Small ubiquitin-like modifier modification of arrestin-3 regulates receptor trafficking

Nonvisual arrestins are regulated by direct post-translational modifications, such as phosphorylation, ubiquitination, and nitrosylation. However, whether arrestins are regulated by other post-translational modifications remains unknown. Here we show that nonvisual arrestins are modified by small ubiquitin-like modifier 1 (SUMO-1) upon activation of β(2)-adrenergic receptor (β(2)AR). Lysine residues 295 and 400 in arrestin-3 fall within canonical SUMO consensus sites, and mutagenic analysis reveals that Lys-400 represents the main SUMOylation site. Depletion of the SUMO E2 modifying enzyme Ubc9 blocks arrestin-3 SUMOylation and attenuates β(2)AR internalization, suggesting that arrestin SUMOylation mediates G protein-coupled receptor endocytosis. Consistent with this, expression of a SUMO-deficient arrestin mutant failed to promote β(2)AR internalization as compared with wild-type arrestin-3. Our data reveal an unprecedented role for SUMOylation in mediating GPCR endocytosis and provide novel mechanistic insight into arrestin function and regulation.     

Future climate‐driven shifts in distribution of Calanus finmarchicus

Calanus finmarchicus is a key‐structural species of the North Atlantic polar biome. The species plays an important trophic role in subpolar and polar ecosystems as a grazer of phytoplankton and as a prey for higher trophic levels such as the larval stages of many fish species. Here, we used a recently developed ecological niche model to assess the ecological niche (sensu Hutchinson) of C. finmarchicus and characterize its spatial distribution. This model explained about 65% of the total variance of the observed spatial distribution inferred from an independent dataset (data of the continuous plankton recorder survey). Comparisons with other types of models (structured population and ecophysiological models) revealed a clear similarity between modeled spatial distributions at the scale of the North Atlantic. Contemporary models coupled with future projections indicated a progressive reduction of the spatial habitat of the species at the southern edge and a more pronounced one in the Georges Bank, the Scotian Shelf and the North Sea and a potential increase in abundance at the northern edge of its spatial distribution, especially in the Barents Sea. These major changes will probably lead to a major alteration of the trophodynamics of North Atlantic ecosystems affecting the trophodynamics and the biological carbon pump.     

Vitellogenin mRNA in locust fat body: coordinate induction of two genes by a juvenile hormone analog

Levels of vitellogenin (Vg) mRNA in Locusta migratoria fat body were determined as indicators of gene expression induced by the juvenile hormone analog methoprene. After injection of methoprene into juvenile hormone-deprived locusts, excised fat bodies were cultured with [3H]leucine for immunochemical assay of Vg synthesis, and RNA was assayed for Vg mRNA content by hybridization with probes from the previously cloned locust Vg genes A and B. In general, the rise in Vg mRNA paralleled the rise in Vg synthesis. During the primary response to methoprene (in female locusts in which the corpora allata had been destroyed immediately after emergence), Vg mRNA was first detected after 18-24 hr and accumulated rapidly between 36 and 48 hr. The secondary response (in locusts allatectomized during vitellogenesis and kept until Vg disappeared) was accelerated, as Vg mRNA was detectable at 12 hr and titers rose steeply after 18 hr. When Vg synthesis was prematurely induced by injection of methoprene into fifth-stage female larvae, the kinetics of mRNA accumulation were similar to those of primary stimulation in the adult. After allatectomy of vitellogenic females, fat body Vg mRNA decayed with a half-life of about 24 hr, roughly paralleling the decline in Vg synthesis. Assays with the two Vg probes showed coordinate accumulation of gene A and gene B messages under all conditions tested: during primary and secondary stimulation in adult females and in the low-level response obtained by treating male larvae with methoprene.     

Long-Term Weight Loss and Breakfast in Subjects in the National Weight Control Registry

Objective: To examine breakfast consumption in subjects maintaining a weight loss in the National Weight Control Registry (NWCR). Research Methods and Procedures: A cross-sectional study in which 2959 subjects in the NWCR completed demographic and weight history questionnaires as well as questions about their current breakfast consumption. All subjects had maintained a weight loss of at least 13.6 kg (30 lb) for at least 1 year; on average these subjects had lost 32 kg and kept it off for 6 years. Results: A large proportion of NWCR subjects (2313 or 78%) reported regularly eating breakfast every day of the week. Only 114 subjects (4%) reported never eating breakfast. There was no difference in reported energy intake between breakfast eaters and non-eaters, but breakfast eaters reported slightly more physical activity than non-breakfast eaters (p = 0.05). Discussion: Eating breakfast is a characteristic common to successful weight loss maintainers and may be a factor in their success.     

Identification of sequence motifs in oligonucleotides whose presence is correlated with antisense activity

Design of antisense oligonucleotides targeting any mRNA can be much more efficient when several activity-enhancing motifs are included and activity-decreasing motifs are avoided. This conclusion was made after statistical analysis of data collected from >1000 experiments with phosphorothioate-modified oligonucleotides. Highly significant positive correlation between the presence of motifs CCAC, TCCC, ACTC, GCCA and CTCT in the oligonucleotide and its antisense efficiency was demonstrated. In addition, negative correlation was revealed for the motifs GGGG, ACTG, AAA and TAA. It was found that the likelihood of activity of an oligonucleotide against a desired mRNA target is sequence motif content dependent.     

Protective immunity in macaques vaccinated with a modified vaccinia virus Ankara-based measles virus vaccine in the presence of passively acquired antibodies

Recombinant modified vaccinia virus Ankara (MVA), encoding the measles virus (MV) fusion (F) and hemagglutinin (H) (MVA-FH) glycoproteins, was evaluated in an MV vaccination-challenge model with macaques. Animals were vaccinated twice in the absence or presence of passively transferred MV-neutralizing macaque antibodies and challenged 1 year later intratracheally with wild-type MV. After the second vaccination with MVA-FH, all the animals developed MV-neutralizing antibodies and MV-specific T-cell responses. Although MVA-FH was slightly less effective in inducing MV-neutralizing antibodies in the absence of passively transferred antibodies than the currently used live attenuated vaccine, it proved to be more effective in the presence of such antibodies. All vaccinated animals were effectively protected from the challenge infection. These data suggest that MVA-FH should be further tested as an alternative to the current vaccine for infants with maternally acquired MV-neutralizing antibodies and for adults with waning vaccine-induced immunity.     

Implementing a mathematical model to compare oxygen uptake kinetics between cyclists and noncyclists during steady state

The purpose was to compare a mathematical model of oxygen uptake and bioenergetic systems to an experimental protocol. Twelve (N = 12) noncyclists (NC), age (21.8 ± 1.4 years), and 8 (N = 8) cyclists (C), age (30.5 ± 5.7 years), were subjects. All subjects signed an informed consent. Oxygen consumption (VO2, ml·kg?1·min?1) was measured with steady-state VO2 requirements and responses determined using the mathematical model from the following equation: VO2 (WR) = VO2 (rest) + VO2 (unloading pedaling) + α.WR; ΔVO2(t, WR) = ΔVO2 (WR) = [1-e[-(t-td)/tO2]. Exercise means (SD) included the following: VO2NC(WR) = 48.4 (16.6) ml?1·min?1 for NCs and VO2C(WR) = 56.4 (24.95) ml?1·min?1 for Cs ; ΔVO2C(t, WR) = 6:38 ml?1·min?1 for NCs and ΔVO2C(t, WR) = 7.44 ml?1·min?1 for Cs. The correlation between the mathematical model and actual measure was statistically significant (p < 0.01) with a coefficient of r = 0.947. The experimental protocol was significantly associated with the mathematical model. This allows for a quantitative analysis and safe prediction of steady-state oxygen uptake conditions on populations before exposure to exercising conditions. Through more precise analysis of conditions, greater specificity of training may lead to more predictable adaptation outcomes.     

Relation of R Factor and Chromosomal β-Lactamase with the Periplasmic Space

The release of several R factor and chromosomal beta-lactamases by osmotic shock treatment was studied. It was found that those beta-lactamases with a molecular weight of about 20,000 were released, but those with a molecular weight of about 30,000 to 44,000 were not released during osmotic shock. This differential release did not depend on whether the structural genes were on the chromosome or on the genome of an R factor. The release or retention of the beta-lactamases appeared to be a characteristic of the enzyme rather than the host cell since the same results were obtained when the R factors were harbored by a variety of host bacteria. Studies with bacteria which produced more than one beta-lactamase showed that each enzyme reacted independently to the presence of other beta-lactamases produced by the host bacterium.