Determinants of habitat suitability models transferability across geographically disjunct populations: Insights from Vipera ursinii urs inii

Transferability of habitat suitability models (HSMs), essential to accurately predict outside calibration conditions, has been seldom investigated at intraspecific level. We targeted Vipera ursinii ursinii, a meadow viper from southeastern France and central Italy, to assess determinants of transferability among geographically disjunct populations. We fitted HSMs upon occurrences of the Italian and French populations separately, as well as on the combined occurrence dataset. Internal transferability of HSMs, on spatially independent test data drawn from the calibration region, and their external transferability on the geographically disjunct populations were evaluated according to (a) use of full or spatially rarefied presence datasets; (b) ecology‐driven or statistics‐driven filtering of predictors; (c) modeling algorithm, testing generalized additive models and gradient boosting models; and (d) multivariate environmental novelty within test data. Niche overlap between French and Italian populations was also tested. Niche overlap was low, but niche divergence between the two populations’ clusters was not corroborated. Nonetheless, wider niche breadth and heterogeneity of background environmental conditions characterizing the French populations led to low intercluster transferability. Although models fitted on the combined datasets did not attain consistently higher internal transferability than those separately fitted for the French and Italian populations, ensemble projection from the HSMs fitted on the joint occurrences produced more consistent suitability predictions across the full range of V. u. ursinii. Spatial thinning of occurrences ameliorated internal transferability but did not affect external transferability. The two approaches to predictors filtering did not differ in transferability of the respective HSMs but led to discrepant estimated environment–occurrence relationships and spatial predictions, while the two algorithms attained different relative rankings depending on the considered prediction task. Multivariate novelty of projection sites was negatively correlated to both internal transferability and external transferability. Our findings clarify issues researchers should keep in mind when using HSMs to get predictions across geographically disjunct populations.     

Interaction of Mannitol and Sucrose with Gellan Gum in Freeze-Dried Gel Systems

The effect of sucrose and mannitol addition to low-acyl (LA) gellan gum gels at both the molecular and macroscopic levels prior to, and after freeze-drying has been investigated. It has been shown that the gel network order as well as the mechanical properties are changed with the solute content, especially in the case of sucrose. The freeze-dried gel structure, containing either mannitol or sucrose, was studied, reporting for the first time the interaction of mannitol with the gellan gum gel. The generated freeze-dried gel network was evaluated in terms of porosity, pore size and wall thickness distributions. The solute physical state was correlated the water activity trend as a function of the solute content. Since mannitol is crystalline, the water activity decreases, in contrast with the amorphous sucrose. The rehydration mechanism was investigated and associated with the solute release from the structure. Specifically, the material properties (surface and bulk) as well as the role of the dissolution medium over time were assessed. It was found that the rehydration for both the gellan/sucrose and gellan/mannitol systems was highly influenced by the additive content, as an increase in water uptake was measured up to 10 wt%. A further increase in solute led to a considerable drop in the rehydration rate and extent due to the change in the freeze-dried structure, with smaller pores and with higher wall thickness values.     

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.     

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.