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Archive - 2015

November 13th

TITAN Technology with Functionalized “Dendrimers” Used to Analyze Endocytosis

Purdue researchers have devised a way to capture the finer details of complex cell processes by using tiny synthetic particles known as dendrimers, in a method that could lead to more targeted treatment for cancer. In particular, they have developed a novel proteomic strategy named TITAN (Tracing Internalization and TrAfficking of Nanomaterials) to reveal real-time protein–dendrimer interactions using a systems biology approach. Dendrimers are symmetrically branched nanoparticles, similar in size to naturally occurring proteins. Dendrimers are similar in size to naturally occurring proteins. A dendrimer's small size and its branched structure make it an ideal courier for transporting a variety of molecules via its many branches into a cell. A precise understanding of how cells engulf small particles, in a process known as endocytosis, could help researchers improve drug delivery and reveal the mechanisms of viruses. But the particles "eaten" by cells and the proteins that control cell entry pathways are too small for conventional technologies to detect. W. Andy Tao, Ph.D., Professor of Biochemistry, Purdue University, and his Purdue collaborators, have developed the TITAN method that sends “dendrimers” into cells to track, capture, and isolate the proteins that regulate the cell internalization process, identifying 809 proteins involved in cell entry pathways. The TITAN method "helps us understand how cells internalize extracellular particles and how they move these particles around," Dr. Tao said. The Purdue group’s article was originally published online on October 1, 2015 in the Journal of the American Chemical Society (JACS). The JACS article is titled “Time-Resolved Proteomic Visualization of Dendrimer Cellular Entry and Trafficking.”

November 13th

Increased Dietary Potassium May Reduce Risk of Kidney Failure and Heart Disease in Type 2 Diabetes

Diets rich in potassium may help protect the heart and kidney health of patients with type 2 diabetes, according to a study published online on November 12, 2015 in the Clinical Journal of the American Society of Nephrology (CJASN). The article is titled “Urinary Potassium Excretion and Renal and Cardiovascular Complications in Patients with Type 2 Diabetes and Normal Renal Function." Individuals with type 2 diabetes are at increased risk of developing kidney failure and heart disease, which are are common life-threatening complications of diabetes To examine whether higher intake sodium and potassium are associated with these risks, Shin-ichi Araki, M.D., Ph.D., Shiga University of Medical Science, in Japan, and his colleagues studied a group of 623 patients with type 2 diabetes and normal kidney function. Patients were enrolled between 1996 and 2003 and were followed-up until 2013. Higher levels of urinary potassium excretion, which closely correlate with potassium intake amounts, were linked with a slower decline of kidney function and a lower incidence of cardiovascular complications. Sodium levels were not associated with kidney or heart health during follow-up. "For many individuals with diabetes, the most challenging part of a treatment plan is to determine what to eat. The results in our study highlight the importance of a diet high in potassium in diabetes nutrition therapy," said Dr. Araki.

[Press release] [Clinical Journal of the American Society of Nephrology article]

Birds Have Retained “Unique” Ascending Process of Dinosaur Ankle, But Re-Evolved Its Developmental Mechanism

In the 19th century, Darwin’s most vocal scientific advocate was Thomas Henry Huxley, who is also remembered as a pioneer of the hypotheses that birds are living dinosaurs. Huxley noticed several similarities of the skeleton of living birds and extinct dinosaurs, among them, a pointed portion of the anklebone projecting upwards onto the shank bone (also known as the “drumstick”). This “ascending process” is well known to specialists as a unique trait of dinosaurs. However, until the late 20th century, many scientists were doubtful about the dinosaur-bird link. Some pointed out that the ascending process in most birds was a projection of the neighboring heel bone, rather than the anklebone. If so, it would not be comparable, and would not support the dinosaur-bird link. Some argued that, in bird embryos, the ascending process develops from the anklebone in dinosaur-like fashion, while others considered that its development in birds is unique and different from dinosaurs. Nowadays, the dinosaur-bird link is mainstream science, thanks to new methods of data analysis, and a dense series of intermediate fossils (including feathered dinosaurs). However, the disagreements about the composition and embryology of the avian ankle were never clarified fully. Now, a new study, published online on November 13, 2015 in an open-access article in Nature Communications, and authored by Luis Ossa, Ph.D., Jorge Mpodozis, Ph.D., and Alexander Vargas, Ph.D., all from the University of Chile, provides a careful re-examination of ankle development in six different major groups of birds, selected specifically to clarify conditions in their last common ancestor. The study also utilizes new techniques that allow three-dimensional analysis of fluorescent embryonic skeletons, using advanced spin-disc confocal microscopy and software.

Ancient Bees Collected Pollen in Two Different Ways--As Specialists & Generalists; Study of 50-Million-Year-Old Specimens of Bees & Pollen Suggests Specialist-Only Pollen Collection Was Very Rare Phenomenon

Were ancient bees specialists, devoting their pollen-collecting attentions to very specific plant partners? Or were they generalists, buzzing around to collect pollen from a variety of flowers in their midst? Researchers who have studied an ancient lineage of bees now say, in an open-access article published online on November 12, 2015 in the Cell Press journal Current Biology, that the answer to both questions is “yes.” Bees living some 50 million years ago simultaneously relied on both strategies in foraging for pollen. The new Current Biology article is titled “Specialized and Generalized Pollen-Collection Strategies in an Ancient Bee Lineage.” "Because the fossil record of bees extends to the Late Cretaceous, and an early bee-like ancestor is known from 100 million-year-old amber, it could very well be that this dual foraging behavior may be as old as bees themselves," says Conrad Labandeira, Ph.D., of the Smithsonian Institution in Washington, D.C.. and a Fellow at the Paleontological Society. "If this is the case, then the controversy as to whether the earliest bees were generalist or specialist pollen collectors may be moot: the earliest bees during the mid-Cretaceous may have been simultaneously generalists and specialists!” The researchers, led by Heisenberg Fellow of the German Science Foundation Torsten Wappler, Ph.D., from the University of Bonn in Germany, identified pollen found on the bodies of eleven individuals from six bee species of the tribe Electrapini collected from two sites in Germany. The bee specimens were 44 million to 48 million years old, with pollen well preserved across their bodies. The researchers found pollen from a wide variety of nectar-producing flower types all across the bees' bodies--except, that is, on their legs.

November 12th

Marshfield Clinic Data (37,000 Patients) Review Shows Those Receiving L-DOPA for Parkinson’s Demonstrate Resistance to Age-Related Macular Degeneration (AMD); Later Review of Data for 87 Million Patients Confirms This Finding

In what may prove to be a major scientific breakthrough, reviews of voluminous medical records data indicate that a drug (L-DOPA) used to treat Parkinson's and related diseases may be able to delay or prevent macular degeneration, the most common form of blindness among older Americans. The findings, published online on October 30, 2015 in an open-access article in the American Journal of Medicine (AJM), represent possibly ground-breaking progress in the fight against age-related macular degeneration (AMD), which affects as many as 11 million Americans. The title of the new AJM article is “Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration." AMD hinders central vision, and even when it does not lead to blindness, it can severely reduce the ability to read, drive, and recognize faces. In the new study, supported in part by the BrightFocus Foundation, researchers discovered a biological connection between more darkly pigmented eyes, which are known to be resistant to AMD, and increased levels of a chemical called L-DOPA in those eyes. Because L-DOPA is frequently prescribed for Parkinson's patients, the researchers wanted to know whether patients who received the drug L-DOPA as treatment for Parkinson's or other diseases were protected from AMD. By combing through massive databases of medical chart data, they reported that patients receiving L-DOPA were, in fact, significantly less likely to get AMD, and when they did, its onset was significantly delayed. "Rather than looking at what might cause AMD, we instead wondered why certain people are protected from AMD. This approach had never been [taken] before," says senior author Brian McKay, Ph.D., of the University of Arizona.

New Tool (iSRAP) Developed for Rapid Profiling of Small RNA-Seq Data

A new open-access article, published online today (November 12, 2015) in the Journal of Extracellular Vesicles (JEV), describes the development of a one-touch, integrated small RNA analysis pipeline (iSRAP) research tool that is composed of widely used tools for rapid profiling of small RNAs. The authors say that their performance test of the new iSRAP tool, using publicly and in-house available data sets, demosntrates its ability at comprehensive profiling of small RNAs of various classes, and at analysis of differentially expressed small RNAs. They further assert the the iSRAP tool offers comprehensive analysis of small RNA sequencing data that leverage informed decisions on the downstream analyses of small RNA studies, including those of extracellular vesicles (EVs) such as exosomes. In their article summary, the authors state the new iSRAP tool “provides a flexible and integrated environment for small RNA expression analysis using a single command. The flexible and powerful features of iSRAP enable a comprehensive analysis of small RNAs, which covers from quality assessment of input data to differential expression analysis and visualization of results with the ease of use. iSRAP can potentially serve as a platform for rapid analysis of transcriptomic data so that a better-informed decision can be made on the downstream analyses.” In the background for their report, the authors note that “small non-coding RNAs have been significantly recognized as the key modulators in many biological processes, and are emerging as promising biomarkers for several diseases.” They say that “these RNA species are transcribed in cells and can be packaged in extracellular vesicles, which are small vesicles released from many biotypes, and are involved in intercellular communication.”

TGen Shows That Small-Molecule TROY-Inhibitor PPF May Work As Adjuvant, Together with Standard-of-Care TMZ & Radiation, to Limit Glioblastoma Invasion and Improve Clinical Outcome for GBM Patients

In what may be a significant breakthrough, the Translational Genomics Research Institute (TGen) in Phoenix, Arizona has identified a drug, propentofylline (PPF), that could help treat patients with deadly brain cancer. In a study published online on November 12, 2015 in the Journal of NeuroOncology, TGen researchers report that PPF works to limit the spread of glioblastoma multiforme (GBM), the most common primary tumor of the brain and central nervous system, by targeting a protein called TROY. In addition, TGen laboratory research also found that PPF increases the effectiveness of a a current standard-of-care chemotherapy drug called temozolomide (TMZ), and radiation, to treat glioblastoma. "We showed that PPF decreased glioblastoma cell expression of TROY, inhibited glioma cell invasion, and made brain cancer cells more vulnerable to TMZ and radiation," said Dr. Nhan Tran, Associate Professor and Head of TGen's Central Nervous System Tumor Research Lab. An advantage of small-molecule PPF, which has previously been used in clinical trials in an attempt to treat Alzheimer's disease and dementia, is that it can penetrate the blood-brain barrier and reach the tumor. And, the FDA has already approved it. The Journal of Neuro-Oncology article is titled “Propentofylline Inhibits Glioblastoma Cell Invasion and Survival by Targeting the TROY Signaling Pathway.” "Our data suggests that PPF, working in combination with TMZ and radiation, could limit glioblastoma invasion and improve the clinical outcome for brain tumor patients," said Dr. Tran, the study's senior author. This study was funded, in part, by The Ben & Catherine Ivy Foundation.

Single-Molecule, Real-Time (SMRT) Sequencing Using PacBio RS II Sequencing System Enables Genome Sequencing of Drought-Tolerant “Resurrection Plant” The Effort Is Part of PacBio’s “Most Interesting Genome in the World" Grant Program

A new paper published online on November 11, 2015 in an open-access article in Nature reports the virtually complete draft genome sequence of Oropetium thomaeum, a grass species that can re-grow after exposed to extreme drought when water again becomes available. The plant's 245-Mb genome was analyzed with 72X coverage on the PacBio® RS II Sequencing System by researchers at the Donald Danforth Plant Science Center (DDPSC) in St. Louis, Missouri. The resulting assembly has an accuracy of 99.99995% and includes telomere and centromere sequences, long terminal repeat retrotransposons, tandem duplicated genes, and other difficult-to-assemble genomic elements. This plant was sequenced through the Pacific Biosciences "Most Interesting Genome in the World" grant program designed to help scientists determine the biological mechanisms behind its extreme drought tolerance for potential application in crop improvement. The Nature article is titled “Single-Molecule Sequencing of the Desiccation Tolerant Grass Oropetium thomaeum.” The senior author of the Nature article is is Todd Mockler, Ph.D., Associate Member, DDPSC, Geraldine and Robert Virgil Distinguished Investigator, DDPSC; and the lead authors are Post-Doctoral Associate Robert VanBuren, Ph.D., DDPSC; and Doug Bryant, Ph.D., DDPSC. Scientists from numerous other institutions (see below) also contributed to this effort. "We submitted the idea to sequence the resurrection grass Oropetium thomaeum to PacBio because it has the smallest known genome among the grasses. Having the genomic data of a highly drought-tolerant species is really powerful in facilitating crop improvement, and providing a valuable resource for the plant comparative genomics community.

Longer Reproductive Period, Contraceptive Use, IUD Use All Associated with Better Cognitive Function in Elderly Women; Shorter Reproductive Period, More Full-Term Pregnancies, & No Incomplete Pregnancies All Linked to Worse Cognitive Function

Researchers led by Professor Jun-Fen Lin at the Zhejiang Provincial Center for Disease Control and Prevention in China have found that reproductive history, an important modifier of estrogen exposure across women's lifetimes, is associated with risk of cognitive impairment in post-menopausal women. These findings are published online on September 28, 2015 in the Journal of Alzheimer's Disease. In particular, the scientists found a longer reproductive period (menarche to menopause) was associated with significantly better cognitive function in elderly women. On the other hand, shorter reproductive period, higher number of full-term pregnancies, and no incomplete pregnancies are all significantly associated with increased risk of cognitive impairment. Further, the use of contraceptives and/or IUDs was associated with decreased risk of cognitive impairment. The article is titled “Reproductive History and Risk of Cognitive Impairment in Elderly Women: A Cross-Sectional Study in Eastern China.” Professor Lin notes that post-menopausal women carry an increased risk of developing Alzheimer's disease (AD) than age-matched men, probably due to the marked reduction of estrogen level that occurs following menopause. Animal and in vitro studies have identified that estrogen has several possible neuroprotective effects on cognitive function. There has been substantial research on the association between reproductive history, as an important modifer of estrogen exposure, and risk of cognitive impairment. However, there are still inconsistencies in some epidemiological and clinical studies. Only a few studies have been conducted in Chinese populations. The Zhejiang Major Public Health Surveillance Program (ZPHS) is a community-based cohort study focusing on aging and health among elderly in Zhejiang, China.

Mayo Clinic Researchers ID Completely Novel Mechanism for Predisposition to Type 2 Diabetes; Understanding Glucagon-Suppressing Effect of TCF7L2 Gene Variant May Lead to Novel Therapies

Researchers at the Mayo Clinic in Rochester, Minnesota, together with colleagues from the Universita’ di Padova in Italy, have discovered an unexpected effect from a gene already known to increase diabetes risk. The scientists had assumed that the specific allele in the gene TCF7L2 that increases the risk of type 2 diabetes, impairs insulin production in response to increased insulin resistance. Some slight evidence of that was found in the current Mayo Clinic study, but more significantly, the researchers discovered that this variant impaired a person’s ability to balance blood sugar (glucose) by suppressing glucagon – the hormone that raises the level of glucose in the bloodstream. The findings were published online on November 2, 2015, in the journal Diabetes. The article is titled “TCF7L2 Genotype and α-Cell Function in Nondiabetic Humans.” “This was surprising. It demonstrates a completely novel mechanism of predisposition to diabetes that could lead to novel therapies,” says Adrian Vella, M.D., Mayo Clinic endocrinologist and senior author of the study. “Ultimately, this sheds new light on how this gene actually predisposes to diabetes.” Dr. Vella notes that more-detailed clinical studies need to be done to confirm the finding, as well as to better understand how this affects diabetes in more heterogeneous populations over the long term.

[Mayo Clinic press release] [Diabetes abstract]