Lipid Nanoparticles as Carriers for RNAi against Viral Infections: Current Status and Future Perspectives

The efforts made to develop RNAi-based therapies have led to productive research in the field of infections in humans, such as hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), herpetic keratitis, human papillomavirus, or influenza virus. Naked RNAi molecules are rapidly digested by nucleases in the serum, and due to their negative surface charge, entry into the cell cytoplasm is also hampered, which makes necessary the use of delivery systems to exploit the full potential of RNAi therapeutics. Lipid nanoparticles (LNP) represent one of the most widely used delivery systems for in vivo application of RNAi due to their relative safety and simplicity of production, joint with the enhanced payload and protection of encapsulated RNAs. Moreover, LNP may be functionalized to reach target cells, and they may be used to combine RNAi molecules with conventional drug substances to reduce resistance or improve efficiency. This review features the current application of LNP in RNAi mediated therapy against viral infections and aims to explore possible future lines of action in this field.

Current Approaches for Predicting a Lack of Response to Anti-EGFR Therapy in KRAS Wild-Type Patients

Targeting epidermal growth factor receptor (EGFR) has been one of the most effective colorectal cancer strategies. Anti-EGFR antibodies function by binding to the extracellular domain of EGFR, preventing its activation, and ultimately providing clinical benefit. KRAS mutations in codons 12 and 13 are recognized prognostic and predictive biomarkers that should be analyzed at the clinic prior to the administration of anti-EGFR therapy. However, still an important fraction of KRAS wild-type patients do not respond to the treatment. The identification of additional genetic determinants of primary or secondary resistance to EGFR targeted therapy for further improving the selection of patients is urgent. Herein, we review the latest published literature highlighting the most important genes that may predict resistance to anti-EGFR monoclonal antibodies in colorectal cancer patients. According to the available findings, the evaluation of BRAF, NRAS, PIK3CA, and PTEN status could be the right strategy to select patients who are likely to respond to anti-EGFR therapies. In the future, the combination of those biomarkers will help establish consensus that can be introduced into clinical practice.

Feeding ecology of Atlantic bluefin tuna (Thunnus thynnus) in North Carolina: diet, daily ration, and consumption of Atlantic menhaden (Brevoortia tyrannus)

Diet, gastric evacuation rates, daily ration, and population-level prey demand of bluefin tuna (Thunnus thynnus) were estimated in the continental shelf waters off North Carolina. Bluefin tuna stomachs were collected from commercial fishermen during the late fall and winter months of 2003–04, 2004–05, and 2005–06. Diel patterns in mean gut fullness values were used to estimate gastric evacuation rates. Daily ration determined from mean gut fullness values and gastric evacuation rates was used, along with bluefin tuna population size and residency times, to estimate population-level consumption by bluefin tuna on Atlantic menhaden (Brevoortia tyrannus). Bluefin tuna diet (n= 448) was dominated by Atlantic menhaden; other teleosts, portunid crabs, and squid were of mostly minor importance. The time required to empty the stomach after peak gut fullness was estimated to be ~20 hours. Daily ration estimates were approximately 2% of body weight per day. At current western Atlantic population levels, bluefin tuna predation on Atlantic menhaden is minimal compared to predation by other known predators and the numbers taken in commercial harvest. Bluefin tuna appear to occupy coastal waters in North Carolina during winter to prey upon Atlantic menhaden. Thus, changes in the Atlantic menhaden stock status or distribution would alter the winter foraging locations of bluefin

Abundance and population density of cetaceans in the California Current ecosystem

The abundance and population density of cetaceans along the U.S. west coast were estimated from ship surveys conducted in the summer and fall of 1991, 1993, 1996, 2001, and 2005 by using multiple-covariate, line-transect analyses. Overall, approximately 556,000 cetaceans of 21 species were estimated to be in the 1,141,800-km2 study area. Delphinoids (Delphinidae and Phocoenidae), the most abundant group, numbered ~540,000 individuals. Abundance in other taxonomic groups included ~5800 baleen whales (Mysticeti), ~7000 beaked whales (Ziphiidae), and ~3200 sperm whales (Physeteridae). This study provides the longest time series of abundance estimates that includes all the cetacean species in any marine ecosystem. These estimates will be used to interpret the impacts of human-caused mortality (such as that documented in fishery bycatch and that caused by ship strikes and other means) and to evaluate the ecological role of cetaceans in the California Current ecosystem.

Diets of and trophic relationships among dominant marine nekton within the northern California Current ecosystem

In this study we analyzed the diets of 26 nekton species collected from two years (2000 and 2002) off Oregon and northern California to describe dominant nekton trophic groups of the northern California Current (NCC) pelagic ecosystem. We also examined interannual variation in the diets of three nekton species. Cluster analysis of predator diets resulted in nekton trophic groups based on the consumption of copepods, euphausiids, brachyuran larvae, larval juvenile fishes, and adult nekton. However, many fish within trophic groups consumed prey from multiple trophic levels—euphausiids being the most widely consumed. Comparison of diets between years showed that most variation occurred with changes in the contribution of euphausiids and brachyuran larvae to nekton diets. The importance of euphausiids and other crustacean prey to nekton indicates that omnivory is an important characteristic of the NCC food web; however it may change during periods of lower or higher upwelling and ecosystem production.

The effect of predation (current and historical) by humpback whales (Megaptera novaeangliae) on fish abundance near Kodiak Island, Alaska

Humpback whales (Megaptera novaeangliae) are significant marine consumers. To examine the potential effect of predation by humpback whales, consumption (kg of prey daily) and prey removal (kg of prey annually) were modeled for a current and historic feeding aggregation of humpback whales off northeastern Kodiak Island, Alaska. A current prey biomass removal rate was modeled by using an estimate of the 2002 humpback whale abundance. A historic rate of removal was modeled from a prewhaling abundance estimate (population size prior to 1926). Two provisional humpback whale diets were simulated in order to model consumption rate. One diet was based on the stomach contents of whales that were commercially harvested from Port Hobron whaling station in Kodiak, Alaska, between 1926 and 1937, and the second diet, based on local prey availability as determined by fish surveys conducted within the study area, was used to model consumption rate by the historic population. The latter diet was also used to model consumption by the current population and to project a consumption rate if the current population were to grow to reach the historic population size. Models of these simulated diets showed that the current population likely removes nearly 8.83

Valuing Africa's inland fisheries: overview of current methodologies with an emphasis on livelihood analysis

While Africa’s inland fisheries are widely recognized to be of great importance to local people, accurate and up-to-date information on their value is sparse and its absence is a serious constraint to the formulation of effective fisheries policies and management practices. As a contribution to current efforts to address this constraint, this paper reviews the different methods that are potentially applicable to the valuation of inland fisheries and discusses their respective rationales and limitations within a multi-sectoral, multi-user context. The livelihood analysis approach is given special emphasis. The complementarity of this recently developed approach with the other, more conventional, environmental economics methods is illustrated.

Anisotropic expansion and SNIa: An open issue

We review the appropriateness of using SNIa observations to detect potential signatures of anisotropic expansion in the Universe. We focus on Union2 and SNLS3 SNIa datasets and use the hemispherical comparison method to detect possible anisotropic features. Unlike some previous works where nondiagonal elements of the covariance matrix were neglected, we use the full covariance matrix of the SNIa data, thus obtaining more realistic and not underestimated errors. As a matter of fact, the significance of previously claimed detections of a preferred direction in the Union2 dataset completely disappears once we include the effects of using the full covariance matrix. Moreover, we also find that such apreferred direction is aligned with the orthogonal direction of the SDSS observational plane and this suggests a clear indication that the SDSS subsample of the Union2 dataset introduces a significant bias, making the detected preferred direction unphysical. We thus find that current SNIa surveys are inappropriate to test anisotropic features due to their highly non-homogeneous angular distribution in the sky. In addition, after removal of the highest in homogeneous sub-samples, the number of SNIa is too low. Finally, we take advantage of the particular distribution of SNLS SNIa sub- sample in the SNLS3 data set, in which the observations were taken along four different directions. We fit each direction independently and find consistent results at the 1 sigma level. Although the likelihoods peak at relatively different values of Omega(m), the low number of data along each direction gives rise to large errors so that the likelihoods are sufficiently broad as to overlap within 1 sigma. (C) 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons. org/licenses/by/4.0/).

Effects of current speed and turbidity on stationary light-trap catches of larval and juvenile fishes

Light traps are one of a number of different gears used to sample pelagic larval and juvenile fishes. In contrast to conventional towed nets, light traps primarily collect larger size classes, including settlement-size larvae (Choat et al., 1993; Hickford and Schiel, 1999 ; Hernandez and Shaw, 2003), and, therefore, have become important tools for discerning recruitment dynamics (Sponaugle and Cowen, 1996; Wilson, 2001). The relative ease with which multiple synoptic light trap samples can be taken means that larval distribution patterns can be mapped with greater spatial resolution (Doherty, 1987). Light traps are also useful for sampling shallow or structurally complex habitats where towed nets are ineffective or prohibited (Gregory and Powles, 1985; Brogan, 1994; Hernandez and Shaw, 2003).

Historic and Current Use of Lower Cook Inlet, Alaska, by Belugas, Delphinapterus leucas

Dedicated at-sea surveys for marine birds and mammals conducted in lower Cook Inlet in late July and early August from 1995–99 failed to locate any belugas, Delphinapterus leucas. Surveys covered a total of 6,249 linear km and were conducted in both nearshore and offshore habitats. Sightings included 791 individual marine mammals of 10 species. Both historical data and local knowledge indicate that belugas were regularly seen in summer in nearshore and offshore areas of lower Cook Inlet up until the early 1990’s. Diminished presence of belugas in lower Cook Inlet may be a direct function of reduced numbers but may also indicate changes in habitat quality that may inhibit recovery.