Environmental thresholds of dragonflies and damselflies from a Cerrado-Caatinga ecotone.

Aquatic ecosystems are affected by different land uses that modify gradients of environmental conditions. These impacts act directly on the community structure, especially the most sensitive ones, such as aquatic insects. Thus, dragonflies have been used as good models to assess these changes, since their suborders Anisoptera and Zygoptera have different ecophysiological and behavioral requirements. This study aimed to evaluate the following hypotheses: (1) dragonfly species composition differs along the environmental gradients of streams; therefore, we expect a higher proportion of species of the suborder Anisoptera in environments with a higher degree of disturbance, since these environmental conditions select heliothermic species with exophytic oviposition; (2) the reduction of habitat integrity and canopy cover will lead to a lower richness of the Zygoptera suborder, due to the restrictions of its thermoregulation and oviposition behavior in relation to Anisoptera, since the higher light input would favor heliothermic and exophytic species; (3) alterations in habitat integrity create ecological thresholds and points of change in the abundance and frequency of Odonata species, generating gradients in the environmental integrity conditions. Specimens were collected from 24 streams (first to third order), in a gradient of land uses. Canopy cover and stream width were predictors of taxonomic richness and abundance of the suborders Anisoptera and Zygoptera, with greater coverage and smaller width, positively affecting Zygoptera and negatively Anisoptera. The turning points were determined by a habitat integrity index, where below 0.38 there is an increase in generalist taxa and a decline in sensitive taxa. On the other hand, above 0.79, there was a sensitive taxa increase in detriment of generalists. Four individual taxa indicators were selected, two of which associated with a negative response (Perithemis tenera and Acanthagrion aepiolum) and two with positive responses (Epipleoneura metallica and Zenithoptera lanei) for habitat integrity. Our results are important to guide management strategies, recovery, and protection policies for areas of permanent protection, aiming to conserving biodiversity and natural resources essential to life quality maintenance.

Screening of DNA-Encoded Small Molecule Libraries inside a Living Cell.

DNA-encoded small molecule libraries (DELs) have facilitated the discovery of novel modulators of many different therapeutic protein targets. We report the first successful screening of a multimillion membered DEL inside a living cell. We demonstrate a novel method using oocytes from the South African clawed frog Xenopus laevis. The large size of the oocytes of 1 µL, or 100 000 times bigger than a normal somatic cell, permits simple injection of DELs, thus resolving the fundamental problem of delivering DELs across cell membranes for in vivo screening. The target protein was expressed in the oocytes fused to a prey protein, to allow specific DNA labeling and hereby discriminate between DEL members binding to the target protein and the endogenous cell proteins. The 194 million member DEL was screened against three pharmaceutically relevant protein targets, p38α, ACSS2, and DOCK5. For all three targets multiple chemical clusters were identified. For p38α, validated hits with single digit nanomolar potencies were obtained. This work demonstrates a powerful new approach to DEL screening, which eliminates the need for highly purified active target protein and which performs the screening under physiological relevant conditions and thus is poised to increase the DEL amenable target space and reduce the attrition rates.

A new imaging technology based on Compton X-ray scattering.

A feasible implementation of a novel X-ray detector for highly energetic X-ray photons with a large solid angle coverage, optimal for the detection of Compton X-ray scattered photons, is described. The device consists of a 20 cm-thick sensitive volume filled with xenon at atmospheric pressure. When the Compton-scattered photons interact with the xenon, the released photoelectrons create clouds of secondary ionization, which are imaged using the electroluminescence produced in a custom-made multi-hole acrylic structure. Photon-by-photon counting can be achieved by processing the resulting image, taken in a continuous readout mode. Based on Geant4 simulations, by considering a realistic detector design and response, it is shown that photon rates up to at least 1011 photons s-1 on-sample (5 µm water-equivalent cell) can be processed, limited by the spatial diffusion of the photoelectrons in the gas. Illustratively, if making use of the Rose criterion and assuming the dose partitioning theorem, it is shown how such a detector would allow obtaining 3D images of 5 µm-size unstained cells in their native environment in about 24 h, with a resolution of 36 nm.

First detection of OsHV-1 in the cephalopod Octopus vulgaris. Is the octopus a dead-end for OsHV-1?

The ostreid herpes virus (OsHV-1), associated with massive mortalities in the bivalve Crassostrea gigas, was detected for the first time in the cephalopod Octopus vulgaris. Wild adult animals from a natural breeding area in Spain showed an overall prevalence of detection of 87.5% between 2010 and 2015 suggesting an environmental source of viral material uptake. Overall positive PCR detections were significantly higher in adult animals (p = 0.031) compared to newly hatched paralarvae (62%). Prevalence in embryos reached 65%. Sequencing of positive amplicons revealed a match with the variant OsHV-1 µVar showing the genomic features that distinguish this variant in the ORF4. Gill tissues from adult animals were also processed for in situ hybridization and revealed positive labelling. Experimental exposure trials in octopus paralarvae were carried out by cohabitation with virus injected oysters and by immersion in viral suspension observing a significant decrease in paralarval survival in both experiments. An increase in the number of OsHV-1 positive animals was detected in dead paralarvae after cohabitation with virus injected oysters. No signs of viral replication were observed based on lack of viral gene expression or visualization of viral structures by transmission electron microscopy. The octopus response against OsHV-1 was evaluated by gene expression of previously reported transcripts involved in immune response in C. gigas suggesting that immune defences in octopus are also activated after exposure to OsHV-1.

Correction to: Scanning electron microscopic observation of the in vitro cultured protozoan, Perkinsus olseni, isolated from the Manila clam, Ruditapes philippinarum.

An amendment to this paper has been published and can be accessed via the original article.

Scanning electron microscopic observation of the in vitro cultured protozoan, Perkinsus olseni, isolated from the Manila clam, Ruditapes philippinarum.

BACKGROUND: Perkinsosis is a major disease affecting the commercially important marine mollusk Ruditapes philippinarum (Manila clam) in Asian waters. In this study, we investigated the morphological characteristics of Perkinsus olseni, the causative agent of perkinsosis, cultured under laboratory conditions at different stages of its life cycle using a scanning electron microscope (SEM). RESULTS: The prezoosporangia formed after induction with Ray's fluid thioglycollate medium (RFTM) developed into zoosporangia. During this process, a discharge tube formed a porous sponge-like structure that detached before the zoospores were released; thus, this organelle operated as a bung. Liberated zoospores gradually transformed into immature trophozoites, during which detachment of the anterior flagella occurred, but the loss of the posterior flagella was not clearly observed in the present study. Mature trophozoites underwent schizogony by cleaving the cell forming some merozoites in schizonts, which were released by the rupturing of the cellular membrane of the schizont within a few days. CONCLUSIONS: Our morphological and ultrastructural studies contribute new information on the life cycle and propagation of P. olseni.

An overview of DNA-encoded libraries: A versatile tool for drug discovery.

DNA-encoded libraries (DELs) are collections of small molecules covalently attached to amplifiable DNA tags carrying unique information about the structure of each library member. A combinatorial approach is used to construct the libraries with iterative DNA encoding steps, facilitating tracking of the synthetic history of the attached compounds by DNA sequencing. Various screening protocols have been developed which allow protein target binders to be selected out of pools containing up to billions of different small molecules. The versatile methodology has allowed identification of numerous biologically active compounds and is now increasingly being adopted as a tool for lead discovery campaigns and identification of chemical probes. A great focus in recent years has been on developing DNA compatible chemistries that expand the structural diversity of the small molecule library members in DELs. This chapter provides an overview of the challenges and accomplishments in DEL technology, reviewing the technological aspects of producing and screening DELs with a perspective on opportunities, limitations, and future directions.

Involvement of sphaeractinomyxon in the life cycle of mugiliform-infecting Myxobolus (Cnidaria, Myxosporea) reveals high functionality of actinospore morphotype in promoting transmission.

Four new actinospore types belonging to the sphaeractinomyxon collective group (Cnidaria, Myxosporea) are described from the coelomic cavity of a marine Baltidrilus sp. (Oligochaeta, Naididae) inhabiting a northern Portuguese estuary. Host identification supports the usage of marine oligochaetes, namely of the family Naididae Ehrenberg, 1828, as definitive hosts for myxosporeans inhabiting estuarine/marine environments. The absence of mixed infections in the host specimens analysed is suggested to reflect the influence of host-, parasite- and environmental-related factors regulating myxosporean-annelid interactions. Molecular analyses matched the SSU rDNA sequences of three of the four new types with those of mugiliform-infecting Myxobolus spp., namely Myxobolus mugiliensis and a Myxobolus sp. from flathead grey mullet Mugil cephalus, and Myxobolus labrosus from thicklip grey mullet Chelon labrosus. These results directly link, for the first time, the sphaeractinomyxon collective group to a myxospore counterpart, further confirming their previously hypothesized specific involvement in the life cycle of myxobolids that infect mullets. Acknowledging this life cycle relationship, the functionality of the sphaeractinomyxon morphotype is suggested to have been decisive for the evolutionary hyperdiversification of the genus Myxobolus in mullets. Unlike other actinospore morphotypes, sphaeractinomyxon lack valvular processes, which implies a limited capability for buoyancy. Considering the benthic-feeding nature of mullets, this feature is most likely crucial in promoting successful transmission to the vertebrate host.

A Pyranoxanthone as a Potent Antimitotic and Sensitizer of Cancer Cells to Low Doses of Paclitaxel.

Microtubule-targeting agents (MTAs) remain a gold standard for the treatment of several cancer types. By interfering with microtubules dynamic, MTAs induce a mitotic arrest followed by cell death. This antimitotic activity of MTAs is dependent on the spindle assembly checkpoint (SAC), which monitors the integrity of the mitotic spindle and proper chromosome attachments to microtubules in order to ensure accurate chromosome segregation and timely anaphase onset. However, the cytotoxic activity of MTAs is restrained by drug resistance and/or toxicities, and had motivated the search for new compounds and/or alternative therapeutic strategies. Here, we describe the synthesis and mechanism of action of the xanthone derivative pyranoxanthone 2 that exhibits a potent anti-growth activity against cancer cells. We found that cancer cells treated with the pyranoxanthone 2 exhibited persistent defects in chromosome congression during mitosis that were not corrected over time, which induced a prolonged SAC-dependent mitotic arrest followed by massive apoptosis. Importantly, pyranoxanthone 2 was able to potentiate apoptosis of cancer cells treated with nanomolar concentrations of paclitaxel. Our data identified the potential of the pyranoxanthone 2 as a new potent antimitotic with promising antitumor potential, either alone or in combination regimens.

The potential role of the sphaeractinomyxon collective group (Cnidaria, Myxozoa) in the life cycle of mugiliform-infecting myxobolids, with the morphological and molecular description of three new types from the oligochaete Tubificoides insularis.

Three new types of sphaeractinomyxon (Cnidaria, Myxozoa) are described from the coelomic cavity of the marine oligochaete Tubificoides insularis, collected from the Alvor estuary, Algarve, Portugal. Another known type is also registered from this location and host: Sphaeractinomyxon type 10 of Rangel et al. (2016), which was originally described from the marine oligochaete Tubificoides pseudogaster in the Aveiro estuary, Portugal. Phylogenetic analysis revealed the case isolates and all other available SSU rRNA sequences of sphaeractinomyxon clustering within a clade containing Myxobolus spp. that infect mullets, thus suggesting that this collective group plays a role in the life cycle of mugiliform-infecting myxobolids. Also clustering within this clade were all types of tetraspora and endocapsa, calling into question the distinctiveness of these collective groups. Acknowledging a previous work showing that the pansporocysts of sphaeractinomyxon produce a variable number of actinospores, we suggest that the tetraspora collective group be deemed invalid and its types transferred to sphaeractinomyxon. In turn, endocapsa requires validation through the description of new types truly differentiating them from sphaeractinomyxon.

New actinosporean description prompts union of the raabeia and echinactinomyxon collective groups (Cnidaria, Myxozoa).

We describe, morphologically and molecularly, a new actinosporean from the intestinal epithelium of the freshwater oligochaete Ilyodrilus templetoni in the upper estuary of the River Minho, Northern Portugal. Mature actinospores resembled both echinactinomyxon and raabeia types, emphasizing the previously known lack of a clear boundary between these 2 collective groups. Historically, raabeia and echinactinomyxon types have been differentiated solely based on the shape of the valvular processes being curved or straight, respectively. Our observations, however, show that this morphological character is too variable for distinguishing between these 2 collective groups, since the actinospores of the raabeia described here displayed valvular processes that could either be straight, downward or upward curved. Several similar cases can be found in the available literature. Considering this overlap in actinospore morphology, we propose that echinactinomyxon be deemed invalid and its types be included in raabeia, as the latter constitutes the older of the 2 groups. Known echinactinomyxon types, however, should not be renamed as raabeia, as this would create unnecessary confusion. Accordingly, a more comprehensive definition of the raabeia collective group is provided. Phylogenetic analyses revealed polyphyletic clustering of raabeia/echinactinomyxon types among members of the myxosporean suborders Variisporina and Platysporina, reiterating the lack of agreement between actinosporean morphotypes and myxosporean genera. The new type described here specifically clusters within the Paramyxidium clade, alongside other SSU rDNA sequences of raabeia, echinactinomyxon, aurantiactinomyxon and synactinomyxon. Considering that most Paramyxidium spp. parasitize Anguilla anguilla (Linnaeus, 1758), future myxozoan surveys in the River Minho should include this species.

Myxozoan biodiversity in mullets (Teleostei, Mugilidae) unravels hyperdiversification of Myxobolus (Cnidaria, Myxosporea).

Mullets are ecologic and commercially important fish species. Their ubiquitous nature allows them to play critical roles in freshwater and marine ecosystems but makes them more vulnerable to diseases and parasitic infection. In this study, a myxozoan survey was performed on three species of mullet captured from a northern Portuguese river. The results disclose a high biodiversity, specifically due to the hyperdiversification of Myxobolus. Thirteen new species of this genus are described based on microscopic and molecular procedures: 7 from the thinlip grey mullet Chelon ramada, 2 from the thicklip grey mullet Chelon labrosus, and 4 from the flathead grey mullet Mugil cephalus. Myxobolus exiguus and Ellipsomyxa mugilis are further registered from their type host C. ramada, as well as six more myxospore morphotypes that possibly represent distinct Myxobolus species. Overall, the results obtained clearly show that the number of host-, site- and tissue-specific Myxobolus spp. is much higher than what would be expected in accordance to available literature. This higher biodiversity is therefore discussed as either being the result of the usage of poor discriminative criteria in previous studies, or as being a direct consequence of the biological and ecological traits of the parasite and of its vertebrate and invertebrate host communities. Bayesian inference, maximum likelihood and maximum parsimony analyses position the new species within a clade comprising all other Myxobolus spp. that infect mugiliform hosts, thus suggesting that this parasitic group has a monophyletic origin. Clustering of species in relation to the host genus is also revealed and strengthens the contention that the evolutionary history of mugiliform-infecting Myxobolus reflects that of its vertebrate hosts. In this view, the hyperdiversification of Myxobolus in mullet hosts is hypothesized to correlate with the processes of speciation that led to the ecological plasticity of mullets.

Description of a new myxozoan Kudoa eugerres n. sp. and reclassification of two Sphaerospora sensu lato species.

Ultrastructural and phylogenetic description of a fish-infecting myxosporean found infecting the gallbladder wall of the teleostean Eugerres brasilianus Cuvier, 1830, collected from the Atlantic coast near the city of Maceió (Alagoas State), Brazil. Groups of mature pseudo-conical myxospores, agglutinated forming pseudocyst structures, occurring in the mucosa of gallbladder were 5.2 ± 0.8 µm (4.5-6.0) (n = 30) long, 4.3 ± 0.6 µm (3.8-4.7) (n = 25) thick, and 2.9 ± 0.2 µm (2.7-3.2) (n = 25) wide. The two ellipsoidal polar capsules, 1.8 ± 0.4 × 1.2 ± 0.4 µm (n = 25), opened close to the sutural line, each containing an isofilar polar tubule. The latter consisted of a single coil with five to six turns, arranged obliquely to the axis of the polar capsule. This myxosporean parasite, while being morphologically similar to Sphaerospora spp., displays tissue tropism and phylogenetic relationships distinct from the latter. Bayesian inference (BI) and maximum likelihood (ML) analyses showed the parasite and two other related species clustering within the marine clade, more specifically within a subclade of the larger Kudoa (Multivalvulida) clade. Consequently, this atypical new myxozoan species was classified as Kudoa eugerres n. sp. and two other histozoic Sphaerospora spp. sensu lato were transferred to the genus Kudoa.

Structures, Activities and Drug-Likeness of Anti-Infective Xanthone Derivatives Isolated from the Marine Environment: A Review.

Marine organisms represent almost half of total biodiversity and are a very important source of new bioactive substances. Within the varied biological activities found in marine products, their antimicrobial activity is one of the most relevant. Infectious diseases are responsible for high levels of morbidity and mortality and many antimicrobials lose their effectiveness with time due to the development of resistance. These facts justify the high importance of finding new, effective and safe anti-infective agents. Among the variety of biological activities of marine xanthone derivatives, one that must be highlighted is their anti-infective properties. In this work, a literature review of marine xanthones with anti-infective activity, namely antibacterial, antifungal, antiparasitic and antiviral, is presented. Their structures, biological activity, sources and the methods used for bioactivity evaluation are described. The xanthone derivatives are grouped in three sets: xanthones, hydroxanthones and glycosylated derivatives. Moreover, molecular descriptors, biophysico-chemical properties, and pharmacokinetic parameters were calculated, and the chemical space occupied by marine xanthone derivatives is recognized. The chemical space was compared with marketed drugs and framed accordingly to the drug-likeness concept in order to profile the pharmacokinetic of anti-infective marine xanthone derivatives.

Evaluating the habitat integrity index as a potential surrogate for monitoring the water quality of streams in the cerrado-caatinga ecotone in northern Brazil.

Human activities have long been altering the natural conditions of streams, including the quality of their water, throughout most of Brazil. This problem is even worse in regions with low rainfall levels, such as the Brazilian Northeast, where water quality needs to be monitored more carefully. In this context, the present study investigated the effects of environmental integrity on the physicochemical characteristics of the streams of the basin of the Itapecuru River in northeastern Brazil. We tested the hypothesis that streams with lower habitat integrity would have higher conductivity, pH, and temperature, due to the reduced input of allochthonous organic matter and the greater washout of sediments to the stream bed. A total of 15 streams, of a sedimentary basin, were evaluated in the municipality of Caxias, in the Brazilian state of Maranhão, between June 2015, and July 2016; each stream was sampled once a month during the drought period in the region, where physicochemical measurements were taken to determine the environmental integrity of the stream through the application of a habitat integrity index. Streams with greater habitat integrity had lower conductivity, pH, and temperature and had higher discharge rates. The index proved to be not an effective tool for the evaluation of water quality, but was found to be important for the management of hydrographic basins by indicating important changes in environmental variables. In this case, the index can be used primarily for the management of hydrographic basins, given that it can be applied straightforwardly, it can be interpreted easily by decision-makers, and it can quantify alterations to the structure of the system with precision.

Simultaneous occurrence of two new myxosporean species infecting the central nervous system of Hypopygus lepturus from Brazil.

This paper describes 2 new myxosporean species, Henneguya lepturus sp. nov. and Thelohanellus lepturus sp. nov., simultaneously infecting the brain and spinal cord of Hypopygus lepturus Hoedeman, 1962 (Teleostei, Hypopomidae) from the Brazilian Amazon (Roraima State). Several spherical cysts of varying dimensions (up to 135 µm) were microscopically observed. The myxospores of H. lepturus sp. nov. measured 25.8 µm in total length, having an ellipsoidal body (12.4 × 6.4 × 2.2 µm) and 2 equal tapering tails (13.4 µm in length). Each of the 2 pyriform polar capsules measured 4.4 × 1.6 µm and possessed a polar filament coiled in 8-9 turns. The myxospores of T. lepturus sp. nov. were pyriform, formed by 2 equal valves (17.7 × 9.1 × 4.3 µm) surrounding a single polar capsule (10.9 × 3.5 µm) that had a coiled polar filament with 13-16 turns and a binucleated sporoplasm that contained several circular sporoplasmosomes. Molecular analysis of the small subunit (SSU) rRNA gene sequences of these 2 species were in agreement with the taxonomic classification derived from the ultrastructure of the myxospores. Histopathology of the host tissue showed degradation of the myelinated axons surrounding the cysts of both species, with the hosts displaying behavioural changes and erratic movements when observed in an aquarium.

Ultrastructural and molecular characteristics of Kudoa crenimugilis n. sp. infecting intestinal smooth muscle of fringelip mullet Crenimugil crenilabis in the Red Sea.

This study describes infection of intestinal smooth muscle in fringelip mullets Crenimugil crenilabis with Kudoa crenimugilis n. sp. Of 30 individuals sampled from the Red Sea off Saudi Arabia, 6 (20%) were infected. Ovoid plasmodia (279-412 × 157-295 µm) in the smooth muscle of the intestine were packed with only mature myxospores with 4 valves. Specifically, light and transmission electron microscopy revealed quadrate myxospores with 4 equal, rounded, spore valves uniting at thin delicate suture lines. The mature myxospores were 8 (7-9) µm long, 5.2 (5-6) µm thick and 7.8 (7-8) µm wide. The 4 polar capsules were equal-sized, elliptical to ovoid, and measured 5 (4-5) µm long and 2 (1.5-3) µm wide, possessing 2 filament coils. The sporoplasm was uninucleated and composed of a primary cell enveloping a secondary cell. The parasite had a significant histopathological impact since the developing plasmodia replaced normal muscle tissue and was associated with the myolysis of local muscle fibres and the inflammatory infiltration of lymphocytes and macrophages. The partial sequences of the 18S and 28S rDNA showed that K. crenimugilis n. sp. has the highest level of nucleotide similarity with K. ciliatae (98.46 and 94.11%, respectively) and K. cookii (97.51 and 92.11%, respectively), both of which have previously been reported from the intestines of their host fish. Phylogenetic analysis revealed that K. crenimugilis consistently clustered with these other 2 intestinal Kudoa species in a well-supported subclade, confirming the evaluative association between Kudoa species infecting the same organs.

Probe-Dependent Negative Allosteric Modulators of the Long-Chain Free Fatty Acid Receptor FFA4.

High-affinity and selective antagonists that are able to block the actions of both endogenous and synthetic agonists of G protein-coupled receptors are integral to analysis of receptor function and to support suggestions of therapeutic potential. Although there is great interest in the potential of free fatty acid receptor 4 (FFA4) as a novel therapeutic target for the treatment of type II diabetes, the broad distribution pattern of this receptor suggests it may play a range of roles beyond glucose homeostasis in different cells and tissues. To date, a single molecule, 4-methyl-N-9H-xanthen-9-yl-benzenesulfonamide (AH-7614), has been described as an FFA4 antagonist; however, its mechanism of antagonism remains unknown. We synthesized AH-7614 and a chemical derivative and demonstrated these to be negative allosteric modulators (NAMs) of FFA4. Although these NAMs did inhibit FFA4 signaling induced by a range of endogenous and synthetic agonists, clear agonist probe dependence in the nature of allosteric modulation was apparent. Although AH-7614 did not antagonize the second long-chain free fatty acid receptor, free fatty acid receptor 1, the simple chemical structure of AH-7614 containing features found in many anticancer drugs suggests that a novel close chemical analog of AH-7614 devoid of FFA4 activity, 4-methyl-N-(9H-xanthen-9-yl)benzamide (TUG-1387), will also provide a useful control compound for future studies assessing FFA4 function. Using TUG-1387 alongside AH-7614, we show that endogenous activation of FFA4 expressed by murine C3H10T1/2 mesenchymal stem cells is required for induced differentiation of these cells toward a more mature, adipocyte-like phenotype.

Polyunsaturated fatty acid receptors, GPR40 and GPR120, are expressed in the hypothalamus and control energy homeostasis and inflammation.

BACKGROUND: The consumption of large amounts of dietary fats is one of the most important environmental factors contributing to the development of obesity and metabolic disorders. GPR120 and GPR40 are polyunsaturated fatty acid receptors that exert a number of systemic effects that are beneficial for metabolic and inflammatory diseases. Here, we evaluate the expression and potential role of hypothalamic GPR120 and GPR40 as targets for the treatment of obesity. METHODS: Male Swiss (6-weeks old), were fed with a high fat diet (HFD, 60% of kcal from fat) for 4 weeks. Next, mice underwent stereotaxic surgery to place an indwelling cannula into the right lateral ventricle. intracerebroventricular (icv)-cannulated mice were treated twice a day for 6 days with 2.0 µL saline or GPR40 and GPR120 agonists: GW9508, TUG1197, or TUG905 (2.0 µL, 1.0 mM). Food intake and body mass were measured during the treatment period. At the end of the experiment, the hypothalamus was collected for real-time PCR analysis. RESULTS: We show that both receptors are expressed in the hypothalamus; GPR120 is primarily present in microglia, whereas GPR40 is expressed in neurons. Upon intracerebroventricular treatment, GW9508, a non-specific agonist for both receptors, reduced energy efficiency and the expression of inflammatory genes in the hypothalamus. Reducing GPR120 hypothalamic expression using a lentivirus-based approach resulted in the loss of the anti-inflammatory effect of GW9508 and increased energy efficiency. Intracerebroventricular treatment with the GPR120- and GPR40-specific agonists TUG1197 and TUG905, respectively, resulted in milder effects than those produced by GW9508. CONCLUSIONS: GPR120 and GPR40 act in concert in the hypothalamus to reduce energy efficiency and regulate the inflammation associated with obesity. The combined activation of both receptors in the hypothalamus results in better metabolic outcomes than the isolated activation of either receptor alone.

Ultrastructural morphology and phylogeny of Henneguya gilbert n. sp. (Myxozoa) infecting the teleostean Cyphocharax gilbert (Characiformes: Curimatidae) from Brazil.

This paper describes light and ultrastructural observations and molecular analysis of a fish-infecting myxosporean, Henneguya gilbert n. sp., which was found infecting the gill epithelium of the commercially important freshwater teleost fish Cyphocharax gilbert (Curimatidae) collected in the estuarine region of Guandu River, Rio de Janeiro State, Brazil. The parasite occurs in the gills, forming whitish spherical to ellipsoidal polysporic cysts measuring up to ~ 750 µm, and displaying asynchronous development. Mature myxospores are ellipsoidal with a bifurcated caudal process. The length, width and thickness of the body of the myxospore are 12.0 × 5.3 × 3.6 µm, respectively; two equal caudal processes are 16.8 µm long, and the total length of the myxospore is 27.2 µm. There are two unequal polar capsules: the larger measures 5.5 µm length × 1.3 µm width and has a polar filament with 9-10 coils; the smaller is 4.0 µm long × 1.3 µm wide and has a polar filament with 7-8 coils. The sporoplasm is binucleated and presents a spherical vacuole surrounded by numerous globular sporoplasmosomes. Phylogenetic analysis, based on the small subunit rRNA sequencing, using maximum likelihood method reveals the parasite clustering together with other myxobolids that are histozoic and parasitize freshwater fish of the order Characiformes, thereby strengthening the contention that the host phylogenetic relationships and aquatic environment are the strongest evolutionary signals for myxosporeans of the family Myxobolidae.