Rise of the Andes

The surface uplift of mountain belts is generally assumed to reflect progressive shortening and crustal thickening, leading to their gradual rise. Recent studies of the Andes indicate that their elevation remained relatively stable for long periods (tens of millions of years), separated by rapid (1 to 4 million years) changes of 1.5 kilometers or more. Periodic punctuated surface uplift of mountain belts probably reflects the rapid removal of unstable, dense lower lithosphere after long-term thickening of the crust and lithospheric mantle.     

MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling

The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene. inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 18 (22%) lung cancer specimens that had developed resistance to gefitinib or erlotinib. We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well.     

Cross-linking cellular prion protein triggers neuronal apoptosis in vivo

Neuronal death is a prominent, but poorly understood, pathological hallmark of prion disease. Notably, in the absence of the cellular prion protein (PrPC), the disease-associated isoform, PrPSc, appears not to be intrinsically neurotoxic, suggesting that PrPC itself may participate directly in the prion neurodegenerative cascade. Here, cross-linking PrPC in vivo with specific monoclonal antibodies was found to trigger rapid and extensive apoptosis in hippocampal and cerebellar neurons. These findings suggest that PrPC functions in the control of neuronal survival and provides a model to explore whether cross-linking of PrPC by oligomeric PrPSc can promote neuronal loss during prion infection.     

Kinetic isotope effects for the reactions of muonic helium and muonium with H2

The neutral muonic helium atom may be regarded as the heaviest isotope of the hydrogen atom, with a mass of ~4.1 atomic mass units ((4.1)H), because the negative muon almost perfectly screens one proton charge. We report the reaction rate of (4.1)H with (1)H(2) to produce (4.1)H(1)H + (1)H at 295 to 500 kelvin. The experimental rate constants are compared with the predictions of accurate quantum-mechanical dynamics calculations carried out on an accurate Born-Huang potential energy surface and with previously measured rate constants of (0.11)H (where (0.11)H is shorthand for muonium). Kinetic isotope effects can be compared for the unprecedentedly large mass ratio of 36. The agreement with accurate quantum dynamics is quantitative at 500 kelvin, and variational transition-state theory is used to interpret the extremely low (large inverse) kinetic isotope effects in the 10(-4) to 10(-2) range.     

A synthetic maternal-effect selfish genetic element drives population replacement in Drosophila

One proposed strategy for controlling the transmission of insect-borne pathogens uses a drive mechanism to ensure the rapid spread of transgenes conferring disease refractoriness throughout wild populations. Here, we report the creation of maternal-effect selfish genetic elements in Drosophila that drive population replacement and are resistant to recombination-mediated dissociation of drive and disease refractoriness functions. These selfish elements use microRNA-mediated silencing of a maternally expressed gene essential for embryogenesis, which is coupled with early zygotic expression of a rescuing transgene.     

N-linked glycan profiling of mature human milk by high-performance microfluidic chip liquid chromatography time-of-flight tandem mass spectrometry

N-Linked glycans of skim human milk proteins were determined for three mothers. N-Linked glycans are linked to immune defense, cell growth, and cell-cell adhesion, but their functions in human milk are undetermined. Protein-bound N-linked glycans were released with peptidyl N-glycosidase F (PNGase F), enriched by graphitized carbon chromatography, and analyzed with Chip-TOF MS. To be defined as N-glycans, compounds were required, in all three procedural replicates, to match, within 6 ppm, against a theoretical human N-glycan library and be at least 2-fold higher in abundance in PNGase F-treated than in control samples. Fifty-two N-linked glycan compositions were identified, and 24 were confirmed via tandem mass spectra analysis. Twenty-seven compositions have been found previously in human milk, and 25 are novel compositions. By abundance, 84% of N-glycans were fucosylated and 47% were sialylated. The majority (70%) of total N-glycan abundance was composed of N-glycans found in all three milk samples.     

Fat extraction from acid- and base-hydrolyzed food samples using accelerated solvent extraction

This paper describes a new in-cell method for pursuing accelerated solvent extraction (ASE) prior to lipid analysis from food samples. It is difficult to pursue direct ASE with acid- or base-hydrolyzed samples due to the corrosive nature of the reagents and material limitations. In this study ion exchange based materials were used to remove acid or base reagents in-cell without compromising the recovery of lipids. The performance data are presented here for the new methods for lipid extraction for a variety of food samples and compared to the Mojonnier method. NIST Standard Reference Materials (SRM-1546 and SRM-1849) were used to validate the ASE methods. Excellent fat recoveries were obtained for the ASE methods. The new methods presented here enhance the utility of ASE and eliminate labor intensive protocols.     

The fate of Amazonian forest fragments: A 32-year investigation

We synthesize findings to date from the world’s largest and longest-running experimental study of habitat fragmentation, located in central Amazonia. Over the past 32 years, Amazonian forest fragments ranging from 1 to 100 ha have experienced a wide array of ecological changes. Edge effects have been a dominant driver of fragment dynamics, strongly affecting forest microclimate, tree mortality, carbon storage, fauna, and other aspects of fragment ecology. However, edge-effect intensity varies markedly in space and time, and is influenced by factors such as edge age, the number of nearby edges, and the adjoining matrix of modified vegetation surrounding fragments. In our study area, the matrix has changed markedly over the course of the study (evolving from large cattle pastures to mosaics of abandoned pasture and regrowth forest) and this in turn has strongly influenced fragment dynamics and faunal persistence. Rare weather events, especially windstorms and droughts, have further altered fragment ecology. In general, populations and communities of species in fragments are hyperdynamic relative to nearby intact forest. Some edge and fragment-isolation effects have declined with a partial recovery of secondary forests around fragments, but other changes, such as altered patterns of tree recruitment, are ongoing. Fragments are highly sensitive to external vicissitudes, and even small changes in local land-management practices may drive fragmented ecosystems in markedly different directions. The effects of fragmentation are likely to interact synergistically with other anthropogenic threats such as logging, hunting, and especially fire, creating an even greater peril for the Amazonian biota.