Localized regulation of axonal RanGTPase controls retrograde injury signaling in peripheral nerve

Peripheral sensory neurons respond to axon injury by activating an importin-dependent retrograde signaling mechanism. How is this mechanism regulated? Here, we show that Ran GTPase and its associated effectors RanBP1 and RanGAP regulate the formation of importin signaling complexes in injured axons. A gradient of nuclear RanGTP versus cytoplasmic RanGDP is thought to be fundamental for the organization of eukaryotic cells. Surprisingly, we find RanGTP in sciatic nerve axoplasm, distant from neuronal cell bodies and nuclei, and in association with dynein and importin-alpha. Following injury, localized translation of RanBP1 stimulates RanGTP dissociation from importins and subsequent hydrolysis, thereby allowing binding of newly synthesized importin-beta to importin-alpha and dynein. Perturbation of RanGTP hydrolysis or RanBP1 blockade at axonal injury sites reduces the neuronal conditioning lesion response. Thus, neurons employ localized mechanisms of Ran regulation to control retrograde injury signaling in peripheral nerve.     

Food Selectivity and Diet Switch Can Explain the Slow Feeding of Herbivorous Coral-Reef Fishes during the Morning

Most herbivorous coral-reef fishes feed slower in the morning than in the afternoon. Given the typical scarcity of algae in coral reefs, this behavior seems maladaptive. Here we suggest that the fishes'' slow feeding during the morning is an outcome of highly selective feeding on scarcely found green algae. The rarity of the food requires longer search time and extended swimming tracks, resulting in lower bite rates. According to our findings by noon the fish seem to stop their search and switch to indiscriminative consumption of benthic algae, resulting in apparent higher feeding rates. The abundance of the rare preferable algae gradually declines from morning to noon and seems to reach its lowest levels around the switch time. Using in situ experiments we found that the feeding pattern is flexible, with the fish exhibiting fast feeding rates when presented with ample supply of preferable algae, regardless of the time of day. Analyses of the fish''s esophagus content corroborated our conclusion that their feeding was highly selective in the morning and non-selective in the afternoon. Modeling of the fishes'' behavior predicted that the fish should perform a diel diet shift when the preferred food is relatively rare, a situation common in most coral reefs found in a warm, oligotrophic ocean.     

Lipoprotein-associated phospholipase A(2) : review of its role as a marker and a potential participant in coronary endothelial dysfunction

The role of inflammation in atherosclerosis continues to emerge. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), a novel plasma biomarker, circulates in the blood bound mainly to low-density lipoprotein (LDL) and promotes vascular inflammation. Several epidemiological studies have shown that circulating levels of Lp-PLA(2) are an independent risk factor for cardiovascular events. Recent studies demonstrate that Lp-PLA(2) is also associated with endothelial dysfunction and early atherosclerosis. This review provides an overview of these studies, suggests plausible mechanisms for the association between endothelial dysfunction and Lp-PLA(2), and highlights future potential therapies.     

Flowers respond to pollinator sound within minutes by increasing nectar sugar concentration

Can plants sense natural airborne sounds and respond to them rapidly? We show that Oenothera drummondii flowers, exposed to playback sound of a flying bee or to synthetic sound signals at similar frequencies, produce sweeter nectar within 3 min, potentially increasing the chances of cross pollination. We found that the flowers vibrated mechanically in response to these sounds, suggesting a plausible mechanism where the flower serves as an auditory sensory organ. Both the vibration and the nectar response were frequency‐specific: the flowers responded and vibrated to pollinator sounds, but not to higher frequency sound. Our results document for the first time that plants can rapidly respond to pollinator sounds in an ecologically relevant way. Potential implications include plant resource allocation, the evolution of flower shape and the evolution of pollinators sound. Finally, our results suggest that plants may be affected by other sounds as well, including anthropogenic ones.     

Plants’ ability to sense and respond to airborne sound is likely to be adaptive: reply to comment by Pyke et al

Ecol. Lett. 22, 2019, 1483 demonstrated, for the first time, a rapid response of a plant to the airborne sounds of pollinators. Pyke et al. argue that this response is unlikely to be adaptive. Here we clarify some misunderstandings, and demonstrate the potential adaptive value using theoretical modelling and field observations.     

Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in middle eastern families

Background

Identification of genes responsible for medically important traits is a major challenge in human genetics. Due to the genetic heterogeneity of hearing loss, targeted DNA capture and massively parallel sequencing are ideal tools to address this challenge. Our subjects for genome analysis are Israeli Jewish and Palestinian Arab families with hearing loss that varies in mode of inheritance and severity.

Results

A custom 1.46 MB design of cRNA oligonucleotides was constructed containing 246 genes responsible for either human or mouse deafness. Paired-end libraries were prepared from 11 probands and bar-coded multiplexed samples were sequenced to high depth of coverage. Rare single base pair and indel variants were identified by filtering sequence reads against polymorphisms in dbSNP132 and the 1000 Genomes Project. We identified deleterious mutations in CDH23, MYO15A, TECTA, TMC1, and WFS1. Critical mutations of the probands co-segregated with hearing loss. Screening of additional families in a relevant population was performed. TMC1 p.S647P proved to be a founder allele, contributing to 34% of genetic hearing loss in the Moroccan Jewish population.

Conclusions

Critical mutations were identified in 6 of the 11 original probands and their families, leading to the identification of causative alleles in 20 additional probands and their families. The integration of genomic analysis into early clinical diagnosis of hearing loss will enable prediction of related phenotypes and enhance rehabilitation. Characterization of the proteins encoded by these genes will enable an understanding of the biological mechanisms involved in hearing loss.     

In vivo characteristics of targeted drug-carrying filamentous bacteriophage nanomedicines

Background

The interest in introducing ecologically-clean, and efficient enzymes into modern industry has been growing steadily. However, difficulties associated with controlling their orientation, and maintaining their selectivity and reactivity is still a significant obstacle. We have developed precise immobilization of biomolecules, while retaining their native functionality, and report a new, fast, easy, and reliable procedure of protein immobilization, with the use of Adenylate kinase as a model system.

Methods

Self-assembled monolayers of hexane-1,6-dithiol were formed on gold surfaces. The monolayers were characterized by contact-angle measurements, Elman-reagent reaction, QCM, and XPS. A specifically designed, mutated Adenylate kinase, where cysteine was inserted at the 75 residue, and the cysteine at residue 77 was replaced by serine, was used for attachment to the SAM surface via spontaneously formed disulfide (S-S) bonds. QCM, and XPS were used for characterization of the immobilized protein layer. Curve fitting in XPS measurements used a Gaussian-Lorentzian function.

Results and Discussion

Water contact angle (65-70°), as well as all characterization techniques used, confirmed the formation of self-assembled monolayer with surface SH groups. X-ray photoelectron spectroscopy showed clearly the two types of sulfur atom, one attached to the gold (triolate) and the other (SH/S-S) at the ω-position for the hexane-1,6-dithiol SAMs. The formation of a protein monolayer was confirmed using XPS, and QCM, where the QCM-determined amount of protein on the surface was in agreement with a model that considered the surface area of a single protein molecule. Enzymatic activity tests of the immobilized protein confirmed that there is no change in enzymatic functionality, and reveal activity ~100 times that expected for the same amount of protein in solution.

Conclusions

To the best of our knowledge, immobilization of a protein by the method presented here, with the resulting high enzymatic activity, has never been reported. There are many potential applications for selective localization of active proteins at patterned surfaces, for example, bioMEMS (MEMS - Micro-Electro-Mechanical Systems. Due to the success of the method, presented here, it was decided to continue a research project of a biosensor by transferring it to a high aspect ratio platform - nanotubes.