Destabilization of the neuromuscular junction by proteolytic cleavage of agrin results in precocious sarcopenia

Etiology and pathogenesis of sarcopenia, the progressive decline in skeletal muscle mass and strength that occurs with aging, are still poorly understood. We recently found that overexpression of the neural serine protease neurotrypsin in motoneurons resulted in the degeneration of their neuromuscular junctions (NMJ) within days. Therefore, we wondered whether neurotrypsin-dependent NMJ degeneration also affected the structure and function of the skeletal muscles. Using histological and functional analyses of neurotrypsin-overexpressing and neurotrypsin-deficient mice, we found that overexpression of neurotrypsin in motoneurons installed the full sarcopenia phenotype in young adult mice. Characteristic muscular alterations included a reduced number of muscle fibers, increased heterogeneity of fiber thickness, more centralized nuclei, fiber-type grouping, and an increased proportion of type I fibers. As in age-dependent sarcopenia, excessive fragmentation of the NMJ accompanied the muscular alterations. These results suggested the destabilization of the NMJ through proteolytic cleavage of agrin at the onset of a pathogenic pathway ending in sarcopenia. Studies of neurotrypsin-deficient and agrin-overexpressing mice revealed that old-age sarcopenia also develops without neurotrypsin and is not prevented by elevated levels of agrin. Our results define neurotrypsin- and age-dependent sarcopenia as the common final outcome of 2 etiologically distinct entities.     

Agonistic behavior and feeding competition in the largest piranha species,Pygocentrus piraya,in a zoo

Journal of Ethology - In the wild, piranhas are thought to feed in groups. Previous studies on piranhas in aquariums have variously observed either social attraction or aggressive dominance. The...     

Long-term changes in forest response to extreme atmospheric dryness

Atmospheric dryness, as indicated by vapor pressure deficit (VPD), has a strong influence on forest greenhouse gas exchange with the atmosphere. In this study, we used long-term (10–30 years) net ecosystem productivity (NEP) measurements from 60 forest sites across the world (1003 site-years) to quantify long-term changes in forest NEP resistance and NEP recovery in response to extreme atmospheric dryness. We tested two hypotheses: first, across sites differences in NEP resistance and NEP recovery of forests will depend on both the biophysical characteristics (i.e., leaf area index [LAI] and forest type) of the forest as well as on the local meteorological conditions of the site (i.e., mean VPD of the site), and second, forests experiencing an increasing trend in frequency and intensity of extreme dryness will show an increasing trend in NEP resistance and NEP recovery over time due to emergence of long-term ecological stress memory. We used a data-driven statistical learning approach to quantify NEP resistance and NEP recovery over multiple years. Our results showed that forest types, LAI, and median local VPD conditions explained over 50% of variance in both NEP resistance and NEP recovery, with drier sites showing higher NEP resistance and NEP recovery compared to sites with less atmospheric dryness. The impact of extreme atmospheric dryness events on NEP lasted for up to 3 days following most severe extreme events in most forests, indicated by an NEP recovery of less than 100%. We rejected our second hypothesis as we found no consistent relationship between trends of extreme VPD with trends in NEP resistance and NEP recovery across different forest sites, thus an increase in atmospheric dryness as it is predicted might not increase the resistance or recovery of forests in terms of NEP.     

The effect of cryptic female choice on sex allocation in simultaneous hermaphrodites

Sex allocation theory for simultaneous hermaphrodites has focused primarily on the effects of sperm competition, but the role of mate choice has so far been neglected. We present a model to study the coevolution of cryptic female choice and sex allocation in simultaneous hermaphrodites. We show that the mechanism of cryptic female choice has a strong effect on the evolutionary outcome: if individuals remove a fixed proportion of less-preferred sperm, the optimal sex allocation is more female biased (i.e. more biased towards egg production) than without cryptic female choice; conversely, if a fixed amount of sperm is removed, sex allocation is less female-biased than without cryptic female choice, and can easily become male biased (i.e. biased towards sperm production). Under male-biased sex allocation, hermaphroditism can become unstable and the population can split into pure males and hermaphrodites with a female-biased allocation. We discuss the idea that the evolution of sex allocation may depend on the outcome of sexual conflict over the fate of received sperm: the sperm donor may attempt to manipulate or by-pass cryptic female choice and the sperm recipient is expected to resist such manipulation. We conclude that cryptic female choice can have a strong influence on sex allocation in simultaneous hermaphrodites and strongly encourage empirical work on this question.     

Kv4.2 is a locus for PKC and ERK/MAPK cross-talk

Transient outward K+ currents are particularly important for the regulation of membrane excitability of neurons and repolarization of action potentials in cardiac myocytes. These currents are modulated by PKC (protein kinase C) activation, and the K+- channel subunit Kv4.2 is a major contributor to these currents. Furthermore, the current recorded from Kv4.2 channels expressed in oocytes is reduced by PKC activation. The mechanism underlying PKC regulation of Kv4.2 currents is unknown. In the present study, we determined that PKC directly phosphorylates the Kv4.2 channel protein. In vitro phosphorylation of the intracellular N- and C-termini of Kv4.2 GST (glutathione transferase) tagged fusion protein revealed that the C-terminal of Kv4.2 was phosphorylated by PKC, whereas the N-terminal was not. Amino acid mapping and site-directed mutagenesis revealed that the phosphorylated residues on the Kv4.2 C-terminal were Ser447 and Ser537. A phospho-site-specific antibody showed that phosphorylation at the Ser537 site was increased in the hippocampus in response to PKC activation. Surface biotinylation experiments revealed that mutation to alanine of both Ser447 and Ser537 in order to block phosphorylation at both of the PKC sites increased surface expression compared with wild-type Kv4.2. Electrophysiological recordings of the wild-type and both the alanine and aspartate mutant Kv4.2 channels expressed with KChIP3 (Kv4 channel-interacting protein 3) revealed no significant difference in the half-activation or half-inactivation voltage of the channel. Interestingly, Ser537 lies within a possible ERK (extracellular-signal-regulated kinase)/MAPK (mitogen-activated protein kinase) recognition (docking) domain in the Kv4.2 C-terminal sequence. We found that phosphorylation of Kv4.2 by PKC enhanced ERK phosphorylation of the channel in vitro. These findings suggest the possibility that Kv4.2 is a locus for PKC and ERK cross-talk.     

The demographic drivers of local population dynamics in two rare migratory birds

The exchange of individuals among populations can have strong effects on the dynamics and persistence of a given population. Yet, estimation of immigration rates remains one of the greatest challenges for animal demographers. Little empirical knowledge exists about the effects of immigration on population dynamics. New integrated population models fitted using Bayesian methods enable simultaneous estimation of fecundity, survival and immigration, as well as the growth rate of a population of interest. We applied this novel analytical framework to the demography of two populations of long-distance migratory birds, hoopoe Upupa epops and wryneck Jynx torquilla, in a study area in south-western Switzerland. During 2002–2010, the hoopoe population increased annually by 11%, while the wryneck population remained fairly stable. Apparent juvenile and adult survival probability was nearly identical in both species, but fecundity and immigration were slightly higher in the hoopoe. Hoopoe population growth rate was strongly correlated with juvenile survival, fecundity and immigration, while that of wrynecks strongly correlated only with immigration. This indicates that demographic components impacting the arrival of new individuals into the populations were more important for their dynamics than demographic components affecting the loss of individuals. The finding that immigration plays a crucial role in the population growth rates of these two rare species emphasizes the need for a broad rather than local perspective for population studies, and the development of wide-scale conservation actions.     

Understanding the Sequence Specificity of tRNA Binding to Elongation Factor Tu using tRNA Mutagenesis

Measuring the binding affinities of 42 single-base-pair mutants in the acceptor and TΨC stems of Saccharomyces cerevisiae tRNA^Phe to Thermus thermophilus elongation factor Tu (EF-Tu) revealed that much of the specificity for tRNA occurs at the 49-65, 50-64, and 51-63 base pairs. Introducing the same mutations at the three positions into Escherichia coli tRNA_CAG^Leu resulted in similar changes in binding affinity. Swapping the three pairs from several E. coli tRNAs into yeast tRNA^Phe resulted in chimeras with EF-Tu binding affinities similar to those for the donor tRNA. Finally, analysis of double- and triple-base-pair mutants of tRNA^Phe showed that the thermodynamic contributions at the three sites are additive, permitting reasonably accurate prediction of the EF-Tu binding affinity for all E. coli tRNAs. Thus, it appears that the thermodynamic contributions of three base pairs in the TΨC stem primarily account for tRNA binding specificity to EF-Tu.     

Are plant communities on the Canary Islands resistant to plant invasion?

Oceanic islands are renowned for their unique flora and high levels of endemism. Native island plants, however, are imperilled by non-native species that can become invasive by outcompeting natives. The threat of native island assemblages generally increases with isolation and the number of endemics featured, but also with human-associated disturbance and land use. Based on this, the Canary Island native plant systems should be highly threatened by invasives, similar to other oceanic islands globally. However, Canarian native plant systems are only weakly infiltrated and are rarely directly threatened by invasive plants. Further, highly disturbed areas, usually among the first colonized by invasives on islands, are recolonized here by natives. Based on this, we postulate four hypotheses (climatic filter, well-preservation status, human legacy and permanent colonization) for explaining this unusual behaviour of plant systems on the Canary Islands, providing an opportunity to understand the drivers and processes behind invasion into plant communities on islands.     

Functional Impact of 14 Single Nucleotide Polymorphisms Causing Missense Mutations of Human α7 Nicotinic Receptor

The α7nicotinic receptor (nAChR) is a major subtype of the nAChRs in the central nervous system, and the receptor plays an important role in brain function. In the dbSNP database, there are 55 single nucleotide polymorphisms (SNPs) that cause missense mutations of the human α7nAChR in the coding region. In this study, we tested the impact of 14 SNPs that cause missense mutations in the agonist binding site or the coupling region between binding site and channel gate on the receptor function. The wild type or mutant receptors were expressed or co-expressed in Xenopus oocytes, and the agonist-induced currents were tested using two-electrode voltage clamp. Our results demonstrated that 6 mutants were nonfunctional, 4 mutants had reduced current expression, and 1 mutants altered ACh and nicotine efficacy in the opposite direction, and one additional mutant had slightly reduced agonist sensitivity. Interestingly, the function of most of these nonfunctional mutants could be rescued by α7nAChR positive allosteric modulator PNU-120596 and agonist-PAM 4BP-TQS. Finally, when coexpressed with the wild type, the nonfunctional mutants could also influence the receptor function. These changes of the receptor properties by the mutations could potentially have an impact on the physiological function of the α7nAChR-mediated cholinergic synaptic transmission and anti-inflammatory effects in the human SNP carriers. Rescuing the nonfunctional mutants could provide a novel way to treat the related disorders.