Long Lasting Protein Synthesis- and Activity-Dependent Spine Shrinkage and Elimination after Synaptic Depression

Neuronal circuits modify their response to synaptic inputs in an experience-dependent fashion. Increases in synaptic weights are accompanied by structural modifications, and activity dependent, long lasting growth of dendritic spines requires new protein synthesis. When multiple spines are potentiated within a dendritic domain, they show dynamic structural plasticity changes, indicating that spines can undergo bidirectional physical modifications. However, it is unclear whether protein synthesis dependent synaptic depression leads to long lasting structural changes. Here, we investigate the structural correlates of protein synthesis dependent long-term depression (LTD) mediated by metabotropic glutamate receptors (mGluRs) through two-photon imaging of dendritic spines on hippocampal pyramidal neurons. We find that induction of mGluR-LTD leads to robust and long lasting spine shrinkage and elimination that lasts for up to 24 hours. These effects depend on signaling through group I mGluRs, require protein synthesis, and activity. These data reveal a mechanism for long lasting remodeling of synaptic inputs, and offer potential insights into mental retardation.     

Prolactin and vasoinhibins: Endogenous players in diabetic retinopathy

Diabetic retinopathy is a disease of the retinal microvasculature that develops as a complication of diabetes mellitus and constitutes a major cause of blindness in adults of all ages. Diabetic retinopathy is characterized by the loss of capillary cells leading to increased vasopermeability, ischemia, and hypoxia that trigger the excessive formation of new blood vessels in the retina. The influence of the pituitary gland in the pathophysiology of diabetic retinopathy was recognized nearly six decades ago, but the contribution of pituitary hormones to this disease remains unclear. Recent studies have shown that the pituitary hormone prolactin is proteolytically cleaved to vasoinhibins, a family of peptides with potent antivasopermeability, vasoconstrictive, and antiangiogenic actions that can protect the eye against the deleterious effects of the diabetic state. In this review, we summarize what is known about the changes in the circulating levels of prolactin and vasoinhibins during diabetes and diabetic retinopathy as well as the implications of these changes for the development and progression of the disease with particular attention to hyperprolactinemia in pregnancy and postpartum. We discuss the effects of prolactin and vasoinhibins that may impact diabetic retinopathy and suggest these hormones as important targets for therapeutic interventions.     

Reactive oxygen species participate in the p38-mediated apoptosis induced by potassium deprivation and staurosporine in cerebellar granule neurons

Apoptosis induced by low potassium (K5) or staurosporine in cerebellar granule neurons triggers an increase in reactive oxygen species (ROS) levels. ROS inhibition by antioxidants or inhibitors of the NADPH oxidase (NOX) activity reduces the apoptosis induced by both stimuli. It has been reported that JNK mediates the apoptosis induced by K5 but not by staurosporine. No information is available about the role of other signaling pathways such as p38 in staurosporine-induced apoptosis, and whether p38 activation could be related to ROS levels induced by both K5 and staurosporine. Here, we explored this possibility and found that K5 activates p38 and ATF2 and that the inhibition of p38 activity prevents the apoptosis induced by this treatment. We also found that p38 is downstream of ROS generation induced by K5. On the other hand, staurosporine promotes a sustained activation of p38. We found that p38 inhibition markedly decreases ROS generation, NOX activity and apoptosis induced by staurosporine. Furthermore, antioxidants inhibit p38 activation induced by staurosporine. These data indicate that apoptosis induced by both K5 and staurosporine is dependent on p38 activation, which is mediated by ROS. In addition, p38 activation by staurosporine induces a further production of ROS through NOX activation.     

Seed viability in Bursera: The relative contribution of environmental variation and phylogenetic relatedness

Seed viability is a crucial factor affecting the regeneration potential of seeds, but there is little information on how this trait varies across habitats, populations, species, and higher taxonomic units, as well as on the relative contributions of evolutionary history and environmental factors to this trait. Here we evaluate the relative contributions of climatic variability and phylogenetic history to seed viability in a group of species of Bursera that belong to two distinct lineages (sections Bursera and Bullockia). We analyzed 39 seed lots from 11 species, comprising several populations and 2 years, and estimated embryo presence and viability in each lot. We examined spatial and temporal variation in viability and analyzed the relationship between this trait and water availability using regression models; the amount of phylogenetic signal in seed viability was also estimated. Mean seed viability was consistently low in species of section Bursera (mean 29.7%) and substantially higher in species of section Bullockia (mean 79.6%). A high proportion of unviable seeds were embryoless. Spatial and temporal variation in seed viability was significant but usually low among populations and species. The relationship between water availability and seed viability was not significant, but the amount of phylogenetic signal in seed viability was high and significant (λ = 0.74). There is a clear difference in seed viability among the two sections of Bursera. During the split of the two sections in the middle Eocene, the reorganization of the genome may have involved changes in fruit morphology associated with differences in parthenocarpy among them.     

The cattle tick antigen, Bm95, expressed in Pichia pastoris contains short chains of N- and O-glycans

Bm95 is an antigen isolated from Boophilus microplus strains with low susceptibility to antibodies developed in cattle vaccinated with the recombinant Bm86 antigen (Gavac, HeberBiotec S.A., Cuba). It is a Bm86-like surface protein, which by similarity contains seven EGF-like domains and a lipid-binding GPI-anchor site at the C-terminal region. The primary structure of the recombinant (rBm95) protein expressed in Pichia pastoris was completely verified by LC/MS. The four potential glycosylation sites (Asn 122, 163, 329, and 363) are glycosylated partially with short N-glycans, from Man(5)GlcNAc(2) to Man(9)GlcNAc(2) of which, Man(8-9)GlcNAc(2) were the most abundant. O-Glycopeptides are distributed mostly towards the protein N-terminus. While the first N-glycosylated site (Asn(122)) is located between EGF-like domains 2 and 3, where the O-glycopeptides were found, two other N-glycosylated sites (Asn(329) and Asn(363)) are located between EGF-like domains 5 and 6, a region devoid of O-glycosylated Ser or Thr.     

Volatile compounds from beneficial or pathogenic bacteria differentially regulate root exudation,transcription of iron transporters,and defense signaling pathways in <Emphasis Type="Italic">Sorghum bicolor</Emphasis>

Key message

Our results show that Sorghum bicolor is able to recognize bacteria through its volatile compounds and differentially respond to beneficial or pathogens via eliciting nutritional or defense adaptive traits.

Abstract

Plants establish beneficial, harmful, or neutral relationships with bacteria. Plant growth promoting rhizobacteria (PGPR) emit volatile compounds (VCs), which may act as molecular cues influencing plant development, nutrition, and/or defense. In this study, we compared the effects of VCs produced by bacteria with different lifestyles, including Arthrobacter agilis UMCV2, Bacillus methylotrophicus M4-96, Sinorhizobium meliloti 1021, the plant pathogen Pseudomonas aeruginosa PAO1, and the commensal rhizobacterium Bacillus sp. L2-64, on S. bicolor. We show that VCs from all tested bacteria, except Bacillus sp. L2-64, increased biomass and chlorophyll content, and improved root architecture, but notheworthy A. agilis induced the release of attractant molecules, whereas P. aeruginosa activated the exudation of growth inhibitory compounds by roots. An analysis of the expression of iron-transporters SbIRT1, SbIRT2, SbYS1, and SbYS2 and genes related to plant defense pathways COI1 and PR-1 indicated that beneficial, pathogenic, and commensal bacteria could up-regulate iron transporters, whereas only beneficial and pathogenic species could induce a defense response. These results show how S. bicolor could recognize bacteria through their volatiles profiles and highlight that PGPR or pathogens can elicit nutritional or defensive traits in plants.

     

New ester derivatives of dehydroepiandrosterone as 5α-reductase inhibitors

The aim of this study was to synthesize different ester derivatives of dehydroepiandrosterone with therapeutic potential as antiandrogens.The biological effect of these steroids was demonstrated in in vivo as well as in vitro experiments. In the in vivo experiments, we measured the activity of seven steroids on the weight of the prostate and seminal vesicles of gonadectomized hamsters treated with testosterone. For the in vitro studies, we determined the IC₅₀ values by measuring the concentration of the steroidal derivatives that inhibits 50% of the activity of 5α-reductase present in human prostate and also its binding capacity to the androgen receptors (AR) obtained from rat’s prostate cytosol. The results from these experiments indicated that compounds 7 5α,6β-dibromo-3β-propanoyloxyandrostan-17-one, 8 5α,6β-dibromo-3β-butanoyloxyandrostan-17-one and 9 5α,6β-dibromo-3β-(3′-oxapentanoyloxy)-androstan-17-one, significantly decreased the weight of the prostate and seminal vesicles as compared to testosterone treated animals; this reduction of the weight of these glands was comparable to that produced by Finasteride 11. On the other hand, compounds 4 3β-acetoxyandrost-5-en-17-one, 5 3β-hexanoyloxyandrost-5-en-17-one 6 3β-(3′-oxapentanoyloxy)-androst-5-en-17-one, 7 and 12 dehydroepiandrosterone, (commercially available) inhibited the enzyme 5α-reductase. Compounds 4, 5, 6, 8 and 9 (IC₅₀ values of 5.2 ± 1.2, 0.049 ± 0.002, 6.4 ± 1.1, 0.10 ± 0.045, and 6.8 ± 0.9 nM, respectively) exhibited the highest inhibitory activity. However, none of these compounds binds to the AR.     

Synaptic competition in structural plasticity and cognitive function

Connections between neurons can undergo long-lasting changes in synaptic strength correlating with changes in structure. These events require the synthesis of new proteins, the availability of which can lead to cooperative and competitive interactions between synapses for the expression of plasticity. These processes can occur over limited spatial distances and temporal periods, defining dendritic regions over which activity may be integrated and could lead to the physical rewiring of synapses into functional groups. Such clustering of inputs may increase the computational power of neurons by allowing information to be combined in a greater than additive manner. The availability of new proteins may be a key modulatory step towards activity-dependent, long-term growth or elimination of spines necessary for remodelling of connections. Thus, the aberrant growth or shrinkage of dendritic spines could occur if protein levels are misregulated. Indeed, such perturbations can be seen in several mental retardation disorders, wherein either too much or too little protein translation exists, matching an observed increase or decrease in spine density, respectively. Cellular events which alter protein availability could relieve a constraint on synaptic competition and disturb synaptic clustering mechanisms. These changes may be detrimental to modifications in neural circuitry following activity.