Effects of hyperactive Janus kinase 2 signaling in mammary epithelial cells

Ornithine decarboxylase (ODC), the first rate-limiting enzyme in the polyamine biosynthesis is one of the most rapidly degraded proteins in eukaryotic cells. Mammalian ODC is a notable exception to the widely accepted dogma that ubiquitination is always required for targeting a protein to degradation by the 26S proteasome. However, while it is well established that in mammalian cells degradation of ODC is ubiquitin independent, the requirement of ubiquitination for degradation of ODC in yeast cells remained undetermined. We have investigated ODC degradation in three mutant strains of Saccharomyces cerevisiae in which ubiquitin-dependent protein degradation activity is severely compromised. While yeast ODC was rapidly degraded in all these mutant strains the degradation of N-end rule substrates was inhibited. A mutant mouse ODC that fails to interact with Az was rapidly degraded in yeast cells but was stable in mammalian cells suggesting that interaction with a mammalian Az like yeast protein is not necessary for the degradation of ODC in yeast cells. Deletion analysis revealed that sequences from its unique N-terminus are involved in targeting yeast ODC to rapid degradation in yeast cells.     

Widespread Changes in White Matter Microstructure after a Day of Waking and Sleep Deprivation

BackgroundElucidating the neurobiological effects of sleep and waking remains an important goal of the neurosciences. Recently, animal studies indicated that sleep is important for cell membrane and myelin maintenance in the brain and that these structures are particularly susceptible to insufficient sleep. Here, we tested the hypothesis that a day of waking and sleep deprivation would be associated with changes in diffusion tensor imaging (DTI) indices of white matter microstructure sensitive to axonal membrane and myelin alterations.MethodsTwenty-one healthy adult males underwent DTI in the morning [7:30AM; time point (TP)1], after 14 hours of waking (TP2), and then after another 9 hours of waking (TP3). Whole brain voxel-wise analysis was performed with tract based spatial statistics.ResultsA day of waking was associated with widespread increases in white matter fractional anisotropy, which were mainly driven by radial diffusivity reductions, and sleep deprivation was associated with widespread fractional anisotropy decreases, which were mainly explained by reductions in axial diffusivity. In addition, larger decreases in axial diffusivity after sleep deprivation were associated with greater sleepiness. All DTI changes remained significant after adjusting for hydration measures.ConclusionsThis is the first DTI study of sleep deprivation in humans. Although previous studies have observed localized changes in DTI indices of cerebral microstructure over the course of a few hours, further studies are needed to confirm widespread DTI changes within hours of waking and to clarify whether such changes in white matter microstructure serve as neurobiological substrates of sleepiness.     

Precipitation and Primary Health Care Visits for Gastrointestinal Illness in Gothenburg,Sweden

Background

The river Göta Älv is a source of freshwater for the City of Gothenburg, Sweden, and we recently identified a clear influence of upstream precipitation on concentrations of indicator bacteria in the river water, as well as an association with the daily number of phone calls to the nurse advice line related to acute gastrointestinal illnesses (AGI calls). This study aimed to examine visits to primary health-care centers owing to similar symptoms (AGI visits) in the same area, to explore associations with precipitation, and to compare variability in AGI visits and AGI calls.

Methods

We obtained data covering six years (2007–2012) of daily AGI visits and studied their association with prior precipitation (0–28 days) using a distributed lag nonlinear Poisson regression model, adjusting for seasonal patterns and covariates. In addition, we studied the effects of prolonged wet and dry weather on AGI visits. We analyzed lagged short-term relations between AGI visits and AGI calls, and we studied differences in their seasonal patterns using a binomial regression model.

Results

The study period saw a total of 17,030 AGI visits, and the number of daily visits decreased on days when precipitation occurred. However, prolonged wet weather was associated with an elevated number of AGI visits. Differences in seasonality patterns were observed between AGI visits and AGI calls, as visits were relatively less frequent during winter and relatively more frequent in August, and only weak short-term relations were found.

Conclusion

AGI visits and AGI calls seems to partly reflect different types of AGI illnesses, and the patients’ choice of medical contact (in-person visits versus phone calls) appears to depend on current weather conditions. An association between prolonged wet weather and increased AGI visits supports the hypothesis that the drinking water is related to an increased risk of AGI illnesses.     

A test of the "sexy son" hypothesis: sons of polygynous collared flycatchers do not inherit their fathers' mating status

According to the original "sexy son" hypothesis, a female may benefit from pairing with an already-mated male despite a reduction in fecundity because her sons inherit their father's attractiveness. We used data from a long-term study of collared flycatchers (Ficedula albicollis) collected during 24 years to test this prediction. Our results show that the sons of polygynously mated females fledged in poor condition and therefore did not inherit their father's large forehead patch (a condition-dependent display trait) or mating status. From the female's perspective, polygynous pairing resulted in fewer recruited grandchildren than did a monogamous pairing. The reproductive value of sons did not outweigh the fecundity costs of polygyny because the low paternal care reduced the attractiveness of sons. When there are long-lasting parental effects on offspring attractiveness, costs of polygyny may include the production of nonsexy sons.     

Environmental enrichment promotes neural plasticity and cognitive ability in fish

Different kinds of experience during early life can play a significant role in the development of an animal''s behavioural phenotype. In natural contexts, this influences behaviours from anti-predator responses to navigation abilities. By contrast, for animals reared in captive environments, the homogeneous nature of their experience tends to reduce behavioural flexibility. Studies with cage-reared rodents indicate that captivity often compromises neural development and neural plasticity. Such neural and behavioural deficits can be problematic if captive-bred animals are being reared with the intention of releasing them as part of a conservation strategy. Over the last decade, there has been growing interest in the use of environmental enrichment to promote behavioural flexibility in animals that are bred for release. Here, we describe the positive effects of environmental enrichment on neural plasticity and cognition in juvenile Atlantic salmon (Salmo salar). Exposing fish to enriched conditions upregulated the forebrain expression of NeuroD1 mRNA and improved learning ability assessed in a spatial task. The addition of enrichment to the captive environment thus promotes neural and behavioural changes that are likely to promote behavioural flexibility and improve post-release survival.     

Localization of a Single Transglutaminase-Reactive Glutamine in the Third Domain of RAP, the α2-Macroglobulin Receptor-Associated Protein

The 39-kDa receptor-associated protein (RAP) is an intracellular glycoprotein that interacts with hitherto unknown sites in several members of the low-density-lipoprotein receptor gene family. Upon binding to these receptors, RAP inhibits all ligand interactions with the receptors. In the present study, the transglutaminase-catalyzed incorporation of radioactively labeled putrescine and a dansylated glutamine-containing peptide into human RAP has been studied. The results indicate the presence of both glutamine and lysine residues in RAP, accessible for transglutaminase cross-linking. Moreover, enzymatic digestion followed by sequence analysis of radiolabeled fractions demonstrated that Gln²⁶¹ acts as the amine acceptor site. This residue is located in the third domain of RAP and is conserved among the RAP interspecies homologues. Insertion of a reporter group into the protein could prove useful to assess ligand/receptor interactions.