High genetic diversity, phenotypic plasticity, and invasive potential of a recently introduced calcareous sponge, fast spreading across the Atlanto‑Mediterranean basin

16 páginas, 6 tablas, 8 figuras.Sponges are considered poor invaders, and no genetic studies on introduced sponges have been performed up to now. Paraleucilla magna is the first calcareous sponge introduced to the Mediterranean and Northeastern Atlantic. The study aimed at investigating the genetic makeup and connectivity of the introduced populations of P. magna and at exploring signs of local phenotypic adaptation, to gain insight on the species invasive potential. Ten populations along the species introduction range (Brazil, Açores, Madeira, and continental Europe) were genetically characterized by using nine microsatellite markers. Most populations were genetically structured as suggested by significant Dst and Fst values, significant differences among populations (AMOVA) and the presence of private alleles. The analyzed populations belonged to three genetically homogeneous groups (K) according to the Bayesian algorithm (structure software) and the UPGMA dendrogram. Genetic diversity within populations was higher than expected. Recurrent introductions of non-randomly selected individuals from the native sources may have contributed to the heterozygote deficit found in all populations by forming pedigree structures with mating among relatives. Moreover, the species biological cycle was monitored in a population established on native Mediterranean assemblages (41°40′27″N, 2°47′25″E) and compared with the species cycle in other habitats. Contrasting life spans, growth habits, and reproduction cycles, depending on the habitat conditions, were recorded. To summarize, high genetic diversity, phenotypic local adaptation, and high reproduction rates altogether allow predicting the fast proliferation of P. magna in newly colonized regions and point to its strong invasive potential.This study has been partially funded by MARSYMBIOMICS project ref. CTM2013-43287-P (Spanish Ministry of Economy and Competitiveness (MINECO)—FECYT agency, and Consolidate Group Award 2009-SGR655 (Generalitat of Catalonian) to MJU. MG has benefited from a FPU fellowship from the Spanish MINECO and JF from a Marie Curie (EU) fellowship, associated, respectively, with the BENTHOMICS and BIOCAPITAL projects to MJU.Peer reviewe

Synaptic mechanisms of pattern completion in the hippocampal CA3 network

The hippocampal CA3 region plays a key role in learning and memory. Recurrent CA3–CA3 synapses are thought to be the subcellular substrate of pattern completion. However, the synaptic mechanisms of this network computation remain enigmatic. To investigate these mechanisms, we combined functional connectivity analysis with network modeling. Simultaneous recording fromup to eight CA3 pyramidal neurons revealed that connectivity was sparse, spatially uniform, and highly enriched in disynaptic motifs (reciprocal, convergence,divergence, and chain motifs). Unitary connections were composed of one or two synaptic contacts, suggesting efficient use of postsynaptic space. Real-size modeling indicated that CA3 networks with sparse connectivity, disynaptic motifs, and single-contact connections robustly generated pattern completion.Thus, macro- and microconnectivity contribute to efficient memory storage and retrieval in hippocampal networks

Diversity of methicillin-resistant coagulase-negative Staphylococcus spp. and methicillin-resistant Mammaliicoccus spp. isolated from ruminants and New World camelids

Information about livestock carrying methicillin-resistant coagulase-negative staphylococci and mammaliicocci (MRCoNS/MRM) is scarce. The study was designed to gain knowledge of the prevalence, the phenotypic and genotypic antimicrobial resistance and the genetic diversity of MRCoNS/MRM originating from ruminants and New World camelids. In addition, a multi-locus sequence typing scheme for the characterization of Mammaliicoccus (formerly Staphylococcus) sciuri was developed. The study was conducted from April 2014 to January 2017 at the University Clinic for Ruminants and the Institute of Microbiology at the University of Veterinary Medicine Vienna. Seven hundred twenty-three nasal swabs originating from ruminants and New World camelids with and without clinical signs were examined. After isolation, MRCoNS/MRM were identified by MALDI-TOF, rpoB sequencing and typed by DNA microarray-based analysis and PCR. Antimicrobial susceptibility testing was conducted by agar disk diffusion. From all 723 nasal swabs, 189 MRCoNS/MRM were obtained. Members of the Mammaliicoccus (M.) sciuri group were predominant (M. sciuri (n = 130), followed by M. lentus (n = 43), M. fleurettii (n = 11)). In total, 158 out of 189 isolates showed phenotypically a multi-resistance profile. A seven-loci multi-locus sequence typing scheme for M. sciuri was developed. The scheme includes the analysis of internal segments of the house-keeping genes ack, aroE, ftsZ, glpK, gmk, pta1 and tpiA. In total, 28 different sequence types (STs) were identified among 92 selected M. sciuri isolates. ST1 was the most prevalent ST (n = 35), followed by ST 2 (n = 15), ST3 and ST5 (each n = 5), ST4 (n = 3), ST6, ST7, ST8, ST9, ST10 and ST11 (each n = 2)

Munc18 and Munc13 regulate early neurite outgrowth

Background information. During development, growth cones of outgrowing neurons express proteins involved in vesicular secretion, such as SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) proteins, Munc13 and Munc18. Vesicles are known to fuse in growth cones prior to synapse formation, which may contribute to outgrowth

STRASSE: A Silicon Tracker for Quasi-free Scattering Measurements at the RIBF

STRASSE (Silicon Tracker for RAdioactive nuclei Studies at SAMURAI Experiments) is a new detection system under construction for quasi-free scattering (QFS) measurements at 200-250 MeV/nucleon at the RIBF facility of the RIKEN Nishina Center. It consists of a charged-particle silicon tracker coupled with a dedicated thick liquid hydrogen target (up to 150-mm long) in a compact geometry to fit inside large scintillator or germanium arrays. Its design was optimized for two types of studies using QFS: missing-mass measurements and in-flight prompt $\gamma$-ray spectroscopy. This article describes (i) the resolution requirements needed to go beyond the sensitivity of existing systems for these two types of measurements, (ii) the conceptual design of the system using detailed simulations of the setup and (iii) its complete technical implementation and challenges. The final tracker aims at a sub-mm reaction vertex resolution and is expected to reach a missing-mass resolution below 2 MeV in $\sigma$ for $(p,2p)$ reactions when combined with the CsI(Na) CATANA array.Comment: 25 pages, 29 figure

Myosin V regulates synaptopodin clustering and localization in the dendrites of hippocampal neurons

The spine apparatus (SA) is an endoplasmic reticulum-related organelle that is present in a subset of dendritic spines in cortical and pyramidal neurons, and plays an important role in Ca2+ homeostasis and dendritic spine plasticity. The protein synaptopodin is essential for the formation of the SA and is widely used as a maker for this organelle. However, it is still unclear which factors contribute to its localization at selected synapses, and how it triggers local SA formation. In this study, we characterized development, localization and mobility of synaptopodin clusters in hippocampal primary neurons, as well as the molecular dynamics within these clusters. Interestingly, synaptopodin at the shaftassociated clusters is less dynamic than at spinous clusters. We identify the actin-based motor proteins myosin V (herein referring to both the myosin Va and Vb forms) and VI as novel interaction partners of synaptopodin, and demonstrate that myosin V is important for the formation and/or maintenance of the SA. We found no evidence of active microtubule-based transport of synaptopodin. Instead, new clusters emerge inside spines, which we interpret as the SA being assembled on-site

Microsecond Isomer at the N=20 Island of Shape Inversion Observed at FRIB

Excited-state spectroscopy from the first Facility for Rare Isotope Beams (FRIB) experiment is reported. A 24(2)-$\mu$s isomer was observed with the FRIB Decay Station initiator (FDSi) through a cascade of 224- and 401-keV $\gamma$ rays in coincidence with $^{32}\textrm{Na}$ nuclei. This is the only known microsecond isomer ($1{\text{ }\mu\text{s}}\leq T_{1/2} < 1\text{ ms}$) in the region. This nucleus is at the heart of the $N=20$ island of shape inversion and is at the crossroads of spherical shell-model, deformed shell-model, and ab initio theories. It can be represented as the coupling of a proton hole and neutron particle to $^{32}\textrm{Mg}$, $^{32}\textrm{Mg}+\pi^{-1} + \nu^{+1}$. This odd-odd coupling and isomer formation provides a sensitive measure of the underlying shape degrees of freedom of $^{32}\textrm{Mg}$, where the onset of spherical-to-deformed shape inversion begins with a low-lying deformed $2^+$ state at 885 keV and a low-lying shape-coexisting $0_2^+$ state at 1058 keV. We suggest two possible explanations for the 625-keV isomer in $^{32}$Na: a $6^-$ spherical shape isomer that decays by $E2$ or a $0^+$ deformed spin isomer that decays by $M2$. The present results and calculations are most consistent with the latter, indicating that the low-lying states are dominated by deformation.Comment: 7 pages, 5 figures, accepted by Physical Review Letter

Estrus cyclicity of spinogenesis: underlying mechanisms

Hippocampal spine density varies with the estrus cycle. The cyclic change in estradiol levels in serum was hypothesized to underlie this phenomenon, since treatment of ovariectomized animals with estradiol induced an increase in spine density in hippocampal dendrites of rats, as compared to ovariectomized controls. In contrast, application of estradiol to hippocampal slice cultures did not promote spinogenesis. In addressing this discrepancy, we found that hippocampal neurons themselves are capable of synthesizing estradiol de novo. Estradiol synthesis can be suppressed by aromatase inhibitors and by knock-down of Steroid Acute Regulatory Protein (StAR) and enhanced by substrates of steroidogenesis. Expression of estrogen receptors (ERs) and synaptic proteins, synaptogenesis, and long-term potentiation (LTP) correlated positively with aromatase activity in hippocampal cultures without any difference between genders. All effects due to inhibition of aromatase activity were rescued by application of estradiol to the cultures. Most importantly, gonadotropin-releasing hormone (GnRH) increased estradiol synthesis dose-dependently via an aromatase-mediated mechanism and consistently increased spine synapse density and spinophilin expression. As a consequence, our data suggest that cyclic fluctuations in spine synapse density result from pulsative release of GnRH from the hypothalamus and its effect on hippocampal estradiol synthesis, rather than from varying levels of serum estradiol. This hypothesis is further supported by higher GnRH receptor (GnRH-R) density in the hippocampus than in the cortex and hypothalamus and the specificity of estrus cyclicity of spinogenesis in the hippocampus, as compared to the cortex

Stochastic models for the in silico simulation of synaptic processes

Background: Research in life sciences is benefiting from a large availability of formal description techniques and analysis methodologies. These allow both the phenomena investigated to be precisely modeled and virtual experiments to be performed in silico. Such experiments may result in easier, faster, and satisfying approximations of their in vitro/vivo counterparts. A promising approach is represented by the study of biological phenomena as a collection of interactive entities through process calculi equipped with stochastic semantics. These exploit formal grounds developed in the theory of concurrency in computer science, account for the not continuous, nor discrete, nature of many phenomena, enjoy nice compositional properties and allow for simulations that have been demonstrated to be coherent with data in literature. Results: Motivated by the need to address some aspects of the functioning of neural synapses, we have developed one such model for synaptic processes in the calyx of Held, which is a glutamatergic synapse in the auditory pathway of the mammalia. We have developed such a stochastic model starting from existing kinetic models based on ODEs of some sub-components of the synapse, integrating other data from literature and making some assumptions about non-fully understood processes. Experiments have confirmed the coherence of our model with known biological data, also validating the assumptions made. Our model overcomes some limitations of the kinetic ones and, to our knowledge, represents the first model of synaptic processes based on process calculi. The compositionality of the approach has permitted us to independently focus on tuning the models of the pre- and post- synaptic traits, and then to naturally connect them, by dealing with “interface” issues. Furthermore, we have improved the expressiveness of the model, e.g. by embedding easy control of element concentration time courses. Sensitivity analysis over several parameters of the model has provided results that may help clarify the dynamics of synaptic transmission, while experiments with the model of the complete synapse seem worth explaining short-term plasticity mechanisms. Conclusions: Specific presynaptic and postsynaptic mechanisms can be further analysed under various conditions, for instance by studying the presynaptic behaviour under repeated activations. The level of details of the description can be refined, for instance by further specifying the neurotransmitter generation and release steps. Taking advantage of the compositionality of the approach, an enhanced model could then be composed with other neural models, designed within the same framework, in order to obtain a more detailed and comprehensive model. In the long term, we are interested, in particular, in addressing models of synaptic plasticity, i.e. activity dependent mechanisms, which are the bases of memory and learning processes. More on the computer science side, we plan to follow some directions to improve the underlying computational model and the linguistic primitives it provides as suggested by the experiments carried out, e.g. by introducing a suitable notion of (spatial) locality

Hydroxybenzothiazoles as New Nonsteroidal Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1)

17β-estradiol (E2), the most potent estrogen in humans, known to be involved in the development and progession of estrogen-dependent diseases (EDD) like breast cancer and endometriosis. 17β-HSD1, which catalyses the reduction of the weak estrogen estrone (E1) to E2, is often overexpressed in breast cancer and endometriotic tissues. An inhibition of 17β-HSD1 could selectively reduce the local E2-level thus allowing for a novel, targeted approach in the treatment of EDD. Continuing our search for new nonsteroidal 17β-HSD1 inhibitors, a novel pharmacophore model was derived from crystallographic data and used for the virtual screening of a small library of compounds. Subsequent experimental verification of the virtual hits led to the identification of the moderately active compound 5. Rigidification and further structure modifications resulted in the discovery of a novel class of 17β-HSD1 inhibitors bearing a benzothiazole-scaffold linked to a phenyl ring via keto- or amide-bridge. Their putative binding modes were investigated by correlating their biological data with features of the pharmacophore model. The most active keto-derivative 6 shows IC50-values in the nanomolar range for the transformation of E1 to E2 by 17β-HSD1, reasonable selectivity against 17β-HSD2 but pronounced affinity to the estrogen receptors (ERs). On the other hand, the best amide-derivative 21 shows only medium 17β-HSD1 inhibitory activity at the target enzyme as well as fair selectivity against 17β-HSD2 and ERs. The compounds 6 and 21 can be regarded as first benzothiazole-type 17β-HSD1 inhibitors for the development of potential therapeutics