Patterns of vertebrate biodiversity in a tropical dry and mangrove forest matrix / Patrones de biodiversidad de vertebrados en una matriz de bosque seco tropical y manglar

Introduction: Tropical dry forests and mangroves, two of the world's most endangered ecosystems, each host a different set of environmental conditions which may support unique assemblages of species. However, few studies have looked at the unique vertebrate biodiversity in regions where both habitats occur side-by-side. Objective: To assess the vertebrate diversity and patterns of habitat usage in a mangrove and tropical dry forest matrix in an unprotected region of Northwestern Costa Rica. Methods: The study was conducted in a 7 km2 matrix of mangrove and tropical dry forests between Cabuyal and Zapotillal bays in Northwestern Costa Rica, south of Santa Rosa National Park. From September 2017 to March 2018, we used 13 automatic camera traps over 1 498 trap days to capture species utilizing the region and assess their patterns of habitat usage both spatially and temporally. Results: Seventy vertebrate species from 42 families in 27 orders were detected, including several globally threatened species. Over half of all species were detected in only one habitat, particularly amongst avian (78 %) and mammalian (42 %) species. Tropical dry forests hosted the greatest number of unique species and supported a greater percentage of herbivores than mangrove or edge habitats, which were dominated by carnivorous and omnivorous species. Mean detections per camera trap of all species increased significantly from the coldest and wettest month (Oct) to the hottest and driest months (Jan & Feb) in tropical dry forests. Sample-based rarefaction analysis revealed that survey length was sufficient to sample the tropical dry forest and edge habitats, though mangroves require further sampling. Conclusions: Taxa found to utilize different forest types may utilize each for different stages of their life cycle, moving between areas as environmental conditions change throughout the year. General patterns of global biodiversity favoring carnivore and omnivore usage of mangrove forests was confirmed in our study.

Introducción: Los bosques secos tropicales y los manglares, dos de los ecosistemas más amenazados del mundo, albergan cada uno un grupo de condiciones ambientales que pueden albergar conjuntos únicos de especies. Sin embargo, pocos estudios han analizado la biodiversidad única de vertebrados en regiones donde ambos hábitats se encuentran uno al lado del otro. Objetivo: Evaluar la diversidad de vertebrados y los patrones de uso del hábitat en una matriz de manglar y bosque seco tropical en una región no protegida del noroeste de Costa Rica. Métodos: El estudio se realizó en una matriz de 7 km2 de manglares y bosques secos tropicales en las bahías de Cabuyal y Zapotillal en el noroeste de Costa Rica, al sur del Parque Nacional Santa Rosa. De septiembre 2017 a marzo 2018, utilizamos 13 cámaras trampa automáticas durante 1 498 días trampa para capturar especies que utilizan la región y evaluar sus patrones de uso espacial y temporal del hábitat. Resultados: Se detectaron 70 especies de vertebrados de 42 familias y 27 órdenes, incluidas varias especies amenazadas a nivel mundial. Más de la mitad de todas las especies se encontraron en un solo hábitat, particularmente aves (78 %) y mamíferos (42 %). Los bosques secos tropicales albergan el mayor número de especies únicas y sustentan un mayor porcentaje de herbívoros que los hábitats de borde de manglares, que estaban dominados u hospedados por especies carnívoras y omnívoras. Las detecciones promedio por cámara trampa de todas las especies aumentaron significativamente desde el mes más frío y húmedo (octubre) hasta los meses más cálidos y secos (enero y febrero) en los bosques secos tropicales. El análisis de rarefacción basado en muestras reveló que la duración del estudio fue suficiente para muestrear los hábitats de bosque seco tropical y de borde, aunque los manglares requieren más muestreo. Conclusiones: Se encontró que los taxones pueden usar varios tipos de bosque en las diferentes etapas de su ciclo de vida, moviéndose entre áreas a medida que las condiciones ambientales cambian a lo largo del año. En nuestro estudio se confirmaron patrones generales de la biodiversidad global que favorecen el uso de los bosques de manglar por parte de carnívoros y omnívoros.

Mini review: immunologic functions of dual oxidases in mucosal systems of vertebrates / Minirrevisão: funções imunológicas de oxidases duplas em sistemas mucosos de vertebrados

Abstract Mucosal epithelial cells act as the first immunologic barrier of organisms, and contact directly with pathogens. Therefore, hosts must have differential strategies to combat pathogens efficiently. Reactive oxygen species (ROS), as a kind of oxidizing agents, participates in the early stage of killing pathogens quickly. Recent reports have revealed that dual oxidase (DUOX) plays a key role in mucosal immunity. And the DUOX is a transmembrane protein which produces ROS as their primary enzymatic products. This process is an important pattern for eliminating pathogens. In this review, we highlight the DUOX immunologic functions in the respiratory and digestive tract of vertebrates.

Resumo As células epiteliais da mucosa atuam como a primeira barreira imunológica dos organismos e entram em contato direto com os patógenos. Portanto, os hospedeiros devem ter estratégias diferenciadas para combater os patógenos de forma eficiente. Trabalhos recentes revelaram que a oxidase dupla (DUOX) desempenha um papel fundamental para a imunidade da mucosa. A DUOX é uma proteína transmembrana geradora de espécies reativas de oxigênio (EROs) como seus principais produtos enzimáticos. Nesta revisão, apresentaremos as funções imunológicas da DUOX no trato respiratório e digestivo dos vertebrados.

Cresta neural, cuarta hoja, germinativa embrionaria / Neural crest, fourth embryonary germinative leaf

RESUMEN Las células de la cresta neural son pluripotenciales y son llamadas la cuarta hoja germinativa del embrión. Con el objetivo de estructurar los referentes teóricos actualizados que sustenten la afirmación precedente y que constituirá material de estudio para los estudiantes de las Ciencias Médicas, se realizó la revisión de 28 referencias bibliográficas, de ellas 89% actualizadas. Estas células aparecen durante la neurulación y pasado este proceso transitan de epitelial a mesenquimatosa; migran siguiendo señales de la matriz extracelular a todo el cuerpo del embrión diferenciándose en tejidos disimiles. Muy vinculados en su evolución a mecanismos epigenéticos, hacen a esta población celular vulnerables a ser dañadas invocándose en la etiología de diferentes defectos congénitos y enfermedades crónicas no trasmisibles como cáncer. Como conclusión por su pluripotencialidad y por los mecanismos moleculares que distinguen su evolución son consideradas por muchos autores la cuarta hoja germinativa del embrión (AU).

SUMMARY Neural crest cells are pluripotentials, and are called the fourth germinative leaf of the embryo. With the objective of structuring the updated theoretical referents backing up the precedent affirmation that will be study material for the students of Medical Sciences, the authors reviewed 28 bibliographic references, 89 % of them updated. These cells appear during neurulation and after this process they transit from epithelial to mesenchymal; following extracellular matrix signals, they migrate to the whole embryo body differentiating themselves in dissimilar tissues. Tightly related in their evolution to epigenetic mechanisms, this cell population is very likely to be damaged and so they are invoked in the etiology of different congenital defects and noncommunicable chronic diseases like cancer. In conclusion, due to their pluripotentiality and the molecular mechanisms distinguishing their evolution, many authors consider them the embryo´s fourth germinative leaf (AU).

Future Management Strategies for Zoonoses Based on One Health / 農村醫學 地域保健

Zoonoses are the diseases that are transmitted to human being from vertebrate animals either from livestock animals or from wildlife. Recently, zoonoses are increasingly common as a result of incremental human-animal contact. Propagative infections in wild animals and livestock are transmitted to human beings who are encountered with them. In general, wild animals can transmit infectious agents to livestock, and then livestock further transmit them to human being is a simple model of on how zoonotic diseases get transmitted to human being. This model emphasizes the importance of early detection of zoonoses by surveillance at its incipient stage. Cooperation between the respective ministries plays an important role in the identification of zoonoses and planning for the formulation of better preventive and control policy and strategy. We will be able to predict the occurrence of zoonotic diseases in human on the basis of disease trends in wildlife and livestock once when we obtain the surveillance data and data generated by respective ministries through sound cooperation and collaboration.

Generation of novel hyaluronic acid biomaterials for study of pain in third molar intervention: a review

Hyaluronic acid (HA) has long been studied in diverse applications. It is a naturally occurring linear polysaccharide in a family of unbranched glycosaminoglycans, which consists of repeating di-saccharide units of N-acetyl-D-glucosamine and D-glucuronic acid. It is almost ubiquitous in humans and other vertebrates, where it participates in many key processes, including cell signaling, tissue regeneration, wound healing, morphogenesis, matrix organization, and pathobiology. HA is biocompatible, biodegradable, muco-adhesive, hygroscopic, and viscoelastic. These unique physico-chemical properties have been exploited for several medicinal purposes, including recent uses in the adjuvant treatment for chronic inflammatory disease and to reduce pain and accelerate healing after third molar intervention. This review focuses on the post-operative effect of HA after third molar intervention along with its various physio-chemical, biochemical, and pharmaco-therapeutic uses.

Effects of roads on the vertebrates diversity of the Indigenous Territory Paresi and its surrounding / Efeitos das rodovias MT 235 e 358 sob a diversidade de vertebrados no sudoeste de Mato Grosso

Abstract Roadkill impact is still underestimated due to the lack of knowledge of its intensity and effect on animal populations. To assess differences between animal roadkills on roads in distinct landscapes, this study recorded meso- and megavertebrate roadkills along 50 km during a year in two highways in the transitional area of Amazonia/Cerrado in Tangará da Serra, Mato Grosso: MT-358 and MT-235, the latter crossing the Paresi Indigenous Land. We assessed roadkill rates and points with higher rates of roadkills, recording the most impacted species, seasonal effects, biomass loss, activity period of species, and traffic volume. We recorded 178 roadkills in 4,950 km travelled, a rate of 0.035 animal/km-travelled. Mammals were the most impacted with 135 roadkills (75.8%), followed by reptiles (6.2%), amphibians (5.6%) and birds (5.1%). Among mammals 51.1% were Carnivora, and the most impacted species was Cerdocyon thous (n = 42). On highway MT-358 (human-modified landscape), we recorded 155 roadkilled mammals, and the most impacted were C. thous (23.9%) and Euphractus sexcinctus (13.5%). Whilst on highway MT-235 (Paresi Indigenous Land), we recorded 23 roadkilled mammals, and the most impacted were Myrmecophaga tridactyla (26.1%) and C. thous (21.7%). The low roadkill rate in the Paresi Indigenous Land might be related to the presence of fauna pathways along the highway and the availability of a forested landscape.

Resumo O impacto de atropelamentos por veículos sobre populações animais ainda é subestimado devido ao pouco conhecimento existente sobre sua intensidade e seus efeitos. Para avaliar diferenças entre atropelamentos de animais em rodovias inseridas em paisagens distintas, este trabalho registrou atropelamentos de meso e mega vertebrados em trechos de 50 km durante um ano em duas rodovias na região de transição Amazônia/Cerrado em Tangará da Serra, Mato Grosso: MT-358 e MT-235, sendo que a segunda cruza a Terra Indígena Paresi. Avaliamos as taxas de atropelamento e os locais de maior intensidade, registrando as espécies mais impactadas. Avaliamos efeitos de sazonalidade, perda de biomassa, horário de atividade das espécies e horário de maior fluxo de veículos. Foram 178 animais atropelados em 4.950 km percorridos, com 33 espécies (15 ordens), totalizando 0,035 animais/km-percorrido. Os mamíferos foram os mais atingidos com 135 atropelamentos (75,8%), seguidos por répteis (6,2%), anfíbios (5,6%) e aves (5,1%). Entre os mamíferos atropelados 51,1% pertencem à ordem carnívora, e a espécie mais atropelada foi Cerdocyon thous (n = 42). Na rodovia MT-358 (antropizada) foram registrados 155 atropelamentos de mamíferos, sendo que C. thous (23,9%) e Euphractus sexcinctus (13,5%) foram os mais atropelados. Enquanto na rodovia MT-235 foram registrados 23 atropelamentos sendo Myrmecophaga tridactyla (26.1%) e C. thous (21,7%) as espécies mais afetadas. Observamos menor taxa de atropelamentos dentro da Terra Indígena Paresi, possivelmente devido a presença de passagens para fauna ao longo da rodovia e maior quantidade de áreas florestadas.

Two combined amino acids promote sleep activity in caffeine-induced sleepless model systems

BACKGROUND/OBJECTIVES: The aim of this study was to evaluate the biological and sleep-promoting effects of combined γ-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) using caffeine-induced sleepless fruit flies, ICR mice, and Sprague-Dawley rats. MATERIALS/METHODS: Video-tracking analysis was applied to investigate behavioral changes of Drosophila melanogaster. Pentobarbital-induced sleep test and electroencephalogram (EEG) patterns were used for analysis of sleep latency, duration, and quantity and quality of sleep in vertebrate models. RESULTS: Administration of combined GABA/5-HTP could significantly reverse the caffeine induced total distance of flies (P < 0.001). Also, individually administered and combined GABA/5-HTP significantly increased the total sleeping time in the caffeine-induced sleepless ICR mice (P < 0.001). In the caffeine-induced sleepless SD-rats, combined GABA/5-HTP showed significant differences in sleep quality between individual amino acid administrations (P < 0.05). CONCLUSIONS: Taken together, we identified inhibitory effects of combined GABA/5-HTP in locomotor activity, sleep quantity and quality in caffeine-induced sleepless models, indicating that combined GABA/5-HTP may be effective in patients with insomnia by providing sufficient sleep.

Comparative aspects of microRNA expression in canine and human cancers

MicroRNAs (miRNAs) have important roles in all biological pathways in multicellular organisms. Over 1,400 human miRNAs have been identified, and many are conserved among vertebrates and invertebrates. Regulation of miRNA is the most common mode of post-transcriptional gene regulation. The miRNAs that are involved in the initiation and progression of cancers are termed oncomiRs and several of them have been identified in canine and human cancers. Similarly, several miRNAs have been reported to be down-regulated in cancers of the two species. In this review, current information on the expression and roles of miRNAs in oncogenesis and progression of human and canine cancers, as well the roles miRNAs have in cancer stem cell biology, are highlighted. The potential for the use of miRNAs as therapeutic targets in personalized cancer therapy in domestic dogs and their possible application in human cancer counterparts are also discussed.

Tick-Borne Pathogens in Ixodid Ticks from Poyang Lake Region, Southeastern China

Ticks are the vectors of various pathogens, threatening human health and animal production across the globe. Here, for the first time we detected Ricketssia spp., Borrelia spp. and protozoan in ticks from Poyang Lake region in Jiangxi Province of eastern China. In 3 habitat categories and on 12 host species, 311 ticks from 11 species were collected. Haemaphysalis longicornis was the predominant species, accounting for 55.63%, followed by Rhipicephalus microplus, Haemaphysalis flava and Ixodes granulatus. Of the collected ticks, 7.07% were positive for tick-borne pathogens, and H. longicornis and H. flava were found to be co-infected with Ricketssia spp. and protozoan. H. flava was the most detected positive for tick-borne pathogens, whereas H. longicornis had the lowest infection rate, and the difference in infection rates between tick species was significant (χ²=61.24, P < 0.001). Furthermore, adult ticks demonstrated remarkably greater infection rate than immature ticks (χ²=10.12, P=0.018), meanwhile ticks on Erinaceidae showed significantly higher positivity than ticks collected on other host species (χ²=108.44, P < 0.001). Genetic fragment sequencing and analyses showed at least 4 pathogen species presence in ticks, namely Borrelia yangtzensis, Rickettsia slovaca or Rickettsia raoultii related genospecies, Babesia vogeli and Hepatozoon canis or Hepatozoon felis related genospecies. The finding indicates that the abundant ticks can carry diverse pathogens in Poyang Lake region, and pathogen infection is highly related to species, vertebrate hosts and life stages of ticks.

Immune Responses Induced by HSP60 DNA Vaccine against Toxoplasma gondii Infection in Kunming Mice

Toxoplasma gondii can infect all the vertebrates including human, and leads to serious toxoplasmosis and considerable veterinary problems. T. gondii heat shock protein 60 (HSP60) is associated with the activation of antigen presenting cells by inducing initial immune responses and releasing inflammatory cytokines. It might be a potential DNA vaccine candidate for this parasite. A pVAX-HSP60 DNA vaccine was constructed and immune responses was evaluated in Kunming mice in this study. Our data indicated that the innate and adaptive immune responses was elicited by successive immunizations with pVAX-HSP60 DNA, showing apparent increases of CD3e+CD4+ and CD3e+CD8a+ T cells in spleen tissues of the HSP60 DNA-immunized mice (24.70±1.23% and 10.90±0.89%, P < 0.05) and higher levels of specific antibodies in sera. Furthermore, the survival period of the immunized mice (10.53±4.78 day) were significantly prolonged during the acute T. gondii infection. Decrease of brain cysts was significant in the experimental group during the chronic infection (P < 0.01). Taken together, TgHSP60 DNA can be as a vaccine candidate to prevent the acute and chronic T. gondii infections.

A Novel Homozygous Variant of SETX Causes Ataxia with Oculomotor Apraxia Type 2

BACKGROUND AND PURPOSE: Autosomal recessive cerebellar ataxias constitute a highly heterogeneous group of neurodegenerative disorders. This study was carried out to determine the clinical and genetic causes of ataxia in two families from Pakistan. METHODS: Detailed clinical investigations were carried out on probands in two consanguineous families. Magnetic resonance imaging was performed. Exome sequencing data were examined for likely pathogenic variants. Candidate variants were checked for cosegregation with the phenotype using Sanger sequencing. Public databases including ExAC, GnomAD, dbSNP, and the 1,000 Genome Project as well as ethnically matched controls were checked to determine the frequencies of the alleles. Conservation of missense variants was ensured by aligning orthologous protein sequences from diverse vertebrate species. RESULTS: Reverse phenotyping identified spinocerebellar ataxia, autosomal recessive 1 [OMIM 606002, also referred to as ataxia oculomotor apraxia type 2 (AOA2)] and ataxia telangiectasia (OMIM 208900) in the two families. A novel homozygous missense mutation c.202 C>T (p.Arg68Cys) was identified within senataxin, SETX in the DNA of both patients in one of the families with AOA2. The patients in the second family were homozygous for a known variant in ataxia-telangiectasia mutated (ATM) gene: c.7327 C>T (p.Arg2443Ter). Both variants were absent from 100 ethnically matched control chromosomes and were either absent or present at very low frequencies in the public databases. CONCLUSIONS: This report extends the allelic heterogeneity of SETX mutations causing AOA2 and also presents an asymptomatic patient with a pathogenic ATM variant.

Bitter Taste, Rising New Functions and Significance of Extra-oral Expressions

Taste is closely related to intake of food. Taste perception is also influenced by type of food ingested, and nutrition and health status. Bitter taste plays an important role in the survival of human and animals to avoid probable toxic and harmful substances. Vertebrate animals recognize bitter taste through type 2 taste receptors (T2Rs). Several T2Rs have been expressed extra-oral such as the gastrointestinal tract, respiratory tract, urogenital tract, brain and immune cells, and parts of their functions are being revealed. This review will discuss physiological roles of T2Rs in relation to innate immunity, secretion and smooth muscle contraction expressed in extra-oral cells and tissues, and we summarize relationships between polymorphisms in T2Rs and general or oral diseases. It is not a coincidence that animals pay much genetic costs for taste and smell during evolution.

Relación entre áreas y variables ambientales espaciales con el atropellamiento y cruce de la fauna silvestre en la carretera de la Franja Transversal del Norte, Cobán, Guatemala / Areas and spatial environmental variables related with the trampling and wildlife crossing in the Northern Transversal Road in Coban, Guatemala

Dentro del Proyecto vial de la Franja Transversal del Norte en Cobán se planea asfaltar 10 km del trayecto en el Parque Nacional Laguna Lachuá. Esto impactará a la fauna de no considerarse medidas de mitigación del atropellamiento. La investigación evaluó los patrones espaciales del atropellamiento de vertebrados, la frecuencia de cruce de aves y categorizó las secciones de la carretera en dicho trayecto, según variables ambientales (humedales, usos del suelo, cobertura; y ancho, asfaltado y ubicación de la carretera) con el fin de determinar los sitios más eficientes para la aplicación de medidas de mitigación. En el 2016, se realizaron 20 recorridos, donde se georreferenció, fotografió e identificó a los individuos atropellados; tres recorridos en los meses de febrero, marzo y abril, cinco en mayo y seis en junio; 12 recorridos fueron realizados adicionalmente cuantificando el cruce de aves para determinar que sitios podrían ser futuramente impactados. Finalmente, para un análisis más completo, el trayecto de la carretera bajo estudio fue dividido en 19 secciones (T1-T19) de 550 m cada uno. Fueron empleadas: estadística descriptiva, análisis de componentes principales (ACP), correspondencia canónica (CCA) y análisis de correspondencia (AC), para relacionar variables ambientales con atropellamiento y frecuencia de cruce. La mayoría de atropellamientos (80 %) ocurrieron en zonas asfaltadas, los anfibios fueron los más atropellados (125 individuos, 75 %), seguido por reptiles 21 (12 %), mamíferos 11 (7 %) y aves 10 (6 %). La mayor frecuencia de cruce ocurrió en zonas con humedales y alta cobertura boscosa (T1, T3, T6, T7 y T10) siendo estas secciones prioritarias para mitigación.

The Franja Transversal del Norte road project in the Coban Province plans to pave a 10 km long dirt road inside the Laguna Lachua National Park. This will impact the fauna if no mitigation measure for wildlife-vehicle collision is considered. The research evaluated the spatial patterns of the vertebrate´s roadkills, the bird's road-crossing frequency, and categorized the road section based on environmental variables (wetlands, land use, coverture; and road's width, location, and paved or not paved) to determine the most efficient sites for the application of mitigation measures. In 2016, 20 treks were made to detect, geo-reference, photograph and identify road killed individuals, three treks in the months of February, March, and April, five in May and six in June; 12 additional treks were made to quantify birds' road-crossing to determine the sites that could be impacted in the future. Finally, for a further analysis, the road section under study was divided into 19 segments (T1-T19), 550 m long each. A combination of descriptive statistics, principal component analysis (PCA), canonical correspondence analysis (CCA) and correspondence analysis (CA) were employed to relate the spatial environmental variables with roadkill and road-crossing frequency. Eighty percent of the roadkill's occurred in the paved zones, the amphibians were the most affected (125 carcasses, 75 %), followed by reptiles 21 (12 %), mammals 11 (7 %) and birds 10 (6 %). The highest road-crossing frequencies were related to wetlands and high forest cover (T1, T3, T6, T7, T10) being priority areas for the application of mitigation measures.

Inhibition of Cyclooxygenase-2 Alters Wnt/β-Catenin Signaling in the Regenerating Tail of Lizard Hemidactylus flaviviridis

Epimorphic regeneration in vertebrates involves the restoration of lost tissue or organs through the formation of a regeneration blastema and occurs through a complex interaction of a number of molecular signaling pathways. Of the many effectors of successful tail regeneration in the lizard Hemidactylus flaviviridis, one crucial pathway is the cyclooxygenase-2 (COX-2) mediated PGE2 signaling pathway. The current study was aimed at understanding whether COX-2 signaling plays any role in the expression of Wnt/β-Catenin signaling components during regenerative outgrowth in H. flaviviridis. Etoricoxib—selective inhibitor of the inducible isoform of COX-2—was administered to lizards orally. We tested the expression of β-Catenin during wound epidermis and blastema stages in the regenerating tail and found a reduction in its expression in response to drug treatment. Further, it was observed that the expression of canonical Wnt ligands was greatly altered due to COX-2 inhibition. Our results provide evidence of a cross-talk between the COX-2 induced PGE₂ pathway and Wnt/β-Catenin signaling in the regenerating lizard tail. An understanding of the interaction among various signaling pathways will help elucidate the mechanism underlying epimorphosis in lizards, the only amniotes capable of appendage regeneration.

Corticosteroids Treatment in Spinal Cord and Neuromuscular Disorders

Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of the vertebrates, as well as the synthetic analogs of these hormones that are synthesized in the laboratories. Two main classes of corticosteroids, glucocorticoids, and mineralocorticoids, are involved in a wide range of physiologic processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior. Corticosteroids have been used for almost 60 years in medicine and their roles in patients have always been discussed by researchers and clinicians dedicated in the related field. Currently, they are still used in the treatment of patients with neurological disorders. Usually, corticosteroids are used in the treatment of various inflammatory diseases and conditions. In this review, we present five key indications, i.e., neuromyelitis optica, acute spinal cord injury, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, polymyositis/dermatomyositis for the systemic use of corticosteroids in neurology based on a mix of quality of evidence, prevalence, and impact on disease management.

Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors

Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples.

Transcriptional Network Controlling Endochondral Ossification

Endochondral ossification is the fundamental process of skeletal development in vertebrates. Chondrocytes undergo sequential steps of differentiation, including mesenchymal condensation, proliferation, hypertrophy, and mineralization. These steps, which are required for the morphological and functional changes in differentiating chondrocytes, are strictly regulated by a complex transcriptional network. Biochemical and mice genetic studies identified chondrogenic transcription factors critical for endochondral ossification. The transcription factor sex-determining region Y (SRY)-box 9 (Sox9) is essential for early chondrogenesis, and impaired Sox9 function causes severe chondrodysplasia in humans and mice. In addition, recent genome-wide chromatin immunoprecipitation-sequencing studies revealed the precise regulatory mechanism of Sox9 during early chondrogenesis. Runt-related transcription factor 2 promotes chondrocyte hypertrophy and terminal differentiation. Interestingly, endoplasmic reticulum (ER) stress-related transcription factors have recently emerged as novel regulators of chondrocyte differentiation. Here we review the transcriptional mechanisms that regulate endochondral ossification, with a focus on Sox9.

The Scaffolding Protein, Grb2-associated Binder-1, in Skeletal Muscles and Terminal Schwann Cells Regulates Postnatal Neuromuscular Synapse Maturation

The vertebrate neuromuscular junction (NMJ) is considered as a “tripartite synapse” consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice. The mutant mice showed delayed postnatal maturation of the NMJ. Furthermore, the selective loss of the gab1 gene in terminal Schwann cells produced delayed synaptic elimination with abnormal morphology of the motor endplate, suggesting that Gab1 in both muscles and terminal Schwann cells is required for proper NMJ development. Gab1 in terminal Schwann cells appeared to regulate the number and process elongation of terminal Schwann cells during synaptic elimination. However, Gab2 knockout mice did not show any defects in the development of the NMJ. Considering the role of Gab1 in postnatal peripheral nerve myelination, our findings suggest that Gab1 is a pleiotropic and important component of NRG1 signals during postnatal development of the peripheral neuromuscular system.

Chigger Mite (Acari: Trombiculidae) Survey of Rodents in Shandong Province, Northern China

Chigger mites are parasites of rodents and other vertebrates, invertebrates, and other arthropods, and are the only vectors of scrub typhus, in addition to other zoonoses. Therefore, investigating their distribution, diversity, and seasonal abundance is important for public health. Rodent surveillance was conducted at 6 districts in Shandong Province, northern China (114–112°E, 34–38°N), from January to December 2011. Overall, 225/286 (78.7%) rodents captured were infested with chigger mites. A total of 451 chigger mites were identified as belonging to 5 most commonly collected species and 3 genera in 1 family. Leptotrombidium scutellare and Leptotrombidium intermedia were the most commonly collected chigger mites. L. scutellare (66.2%, 36.7%, and 49.0%) was the most frequently collected chigger mite from Apodemus agrarius, Rattus norvegicus, and Microtus fortis, respectively, whereas L. intermedia (61.5% and 63.2%) was the most frequently collected chigger mite from Cricetulus triton and Mus musculus, respectively. This study demonstrated a relatively high prevalence of chigger mites that varied seasonally in Shandong Province, China.

Act on the Registration and Evaluation of Chemicals (K-REACH) and replacement, reduction or refinement best practices

OBJECTIVES: Korea's Act on the Registration and Evaluation of Chemicals (K-REACH) was enacted for the protection of human health and the environment in 2015. Considering that about 2000 new substances are introduced annually across the globe, the extent of animal testing requirement could be overwhelming unless regulators and companies work proactively to institute and enforce global best practices to replace, reduce or refine animal use. In this review, the way to reduce the animal use for K-REACH is discussed. METHODS: Background of the enforcement of the K-REACH and its details was reviewed along with the papers and regulatory documents regarding the limitation of animal experiments and its alternatives in order to discuss the regulatory adoption of alternative tests. RESULTS: Depending on the tonnage of the chemical used, the data required ranges from acute and other short-term studies for a single exposure route to testing via multiple exposure routes and costly, longer-term studies such as a full two-generation reproducibility toxicity. The European Registration, Evaluation, Authorization and Restriction of Chemicals regulation provides for mandatory sharing of vertebrate test data to avoid unnecessary duplication of animal use and test costs, and obligation to revise data requirements and test guidelines “as soon as possible” after relevant, validated replacement, reduction or refinement (3R) methods become available. Furthermore, the Organization for Economic Cooperation and Development actively accepts alternative animal tests and 3R to chemical toxicity tests. CONCLUSIONS: Alternative tests which are more ethical and efficient than animal experiments should be widely used to assess the toxicity of chemicals for K-REACH registration. The relevant regulatory agencies will have to make efforts to actively adopt and uptake new alternative tests and 3R to K-REACH.