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Archive - Jan 10, 2017

Mechanism for Coping with Ribosomes Stalled on mRNAs with Premature Stop Codons

New research from the Case Western Reserve University School of Medicine describes a mechanism by which an essential quality control system in cells identifies and destroys faulty genetic material. The findings were published online on December 23, 2016 in Nature Communications. The open-access article is titled ATP Hydrolysis by UPF1 Is Required for Efficient Translation Termination at Premature Stop Codons.” Kristian Baker Ph.D., Associate Professor in the Center for RNA Molecular Biology at Case Western Reserve University School of Medicine, led the study that provided evidence for direct communication between the cell's protein synthesis machinery - the ribosome - and the protein complex that recognizes and destroys defective genetic intermediates called messenger RNAs (mRNAs). "We aimed to understand how cells are able to recognize mRNA that is defective and distinguish it from normal mRNA. For most cells, this process is critical for survival, but we didn't yet understand how it works, especially when the difference between the two is very subtle," said Dr. Baker. "Our findings clearly show that surveillance machinery involved in identifying faulty mRNA functionally interacts with the ribosome, the apparatus responsible for synthesizing proteins in the cell. It is now clear that these two elements communicate and work closely together to recognize and eliminate aberrant mRNA from the cell." Cells convert sections of DNA encoding genes into mRNA that serves as a blueprint for the synthesis of a protein.

Bacteria Not Initially Sensitive to Phage Become Sensitive After Molecular Exchange of Membrane Vesicles from Sensitive Bacteria

Bacteriophages (phages) are probably the most abundant entities in nature, often exceeding bacterial densities by an order of magnitude. As viral predators of bacteria, phages have a major impact on bacterial communities by reducing some bacteria and enabling others to flourish. Phages also occasionally package host DNA and deliver it to other bacteria, in a process known as horizontal gene transfer (HGT). The biology of phage infection has been extensively studied since the beginning of the 20th century. However, the fate of phages in complex bacterial communities resembling their natural ecosystem has not been studied at the cellular level. To investigate the biology of phage infection in complex bacterial communities, researchers followed phage dynamics in communities harboring phage-resistant (R) and phage-sensitive (S) bacteria, a common scenario in nature. Now, in new research, published online on December 29, 2016 in Cell, researchers at the Hebrew University of Jerusalem's Faculty of Medicine provide the first demonstration of a mechanism by which bacteria entirely resistant to a given phage become susceptible to it upon co-incubation with sensitive bacteria. The researchers show how phage-sensitive bacteria harboring phage receptor can deliver the receptor to nearby phage-resistant cells that lack the phage receptor, via a molecular transfer they call "acquisition of sensitivity" (ASEN). This process involves a molecular exchange driven by membrane vesicles (MVs), in which phage-resistant cells transiently gain phage attachment molecules released from neighboring phage-sensitive cells. By exploiting this novel delivery system, phages can invade bacteria lacking their receptor.

BRCA2 Gene Mutation Associated with Aggressive Prostate Cancer in Men with Family History; Early on, These Patients Have Molecular Profile Similar to That of Those with Advanced Cancer

A landmark study, led by Monash University's Biomedicine Discovery Institute (BDI) with the involvement of the Peter MacCallum Cancer Centre, both in Australia, has revealed the reason why men with a family history of prostate cancer who also carry the BRCA2 gene fault have a more aggressive form of prostate cancer. The study, published online on January 9, 2017 in Nature Communications, involving a consortium of Melbourne and Toronto researchers and clinicians, reports the molecular profile of the prostate cancers in men with the BRCA2 fault is similar to the profile seen in patients with advanced cancer: explaining why - right from diagnosis - BRCA2 patients have a poor outcome. The international team of scientists, led by Professor Gail Risbridger and Dr. Renea Taylor from the BDI and Dr. Rob Bristow from the Princess Margaret Cancer Centre in Toronto, Canada, in collaboration with clinicians from the Peter MacCallum Cancer Centre, kConFab, Austin Health, and the Olivia Newton-John Cancer Centre, worked to unlock the secrets of why prostate cancer in BRCA2 men behaves aggressively. The open-access article is titled “Germline BRCA2 Mutations Drive Prostate Cancers with Distinct Evolutionary Trajectories.” This study, part of a larger Victorian Cancer Agency-funded program of translational research, had previously reported that men who carried the BRCA2 gene fault were at a higher risk of having a more aggressive form of prostate cancer if a cell pathology known as IDCP (intraductal carcinoma of the prostate) was present; the IDCP cell pathology predicted these men were much more likely to have a poor clinical outcome.

“Dementia” Gene Associated with High Risk for Alzheimer's Disease and Cardiovascular Disease May Have Conferred an Evolutionary Advantage for Humans at High Risk for Parasitic Infections (Balanced Polymorphism)

New research published online on December 28, 2017 in The FASEB Journal, suggests that carriers of the apolipoprotein E4 allele, which is the single strongest genetic predictor of Alzheimer's disease and is associated with cognitive decline and cardiovascular disease, may have a reduced risk of cognitive decline associated with parasitic diseases. This protective effect may help explain why this "disease" gene has persisted over the millennia, as well as offering insights into preventing and treating the cognitive problems caused by human parasites. "While being an E4 carrier is the strongest risk factor to date of Alzheimer's dementia and cognitive decline in industrial populations, it is associated with greater cognitive performance in individuals facing a high parasite and pathogen load, suggesting advantages to the E4 allele under certain environmental conditions," said Benjamin C. Trumble, Ph.D., a researcher involved in the work at the School of Human Evolution and Social Change and the Center for Evolution and Medicine at Arizona State University in Tempe, Arizona. "The current mismatch between sedentary postindustrial lifestyles and active parasite-rich lifeways experienced throughout most of human history may be critical for understanding genetic risk for cognitive aging." Dr. Trumble and colleagues examined cognitive performance and parasite exposure data from a remote population of forager-horticulturalists in the Bolivian Amazon, called the Tsimane. The Tsimane experience high parasite loads, making them a suitable population for study for the role of the E4 allele in this circumstance. The researchers undertook a genetic analysis, measured immune markers of parasitic infection, and conducted cognitive tests on 372 Tsimane men and women aged 6 to 88 years.

Study Suggests Ancient Marine Origin of Retroviruses

Retroviruses - the family of viruses that includes HIV - are almost half a billion years old, according to new research by scientists at Oxford University. That's several hundred million years older than previously thought and suggests retroviruses have ancient marine origins, having been with their animal hosts through the evolutionary transition from sea to land. The findings, reported online on January 10,2017 in jNature Communications, will help us understand more about the continuing “arms race” between viruses and their hosts. The open-access article is titled “Marine Origin of Retroviruses in The Early Palaeozoic Era.” Study co-author author Dr. Aris Katzourakis, from Oxford University's Department of Zoology, said: “Very little has been known about the ancient origin of retroviruses, partly because of the absence of geological fossil records. Retroviruses are broadly distributed among vertebrates and can also transmit between hosts, leading to novel diseases such as HIV, and they have been shown to be capable of leaping between distantly related hosts such as birds and mammals. But until now, it was thought that retroviruses were relative newcomers - possibly as recent as 100 million years in age.” “Our new research shows that retroviruses are at least 450 million years old, if not older, and that they must have originated together with, if not before, their vertebrate hosts in the early Paleozoic era. Furthermore, they would have been present in our vertebrate ancestors prior to the colonization of land and have accompanied their hosts throughout this transition from sea to land, all the way up until the present day.” Retroviruses are a family of viruses that includes the HIV virus responsible for the AIDS pandemic. They can also cause cancers and immunodeficiencies in a range of animals.