Genetic conflicts in budding yeast: The 2µ plasmid as a model selfish element.

Antagonistic coevolution, arising from genetic conflict, can drive rapid evolution and biological innovation. Conflict can arise both between organisms and within genomes. This review focuses on budding yeasts as a model system for exploring intra- and inter-genomic genetic conflict, highlighting in particular the 2-micron (2µ) plasmid as a model selfish element. The 2µ is found widely in laboratory strains and industrial isolates of Saccharomyces cerevisiae and has long been known to cause host fitness defects. Nevertheless, the plasmid is frequently ignored in the context of genetic, fitness, and evolution studies. Here, I make a case for further exploring the evolutionary impact of the 2µ plasmid as well as other selfish elements of budding yeasts, discuss recent advances, and, finally, future directions for the field.

106-fold faster C-H bond hydroxylation by a CoIII,IV2(µ-O)2 complex [via a CoIII2(µ-O)(µ-OH) intermediate] versus its FeIIIFeIV analog.

The hydroxylation of C-H bonds can be carried out by the high-valent CoIII,IV2(µ-O)2 complex 2a supported by the tetradentate tris(2-pyridylmethyl)amine ligand via a CoIII2(µ-O)(µ-OH) intermediate (3a). Complex 3a can be independently generated either by H-atom transfer (HAT) in the reaction of 2a with phenols as the H-atom donor or protonation of its conjugate base, the CoIII2(µ-O)2 complex 1a. Resonance Raman spectra of these three complexes reveal oxygen-isotope-sensitive vibrations at 560 to 590 cm-1 associated with the symmetric Co-O-Co stretching mode of the Co2O2 diamond core. Together with a Co•••Co distance of 2.78(2) Å previously identified for 1a and 2a by Extended X-ray Absorption Fine Structure (EXAFS) analysis, these results provide solid evidence for their "diamond core" structural assignments. The independent generation of 3a allows us to investigate HAT reactions of 2a with phenols in detail, measure the redox potential and pKa of the system, and calculate the O-H bond strength (DO-H) of 3a to shed light on the C-H bond activation reactivity of 2a. Complex 3a is found to be able to transfer its hydroxyl ligand onto the trityl radical to form the hydroxylated product, representing a direct experimental observation of such a reaction by a dinuclear cobalt complex. Surprisingly, reactivity comparisons reveal 2a to be 106-fold more reactive in oxidizing hydrocarbon C-H bonds than corresponding FeIII,IV2(µ-O)2 and MnIII,IV2(µ-O)2 analogs, an unexpected outcome that raises the prospects for using CoIII,IV2(µ-O)2 species to oxidize alkane C-H bonds.

Selective Action Prediction in Infancy Depending on Linguistic Cues: An EEG and Eyetracker Study.

Humans' capacity to predict actions and to socially categorize individuals is at the basis of social cognition. Such capacities emerge in early infancy. By 6 months of age, infants predict others' reaching actions considering others' epistemic state. At a similar age, infants are biased to attend to and interact with more familiar individuals, considering adult-like social categories such as the language people speak. We report that these two core processes are interrelated early on in infancy. In a belief-based action prediction task, 6-month-old infants (males and females) presented with a native speaker generated online predictions about the agent's actions, as revealed by the activation of participants' sensorimotor areas before the agent's movement. However, infants who were presented with a foreign speaker did not recruit their motor system before the agent's action. The eyetracker analysis provided further evidence that linguistic group familiarity influences how infants predict others' actions, as only infants presented with a native speaker modified their attention to the stimuli as a function of the agent's forthcoming behavior. The current findings suggest that infants' emerging capacity to predict others' actions is modulated by social cues, such as others' linguistic group. A facilitation to predict and encode the actions of native speakers relative to foreign speakers may explain, in part, why infants preferentially attend to, imitate, and learn from the actions of native speakers.

Opioid-Induced Hyperalgesia and Tolerance Are Driven by HCN Ion Channels.

Prolonged exposure to opioids causes an enhanced sensitivity to painful stimuli (opioid-induced hyperalgesia, OIH) and a need for increased opioid doses to maintain analgesia (opioid-induced tolerance, OIT), but the mechanisms underlying both processes remain obscure. We found that pharmacological block or genetic deletion of HCN2 ion channels in primary nociceptive neurons of male mice completely abolished OIH but had no effect on OIT. Conversely, pharmacological inhibition of central HCN channels alleviated OIT but had no effect on OIH. Expression of C-FOS, a marker of neuronal activity, was increased in second-order neurons of the dorsal spinal cord by induction of OIH, and the increase was prevented by peripheral block or genetic deletion of HCN2, but block of OIT by spinal block of HCN channels had no impact on C-FOS expression in dorsal horn neurons. Collectively, these observations show that OIH is driven by HCN2 ion channels in peripheral nociceptors, while OIT is driven by a member of the HCN family located in the CNS. Induction of OIH increased cAMP in nociceptive neurons, and a consequent shift in the activation curve of HCN2 caused an increase in nociceptor firing. The shift in HCN2 was caused by expression of a constitutively active µ-opioid receptor (MOR) and was reversed by MOR antagonists. We identified the opioid-induced MOR as a six-transmembrane splice variant, and we show that it increases cAMP by coupling constitutively to Gs HCN2 ion channels therefore drive OIH, and likely OIT, and may be a novel therapeutic target for the treatment of addiction.

Interneurons in the CA1 stratum oriens expressing αTTP may play a role in the delayed-ageing Pol µ mouse model.

Neurodegeneration associated with ageing is closely linked to oxidative stress (OS) and disrupted calcium homeostasis. Some areas of the brain, like the hippocampus - particularly the CA1 region - have shown a high susceptibility to age-related changes, displaying early signs of pathology and neuronal loss. Antioxidants such as α-tocopherol (αT) have been effective in mitigating the impact of OS during ageing. αT homeostasis is primarily regulated by the α-tocopherol transfer protein (αTTP), which is widely distributed throughout the brain - where it plays a crucial role in maintaining αT levels within neuronal cells. This study investigates the distribution of αTTP in the hippocampus of 4- and 24-month-old Pol µ knockout mice (Pol µ-/-), a delayed-ageing model, and the wild type (Pol µ+/+). We also examine the colocalisation in the stratum oriens (st.or) of CA1 region with the primary interneuron populations expressing calcium-binding proteins (CBPs) (calbindin (CB), parvalbumin (PV), and calretinin (CR)). Our findings reveal that αTTP immunoreactivity (-IR) in the st.or of Pol µ mice is significantly reduced. The density of PV-expressing interneurons (INs) increased in aged mice in both Pol µ genotypes (Pol µ-/- and Pol µ+/+), although the density of PV-positive INs was lower in the aged Pol µ-/- mice compared to wild-type mice. By contrast, CR- and CB-positive INs in Pol µ mice remained unchanged during ageing. Furthermore, double immunohistochemistry reveals the colocalisation of αTTP with CBPs in INs of the CA1 st.or. Our study also shows that the PV/αTTP-positive IN population remains unchanged in all groups. A significant decrease of CB/αTTP-positive INs in young Pol µ-/- mice has been detected, as well as a significant increase in CR/αTTP-IR in older Pol µ-/- animals. These results suggest that the differential expression of αTTP and CBPs could have a crucial effect in aiding the survival and maintenance of the different IN populations in the CA1 st.or, and their coexpression could contribute to the enhancement of their resistance to OS-related damage and neurodegeneration associated with ageing.

mGluR5 from Primary Sensory Neurons Promotes Opioid-Induced Hyperalgesia and Tolerance by Interacting with and Potentiating Synaptic NMDA Receptors.

Aberrant activation of presynaptic NMDARs in the spinal dorsal horn is integral to opioid-induced hyperalgesia and analgesic tolerance. However, the signaling mechanisms responsible for opioid-induced NMDAR hyperactivity remain poorly identified. Here, we show that repeated treatment with morphine or fentanyl reduced monomeric mGluR5 protein levels in the dorsal root ganglion (DRG) but increased levels of mGluR5 monomers and homodimers in the spinal cord in mice and rats of both sexes. Coimmunoprecipitation analysis revealed that monomeric and dimeric mGluR5 in the spinal cord, but not monomeric mGluR5 in the DRG, directly interacted with GluN1. By contrast, mGluR5 did not interact with µ-opioid receptors in the DRG or spinal cord. Repeated morphine treatment markedly increased the mGluR5-GluN1 interaction and protein levels of mGluR5 and GluN1 in spinal synaptosomes. The mGluR5 antagonist MPEP reversed morphine treatment-augmented mGluR5-GluN1 interactions, GluN1 synaptic expression, and dorsal root-evoked monosynaptic EPSCs of dorsal horn neurons. Furthermore, CRISPR-Cas9-induced conditional mGluR5 knockdown in DRG neurons normalized mGluR5 levels in spinal synaptosomes and NMDAR-mediated EPSCs of dorsal horn neurons increased by morphine treatment. Correspondingly, intrathecal injection of MPEP or conditional mGluR5 knockdown in DRG neurons not only potentiated the acute analgesic effect of morphine but also attenuated morphine treatment-induced hyperalgesia and tolerance. Together, our findings suggest that opioid treatment promotes mGluR5 trafficking from primary sensory neurons to the spinal dorsal horn. Through dimerization and direct interaction with NMDARs, presynaptic mGluR5 potentiates and/or stabilizes NMDAR synaptic expression and activity at primary afferent central terminals, thereby maintaining opioid-induced hyperalgesia and tolerance.SIGNIFICANCE STATEMENT Opioids are essential analgesics for managing severe pain caused by cancer, surgery, and tissue injury. However, these drugs paradoxically induce pain hypersensitivity and tolerance, which can cause rapid dose escalation and even overdose mortality. This study demonstrates, for the first time, that opioids promote trafficking of mGluR5, a G protein-coupled glutamate receptor, from peripheral sensory neurons to the spinal cord; there, mGluR5 proteins dimerize and physically interact with NMDARs to augment their synaptic expression and activity. Through dynamic interactions, the two distinct glutamate receptors mutually amplify and sustain nociceptive input from peripheral sensory neurons to the spinal cord. Thus, inhibiting mGluR5 activity or disrupting mGluR5-NMDAR interactions could reduce opioid-induced hyperalgesia and tolerance and potentiate opioid analgesic efficacy.

Design, synthesis, and mechanism of action of novel µ-conotoxin KIIIA analogues for inhibition of the voltage-gated sodium channel Nav1.7.

µ-Conotoxin KIIIA, a selective blocker of sodium channels, has strong inhibitory activity against several Nav isoforms, including Nav1.7, and has potent analgesic effects, but it contains three pairs of disulfide bonds, making structural modification difficult and synthesis complex. To circumvent these difficulties, we designed and synthesized three KIIIA analogues with one disulfide bond deleted. The most active analogue, KIIIA-1, was further analyzed, and its binding pattern to hNav1.7 was determined by molecular dynamics simulations. Guided by the molecular dynamics computational model, we designed and tested 32 second-generation and 6 third-generation analogues of KIIIA-1 on hNav1.7 expressed in HEK293 cells. Several analogues showed significantly improved inhibitory activity on hNav1.7, and the most potent peptide, 37, was approximately 4-fold more potent than the KIIIA Isomer I and 8-fold more potent than the wildtype (WT) KIIIA in inhibiting hNav1.7 current. Intraperitoneally injected 37 exhibited potent in vivo analgesic activity in a formalin-induced inflammatory pain model, with activity reaching ∼350-fold of the positive control drug morphine. Overall, peptide 37 has a simplified disulfide-bond framework and exhibits potent in vivo analgesic effects and has promising potential for development as a pain therapy in the future.

Dopamine enhances GABAA receptor-mediated current amplitude in a subset of intrinsically photosensitive retinal ganglion cells.

Neuromodulation in the retina is crucial for effective processing of retinal signal at different levels of illuminance. Intrinsically photosensitive retinal ganglion cells (ipRGCs), the neurons that drive nonimage-forming visual functions, express a variety of neuromodulatory receptors that tune intrinsic excitability as well as synaptic inputs. Past research has examined actions of neuromodulators on light responsiveness of ipRGCs, but less is known about how neuromodulation affects synaptic currents in ipRGCs. To better understand how neuromodulators affect synaptic processing in ipRGC, we examine actions of opioid and dopamine agonists have on inhibitory synaptic currents in ipRGCs. Although µ-opioid receptor (MOR) activation had no effect on γ-aminobutyric acid (GABA) currents, dopamine [via the D1-type dopamine receptor (D1R)]) amplified GABAergic currents in a subset of ipRGCs. Furthermore, this D1R-mediated facilitation of the GABA conductance in ipRGCs was mediated by a cAMP/PKA-dependent mechanism. Taken together, these findings reinforce the idea that dopamine's modulatory role in retinal adaptation affects both nonimage-forming and image-forming visual functions.NEW & NOTEWORTHY Neuromodulators such as dopamine are important regulators of retinal function. Here, we demonstrate that dopamine increases inhibitory inputs to intrinsically photosensitive retinal ganglion cells (ipRGCs), in addition to its previously established effect on intrinsic light responsiveness. This indicates that dopamine, in addition to its ability to intrinsically modulate ipRGC activity, can also affect synaptic inputs to ipRGCs, thereby tuning retina circuits involved in nonimage-forming visual functions.

Dimerization of Fe(III) Ion in an Aqueous Medium: Mechanistic Modelling and Effects of Ligands.

Aqueous iron solutions generally undergo spontaneous hydrolysis followed by aggregation resulting in the precipitation of nanocrystalline oxyhydroxide minerals. The mechanism of nucleation of such multinuclear oxyhydroxide clusters are unclear due to limited experimental evidence. Here, we investigate the mechanistic pathway of dimerization of Fe(III) ions using density functional theory (DFT) in aqueous medium considering effects of other ligands. Two hydrolyzed monomeric Fe(III) ions in aqueous medium may react to form two closely related binuclear products, the µ-oxo and the dihydroxo Fe2 dimer. Our studies indicate that the water molecules in the second coordination sphere and those co-ordinated to the Fe(III) ion, both participate in the dimerization process. The proposed mechanism effectively explains the formation of dihydroxo and µ-oxo Fe2 dimers with interconversion possibilities, for the first time. Results show, with only water molecules present in the second co-ordination sphere, dihydroxo Fe2 dimer is the thermodynamically and kinetically favored product with a low activation free energy. We calculated the step-wise reaction free energies of dimerization in the presence of nitrate ions in the first and second coordination sphere of Fe(III) ion separately, which shows that with nitrate ions in the second co-ordination sphere, the µ-oxo Fe2 dimer is the kinetically favored product.

Using the IUCN Environmental Impact Classification for Alien Taxa to inform decision-making.

The Environmental Impact Classification for Alien Taxa (EICAT) is an important tool for biological invasion policy and management and has been adopted as an International Union for Conservation of Nature (IUCN) standard to measure the severity of environmental impacts caused by organisms living outside their native ranges. EICAT has already been incorporated into some national and local decision-making procedures, making it a particularly relevant resource for addressing the impact of non-native species. Recently, some of the underlying conceptual principles of EICAT, particularly those related to the use of the precautionary approach, have been challenged. Although still relatively new, guidelines for the application and interpretation of EICAT will be periodically revisited by the IUCN community, based on scientific evidence, to improve the process. Some of the criticisms recently raised are based on subjectively selected assumptions that cannot be generalized and may harm global efforts to manage biological invasions. EICAT adopts a precautionary principle by considering a species' impact history elsewhere because some taxa have traits that can make them inherently more harmful. Furthermore, non-native species are often important drivers of biodiversity loss even in the presence of other pressures. Ignoring the precautionary principle when tackling the impacts of non-native species has led to devastating consequences for human well-being, biodiversity, and ecosystems, as well as poor management outcomes, and thus to significant economic costs. EICAT is a relevant tool because it supports prioritization and management of non-native species and meeting and monitoring progress toward the Kunming-Montreal Global Biodiversity Framework (GBF) Target 6.

Uso de la Clasificación de Impacto Ambiental de los Taxones Exóticos de la UICN para la toma de decisiones Resumen La Clasificación de Impacto Ambiental de los Taxones Exóticos (EICAT, en inglés) es una herramienta importante para las políticas y manejo de las invasiones biológicas y ha sido adoptada como un estándar de la Unión Internacional para la Conservación de la Naturaleza (UICN) para medir la seriedad del impacto ambiental causado por los organismos que viven fuera de su extensión nativa. La EICAT ya ha sido incorporada a algunos procedimientos locales y nacionales de toma de decisiones, lo que la vuelve un recurso particularmente relevante para abordar el impacto de las especies no nativas. Algunos principios conceptuales subyacentes de la EICAT han sido cuestionados recientemente, en particular aquellos relacionados con el uso del principio de precaución. Aunque todavía son relativamente nuevas, las directrices para la aplicación e interpretación de la EICAT tendrán una revisión periódica, basada en evidencia científica, por parte de la comunidad de la UICN para mejorar el proceso. Algunas de las críticas recientes están basadas en suposiciones seleccionadas subjetivamente que no pueden generalizarse y podrían perjudicar los esfuerzos globales para manejar las invasiones biológicas. La EICAT adopta un principio de precaución cuando considera el historial de impacto de una especie en cualquier otro lugar ya que algunos taxones tienen características que podrían volverlos más dañinos. Además, las especies no nativas suelen ser factores de pérdida de bidiversidad, incluso bajo otras presiones. Cuando ignoramos el principio de precaución al abordar el impacto de las especies no nativas, hay consecuencias devastadoras para el bienestar humano, la biodiversidad y los ecosistemas, así como resultados pobres de conservación, y por lo tanto con costos económicos importantes. La EICAT es una herramienta relevante porque respalda la priorización y el manejo de las especies no nativas y ayuda con el cumplimiento y monitoreo del progreso para llegar al objetivo 6 del Marco Mundial de Biodiversidad Kunming­Montreal.

Global drivers of the conservation-invasion paradox.

The conservation-invasion paradox (CIP) refers to a long-term phenomenon wherein species threatened in their native range can sustain viable populations when introduced to other regions. Understanding the drivers of CIP is helpful for conserving threatened species and managing invasive species, which is unfortunately still lacking. We compiled a global data set of 1071 introduction events, including 960 CIP events (successful establishment of threatened species outside its native range) and 111 non-CIP events (unsuccessful establishment of threatened species outside its native range after introduction), involving 174 terrestrial vertebrates. We then tested the relative importance of various predictors at the location, event, and species levels with generalized linear mixed models and model averaging. Successful CIP events occurred across taxonomic groups and biogeographic realms, especially for the mammal group in the Palearctic and Australia. Locations of successful CIP events had fewer native threat factors, especially less climate warming in invaded regions. The probability of a successful CIP event was highest when species introduction efforts were great and there were more local congeners and fewer natural enemies. These results can inform threatened species ex situ conservation and non-native invasive species mitigation.

Causantes mundiales de la paradoja conservación­invasión Resumen La paradoja de conservación­invasión (PCI) se refiere al evento a largo plazo en el que las especies amenazadas en su distribución nativa puedan mantener poblaciones viables cuando se les introduce a otras regiones. Es de mucha ayuda para la conservación de especies amenazadas y el manejo de especies invasoras entender las causantes de la PCI, entendimiento que todavía es escaso. Compilamos un conjunto mundial de datos de 174 vertebrados terrestres en 1071 eventos de introducción, incluyendo 960 eventos de PCI (el establecimiento exitoso de especies amenazadas fuera de su distribución nativa) y 111 eventos no PCI (el fracaso en el establecimiento de especies amenazadas fuera de su distribución nativa después de la introducción). Después analizamos con modelos lineales mixtos generalizados y promedio de modelos la importancia relativa de varios pronosticadores en la localidad, en el evento y a nivel de especie. Los eventos exitosos de PCI ocurrieron en todos los grupos taxonómicos y en todos los reinos biogeográficos, especialmente para los mamíferos del Paleártico y Australia. Las localidades de los eventos exitosos de PCI tuvieron menos factores nativos de amenaza, especialmente un menor calentamiento climático en las regiones invadidas. La probabilidad de que un evento de PCI sea exitoso fue mayor cuando los esfuerzos de introducción fueron mayores y hubo más congéneres locales y menos enemigos naturales. Estos resultados pueden orientar la conservación ex situ de especies y la mitigación de especies invasoras no nativas.

A case for stronger integration of physical landscape processes in conservation science and practice.

I argue that the dynamic nature of contemporary, landscape-shaping (geomorphic) processes deserves more consideration in conservation science and practice. In an analysis of a sample of fundamental terms related to geomorphology and area-based conservation in the Web of Science, I found that the terms co-occurred in <2% of the analyzed entries (titles, abstracts, and keywords) from 2000 to 2020. This result is indicative of the rather peripheral attention that, more broadly, landscape-shaping processes seem to receive in the conservation literature. Among conservation scientists and practitioners, landforms that define the physical structure of habitat are often perceived as largely static, whereas the consideration of their dynamic adjustments to geomorphic processes is often limited to extreme events. I use examples derived from river-floodplain environments to illustrate strong, multifaceted, and reciprocal interactions between biota and various erosional and depositional processes. These ubiquitous interdependencies clearly demonstrate that geomorphic processes are an integral part of ecosystem dynamics at time scales relevant for conservation. Crucially, erosional and depositional processes modulate many environmental impacts of past and current anthropogenic activities. I conclude that the absence of a more explicit and widespread consideration of geomorphic processes in conservation science and practice is surprising and detrimental to their effectiveness. I call for bolstered efforts among the conservation and geoscience communities to better integrate landscape dynamics within the field of conservation. The rise of the ecosystem-based and social-ecological systems approaches to conservation and the growth of interdisciplinary geoscience branches (e.g., biogeomorphology, ecohydraulics, and geoconservation) will facilitate such an integration.

Un caso para una mayor integración de los procesos paisajísticos físicos en las ciencias y prácticas de la conservación Resumen En este artículo sostengo que la naturaleza dinámica de los procesos paisajísticos (geomórficos) contemporáneos merecen ser mejor considerados en las ciencias y práctica de la conservación. Con el análisis de una muestra de términos fundamentales de Web of Science relacionados con la geomorfología y la conservación basada en el área, encontré que los términos tuvieron una coocurrencia en <2% de las entradas analizadas (títulos, resúmenes y palabras clave) entre el 2000 y 2020. Este resultado indica que hay una atención relativamente periférica que, en términos más generales, parece que reciben los procesos paisajísticos dentro de la literatura de la conservación. Los científicos y practicantes de la conservación con frecuencia perciben el relieve que define la estructura física del hábitat como estático, mientras que la consideración de sus ajustes dinámicos a los procesos geomórficos está casi siempre limitado a eventos extremos. En las llanuras aluviales existen interacciones fuertes, multifacéticas y recíprocas entre la biota y varios procesos de erosión y deposición. Estas interdependencias predominantes demuestran con claridad que los procesos geomórficos son una parte integral de las dinámicas ambientales en escalas de tiempo relevantes para la conservación. Es destacable que los procesos de erosión y deposición modulan muchos impactos ambientales del pasado y actividades antropogénicas actuales. Concluyo que la ausencia de una consideración más explícita y extendida de los procesos geomórficos dentro de las ciencias y práctica de la conservación es sorprendente y nociva para su efectividad. Hago un llamado para fortalecer esfuerzos dentro de las comunidades de conservación y geociencias para integrar de mejor manera las dinámicas del paisaje dentro del campo de conservación. El incremento en las estrategias basadas en ecosistemas y sistemas socio­ecológicos en la conservación y el aumento de ramas interdisciplinarias de las geociencias (p. ej.: biogeomorfología, ecohidráulica y geoconservación) facilitarán dicha integración.

Effective conservation of subterranean-roosting bats.

Bats frequently inhabit caves and other subterranean habitats and play a critical role in subterranean food webs. With escalating threats to subterranean ecosystems, identifying the most effective measures to protect subterranean-roosting bats is critical. We conducted a meta-analysis to evaluate the effectiveness of conservation and management interventions for subterranean-roosting bats. We used network analyses to determine to what extent interventions for bats overlap those used for other subterranean taxa. We conducted our analyses with data extracted from 345 papers recommending a total of 910 conservation interventions. Gating of roost entrances was applied to preserve bat populations in 21 studies, but its effectiveness was unclear. Habitat restoration and disturbance reduction positively affected bat populations and bat behavior, respectively, in ≤4 studies. Decontamination was assessed in 2 studies and positively affected bat populations, particularly in studies focused on reducing fungal spores associated with white-nose syndrome in North America. Monitoring of bat populations as an effective conservation strategy was unclear and infrequently tested. Only 4% of bat studies simultaneously considered other subterranean organisms. However, effective interventions for bat conservation had similarities with all other organisms. If other subterranean organisms are considered when applying interventions to conserve bats, they might also benefit.

Conservación eficiente de murciélagos subterráneos Resumen Es común que los murciélagos habiten en cuevas y otros hábitats subterráneos y contribuyan a las redes alimenticias bajo tierra. Ya que estos ecosistemas cada vez se enfrentan a más amenazas, es importante identificar las medidas más efectivas para proteger a los murciélagos subterráneos. Realizamos un metaanálisis para evaluar la eficiencia de la conservación y las intervenciones de manejo para estos mamíferos. Usamos un análisis de redes para determinar el grado al que las intervenciones en pro de los murciélagos se traslapan con aquellas usadas para otros taxones subterráneos. Realizamos nuestros análisis con datos extraídos de 345 artículos que recomendaban 910 intervenciones de conservación. Se aplicó la colocación de compuertas en la entrada de los dormideros para conservar la población de murciélagos en 21 estudios, pero no quedó clara su efectividad. La restauración del hábitat y la reducción de las perturbaciones afectaron, respectivamente, a las poblaciones y al comportamiento de los murciélagos en ≤ 4 cuatro estudios. Se evaluó a la desinfección en dos estudios y ésta tuvo un efecto positivo sobre las poblaciones, particularmente en los estudios enfocados en la reducción de esporas micóticas asociadas con el síndrome de nariz blanca en América del Norte. La eficiencia del monitoreo de las poblaciones de murciélagos como una estrategia de conservación no fue clara y casi nunca se evaluó. Sólo el 4% de los estudios sobre murciélagos consideró simultáneamente a otros organismos subterráneos. Sin embargo, las intervenciones eficientes para la conservación de murciélagos tuvieron similitudes con las de todos los demás organismos. Otros organismos pueden beneficiarse si se les considera cuando se aplican las intervenciones para conservar a los murciélagos.

Cathodoluminescence investigations of dark-line defects in platelet-based InGaN nano-LED structures.

We have investigated the optical properties of heterostructured InGaN platelets aiming at red emission, intended for use as nano-scaled light-emitting diodes. The focus is on the presence of non-radiative emission in the form of dark line defects. We have performed the study using hyperspectral cathodoluminescence imaging. The platelets were grown on a template consisting of InGaN pyramids, flattened by chemical mechanical polishing. These templates are defect free, whereas the dark line defects are introduced in the lower barrier and tend to propagate through all the subsequent layers, as revealed by the imaging of different layers in the structure. We conclude that the dark line defects are caused by stacking mismatch boundaries introduced by multiple seeding and step bunching at the edges of the as-polished, dome shaped templates. To avoid these defects, we suggest that the starting material must be flat rather than dome shaped.

The P2Y1 receptor in the colonic myenteric plexus of rats and its correlation with opioid-induced constipation.

This study was designed to explore the expression changes of P2Y1 receptors in the distal colonic myenteric layer of rats. An opioid induced constipation(OIC) rat model was generated by intraperitoneal (i.p) injection of loperamide. At 7 days post-treatment, the model rats were assessed by calculating the fecal water content and the gastrointestinal transit ratio. The immunofluorescence (IF)-based histochemical study was used to observe the distribution of P2Y1 receptors in the distal colonic myenteric plexus. Western blotting (WB) was performed to evaluate the expression changes of P2Y1 proteins in the myenteric layer, and the electrophysiological approaches were carried out to determine the regulatory roles of P2Y1 receptors on distal colonic motor function. IF showed that P2Y1 receptors are co-expressed MOR in the enteric nerve cells of the distal colonic myenteric plexus. Moreover, the WB revealed that the protein levels of P2Y1 were significantly decreased in the distal colonic myenteric layer of OIC rats. In vitro tension experiments exhibited that the P2Y1 receptor antagonist MRS2500 enhanced the spontaneous contraction amplitude, adding EM2 and ß-FNA did not have any effect on MRS2500. Therefore, P2Y1 receptor expression could be associated with the occurrence of OIC in this rat model and the regulation of colonic motility by MOR may be related to the release of purine neurotransmitters such as ATP in the colonic nervous system.

Recycled Iron Phosphates: A New Phosphorus Fertilizer for Paddy Rice.

The potential of recycled iron phosphates (FePs), e.g., vivianites (Fe3(PO4)2·8H2O) and Fe(III)-rich phosphorus (P) adsorbent materials, as phosphorus fertilizer is limited by the strong interaction between Fe and P. In this study, the efficiency of FePs as P fertilizer was explored by applying them as granules or powder in flooded strongly P-fixing soils (acid and calcareous), thereby taking advantage of increased P release induced by reductive dissolution of P-bearing Fe(III) minerals. First, no P diffusion from granular FeP fertilizers into flooded soils was detectable by the diffusive gradient in thin films (DGT) technique and microfocused X-ray fluorescence (µ-XRF) analysis of thin soil sections, in contrast to detectable P diffusion away from granules of soluble triple superphosphate (TSP) fertilizer. On the contrary, powdered FePs demonstrated an excellent increase in extractable P (1 mM CaCl2) in a 120-day incubation experiment in flooded soils. Second, a pot experiment was performed with rice (Oryza sativa) grown in flooded acid and calcareous soils. The fertilizer value of FePs was remarkable when dosed as powder, as it was even up to 3-fold higher than TSP in the acid soil and similar to TSP in the calcareous soil. The beneficial effect of FeP over TSP in the acid soil is attributed to the slow release of P from FePs, which allows to partly overcome P fixation. The promising results of FePs as P fertilizer applied as powders in flooded soils debunk the generally accepted idea that FePs are poor sources of P while demonstrating the importance of the timing of FeP fertilizer application.

Soft ionization mechanisms in flexible µ-tube plasma-from FµTP to closed µ-tube plasma.

In order to find an explanation for the mechanism in a plasma operated with an alternating voltage, or rather a square wave voltage, such a plasma was investigated. It was found that Penning ionization, charge transfer, and photoionization played a minor or even no role in the soft ionization mechanism of a FµTP. If the collision of plasma gases with air does not contribute to soft ionization, it should also be possible to use a separated plasma for soft ionization. Preliminary investigations show that it is possible to ignite a diagnosis gas with a plasma gas even when there is a barrier such as glass between those gases. A temporally and locally limited potential must be produced at the outer surface to achieve this. This potential should be sufficient to ionize the environment softly and to be able to use this so-called closed µ-tube plasma as a new ionization source.

Soft ionization mechanisms in flexible µ-tube plasma-elucidation of He-, Ar-, Kr-, and Xe-FµTP.

The soft ionization mechanism of helium-based plasma seems to be understood while it still remains challenging in argon-based plasma, although many studies have used argon plasmas as a soft ionization source with good ionization efficiencies. In this study, helium, argon, krypton, and xenon were fed into the same discharge geometry, a flexible micro-tube plasma (FµTP), to determine the ionization mechanisms. The FµTPs operated with the named noble gases obtained comparable ionization efficiencies by MS measurements. The optical emission results showed that N2+ were the dominant ions within the helium-FµTP and noble gas ions were dominant for the other plasmas. These ions support the development of excitation and eventually stop at the end of the capillary. Therefore, Penning ionization and charge transfer between plasma and ambient air/analytes in the open atmosphere have been proven not to be the primary soft ionization mechanism. Furthermore, it was found that photoionization played a minor role in soft ionization. Using helium as a diagnosis gas in front of the discharge capillary nozzle of the FµTP, where the sample is usually positioned, shows that helium can be ignited by all of these FµTPs. This demonstrates that the excitation of a diagnosis gas as well as the ionization of analytes is independent of the type of the discharge gas. An alternative mechanism that a transient potential created by the ions is responsible for the soft ionization is subsequently proposed.

Novel insights into the dependence of adsorption-desorption kinetics on particle geometry in chiral chromatography.

The existence of slow adsorption-desorption kinetics in chiral liquid chromatography is common knowledge. This may significantly contribute to worsening the efficiency and kinetic performance of a chromatographic run, especially when high flow rates are employed. Many attempts and protocols have been proposed to access this term, the so-called c ads , but they are based on different (theoretical) assumptions. As a consequence, no official method is available for the estimation of the adsorption-desorption kinetics term. In this work, a novel approach to access c ads is presented. This procedure combines experimental results obtained with kinetic and thermodynamic measurements. The investigations have been performed on two zwitterionic teicoplanin chiral stationary phases (CSPs) based on 1.9 µ m fully porous and 2.0 µ m superficially porous particles (FPPs and SPPs), using Z-D,L-Methionine as probe molecule. Kinetic studies have been performed through the combination of both stop-flow and dynamic measurements, while adsorption isotherms have been calculated through Inverse Method. This study has confirmed that, on both particle formats, analyte diffusion on the surface of the particle is negligible, meaning that adsorption is localized, and it has been demonstrated that adsorption-desorption kinetics is strongly dependent on particle geometry and, in particular, on the loading of chiral selector. These findings are fundamental not only to unravel novel aspects of the complex enantiorecognition mechanism but also to optimize the employment of CSPs for ultra-fast and preparative applications.

Strategies for developing µ opioid receptor agonists with reduced adverse effects.

Opioids are currently the most effective and widely used painkillers in the world. Unfortunately, the clinical use of opioid analgesics is limited by serious adverse effects. Many researchers have been working on designing and optimizing structures in search of novel µ opioid receptor(MOR) agonists with improved analgesic activity and reduced incidence of adverse effects. There are many strategies to develop MOR drugs, mainly focusing on new low efficacy agonists (potentially G protein biased agonists), MOR agonists acting on different Gα subtype, targeting opioid receptors in the periphery, acting on multiple opioid receptor, and targeting allosteric sites of opioid receptors, and others. This review summarizes the design methods, clinical applications, and structure-activity relationships of small-molecule agonists for MOR based on these different design strategies, providing ideas for the development of safer novel opioid ligands with therapeutic potential.