Annual and seasonal movements of migrating short-tailed shearwaters reflect environmental variation in sub-Arctic and Arctic waters

The marine ecosystems of the Bering Sea and adjacent southern Chukchi Sea are experiencing rapid changes due to recent reductions in sea ice. Short-tailed shearwaters Puffinus tenuirostris visit this region in huge numbers between the boreal summer and autumn during non-breeding season, and represent one of the dominant top predators. To understand the implications for this species of ongoing environmental change in the Pacific sub-Arctic and Arctic seas, we tracked the migratory movements of 19 and 24 birds in 2010 and 2011, respectively, using light-level geolocators. In both years, tracked birds occupied the western (Okhotsk Sea and Kuril Islands) and eastern (southeast Bering Sea) North Pacific from May to July. In August–September of 2010, but not 2011, a substantial proportion (68 % of the tracked individuals in 2010 compared to 38 % in 2011) moved through the Bering Strait to feed in the Chukchi Sea. Based on the correlation with oceanographic variables, the probability of shearwater occurrence was highest in waters with sea surface temperatures (SSTs) of 8–10 °C over shallow depths. Furthermore, shearwaters spent more time flying when SST was warmer than 9 °C, suggesting increased search effort for prey. We hypothesized that the northward shift in the distribution of shearwaters may have been related to temperature-driven changes in the abundance of their dominant prey, krill (Euphausiacea), as the timing of krill spawning coincides with the seasonal increase in water temperature. Our results indicate a flexible response of foraging birds to ongoing changes in the sub-Arctic and Arctic ecosystems

Fine-Scale Movements of the Broadnose Sevengill Shark and Its Main Prey, the Gummy Shark

Information on the fine-scale movement of predators and their prey is important to interpret foraging behaviours and activity patterns. An understanding of these behaviours will help determine predator-prey relationships and their effects on community dynamics. For instance understanding a predator's movement behaviour may alter pre determined expectations of prey behaviour, as almost any aspect of the prey's decisions from foraging to mating can be influenced by the risk of predation. Acoustic telemetry was used to study the fine-scale movement patterns of the Broadnose Sevengill shark Notorynchus cepedianus and its main prey, the Gummy shark Mustelus antarcticus, in a coastal bay of southeast Tasmania. Notorynchus cepedianus displayed distinct diel differences in activity patterns. During the day they stayed close to the substrate (sea floor) and were frequently inactive. At night, however, their swimming behaviour continually oscillated through the water column from the substrate to near surface. In contrast, M. antarcticus remained close to the substrate for the entire diel cycle, and showed similar movement patterns for day and night. For both species, the possibility that movement is related to foraging behaviour is discussed. For M. antarcticus, movement may possibly be linked to a diet of predominantly slow benthic prey. On several occasions, N. cepedianus carried out a sequence of burst speed events (increased rates of movement) that could be related to chasing prey. All burst speed events during the day were across the substrate, while at night these occurred in the water column. Overall, diel differences in water column use, along with the presence of oscillatory behaviour and burst speed events suggest that N. cepedianus are nocturnal foragers, but may opportunistically attack prey they happen to encounter during the day

Malleable Machines in Transcription Regulation: The Mediator Complex

The Mediator complex provides an interface between gene-specific regulatory proteins and the general transcription machinery including RNA polymerase II (RNAP II). The complex has a modular architecture (Head, Middle, and Tail) and cryoelectron microscopy analysis suggested that it undergoes dramatic conformational changes upon interactions with activators and RNAP II. These rearrangements have been proposed to play a role in the assembly of the preinitiation complex and also to contribute to the regulatory mechanism of Mediator. In analogy to many regulatory and transcriptional proteins, we reasoned that Mediator might also utilize intrinsically disordered regions (IDRs) to facilitate structural transitions and transmit transcriptional signals. Indeed, a high prevalence of IDRs was found in various subunits of Mediator from both Saccharomyces cerevisiae and Homo sapiens, especially in the Tail and the Middle modules. The level of disorder increases from yeast to man, although in both organisms it significantly exceeds that of multiprotein complexes of a similar size. IDRs can contribute to Mediator's function in three different ways: they can individually serve as target sites for multiple partners having distinctive structures; they can act as malleable linkers connecting globular domains that impart modular functionality on the complex; and they can also facilitate assembly and disassembly of complexes in response to regulatory signals. Short segments of IDRs, termed molecular recognition features (MoRFs) distinguished by a high protein–protein interaction propensity, were identified in 16 and 19 subunits of the yeast and human Mediator, respectively. In Saccharomyces cerevisiae, the functional roles of 11 MoRFs have been experimentally verified, and those in the Med8/Med18/Med20 and Med7/Med21 complexes were structurally confirmed. Although the Saccharomyces cerevisiae and Homo sapiens Mediator sequences are only weakly conserved, the arrangements of the disordered regions and their embedded interaction sites are quite similar in the two organisms. All of these data suggest an integral role for intrinsic disorder in Mediator's function

Aloe barbadensis: how a miraculous plant becomes reality

Aloe barbadensis Miller is a plant that is native to North and East Africa and has accompanied man for over 5,000 years. The aloe vera plant has been endowed with digestive, dermatological, culinary and cosmetic virtues. On this basis, aloe provides a range of possibilities for fascinating studies from several points of view, including the analysis of chemical composition, the biochemistry involved in various activities and its application in pharmacology, as well as from horticultural and economic standpoints. The use of aloe vera as a medicinal plant is mentioned in numerous ancient texts such as the Bible. This multitude of medicinal uses has been described and discussed for centuries, thus transforming this miracle plant into reality. A summary of the historical uses, chemical composition and biological activities of this species is presented in this review. The latest clinical studies involved in vivo and in vitro assays conducted with aloe vera gel or its metabolites and the results of these studies are reviewed

Adenovirus-5-Vectored P. falciparum Vaccine Expressing CSP and AMA1. Part B: Safety, Immunogenicity and Protective Efficacy of the CSP Component

Background: A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge.\ud \ud Methodology/Principal Findings: NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one adenovector encoding CSP and one encoding apical membrane antigen-1 (AMA1) that was evaluated for safety and immunogenicity in an earlier study (see companion paper, Sedegah et al). Fourteen Ad5 seropositive or negative adults received two doses of NMRC-MV-Ad-PfC sixteen weeks apart, at 1x1010 particle units per dose. The vaccine was safe and well tolerated. All volunteers developed positive ELISpot responses by 28 days after the first immunization (geometric mean 272 spot forming cells/million[sfc/m]) that declined during the following 16 weeks and increased after the second dose to levels that in most cases were less than the initial peak (geometric mean 119 sfc/m). CD8+ predominated over CD4+ responses, as in the first clinical trial. Antibody responses were poor and like ELISpot responses increased after the second immunization but did not exceed the initial peak. Pre-existing neutralizing antibodies (NAb) to Ad5 did not affect the immunogenicity of the first dose, but the fold increase in NAb induced by the first dose was significantly associated with poorer antibody responses after the second dose, while ELISpot responses remained unaffected. When challenged by the bite of P. falciparum-infected mosquitoes, two of 11 volunteers showed a delay in the time to patency compared to infectivity controls, but no volunteers were sterilely protected.\ud \ud Significance: The NMRC-MV-Ad-PfC vaccine expressing CSP was safe and well tolerated given as two doses, but did not provide sterile protection

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo