Variability in the response of amphipods and macroinvertebrate assemblage structure to prolonged drought in forested upland streams

With climate change set to increase the frequency and severity of drought in many parts of the world, there is a need to better understand the effects of drying on stream ecosystems. We investigated the long-term effects of drought on two amphipod taxa Paramoera fontana (Pontogeneiidae) and Austrogammarus australis (Paramelitidae) and macroinvertebrate assemblage structure through an analysis of 13 years of data collected from four forested stream reaches (Victoria, Australia). Abundances of A. australis and P. fontana in the lower reach of Lyrebird Creek declined to zero following surficial streambed drying. Similar declines in abundances were not observed in Sassafras Creek or the two headwater springs, which continued to flow throughout the drought. P. fontana was detected again in the lower reach of Lyrebird Creek 12 months after the final cease-to-flow, however A. australis remained undetected 5 years later, despite an upstream source population within 2 km. Both the entire and shredder macroinvertebrate assemblage structure in Sassafras Creek and the lower reach of Lyrebird Creek shifted significantly pre- and post-surficial streambed drying in the lower reach of Lyrebird Creek. Despite signs of recovery following a return to more average flows, assemblage composition remained considerably different. The substantial differences in the recovery of the two species indicates varying resistance and resilience traits. The failure of A. australis to recolonize after 5 years indicates an absence of any significant resistance or resilience traits. In contrast, the rapid re-colonization of P. fontana may indicate poor resistance traits, but strong resilience traits. The sensitivity of A. australis to cease-to-flow events points to the need to carefully manage water extraction to protect this threatened species. The effective management of macroinvertebrate assemblages in the face of drought requires a clear understanding of their response to drying, the conservation of refugia and the minimization of additional stressors which reduce ecosystem resilience.     

Interdomain salt‐bridges in the Ebola virus protein VP40 and their role in domain association and plasma membrane localization

The Ebola virus protein VP40 is a transformer protein that possesses an extraordinary ability to accomplish multiple functions by transforming into various oligomeric conformations. The disengagement of the C‐terminal domain (CTD) from the N‐terminal domain (NTD) is a crucial step in the conformational transformations of VP40 from the dimeric form to the hexameric form or octameric ring structure. Here, we use various molecular dynamics (MD) simulations to investigate the dynamics of the VP40 protein and the roles of interdomain interactions that are important for the domain–domain association and dissociation, and report on experimental results of the behavior of mutant variants of VP40. The MD studies find that various salt‐bridge interactions modulate the VP40 domain dynamics by providing conformational specificity through interdomain interactions. The MD simulations reveal a novel salt‐bridge between D45‐K326 when the CTD participates in a latch‐like interaction with the NTD. The D45‐K326 salt‐bridge interaction is proposed to help domain–domain association, whereas the E76‐K291 interaction is important for stabilizing the closed‐form structure. The effects of the removal of important VP40 salt‐bridges on plasma membrane (PM) localization, VP40 oligomerization, and virus like particle (VLP) budding assays were investigated experimentally by live cell imaging using an EGFP‐tagged VP40 system. It is found that the mutations K291E and D45K show enhanced PM localization but D45K significantly reduced VLP formation.     

Structural characterization of NRAS isoform 5

It was recently discovered that the NRAS isoform 5 (20 amino acids) is expressed in melanoma and results in a more aggressive cell phenotype. This novel isoform is responsible for increased phosphorylation of downstream targets such as AKT, MEK, and ERK as well as increased cellular proliferation. This structure report describes the NMR solution structure of NRAS isoform 5 to be used as a starting point to understand its biophysical interactions. The isoform is highly flexible in aqueous solution, but forms a helix‐turn‐coil structure in the presence of trifluoroethanol as determined by NMR and CD spectroscopy.     

Adaptive divergence despite strong genetic drift: genomic analysis of the evolutionary mechanisms causing genetic differentiation in the island fox (Urocyon littoralis)

The evolutionary mechanisms generating the tremendous biodiversity of islands have long fascinated evolutionary biologists. Genetic drift and divergent selection are predicted to be strong on islands and both could drive population divergence and speciation. Alternatively, strong genetic drift may preclude adaptation. We conducted a genomic analysis to test the roles of genetic drift and divergent selection in causing genetic differentiation among populations of the island fox (Urocyon littoralis). This species consists of six subspecies, each of which occupies a different California Channel Island. Analysis of 5293 SNP loci generated using Restriction‐site Associated DNA (RAD) sequencing found support for genetic drift as the dominant evolutionary mechanism driving population divergence among island fox populations. In particular, populations had exceptionally low genetic variation, small N_e (range = 2.1–89.7; median = 19.4), and significant genetic signatures of bottlenecks. Moreover, islands with the lowest genetic variation (and, by inference, the strongest historical genetic drift) were most genetically differentiated from mainland grey foxes, and vice versa, indicating genetic drift drives genome‐wide divergence. Nonetheless, outlier tests identified 3.6–6.6% of loci as high F_ST outliers, suggesting that despite strong genetic drift, divergent selection contributes to population divergence. Patterns of similarity among populations based on high F_ST outliers mirrored patterns based on morphology, providing additional evidence that outliers reflect adaptive divergence. Extremely low genetic variation and small N_e in some island fox populations, particularly on San Nicolas Island, suggest that they may be vulnerable to fixation of deleterious alleles, decreased fitness and reduced adaptive potential.     

The role of nanotechnology in control of human diseases: perspectives in ocular surface diseases

Nanotechnology is the creation and use of materials and devices on the same scale as molecules and intracellular structures, typically less than 100?nm in size. It is an emerging science and has made its way into pharmaceuticals to significantly improve the delivery and efficacy of drugs in a number of therapeutic areas, due to development of various nanoparticle-based products. In recent years, there has been increasing evidence that nanotechnology can help to overcome many of the ocular diseases and hence researchers are keenly interested in this science. Nanomedicines offer promise as viable alternatives to conventional drops, gels or ointments to improve drug delivery to the eye. Because of their small size, they are well tolerated, thus preventing washout, increase bioavailability and also help in specific drug delivery. This review describes the application of nanotechnology in the control of human diseases with special emphasis on various eye and ocular surfaces diseases.     

Co-fibrillogenesis of Wild-type and D76N β2-Microglobulin: THE CRUCIAL ROLE OF FIBRILLAR SEEDS*

The amyloidogenic variant of β₂-microglobulin, D76N, can readily convert into genuine fibrils under physiological conditions and primes in vitro the fibrillogenesis of the wild-type β₂-microglobulin. By Fourier transformed infrared spectroscopy, we have demonstrated that the amyloid transformation of wild-type β₂-microglobulin can be induced by the variant only after its complete fibrillar conversion. Our current findings are consistent with preliminary data in which we have shown a seeding effect of fibrils formed from D76N or the natural truncated form of β₂-microglobulin lacking the first six N-terminal residues. Interestingly, the hybrid wild-type/variant fibrillar material acquired a thermodynamic stability similar to that of homogenous D76N β₂-microglobulin fibrils and significantly higher than the wild-type homogeneous fibrils prepared at neutral pH in the presence of 20% trifluoroethanol. These results suggest that the surface of D76N β₂-microglobulin fibrils can favor the transition of the wild-type protein into an amyloid conformation leading to a rapid integration into fibrils. The chaperone crystallin, which is a mild modulator of the lag phase of the variant fibrillogenesis, potently inhibits fibril elongation of the wild-type even once it is absorbed on D76N β₂-microglobulin fibrils.