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Archive - Apr 1, 2015

UCSF-Led Study Suggests Superiority of Non-Invasive, Cell-Free DNA Blood Test in Detecting Down Syndrome; Test Not As Widely Comprehensive for Other Ailments As Standard Tests, However

A blood test undertaken between 10 to 14 weeks of pregnancy may be more effective in diagnosing Down syndrome and two other less common chromosomal abnormalities than standard non-invasive screening techniques, according to a multicenter study led by a University of Californian, San Francisco (UCSF) researcher. In the study, which followed pregnancy outcomes in close to 16,000 women, the cell-free DNA blood test resulted in correctly identifying all 38 fetuses with Down syndrome, a condition associated with cognitive impairments and an increased risk of several medical disorders. The diagnosis was confirmed by newborn exam, prenatal, or postnatal genetic analysis. The test focuses on the small percentage of fetal DNA found floating in a pregnant woman's blood. DNA is amplified with a molecular "photocopying" technique known as polymerase chain reaction (PCR), and sequenced so that comparisons can be made between relative amounts of each chromosome's DNA. A greater quantity of DNA is indicative of some chromosomal conditions, including Down syndrome, which is characterized by an extra copy of chromosome 21, one of the 23 pairs of chromosomes. When the same women underwent standard screening, 30 of the 38 fetuses with Down syndrome were flagged, according to the study published online on April 1, 2015, in the New England Journal of Medicine. The article title is “Cell-Free DNA Analysis for Noninvasive Examination of Trisomy.” The screening comprises a blood draw in which hormones and proteins associated with chromosomal defects are identified, together with an ultrasound of the nuchal fold fluid in the back of the neck, an excess of which is suggestive of Down syndrome.

Scientists Achieve Small Molecule Inhibition of Aberrant Transcription Factor at Root of Recurring Acute Myeloid Leukemia (AML)

A novel molecule designed by scientists at the University of Massachusetts Medical School and the University of Virginia inhibits progression of a hard-to-treat form of recurring acute myeloid leukemia (AML) in patient tissue. The small molecule is one of the first designed to specifically target a cancer-causing transcription factor. Previously thought to be an undruggable target, this strategy may be used to design other novel molecules that can specifically inhibit cancer-causing transcription factors. Details of the work were published in the February 13, 2015 issue of Science. The article is titled “A Small-Molecule Inhibitor of the Aberrant Transcription Factor CBFβ-SMMHC Delays Leukemia in Mice.” Transcription factors are single- or multi-protein complexes that regulate transcription of DNA into messenger RNA and gene expression by binding to regions on the genome next to a gene. Mutations in transcription factors can result in altered gene expression programs that give way to new, cancer-causing functions. Although these aberrant transcription factors are promising targets for new therapeutics, the complexity of interrupting very specific protein-to-protein interactions has made it difficult to find small molecules or design drugs that treat these transcription factor-related cancers. "When we look at inhibitors, they usually target an enzyme or receptor. There aren't a lot of good examples of transcription factor inhibitors in clinical trials," said Lucio H. Castilla, Ph.D., Associate Professor of Molecular, Cell, and Cancer Biology at the U-Mass Medical School, and co-leader of the study. "Here, we've used our extensive knowledge of a mutant transcription factor found in a subset for acute myeloid leukemia patients to design a molecule that can specifically sequester only the oncogenic mutant.

Synchronization of Womb’s and Mother’s Biological Clocks Plays Key Role in Successful Pregnancies

If you are trying to have a baby, a good night's sleep is more important than ever. A new research report appearing in April 2015 issue of The FASEB Journal shows that the womb has its own "body clock" that needs to synchronize with the mother's body clock to ensure optimal conditions for fetal growth and development. The inability of a mother's body clock to synchronize with the womb's clock may be at least part of the reason why some women have difficulty carrying a pregnancy to full term. Specifically, the failed synchronization switches off body clock genes in cells lining the womb, which in turn, may jeopardize the pregnancy. This information may help researchers and fertility experts develop strategies to optimize the fetal environment to help more women have children. "Infertility affects one in six couples across the world. Miscarriage is the most common complication of pregnancy," said Jan Brosens, M.D., a researcher involved in the work from the Division of Translational and Systems Medicine and Reproductive Health at Warwick Medical School at the University of Warwick in Coventry, UK. "Approximately one in seven clinical pregnancies result in miscarriage, mostly prior to 12 weeks of pregnancy. It is estimated that five percent of women experience two clinical miscarriages and approximately one percent have three or more losses. From a medical perspective, recurrent miscarriages and implantation failure have remained frustratingly devoid of effective therapeutic strategies." To make the current discovery, Dr. Brosens and colleagues, obtained womb biopsies from 70 women who have experienced recurrent pregnancy loss. The cells from these biopsies were purified and then treated in such a way as to simulate a pregnancy.

Shorter and Still Effective Cas9 Enzyme from S. aureus Enables Easier Packaging into AAV Delivery Vehicle; Nobelist Sharp Is One of Study Leaders

A collaborative study among researchers from the Broad Institute of MIT and Harvard, Massachusetts Institute of Technology, and the National Center for Biotechnology Information of the National Institutes of Health (NIH-NCBI) has identified a highly efficient Cas9 nuclease that overcomes one of the primary challenges to in vivo genome editing. This finding, published online on April 1, 2015 in Nature, is expected to help make the CRISPR toolbox accessible for in vivo experimental and therapeutic applications. Originally discovered in bacteria, the CRISPR-Cas9 system enables the cutting of DNA as a defense mechanism against viral infection. Although numerous microbial species possess this system, the Cas9 enzyme from Streptococcus pyogenes (SpCas9) was the first to be engineered for altering the DNA of higher organisms, and has since emerged as the basis for a series of highly versatile genome modification technologies. In order to perturb genes in adult animals, key components of the CRISPR-Cas9 system must be introduced into cells using delivery vehicles known as vectors. Adeno-associated virus (AAV) is considered one of the most promising candidate vectors, as it is not known to cause human disease and has already gained clinical regulatory approval in Europe. However, the small cargo capacity of AAV makes it challenging to package both the SpCas9 enzyme and the other components required for gene editing into a single viral particle. The Cas9 nuclease from the bacteria Staphylococcus aureus (SaCas9), presented in this new work, is 25% smaller than SpCas9, offering a solution to the AAV packaging problem. The Broad/MIT team, led by Dr. Feng Zhang, core member of the Broad Institute and investigator at the McGovern Institute for Brain Research at MIT, along with collaborators at MIT, led by MIT Institute Professor Dr.

NO APRIL FOOL'S: Tiny Blackpoll Warbler Migrates 1,500 Miles in Non-Stop “Fly-or-Die” Journey Over Atlantic Ocean in 2-3 Days; “One of the Most Extraordinary Migratory Routes on the Planet” Expert Says

For more than 50 years, scientists had tantalizing clues suggesting that a tiny, boreal forest songbird known as the blackpoll warbler departs each fall from New England and eastern Canada to migrate nonstop in a direct line over the Atlantic Ocean toward South America, but proof was hard to come by. Now, for the first time, an international team of biologists report "irrefutable evidence" that the birds complete a nonstop flight ranging from about 1,410 to 1,721 miles (2,270 to 2,770 km) in just two to three days, making landfall somewhere in Puerto Rico, Cuba and the islands known as the Greater Antilles, from there going on to northern Venezuela and Columbia. Details of the new study, which used light-level, or solar, geolocators, were published online on April 1, 2015 in Biology Letters. First author Dr. Bill DeLuca, an Environmental Conservation Research Fellow at the University of Massachusetts Amherst, with colleagues at the University of Guelph, Ontario, the Vermont Center for Ecostudies, and other institutions, says, "For small songbirds, we are only just now beginning to understand the migratory routes that connect temperate breeding grounds to tropical wintering areas. We're really excited to report that this is one of the longest nonstop overwater flights ever recorded for a songbird, and finally confirms what has long been believed to be one of the most extraordinary migratory feats on the planet."While other birds, such as albatrosses, sandpipers, and gulls are known for trans-oceanic flights, the blackpoll warbler is a forest dweller that migrates boldly where few of its relatives dare to travel. Most migratory songbirds that winter in South America take a less risky, continental route south through Mexico and Central America, the authors note. A water landing would be fatal to a warbler.

New Dual-Affinity Antibody (FcDART) Against H5N1 Influenza Is 100% Protective in Long-Used Ferret Model of the Human Disease

Since 2003, the H5N1 influenza virus, more commonly known as the bird flu, has been responsible for the deaths of millions of chickens and ducks and has infected more than 650 people, leading to a 60 percent mortality rate for the latter. Luckily, this virus has yet to achieve human-to-human transmission, but a small number of mutations could change that, resulting in a pandemic. Now a team of investigators from St. Jude Children’s Research Hospital, Stanford University Medical Center, and MacroGenics has developed an antibody that has proven 100 percent protective against the virus in two species of animal models [ferrets (image) and mice]. The research was published online on February 11, 2015 in the Journal of Virology, a publication of the American Society for Microbiology (ASM). Antivirals have been potential sources of protection, but they are hampered by the propensity of viruses to rapidly mutate, which often results in resistance. “We have seen this in H5N1 viruses,” said corresponding author Richard Webby, Ph.D., a Member in the Infectious Diseases Department at St. Jude Children’s Research Hospital, Memphis, TN, and Director of the World Health Organization (WHO) Collaborating Center for Studies on the Ecology of Influenza Viruses in Lower Animals and Birds. Vaccines, Dr. Webby said, must be developed to match each flu virus, something which would likely take at least six months following the emergence of a pandemic. Additionally, vaccines are somewhat ineffective in the elderly and in immunocompromised individuals. The investigators turned to antibodies, which target antigens on viruses as specifically as keys to locks, thus disabling them. Regardless, mutations can also render antibodies ineffective.