Anesthetics fragment hippocampal network activity,alter spine dynamics,and affect memory consolidation

General anesthesia is characterized by reversible loss of consciousness accompanied by transient amnesia. Yet, long-term memory impairment is an undesirable side effect. How different types of general anesthetics (GAs) affect the hippocampus, a brain region central to memory formation and consolidation, is poorly understood. Using extracellular recordings, chronic 2-photon imaging, and behavioral analysis, we monitor the effects of isoflurane (Iso), medetomidine/midazolam/fentanyl (MMF), and ketamine/xylazine (Keta/Xyl) on network activity and structural spine dynamics in the hippocampal CA1 area of adult mice. GAs robustly reduced spiking activity, decorrelated cellular ensembles, albeit with distinct activity signatures, and altered spine dynamics. CA1 network activity under all 3 anesthetics was different to natural sleep. Iso anesthesia most closely resembled unperturbed activity during wakefulness and sleep, and network alterations recovered more readily than with Keta/Xyl and MMF. Correspondingly, memory consolidation was impaired after exposure to Keta/Xyl and MMF, but not Iso. Thus, different anesthetics distinctly alter hippocampal network dynamics, synaptic connectivity, and memory consolidation, with implications for GA strategy appraisal in animal research and clinical settings.

Amnesia is a central part of the 200 million general anesthesia that are administered worldwide every year, but it is unclear how it affects the hippocampus. This mouse study explores how three commonly used anesthetics influence cellular network activity, spine dynamics and memory consolidation, finding that each of the three anesthetics alters the local field potential, spiking activity and cellular calcium dynamics in a unique way, and they all impact long-term spine dynamics.     

Unraveling the role of microRNA/isomiR network in multiple primary melanoma pathogenesis

Malignant cutaneous melanoma (CM) is a potentially lethal form of skin cancer whose worldwide incidence has been constantly increasing over the past decades. During their lifetime, about 8% of CM patients will develop multiple primary melanomas (MPMs), usually at a young age and within 3 years from the first tumor/diagnosis. With the aim of improving our knowledge on MPM biology and pathogenesis, we explored the miRNome of 24 single and multiple primary melanomas, including multiple tumors from the same patient, using a small RNA-sequencing approach. From a supervised analysis, 22 miRNAs were differentially expressed in MPM compared to single CM, including key miRNAs involved in epithelial–mesenchymal transition. The first and second melanoma from the same patient presented a different miRNA profile. Ten miRNAs, including miR-25-3p, 149-5p, 92b-3p, 211-5p, 125a-5p, 125b-5p, 205-5p, 200b-3p, 21-5p, and 146a-5p, were further validated in 47 single and multiple melanoma samples. Pathway enrichment analysis of miRNA target genes revealed a more differentiated and less invasive status of MPMs compared to CMs. Bioinformatic analyses at the miRNA isoform (isomiR) level detected a panel of highly expressed isomiRs belonging to miRNA families implicated in human tumorigenesis, including miR-200, miR-30, and miR-10 family. Moreover, we identified hsa-miR-125a-5p|0|−2 isoform as tenfold over-represented in melanoma than the canonical form and differentially expressed in MPMs arising in the same patient. Target prediction analysis revealed that the miRNA shortening could change the pattern of target gene regulation, specifically in genes implicated in cell adhesion and neuronal differentiation. Overall, we provided a putative and comprehensive characterization of the miRNA/isomiR regulatory network of MPMs, highlighting mechanisms of tumor development and molecular features differentiating this subtype from single melanomas.Subject terms: Small RNAs, Melanoma     

Laccase-mediated oxidation of natural glycosides

Regioselective oxidations of the primary OH's of natural glycosides (thiocolchicoside, colchicoside, amygdalin, asiaticoside, ginsenoside R_E) have been performed on a preparative scale by exploiting the laccase–2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) methodology. The influence of water-miscible organic cosolvents on the stability and activity of a laccase from Trametes pubescens has been investigated. The enzyme has been covalently linked to Eupergit C250L and its performances evaluated. The recovered immobilized enzyme catalyzed several oxidative cycles of thiocolchicoside, without showing significant loss of activity.     

A molecular dynamics strategy for CSαβ peptides disulfide-assisted model refinement

Many cysteine-stabilized antimicrobial peptides from a variety of living organisms could be good candidates for the development of anti-infective agents. In the absence of experimentally obtained structural data, peptide modeling is an essential tool for understanding structure–activity relationships and for optimizing the bioactive moieties. Focusing on cysteine-rich peptide structures, we reproduced the case of structure predictions in the so-called midnight zone. We developed our protocol on a training set derived by clustering the available cysteine-stabilized αβ (CSαβ) structures in nine different representative families and tested it on peptides randomly selected from each family. Starting from draft models, we tested a structure-based disulfide predictor and we used cysteine distances as constraints during molecular dynamics. Finally, we proposed an analysis for final structure selection. Accordingly, we obtained a mean root mean square deviation improvement of 21% for the test set. Our findings demonstrate that it is possible to predict the network of disulfide bridges in cysteine-stabilized peptides and to use this result to improve the accuracy of structural predictions. Finally, we applied the methods to predict the structure of royalisin, a cysteine-rich peptide with unknown structure.     

Integrating three comprehensive data sets shows that mitochondrial DNA variation is linked to species traits and paleogeographic events in European butterflies

Understanding the dynamics of biodiversity, including the spatial distribution of genetic diversity, is critical for predicting responses to environmental changes, as well as for effective conservation measures. This task requires tracking changes in biodiversity at large spatial scales and correlating with species functional traits. We provide three comprehensive resources to understand the determinants for mitochondrial DNA differentiation represented by (a) 15,609 COI sequences and (b) 14 traits belonging to 307 butterfly species occurring in Western‐Central Europe and (c) the first multi‐locus phylogenetic tree of all European butterfly species. By applying phylogenetic regressions we show that mitochondrial DNA spatial differentiation (as measured with G_ST, G′_ST, D and D_ST) is negatively correlated with species traits determining dispersal capability and colonization ability. Thanks to the high spatial resolution of the COI data, we also provide the first zoogeographic regionalization maps based on intraspecific genetic variation. The overall pattern obtained by averaging the spatial differentiation of all Western‐Central European butterflies shows that the paradigm of long‐term glacial isolation followed by rapid pulses of post‐glacial expansion has been a pervasive phenomenon in European butterflies. The results and the extensive data sets we provide here constitute the basis for genetically‐informed conservation plans for a charismatic group in a continent where flying insects are under alarming decline.     

Control Mechanisms at the Level of FDP-Aldolases in Algae

Abstract

The FDP-aldolase I from Euglena gracilis is a four-chain enzyme, as shown by the amino acid analysis of the C and N terminals. The protein is dissociated by acid pH to a monomer. The reassociation-dissociation process goes through a dimer stage. The enzyme, inhibited either by mercurials or by ATP, is dissociated to a dimer. This process is readly reversible either by mercaptoethanol and by AMP.     

Biomechanical and metabolic responses to seat-tube angle variation during cycling in tri-athletes

One of the most physically demanding parts of triathlon is the transition from cycling to running. Many tri-athletes believe that increasing seat-tube angle (STA) can bring advantages in the following running part. The aim of this study was to evaluate the effects of inverting the support of the seat, for increasing STA, on the metabolic response and on the muscle activation pattern, maintaining a controlled kinematic. Moreover, a muscle-skeletal model was applied to evaluate the hypothesis that increasing STA changes force-producing capabilities of muscles crossing the hip.Ten tri-athletes cycled at two different power levels and with two different STA’s. Gas exchange data, kinematics and surface electromyography (sEMG) were acquired during the tests. sEMG was measured from eight muscles of the right side of the body. A model of muscle mechanics and energy expenditure was applied to estimate variations of force production capabilities and muscle energy consumption between the two STA configurations.Inverting the support of the seat showed no significant effects on kinematic, Oxygen consumption, muscle activations and muscle power production capabilities. Nevertheless, an interesting advantage can be the tendency to less activate gastrocnemius and biceps femoris: this could lead to minor muscle fatigue during the following running phase.