Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells

Scavenger receptor Class B type 1 (SR-B1) is a lipid transporter and sensor. In intestinal epithelial cells, SR-B1-dependent lipid sensing is associated with SR-B1 recruitment in raft-like/ detergent-resistant membrane domains and interaction of its C-terminal transmembrane domain with plasma membrane cholesterol. To clarify the initiating events occurring during lipid sensing by SR-B1, we analyzed cholesterol trafficking and raft-like domain composition in intestinal epithelial cells expressing wild-type SR-B1 or the mutated form SR-B1-Q445A, defective in membrane cholesterol binding and signal initiation. These features of SR-B1 were found to influence both apical cholesterol efflux and intracellular cholesterol trafficking from plasma membrane to lipid droplets, and the lipid composition of raft-like domains. Lipidomic analysis revealed likely participation of d18:0/16:0 sphingomyelin and 16:0/0:0 lysophosphatidylethanolamine in lipid sensing by SR-B1. Proteomic analysis identified proteins, whose abundance changed in raft-like domains during lipid sensing, and these included molecules linked to lipid raft dynamics and signal transduction. These findings provide new insights into the role of SR-B1 in cellular cholesterol homeostasis and suggest molecular links between SR-B1-dependent lipid sensing and cell cholesterol and lipid droplet dynamics.     

hnRNP I/PTB can antagonize the splicing repressor activity of SRp30c

The control of alternative pre-mRNA splicing often requires the participation of factors displaying synergistic or antagonistic activities. In the hnRNP A1 pre-mRNA, three elements promote the exclusion of alternative exon 7B, while a fourth intron element (CE9) represses splicing of exon 7B to the downstream exon. We have shown previously that the 5' portion of the 38-nucleotide-long CE9 element is bound by SRp30c, and that this interaction is important for repression in vitro. To determine whether SRp30c alone can impose repression, we tested a high-affinity SRp30c binding site that we identified using the SELEX protocol. We find that multiple high-affinity SRp30c sites are required to replicate the level of repression obtained with CE9, and that both the 5' and the 3' portions of CE9 contribute to SRp30c binding. Performing RNA affinity chromatography with the complete CE9 element recovered hnRNP I/PTB. Surprisingly however, His-tagged PTB reduced the binding of SRp30c to CE9 in a nuclear extract, stimulated splicing to a downstream 3' splice site, and relieved the CE9-mediated splicing repression in vitro. Our in vivo results are consistent with the notion that increasing PTB levels alleviates the repression imposed by CE9 to a downstream 3' splice site. Thus, PTB can function as an anti-repressor molecule to counteract the splicing inhibitory activity of SRp30c.     

Migrant shorebird use of Akimiski Island, Nunavut: a sub-arctic staging site

Determining the importance of stopover and staging areas to migrating shorebirds (Aves: Charadriiformes) is essential if such habitats are to be successfully protected. Migration chronology, species composition, length of stay, body condition, and estimated total abundance of shorebirds during spring and fall migratory periods of 2008 and 2009 were documented on Akimiski Island, Nunavut, Canada. Fourteen shorebird species were observed during spring point counts and 18 during fall. Semipalmated (Calidris pusilla) and White-rumped (C. fuscicollis) Sandpipers comprised about 80?% of all individuals observed. A greater number of species and individuals were observed during fall than spring in both years. Radio-transmitters attached to juvenile Semipalmated and Least (C. minutilla) Sandpipers indicated highly variable lengths of stay ranging up to 26?days in both species (Semipalmated Sandpiper averaged 6.5?±?2.67?days, n?=?12; Least Sandpipers averaged 7.25?±?3.79?days, n?=?8). In 2009, Semipalmated Sandpipers captured and weighed later in the season were significantly heavier than those captured earlier suggesting that this species is refueling while on Akimiski Island. A fall migration seasonal density of 5,267 (2,193–8,341) shorebirds/km² was estimated given a residence probability (i.e., the probability of an individual being present in consecutive counts) of 0.906?±?0.181. Assuming similar habitat value and shorebird density, an extrapolation of the seasonal plot density of 5,267 birds/km² to the total 192?km² mudflat habitat on Akimiski Island yields an estimate of 1,011,264 (421,098–1,601,429) shorebirds during fall migration, making Akimiski Island of Hemispheric importance as a staging site for migrant arctic-breeding shorebirds.     

Macroecology meets macroevolution: evolutionary niche dynamics in the seaweed Halimeda

Aim Because of their broad distribution in geographical and ecological dimensions, seaweeds (marine macroalgae) offer great potential as models for marine biogeographical inquiry and exploration of the interface between macroecology and macroevolution. This study aims to characterize evolutionary niche dynamics in the common green seaweed genus Halimeda, use the observed insights to gain understanding of the biogeographical history of the genus and predict habitats that can be targeted for the discovery of species of special biogeographical interest. Location Tropical and subtropical coastal waters. Methods The evolutionary history of the genus is characterized using molecular phylogenetics and relaxed molecular clock analysis. Niche modelling is carried out with maximum entropy techniques and uses macroecological data derived from global satellite imagery. Evolutionary niche dynamics are inferred through application of ancestral character state estimation. Results A nearly comprehensive molecular phylogeny of the genus was inferred from a six‐locus dataset. Macroecological niche models showed that species distribution ranges are considerably smaller than their potential ranges. We show strong phylogenetic signal in various macroecological niche features. Main conclusions The evolution of Halimeda is characterized by conservatism for tropical, nutrient‐depleted habitats, yet one section of the genus managed to invade colder habitats multiple times independently. Niche models indicate that the restricted geographical ranges of Halimeda species are not due to habitat unsuitability, strengthening the case for dispersal limitation. Niche models identified hotspots of habitat suitability of Caribbean species in the eastern Pacific Ocean. We propose that these hotspots be targeted for discovery of new species separated from their Caribbean siblings since the Pliocene rise of the Central American Isthmus.     

Unconventional repertoire profile is imprinted during acute chikungunya infection for natural killer cells polarization toward cytotoxicity

Chikungunya virus (CHIKV) is a worldwide emerging pathogen. In humans it causes a syndrome characterized by high fever, polyarthritis, and in some cases lethal encephalitis. Growing evidence indicates that the innate immune response plays a role in controlling CHIKV infection. We show here that CHIKV induces major but transient modifications in NK-cell phenotype and function soon after the onset of acute infection. We report a transient clonal expansion of NK cells that coexpress CD94/NKG2C and inhibitory receptors for HLA-C1 alleles and are correlated with the viral load. Functional tests reveal cytolytic capacity driven by NK cells in the absence of exogenous signals and severely impaired IFN-γ production. Collectively these data provide insight into the role of this unique subset of NK cells in controlling CHIKV infection by subset-specific expansion in response to acute infection, followed by a contraction phase after viral clearance.     

Meta‐population structure and the evolutionary transition to multicellularity

The evolutionary transition to multicellularity has occurred on numerous occasions, but transitions to complex life forms are rare. Here, using experimental bacterial populations as proxies for nascent multicellular organisms, we manipulate ecological factors shaping the evolution of groups. Groups were propagated under regimes requiring reproduction via a life cycle replete with developmental and dispersal (propagule) phases, but in one treatment lineages never mixed, whereas in a second treatment, cells from different lineages experienced intense competition during the dispersal phase. The latter treatment favoured traits promoting cell growth at the expense of traits underlying group fitness – a finding that is supported by results from a mathematical model. Our results show that the transition to multicellularity benefits from ecological conditions that maintain discreteness not just of the group (soma) phase, but also of the dispersal (germline) phase.     

Intra-Rater,Inter-Rater and Test-Retest Reliability of an Instrumented Timed Up and Go (iTUG) Test in Patients with Parkinson’s Disease

Background

The “Timed Up and Go” (TUG) is a widely used measure of physical functioning in older people and in neurological populations, including Parkinson’s Disease. When using an inertial sensor measurement system (instrumented TUG [iTUG]), the individual components of the iTUG and the trunk kinematics can be measured separately, which may provide relevant additional information.

Objective

The aim of this study was to determine intra-rater, inter-rater and test-retest reliability of the iTUG in patients with Parkinson’s Disease.

Methods

Twenty eight PD patients, aged 50 years or older, were included. For the iTUG the DynaPort Hybrid (McRoberts, The Hague, The Netherlands) was worn at the lower back. The device measured acceleration and angular velocity in three directions at a rate of 100 samples/s. Patients performed the iTUG five times on two consecutive days. Repeated measurements by the same rater on the same day were used to calculate intra-rater reliability. Repeated measurements by different raters on the same day were used to calculate intra-rater and inter-rater reliability. Repeated measurements by the same rater on different days were used to calculate test-retest reliability.

Results

Nineteen ICC values (15%) were ≥ 0.9 which is considered as excellent reliability. Sixty four ICC values (49%) were ≥ 0.70 and < 0.90 which is considered as good reliability. Thirty one ICC values (24%) were ≥ 0.50 and < 0.70, indicating moderate reliability. Sixteen ICC values (12%) were ≥ 0.30 and < 0.50 indicating poor reliability. Two ICT values (2%) were < 0.30 indicating very poor reliability.

Conclusions

In conclusion, in patients with Parkinson’s disease the intra-rater, inter-rater, and test-retest reliability of the individual components of the instrumented TUG (iTUG) was excellent to good for total duration and for turning durations, and good to low for the sub durations and for the kinematics of the SiSt and StSi. The results of this fully automated analysis of instrumented TUG movements demonstrate that several reliable TUG parameters can be identified that provide a basis for a more precise, quantitative use of the TUG test, in clinical practice.