and Maternal Inheritance of Blue Egg Color in Cuckoos

Cuckoos are nest parasites, meaning they lay their eggs in other birds' nests. The female cuckoo has to lay eggs that mimic the color, size, and shape of the eggs of the host bird. Using a massive data set, including data from museum eggs that are over 100 years old, researchers from the Norwegian University of Science and Technology (NTNU)an colleagues have determined how the ability to lay blue eggs is inherited in cuckoos. For roughly a century, researchers have been trying to figure out how different female cuckoos manage to lay such a variety of different egg colors to match different host birds. The short answer is that "the female bird decides everything," says researcher Frode Fossøy. Fossøy is part of the cuckoo research group at the Department of Biology at NTNU. The results of the group's work were published on Jabuary 12, 2016 in an open-access article in Nature Communications. "We've been able to show for the first time that the blue egg color is inherited via the female cuckoo only. The father has no effect on the color of his daughter's eggs," says Fossøy. Researchers have investigated a wide variety of samples from Europe and Asia. They found a clear relation between blue eggs and genetic material that only comes from the mother (mitochondrial DNA), and no relation between egg color and genetic material that comes from both parents (nuclear DNA).Cuckoos (Cuculus canorus) are parasitic. Female cuckoos lay their eggs in the nests of other bird species, as is well known. The young cuckoo then usually throws the other chicks out of the nest, getting rid of any competition for the parents' attention.Potential host birds develop traits to prevent being tricked by the parasites—they get rid of eggs that don't look like their own.

January 14th

BioQuick Says Dump Trump Now; Mean School-Yard Bully Has No Place in America’s Highest Office

One only has to view the 30-second video (see below) of Donald Trump mocking a disabled reporter to conclude that Mr. Trump has absolutely no place in the sacred office of President of the United States of America. America was born from the urge to always do what is right, regardless of the cost or consequence; to always stand up to power to protect the oppressed and the downtrodden. You need not have one single nickel to qualify for President of the United States; what you do need is courage, honor, and the driving desire to always do what is right. Hundreds of thousands of US citizens have fought and died to protect and preserve the sacred values that are at the core of America's unique existence and place in the world. While Trump apparently feels quite free to mock a disabled reporter who has had the nerve to ask him a probing question, he is the last person to get involved in a real fight. Much like his much shorter (5'8") forebear Dick Cheney, Trump avoided the Vietnam War draft four times and finally secured a highly dubious permanent deferrment on the basis of an obscure foot problem--perhaps an early identificaion of his "foot-in-mouth" problem.

[Video of Trump mocking disabled reporter]