How a wildebeest herpesvirus threatens cattle
Blue wildebeest (Connochaetes taurinus) in the Maasai Mara National Reserve.
Annual wildebeest migrations through the Serengeti and Maasai Mara national reserves pose challenges for African livestock herders because the ocular and nasal excretions of young wildebeest transmit a virus known as Alcelaphine herpesvirus 1 (AlHV-1) to cattle in their grazing areas. Leonor Palmeira et al. (pp. 8333–8334) explored the long-standing mystery of why AlHV-1 causes no symptoms in wildebeest while triggering a deadly disease called malignant catarrhal fever in cattle. The authors experimentally infected calves with AlHV-1 and found that the virus remains dormant during the development of malignant catarrhal fever, expressing high levels of a latency protein called ORF73. Further analysis revealed that injection of ORF73-deficient recombinant viruses into an experimental rabbit model offered full protection from malignant catarrhal fever. In addition to unveiling a potential strategy for preventing AlHV-1 transmission, the findings illustrate how the coevolution of a virus and its host can lead to a symbiotic adaptation: The wildebeest allows AlHV-1 to persist, while the virus eliminates species that compete with the wildebeest for food and provides weakened cattle for easy predation during the wildebeest calving and migration season, according to the authors. — A.G.
Clathrate hydrates incorporate methanol molecules
Methanol alters the thermodynamics of aqueous solutions and suppresses or delays the formation of icy phases. The antifreeze action of methanol is widely exploited to prevent the formation of ice-like molecular cages known as clathrate hydrates that can block oil and gas pipelines, and is increasingly invoked to explain the existence of liquid methane oceans on icy planetary bodies such as Saturn’s moon Titan. Kyuchul Shin et al. (pp. 8437–8442) report experiments and computations that reveal a dual role for methanol in clathrate hydrate formation, both as an inhibitor and a molecule within hydrate cages. With X-ray diffraction and nuclear magnetic resonance, the authors demonstrated that hydrate lattices can incorporate methanol along with other molecules at temperatures approaching 273 K, and that the amount and species of included methanol depend on the method of sample preparation. In addition, the authors demonstrated that under certain conditions the presence of methanol can accelerate hydrate formation at temperature regimes that characterize icy planetary bodies. The findings suggest that methanol does not inhibit clathrate formation by destabilizing the hydrate structure but rather by stabilizing specific molecules within the aqueous solution, according to the authors. — T.J.
Combating metastatic pancreatic cancer with Listeria
Radioactive Listeria inside tumor cells.
Pancreatic cancer often spreads to distant organs before the original tumor grows large enough to be detected. There are no effective treatments once the disease spreads, and the 5-year survival rate has remained at 4% for the past 25 years. Wilber Quispe-Tintaya et al. (pp. 8668–8673) used an attenuated, radioactive strain of Listeria monocytogenes bacteria to target pancreatic tumors without harming healthy cells. Noting that healthy humans fight off a weakened strain of Listeria, the authors explored whether the bacterium could selectively target the immune-suppressed tumor microenvironment. Live attenuated L. monocytogenes were injected into a pancreatic tumor mouse model; the bacteria grew rapidly in metastatic tumors, slowly in primary pancreatic tumors, and not at all in healthy tissues, where immunity was strong. The authors then attached the radioisotope 188Rhenium to Listeriaat to generate Listeriaat (RL).After daily injections of RL for 1 week, followed by 1 week of rest and four additional daily injections, the authors noted a 90% reduction in the number of metastatic tumors and a 64% reduction in primary tumors. Radiation and Listeria were not detectable 1 week after treatment, and the mice experienced no significant side effects. The findings might lead to a treatment for metastatic pancreatic cancer, the authors suggest. — A.G.
Parkin’s role in lifespan of Drosophila
Researchers have linked both protein misfolding and mitochondrial dysfunction to aging and age-related neurodegenerative disorders. Mutations to, or loss of, the protein Parkin is associated with the accumulation of toxic misfolded proteins, the accumulation of dysfunctional mitochondria, and Parkinson disease. To determine whether Parkin can modulate aging, Anil Rana et al. (pp. 8638–8643) examined how the over-expression of Parkin in Drosophila affects molecular mechanisms associated with aging. The authors genetically engineered Drosophila that overproduce Parkin when treated with the drug RU486. The engineered flies lived up to 28% longer than isogenic flies not treated with RU486. The authors report that the long-lived flies suffered no reduction in reproduction, physical activity, or food intake. Further analysis showed that Parkin overexpression was linked to decreases in proteotoxicity and to reductions in Mitofusin, a mitochondrial fusion-promoting factor that typically increases in abundance during aging. The findings identify Parkin as a molecular link between the aging process and age-related neurodegeneration. According to the authors, treatments designed to enhance Parkin expression during aging may delay the onset and progression of some age-related diseases, such as Parkinson disease. — B.A.
Measuring telomeres in single cells
Variations in single cell telomere length (T/R) of various human individual cells by SCT-pqPCR.
Telomeres are structures that protect the ends of chromosomes; variations in telomere length are associated with embryogenesis, cancer, and diseases of aging. Fang Wang et al. (pp. E1906–E1912) developed a two-step method for measuring the length of telomeres in single cells, allowing the characterization of individual cells within a mixed population. In the first step, a DNA amplification technique called multiplex PCR was used to simultaneously amplify telomeres and a reference gene from a single cell, and the reaction was terminated during the linear phase of DNA amplification. In the second step, the products were further amplified by real-time PCR, enabling quantitation of the ratio of the telomere signal to that of the reference gene, or T/R. Results obtained with this method, termed SCT-pqPCR, were consistent with those obtained by established methods in various cell types. Heterogeneity in T/R was seen to increase with an increasing number of passages of cells in culture, and fibroblast telomeres from an elderly individual were more heterogenous than those from a fetus. In mouse embryos, telomere length increased following each of the first two cell divisions from the zygote stage. According to the authors, SCT-pqPCR might facilitate the identification of cancer cells and stem cells in mixed populations and may be useful in evaluating cell viability for assisted reproduction. — C.B.
Imprints of amnesia in the human brain
Ventral surface of E.P.’s brain: Brownish-tinged cysts occupy the anterior, medial temporal lobe (cysts on left side of brain are indicated by black arrows).
The well-known case of patient H.M., or Henry Molaison, who underwent surgical brain resection as a treatment for epilepsy, offered neuroscientists a rare model for the analysis of brain structure and function. Linking an array of psychological and postmortem histological information on a now-deceased patient called E.P., who in 1992 suffered profound amnesia at age 70 following viral encephalitis, Ricardo Insausti et al. (pp. E1953–E1962) have uncovered another model to link brain structure and function, and found evidence of bilateral, symmetrical damage to a brain region called the medial temporal lobe. The authors compared the pattern of E.P.’s brain damage with that of an age-matched control, and attempted to link the lesions to the patient’s cognitive impairment, documented over 14 years beginning in 1994 through tests of memory, intellectual and perceptual function, semantic knowledge, and spatial cognition, among other faculties. Upon testing, the authors report, E.P. showed no capacity for learning new facts and events despite largely intact intellectual and perceptual functions and immediate and working memory. Further, E.P. could recollect facts and autobiographical events from before age 25, but not between age 25 and the onset of his amnesia, suggesting the salience of early memories. The authors suggest that the patient’s slightly impaired semantic knowledge was likely due to secondary effects on the brain’s lateral temporal cortex. According to the authors, the findings illuminate anatomical links among memory, perception, and semantic knowledge. — P.N.