Selective loss of glycogen synthase kinase-3α in birds reveals distinct roles for GSK-3 isozymes in tau phosphorylation

Mammalian glycogen synthase kinase-3 (GSK-3), a critical regulator in neuronal signaling, cognition, and behavior, exists as two isozymes GSK-3α and GSK-3β. Their distinct biological functions remains largely unknown. Here, we examined the evolutionary significance of each of these isozymes. Surprisingly, we found that unlike other vertebrates that harbor both GSK-3 genes, the GSK-3α gene is missing in birds. GSK-3-mediated tau phosphorylation was significantly lower in adult bird brains than in mouse brains, a phenomenon that was reproduced in GSK-3α knockout mouse brains. Tau phosphorylation was detected in brains from bird embryos suggesting that GSK-3 isozymes play distinct roles in tau phosphorylation during development. Birds are natural GSK-3α knockout organisms and may serve as a novel model to study the distinct functions of GSK-3 isozymes.     

Fluorodeoxyuridine Improves Caenorhabditis elegans Proteostasis Independent of Reproduction Onset

Protein homeostasis (proteostasis) networks are dynamic throughout the lifespan of an organism. During Caenorhabditis elegans adulthood, the maintenance of metastable proteins and the activation of stress responses are inversely associated with germline stem cell proliferation. Here, we employed the thymidylate synthase inhibitor 5-fluoro-2′-deoxyuridine (FUdR) to chemically inhibit reproduction, thus allowing for examination of the interplay between reproduction and somatic proteostasis. We found that treatment with FUdR modulates proteostasis decline both before and after reproduction onset, such that effective induction of the heat shock response was maintained during adulthood and that metastable temperature-sensitive mutant phenotypes were rescued under restrictive conditions. However, FUdR treatment also improved the folding capacity of germline- and gonadogenesis-defective mutants, suggesting that proteostasis modulation by FUdR is independent of germline stem cell proliferation or inhibition of reproduction. Our data, therefore, indicate that FUdR converges on alternative regulatory signals that modulate C. elegans proteostasis capacity during development and adulthood.     

A possible relation between new neuronal recruitment and migratory behavior in Acrocephalus warblers

Evidence suggests a possible correlation between learning abilities of adults and new neuronal recruitment into their brains. The hypothesis is that this brain plasticity enables animals to adapt to environmental changes. We examined whether there are differences in neuronal recruitment between resident and migrant birds. We predicted that migrants, which are more exposed to spatial changes than residents, will recruit more new neurons. To test this, we compared neuronal recruitment in two closely related bird species ‐ the migrant reed warbler (Acrocephalus scirpaceus), and the resident Clamorous warbler (A. Stentoreus) ‐ during spring, summer, and autumn. Wild birds were caught, treated with BrdU and sacrificed five weeks later. New neurons were recorded in the Hippocampus and Nidopallium caudolateral. The results support our hypothesis, as more new neurons were found in the migrant species, in both brain regions and all seasons. We suggest that this phenomenon enables enhanced navigational abilities, which are required for the migratory lifestyle. However, in contrast to our hypothesis, in spring we found less new neurons in adults of both species, as compared to other seasons. We suggest that in spring, when birds settle in breeding territories, they require less spatial skills, and this might enable to reduce the cost of neuronal recruitment, as reflected by less new neurons in their brains. We also found age differences, with overall higher neuronal recruitment in juveniles. Finally, we advocate the importance of studying wild populations, for a better understanding of the adaptive significance of neuronal replacement in the vertebrate brain. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1194–1209, 2014     

Linear Growth and Final Height Characteristics in Adolescent Females with Anorexia Nervosa

Objective

Growth retardation is an established complication of anorexia nervosa (AN). However, findings concerning final height of AN patients are inconsistent. The aim of this study was to assess these phenomena in female adolescent inpatients with AN.

Methods

We retrospectively studied all 211 female adolescent AN patients hospitalized in an inpatient eating disorders department from 1/1/1987 to 31/12/99. Height and weight were assessed at admission and thereafter routinely during hospitalization and follow-up. Final height was measured in 69 patients 2–10 years after discharge. Pre-morbid height data was available in 29 patients.

Results

Patients’ height standard deviation scores (SDS) on admission (−0.285±1.0) and discharge (−0.271±1.02) were significantly (p<0.001) lower than expected in normal adolescents. Patients admitted at age ≤13 years, or less than 1 year after menarche, were more severely growth-impaired than patients admitted at an older age, (p = 0.03). Final height SDS, available for 69 patients, was −0.258±1.04, significantly lower than expected in a normal population (p = 0.04), and was more severely compromised in patients who were admitted less than 1 year from their menarche. In a subgroup of 29 patients with complete growth data (pre-morbid, admission, discharge, and final adult height), the pre-morbid height SDS was not significantly different from the expected (−0.11±1.1), whereas heights at the other time points were significantly (p = 0.001) lower (−0.56±1.2, −0.52±1.2, and −0.6±1.2, respectively).

Conclusions

Our findings suggest that whereas the premorbid height of female adolescent AN patients is normal, linear growth retardation is a prominent feature of their illness. Weight restoration is associated with catch-up growth, but complete catch-up is often not achieved.     

Correlating ribosome function with high-resolution structures

Ribosome research has undergone astonishing progress in recent years. Crystal structures have shed light on the functional properties of the translation machinery and revealed how the striking architecture of the ribosome is ingeniously designed as the framework for its unique capabilities: precise decoding, substrate-mediated peptide-bond formation and efficient polymerase activity. New findings include the two concerted elements of tRNA translocation: sideways shift and a ribosomal-navigated rotatory motion; the dynamics of the nascent-chain exit tunnel and the shelter formed by the ribosome-bound trigger-factor, which acts as a chaperone to prevent nascent-chain aggregation and misfolding. The availability of these structures has also illuminated the action, selectivity, resistance and synergism of antibiotics that target ribosomes.