Comparative genomics uncovers the evolutionary history, demography, and molecular adaptations of South American canids.

The remarkable radiation of South American (SA) canids produced 10 extant species distributed across diverse habitats, including disparate forms such as the short-legged, hypercarnivorous bush dog and the long-legged, largely frugivorous maned wolf. Despite considerable research spanning nearly two centuries, many aspects of their evolutionary history remain unknown. Here, we analyzed 31 whole genomes encompassing all extant SA canid species to assess phylogenetic relationships, interspecific hybridization, historical demography, current genetic diversity, and the molecular bases of adaptations in the bush dog and maned wolf. We found that SA canids originated from a single ancestor that colonized South America 3.9 to 3.5 Mya, followed by diversification east of the Andes and then a single colonization event and radiation of Lycalopex species west of the Andes. We detected extensive historical gene flow between recently diverged lineages and observed distinct patterns of genomic diversity and demographic history in SA canids, likely induced by past climatic cycles compounded by human-induced population declines. Genome-wide scans of selection showed that disparate limb proportions in the bush dog and maned wolf may derive from mutations in genes regulating chondrocyte proliferation and enlargement. Further, frugivory in the maned wolf may have been enabled by variants in genes associated with energy intake from short-chain fatty acids. In contrast, unique genetic variants detected in the bush dog may underlie interdigital webbing and dental adaptations for hypercarnivory. Our analyses shed light on the evolution of a unique carnivoran radiation and how it was shaped by South American topography and climate change.

Whole-genome analysis reveals the diversification of Galapagos rail (Aves: Rallidae) and confirms the success of goat eradication programs.

Similar to other insular birds around the world, the Galapagos rail (Laterallus spilonota Gould, 1841) exhibits reduced flight capacity following its colonization of the archipelago ~1.2 mya. Despite their short evolutionary history, rails have colonized seven different islands spanning the entire width of the archipelago. Galapagos rails were once common on islands with sufficiently high altitudes to support shrubs in humid habitats. After humans introduced goats, this habitat was severely reduced due to overgrazing. Habitat loss devastated some rail populations, with less than 50 individuals surviving, rendering the genetic diversity of Galapagos rail a pressing conservation concern. Additionally, one enigma is the reappearance of rails on the island of Pinta after they were considered extirpated. Our approach was to investigate the evolutionary history and geographic distribution of Galapagos rails as well as examine the genome-wide effects of historical population bottlenecks using 39 whole genomes across different island populations. We recovered an early divergence of rail ancestors leading to the isolated populations on Pinta and a second clade comprising the rest of the islands, historically forming a single landmass. Subsequently, the separation of the landmass ~900 kya may have led to the isolation of the Isabela population with more panmictic populations found on Santa Cruz and Santiago islands. We found that rails genomes contain long runs of homozygosity (>2Mb) that could be related to the introduction of goats. Finally, our findings show that the modern eradication of goats was critical to avoiding episodes of inbreeding in most populations.

Mycobacterium leprae in Armadillo Tissues from Museum Collections, United States.

We examined armadillos from museum collections in the United States using molecular assays to detect leprosy-causing bacilli. We found Mycobacterium leprae bacilli in samples from the United States, Bolivia, and Paraguay; prevalence was 14.8% in nine-banded armadillos. US isolates belonged to subtype 3I-2, suggesting long-term circulation of this genotype.

Fungal feeding preferences and molecular gut content analysis of two abundant oribatid mite species (Acari: Oribatida) under the canopy of Prosopis laevigata (Fabaceae) in a semi-arid land.

Prosopis laevigata (mesquite; Fabaceae) forms fertility islands in soils of semi-arid lands where microbial diversity concentrates in response to the accumulation of resources in the soil beneath individual plants, promoting organic matter decomposition and nutrient cycling. This phenomenon provides suitable conditions for the proliferation of key edaphic elements such as fungi and mites. Mite-fungal interactions are central for our understanding of nutrient cycling processes in resource-limited arid food webs; yet, no information is available about fertility islands in semi-arid lands. Thus, we aimed to determine in vitro fungal-based feeding preferences and molecular gut content of the oribatid mite species Zygoribatula cf. floridana and Scheloribates cf. laevigatus, which are abundant under the canopy of P. laevigata in an intertropical semi-arid zone in Central Mexico. Our results on the gut content analysis of these oribatid species resulted in the ITS-based identification of the following fungi: Aspergillus homomorphus, Beauveria bassiana, Filobasidium sp., Mortierella sp., Roussoella sp., Saccharomyces cerevisiae, Sclerotiniaceae sp. and Triparticalcar sp. Furthermore, under laboratory conditions both oribatid mite species exhibited feeding preferences on melanized fungi, such as Cladosporium spp., whereas A. homomorphus and Fusarium penzigi were avoided. Our findings indicated that the analyzed oribatid mite species have similar feeding preferences for melanized fungi, which might suggest resource partitioning and a degree of preference, explaining the coexistence of both oribatid species.

Chiral C2 -symmetric bis-thioureas as enzyme mimics in enantioselective Michael addition.

We report herein the synthesis and application of enantiopure C2 -symmetric primary amine-1,3-bis-thiourea organocatalysts in enantioselective conjugate 1,4-Michael addition of carbonyl containing nucleophiles, to nitroalkenes and N-phenylmaleimide, leading to final products in good enantioselectivities (up to 99%) and yields (up to 99%). We propose supramolecular noncovalent interactions within the organocatalyst's cleft between the substrate and the catalyst, via hydrogen bonding. Supramolecular interaction thus lowers the transition state energy mimicking an enzyme. Mechanism underlying our experimental results is supported by theorical calculations.

The posterior/medial dry needling approach of the tibialis posterior muscle is an accurate and safe procedure: a cadaveric study.

BACKGROUND: Evidence suggests that tibialis posterior muscle plays an important role in equinovarus foot deformity in patients who had suffered a stroke and it is one of the most frequently injected lower-extremity muscles for the management of spasticity. Our aim was to assess if a needle accurately and safely penetrates the tibialis posterior muscle during the application of dry needling.  METHODS : We conducted a cadaveric descriptive study. Needling insertion of the tibialis posterior was conducted in 11 cryopreserved cadavers with a 70 mm needle. The needle was inserted using two common approaches, at midpoint (posterior/medial approach) and at upper third (anterior approach) of the leg towards the tibialis posterior. The needle was advanced into the tibialis posterior based upon clinician judgement. Cross-sectional anatomical dissections were photographed and analyzed by photometry. Safety was assessed by calculating the distances from the tip and the path of the needle to proximate neurovascular structures. RESULTS: Accurate needle penetration of the tibialis posterior muscle was observed in all cadavers with both approaches. In general, distances from the needle to the neurovascular bundles were larger with the posterior/medial approach than with the anterior approach, reaching statistically significance for needle tip to nerve (mean difference: 0.6 cm, 95%CI 0.35 to 0.85 cm) and vascular bundle (mean difference: 0.55 cm, 95%CI 0.3 to 0.8 cm) distances (P < 0.001) and needle path to vascular bundle distance (difference: 0.25 cm, 95%CI 0.1 to 0.4 cm, P = 0.045). Age and gender did not influence the main results. CONCLUSIONS: This cadaveric study suggests that needling of the tibialis posterior muscle can be accurately and safely conducted. Safety seems to be larger with the posterior/medial approach when compared with the anterior approach.

Antidepressant Low Doses of Ketamine and Melatonin in Combination Produce Additive Neurogenesis in Human Olfactory Neuronal Precursors.

Melatonin (MEL), an indolamine with diverse functions in the brain, has been shown to produce antidepressant-like effects, presumably through stimulating neurogenesis. We recently showed that the combination of MEL with ketamine (KET), an NMDA receptor antagonist, has robust antidepressant-like effects in mice, at doses that, by themselves, are non-effective and have no adverse effects. Here, we show that the KET/MEL combination increases neurogenesis in a clone derived from human olfactory neuronal precursors, a translational pre-clinical model for effects in the human CNS. Neurogenesis was assessed by the formation of cell clusters > 50 µm in diameter, positively stained for nestin, doublecortin, BrdU and Ki67, markers of progenitor cells, neurogenesis, and proliferation. FGF, EGF and BDNF growth factors increased the number of cell clusters in cultured, cloned ONPs. Similarly, KET or MEL increased the number of clusters in a dose-dependent manner. The KET/MEL combination further increased the formation of clusters, with a maximal effect obtained after a triple administration schedule. Our results show that the combination of KET/MEL, at subeffective doses that do not produce adverse effects, stimulate neurogenesis in human neuronal precursors. Moreover, the mechanism by which the combination elicits neurogenesis is meditated by melatonin receptors, CaM Kinase II and CaM antagonism. This could have clinical advantages for the fast treatment of depression.

The Future is Public! The Global Reclaiming and Democratization of Public Ownership Beyond the Market.

Faced with the convergence of economic, social, political and environmental crises, the importance of the public sector has been rediscovered on a global scale. The article offers a review of the evolution of political and academic debates on public ownership in general and public services provision in particular over the last decades, with emphasis on the energy sector. Taking as a temporal and analytical reference the research and advocacy work developed by the authors and other scholar-activists based at the Transnational Institute from 2006 to the present, the article summarizes the main issues currently in the spotlight and highlights gaps in knowledge and points of contention. It also suggests elements for future research and campaign agendas around public ownership in different regions of the world.

Low Doses of Ketamine and Melatonin in Combination Produce Additive Antidepressant-like Effects in Mice.

Major depressive disorder is a disabling disease with the number of affected individuals increasing each year. Current antidepressant treatments take between three to six weeks to be effective with forty percent of patients being resistant to treatment, making it necessary to search for new antidepressant treatments. Ketamine, a phencyclidine hydrochloride derivative, given intravenously, induces a rapid antidepressant effect in humans. In mice, it causes increased neurogenesis and antidepressant-like effects. However, it also produces psychomimetic effects in humans and in rodents increases the locomotor activity. In contrast, melatonin, a hormone secreted by the pineal gland and synthesized in extrapineal sites, increases new neuron formation and causes antidepressant-like effects in adult rodents with no collateral effects. Here, we assessed the effects of a non-effective dose of ketamine in combination with melatonin (KET/MEL), both on neurogenesis as well as on the antidepressant-like effect in mice. Our results showed that KET/MEL combination increased neurogenesis and produced antidepressant-like effects without altering locomotor activity after both single and triple administration protocols. Our data strongly suggest that KET/MEL combination could be used to simultaneously promote neurogenesis, reverting neuronal atrophy and inducing antidepressant-like effects.

Feasibility of an Alzheimer's disease knowledge intervention in the Latino community.

Background: Latinos experience disparities in Alzheimer's disease (AD) knowledge. The aim of this study was to explore the feasibility of a 45-minute culturally-tailored AD knowledge presentation for professionals serving the Latino community and Latinos served by Latino community organizations. Methods: One-session AD knowledge lunch-and-learn events were conducted with 40 professionals and 37 served Latinos. Participants received a pre-post survey including questions on satisfaction, a subjective AD knowledge question and a 14 item objective AD knowledge questionnaire. Results: Professionals (54.3%) and served Latinos (94.6%) reported the session as being very enjoyable and increased in objective AD knowledge (2.1 and 2.5 units, p < .001) and subjective knowledge (1.1 and 1.7 units; p < .001). Discussion: A brief in-person culturally-tailored session of AD education increases short-term AD knowledge and is perceived as interesting and useful among professionals serving the Latino community and Latinos served by Latino community organizations.

Talaromyces australis and Penicillium murcianum pigment production in optimized liquid cultures and evaluation of their cytotoxicity in textile applications.

In this work Talaromyces australis and Penicillium murcianum pigment production in liquid cultures and the cytotoxic effect of such pigments on skin model cells were studied. Response surface methodology (RSM) was used to optimize culture conditions aiming to increase pigment production in malt extract and peptone-glucose-yeast extract medium. Cytotoxicity of fungal pigments and also from lixiviates of wool fabrics dyed with T. australis and P. murcianum pigment was evaluated on mammalian cell lines HEK293 and NIH/3T3. Results showed that variations on initial pH, NaCl and peptone, resulted in increments up to 188.2% for red pigment of T. australis and 107.4% for yellow pigment of P. murcianum, regarding non-optimized conditions. Tested fungi also showed great differences in culture conditions for the maximum pigment production, with P. murcianum requiring an alkaline medium (initial pH 9) supplemented with NaCl and T. australis an acidic medium (initial pH 5) without addition of salt. The cytotoxicity assays provided evidences on the safe nature of these natural pigments when used for textile applications. The cytotoxicity assay showed that the threshold of toxicity, given by the lowest IC50 value (0.21 g L-1) was more than double of the concentration of pigment required to dye the wool samples. In addition, cytotoxicity of lixiviates depicted no toxic effect over tested cells.

The geospatial relationship of pterygium and senile cataract with ambient solar ultraviolet in tropical Ecuador.

Tropical Ecuador presents a unique climate in which we study the relationship between the ambient levels of solar ultraviolet radiation and eye disease in the absence of a latitudinal gradient. The national distribution of surface ultraviolet, taking into account MODIS and OMI satellite observation of aerosol, ozone, surface albedo, local elevation and cloud fractions measured during 2011, was compared with the national pterygium (WHO ICD H11) and senile cataract (WHO ICD H25) incidence projected from the 2010 National Institute of Statistics and Census (Ecuador). Public Health Ministry projections for age categories 0 to 39, 40 to 59 and 60+ years were compared to surface ultraviolet irradiance data in 1040 parishes. Correlations drawn between modelled surface ultraviolet and eye disease incidence show a significant increase in both pterygium and senile cataract in the highest ambient exposure regions of the Pacific coast and western lowlands with incidence rates of 34.39 and 16.17 per 100 000 residents respectively. The lowest rates of incidence for pterygium (6.89 per 100 000) and senile cataract (2.90 per 100 000) were determined in high altitude sites and are attributed here to increased daily cloud fraction for parishes located in the Andean mountain range. The South American Andes experience the highest solar UV exposures on Earth and report frequent high incidence of keratinocyte cancer. Our results show the high Andes to be the location of the lowest eye disease incidence suggesting that both pterygium and senile cataract are the result of cumulative exposure to solar ultraviolet. These findings have clear implications for the agricultural workers and fishermen of the lowland districts of Ecuador, contrary to conventional understanding that greater risks are faced in locations of high altitude.

Synthesis of novel (-)-epicatechin derivatives as potential endothelial GPER agonists: Evaluation of biological effects.

To potentially identify proteins that interact (i.e. bind) and may contribute to mediate (-)-epicatechin (Epi) responses in endothelial cells we implemented the following strategy: 1) synthesis of novel Epi derivatives amenable to affinity column use, 2) in silico molecular docking studies of the novel derivatives on G protein-coupled estrogen receptor (GPER), 3) biological assessment of the derivatives on NO production, 4) implementation of an immobilized Epi derivative affinity column and, 5) affinity column based isolation of Epi interacting proteins from endothelial cell protein extracts. For these purposes, the Epi phenol and C3 hydroxyl groups were chemically modified with propargyl or mesyl groups. Docking studies of the novel Epi derivatives on GPER conformers at 14 ns and 70 ns demostrated favorable thermodynamic interactions reaching the binding site. Cultures of bovine coronary artery endothelial cells (BCAEC) treated with Epi derivatives stimulated NO production via Ser1179 phosphorylation of eNOS, effects that were attenuated by the use of the GPER blocker, G15. Epi derivative affinity columns yielded multiple proteins from BCAEC. Proteins were electrophoretically separated and inmmunoblotting analysis revealed GPER as an Epi derivative binding protein. Altogether, these results validate the proposed strategy to potentially isolate and identify novel Epi receptors that may account for its biological activity.

C2 -symmetric sulfonamides as homogeneous and heterogeneous organocatalysts that mimic enzymes in enantioselective Michael additions.

Herein, we report the synthesis of C2 -symmetric sulfonamides as homogeneous and heterogeneous organocatalysts and their application in the enantioselective conjugate 1,4-Michael addition of carbonylic nucleophiles to ß-nitrostyrene. Organocatalysts hydrogen bond to ß-nitrostyrene and enamine in the transition state, mimicking an enzyme leading to final products in high yields (up to 98%) and good enantioselectivities (up to 96%). In addition, these results were supported by density functional calculations.

Mycelium of Terfezia claveryi as inoculum source to produce desert truffle mycorrhizal plants.

Terfezia claveryi Chatin was the first desert truffle species to be cultivated, the mycorrhizal plants being successfully produced by using both desert truffle spores and mycelia. However, it is more advisable to use mycelium than spores whenever possible and profitable. Given the low yields of mycelia obtained using traditional culture methods of this truffle, the medium composition was modified in an attempt to determine its nutritional requirements. For this, an assay involving response surface methodology was performed using Box-Behnken design to find the optimal parameters for the high production of mycelial biomass. The best results were obtained with glucose as carbon source, buffering the pH at 5 during culture, adding a pool of vitamins, and adjusting the optimal concentrations of carbon and nitrogen sources of the MMN medium. Biomass production increased from 0.3 to 3 g L-1 dry weight and productivity increased from 10.7 to 95.8 mg L-1 day-1 dry weight. The produced mycelium was able to colonize Helianthemum roots efficiently, providing more than 50% ectomycorrhizal colonization.

The Timing of Melatonin Administration Is Crucial for Its Antidepressant-Like Effect in Mice.

Melatonin is synthesized by the pineal gland with a circadian rhythm in synchrony with the environmental light/dark cycle. A gradual increase in circulating levels of melatonin occur after lights off, reaching its maximum around the middle of the dark phase. Agonists of melatonin receptors have proved effectiveness as antidepressants in clinical trials. However, there is contradictory evidence about the potential antidepressant effect of melatonin itself. Herein we studied melatonin administration in mice at two zeitgeber times (ZT; ZT = 0 lights on; 12:12 L/D), one hour before the beginning (ZT11) and at the middle (ZT18) of the dark phase after either a single or a three-dose protocol. Behavioral despair was assessed through a forced-swimming test (FST) or a tail suspension test (TST), at ZT18.5. A single dose of 4 mg/kg melatonin at ZT11 was effective to reduce the immobility time in both tests. However, acute administration of melatonin at ZT18 was not effective in mice subjected to FST, and a higher dose (16 mg/kg) was required to reduce immobility time in the TST. A three-dose administration protocol of 16 mg/kg melatonin (ZT18, ZT11, and ZT18) significantly reduced immobility time in FST. Data indicate that the timely administration of melatonin could improve its antidepressant-like effect.

A novel and highly regioselective synthesis of new carbamoylcarboxylic acids from dianhydrides.

A regioselective synthesis has been developed for the preparation of a series of N,N'-disubstituted 4,4'-carbonylbis(carbamoylbenzoic) acids and N,N'-disubstituted bis(carbamoyl) terephthalic acids by treatment of 3,3',4,4'-benzophenonetetracarboxylic dianhydride (1) and 1,2,4,5-benzenetetracarboxylic dianhydride (2) with arylalkyl primary amines (A-N). The carbamoylcarboxylic acid derivatives were synthesized with good yield and high purity. The specific reaction conditions were established to obtain carbamoyl and carboxylic acid functionalities over the thermodynamically most favored imide group. Products derived from both anhydrides 1 and 2 were isolated as pure regioisomeric compounds under innovative experimental conditions. The chemo- and regioselectivity of products derived from dianhydrides were determined by NMR spectroscopy and confirmed by density functional theory (DFT). All products were characterized by NMR, FTIR, and MS.

Comprehensive Development of a Cellulose Acetate and Soy Protein-Based Scaffold for Nerve Regeneration.

BACKGROUND: The elaboration of biocompatible nerve guide conduits (NGCs) has been studied in recent years as a treatment for total nerve rupture lesions (axonotmesis). Different natural polymers have been used in these studies, including cellulose associated with soy protein. The purpose of this report was to describe manufacturing NGCs suitable for nerve regeneration using the method of dip coating and evaporation of solvent with cellulose acetate (CA) functionalized with soy protein acid hydrolysate (SPAH). METHODS: The manufacturing method and bacterial control precautions for the CA/SPAH NGCs were described. The structure of the NGCs was analyzed under a scanning electron microscope (SEM); porosity was analyzed with a degassing method using a porosimeter. Schwann cell (SCL 4.1/F7) biocompatibility of cell-seeded nerve guide conduits was evaluated with the MTT assay. RESULTS: The method employed allowed an easy elaboration and customization of NGCs, free of bacteria, with pores in the internal surface, and the uniform wall thickness allowed manipulation, which showed flexibility; additionally, the sample was suturable. The NGCs showed initial biocompatibility with Schwann cells, revealing cells adhered to the NGC structure after 5 days. CONCLUSIONS: The fabricated CA/SPAH NGCs showed adequate features to be used for peripheral nerve regeneration studies. Future reports are necessary to discuss the ideal concentration of CA and SPAH and the mechanical and physicochemical properties of this biomaterial.

Using common mycorrhizal networks for controlled inoculation of Quercus spp. with Tuber melanosporum: the nurse plant method.

The high cost and restricted availability of black truffle spore inoculum for controlled mycorrhiza formation of host trees produced for truffle orchards worldwide encourage the search for more efficient and sustainable inoculation methods that can be applied globally. In this study, we evaluated the potential of the nurse plant method for the controlled inoculation of Quercus cerris and Quercus robur with Tuber melanosporum by mycorrhizal networks in pot cultures. Pine bark compost, adjusted to pH 7.8 by liming, was used as substrate for all assays. Initially, Q. robur seedlings were inoculated with truffle spores and cultured for 12 months. After this period, the plants presenting 74 % mycorrhizal fine roots were transferred to larger containers. Nurse plants were used for two treatments of two different nursling species: five sterilized acorns or five 45-day-old, axenically grown Q. robur or Q. cerris seedlings, planted in containers around the nurse plant. After 6 months, colonized nursling plant root tips showed that mycorrhiza formation by T. melanosporum was higher than 45 % in the seedlings tested, with the most successful nursling combination being Q. cerris seedlings, reaching 81 % colonization. Bulk identification of T. melanosporum mycorrhizae was based on morphological and anatomical features and confirmed by sequencing of the internal transcribed spacer region of the ribosomal DNA of selected root tips. Our results show that the nurse plant method yields attractive rates of mycorrhiza formation by the Périgord black truffle and suggest that establishing and maintaining common mycorrhizal networks in pot cultures enables sustained use of the initial spore inoculum.

4-Hy-droxy-6-methyl-pyridin-2(1H)-one.

In the crystal structure of the title compound, C6H7NO2, N-H⋯O and O-H⋯O hydrogen bonds link the mol-ecules, forming a zigzag array along [001] and a layer structure parallel to the ab plane.