Viability and Burden of Leishmania in Extralesional Sites during Human Dermal Leishmaniasis

Understanding of the dynamics and distribution of Leishmania in the human host is fundamental to the targeting of control measures and their evaluation. Amplification of parasite gene sequences in clinical samples from cutaneous leishmaniasis patients has provided evidence of Leishmania in blood, other tissues and sites distinct from the lesion and of persistence of infection after clinical resolution of disease. However, there is uncertainty about the interpretation of the presence of Leishmania DNA as indicative of viable parasites. Because RNA is short-lived and labile, its presence provides an indicator of viability. We amplified Leishmania 7SLRNA, a molecule involved in intracellular protein translocation, to establish viability and estimate parasite load in blood monocytes, tonsil swab samples, and tissue fluid from healthy skin of patients with dermal leishmaniasis. Results showed that during active dermal leishmaniasis, viable Leishmania are present in blood monocytes, tonsils and normal skin in quantities similar to that in lesions, demonstrating widespread dissemination of infection and subclinical involvement of tissues beyond the lesion site. Leishmania 7SLRNA will be useful in deciphering the role of human infection in transmission

Efecto de un suplemento alimenticio a base de insumos naturales y componentes bioactivos de siete raíces sobre el comportamiento sexual en ratas

The present study aimed to determine the effect of a food supplement based on natural inputs and bioactive components of plant species on sexual behavior. It is an experimental, prospective and longitudinal investigation. For the test, 150 albino rats were used: 75 females and 75 males of the Holtzmann breed of 12 weeks of age, with an average weight of 200 to 250 g. (males) and 150 - 200 g. (females). Two products were evaluated: One that contained the extract of the roots of seven plant species at doses of 200 and 400mg / kg and Two that contained the product one plus chestnut flour and Sacha inchi at a dose of 830mg / kg. The trial was carried out for 10 weeks and the evaluations were carried out at the eighth, ninth and tenth weeks (days 1, 7 and 14 respectively). Likewise, the evaluation of the biochemical, hematological, testosterone and prostate-specific antigen (PSA) parameters was carried out. Products One at a dose of 400mg / kg and Two at a dose of 830mg / kg showed a significant effect on sexual behavior compared with the control and standard groups (sildenafil 5mg / kg). There were no changes at the biochemical or hematological level. It is concluded that the tested products had an effect on sexual behavior by increasing libido in male rats, without side effects on biochemical and hematological parameters.El presente estudio tuvo como objetivo determinar el efecto de un suplemento alimenticio a base de insumos naturales y componentes bioactivos de especies vegetales sobre el comportamiento sexual. Es una investigación experimental, prospectiva y longitudinal. Para el ensayo se utilizó 150 ratas albinas: 75 hembras y 75 machos de raza Holtzmann de 12 semanas de edad, con un peso promedio de 200 a 250 g. (machos) y de 150 – 200 g. (hembras). Se evaluaron dos productos: Uno que contenía el extracto de las raíces de siete especies vegetales a dosis de 200 y 400mg/kg y Dos que contenía el producto uno más harina de castaña y Sacha inchi a dosis de 830mg/kg. El ensayo se realizó por 10 semanas y las evaluaciones se ejecutaron a la octava, novena y décima semanas (días 1, 7 y 14 respectivamente). Asimismo, se realizó la evaluación de los parámetros bioquímicos, hematológicos, testosterona y antígeno prostático-específico (PSA). Los productos Uno a dosis de 400mg/kg y Dos a dosis de 830mg/kg presentaron efecto significativo sobre el comportamiento sexual comparados con los grupos control y el estándar (sildenafilo 5mg/kg). No se presentaron cambios a nivel bioquímico ni hematológico. Se concluye que los productos ensayados presentaron efecto sobre el comportamiento sexual aumentando la líbido en las ratas machos, sin efectos secundarios sobre los parámetros bioquímicos y hematológicos

Nuevas evidencias acerca de la presencia de una banda de cizallamiento en la secuencia metapelitica de la Formación Silgará, sector Aratoca-Pescadero (region suroccidental del Macizo de Santander)

La secuencia metamórfica de la Formación Silgará que aflora en el sector Pescadero-Aratoca (región suroccidental del Macizo de Santander), presenta evidencias de haber sufrido un importante cizallamiento durante su etapa de exhumación, el cual afectó gran parte de las rocas metamórficas de las zonas del granate y de la estaurolita-distena. Esta deformación dúctil de carácter extensional generó estructuras tales como lineaciones, sombras de presión, zonas de milonitización, pliegues isoclinales recumbentes, pliegues sin raíz, boudines, así como la elongación de cristales de granate y el truncamiento de su zonación química, lo cual apunta a un colapso gravitacional del paleoorógeno Caledoniano en dirección techo hacia el Este. Estos elementos deformacionales, sumados a las evidencias de una importante circulación de fluidos hidrotermales, hacen que esta región del Macizo de Santander merezca especial atención para trabajos de exploración de depósitos mesotermales, especialmente por presentar condiciones favorables para la removilización de oro.The metamorphic sequence of the Silgara Formation that crops out in Pescadero-Aratoca area (southwestern region of the Santander Massif), presents evidences of having suffered an important shear deformation during its exhumation path, which affected great part of the metamorphic rocks from the garnet and staurolitekyanite zones. This ductile deformation of extensional character generated structures such as lineations, pressure shades, milonitization zones, isoclinal recumbent folds, rootless folds, boudins, as well as the elongation of garnet crystals and the truncation of their chemical zonation, which suggest a proccess of gravitational collapse with an East motion, that affected the Caledonian paleo-orogen. These deformational elements, along with the evidences of an important circulation of hydrothermal fluids, make this region of the Santander Massif an important place to pay attention to explore mesotermal deposits, especially for its favorable conditions for the removization of gold

Fault kinematics in northern Central America and coupling along the subduction interface of the Cocos Plate, from GPS data in Chiapas (Mexico), Guatemala and El Salvador

International audienceNew GPS measurements in Chiapas (Mexico), Guatemala and El Salvador are used to constrain the fault kinematics in the North America (NA), Caribbean (CA) and Cocos (CO) plates triple junction area. The regional GPS velocity field is first analysed in terms of strain partitioning across the major volcano-tectonic structures, using elastic half-space modelling, then inverted through a block model. We show the dominant role of the Motagua Fault with respect to the Polochic Fault in the accommodation of the present-day deformation associated with the NA and CA relative motion. The NA/CA motion decreases from 18-22 mm yr−1 in eastern Guatemala to 14-20 mm yr−1 in central Guatemala (assuming a uniform locking depth of 14-28 km), down to a few millimetres per year in western Guatemala. As a consequence, the western tip of the CA Plate deforms internally, with ≃9 mm yr−1 of east-west extension (≃5 mm yr−1 across the Guatemala city graben alone). Up to 15 mm yr−1 of dextral motion can be accommodated across the volcanic arc in El Salvador and southeastern Guatemala. The arc seems to mark the northern boundary of an independent forearc sliver (AR), pinned to the NA plate. The inversion of the velocity field shows that a four-block (NA, CA, CO and AR) model, that combines relative block rotations with elastic deformation at the block boundaries, can account for most of the GPS observations and constrain the overall kinematics of the active structures. This regional modelling also evidences lateral variations of coupling at the CO subduction interface, with a fairly high-coupling (≃0.6) offshore Chiapas and low-coupling (≃0.25) offshore Guatemala and El Salvador

Sperm cryopreservation with supplementation of a-tocopherol and ascorbic acid in freezing media increase sperm function and fertility rate in Atlantic salmon (Salmo salar)

The use of α-tocopherol and ascorbic acid in freezing medium prevents lipoperoxidation and damage by ROS (reactive oxygen species); however, the effects of these antioxidants in salmonid spermatozoa have not been studied. In this work the protective effects of antioxidants on the enzymatic activity and fertilization capacity of frozen Atlantic salmon spermatozoa were studied. Spermatozoa were frozen in Cortland® medium supplemented with 1.3 M DMSO, 0.3 M glucose, 2% BSA and different concentrations of α-tocopherol and ascorbic acid; spermatozoa frozen without antioxidants were used as control and fresh sperm. Samples loaded in 0.5 ml plastic straws were frozen at 68 °C/min (Freeze Control®). Thawing was carried out at 35 °C and post-thawing lipid peroxidation (LPO) was evaluated along with Glutathione (GSH/GSSG) levels; and Glutathione peroxidase (GPx) and Catalase (CAT) activity. Additionally, percentage of motility, mitochondrial membrane potential (ΔΨM), and fertilization rate were assessed. Results showed significantly lower LPO values (expressed as malondialdehyde concentration) in spermatozoa cryopreserved with α-tocopherol (0.1 mM and 0.5 mM) and with combinations of α-tocopherol/ascorbic acid (0.1 mM/1.0 mM and 0.5 mM/10 mM ratios) (p <.05). Moreover, spermatozoa frozen with α-tocopherol/ascorbic acid also exhibited significantly higher GPx and CAT activity as well as GSH/GSSG ratio compared to controls (p <.05). The production of O2 − i also decreased with the combined treatment, however, no statistically significant difference was found compared to controls. Consistently with the improvement in antioxidant defences, the percentage of motility and ΔΨM were highest and significantly different in spermatozoa cryopreserved with α-tocopherol/ascorbic acid 0.1 mM/1.0 mM compared to controls, supporting the significantly higher fertilization rate exhibited by spermatozoa under the same treatmen

Association of prolactin, oxytocin, and homocysteine with the clinical and cognitive features of a first episode of psychosis over a 1-year follow-up

Background: The clinical debut of schizophrenia is frequently a first episode of psychosis (FEP). As such, there is considerable interest in identifying associations between biological markers and clinical or cognitive characteristics that help predict the progression and outcome of FEP patients. Previous studies showed that high prolactin, low oxytocin, and high homocysteine are factors associated with FEP 6 months after diagnosis, at which point plasma levels were correlated with some clinical and cognitive characteristics. Methods: We reexamined 75 patients at 12 months after diagnosis to measure the evolution of these molecules and assess their association with clinical features. Results: At follow-up, FEP patients had lower prolactin levels than at baseline, and patients treated with risperidone or paliperidone had higher prolactin levels than patients who received other antipsychotic agents. By contrast, no changes in oxytocin and homocysteine plasma levels were observed between the baseline and follow-up. In terms of clinical features, we found that plasma prolactin and homocysteine levels were correlated with the severity of the psychotic symptoms in male FEP patients, suggesting that they might be factors associated with psychotic symptomatology but only in men. Together with oxytocin, these molecules may also be related to sustained attention, verbal ability, and working memory cognitive domains in FEP patients. Conclusion: This study suggests that focusing on prolactin, oxytocin, and homocysteine at a FEP may help select adequate pharmacological treatments and develop new tools to improve the outcome of these patients, where sex should also be borne in mind

Supergravity Brane Cosmologies

Solitonic brane cosmologies are found where the world-volume is curved due to the evolution of the dilaton field on the brane. In many cases, these may be related to the solitonic Dp- and M5-branes of string and M-theory. An eleven-dimensional interpretation of the D8-brane cosmology of the massive type IIA theory is discussed in terms of compactification on a torus bundle. Braneworlds are also found in Horava-Witten theory compactified on a Calabi-Yau three-fold. The possibility of dilaton-driven inflation on the brane is discussed.Comment: 7 pages, In press, Physical Review

Temporal evolution of the microbiome, immune system and epigenome with disease progression in ALS mice

Amyotrophic lateral sclerosis (ALS) is a terminal neurodegenerative disease. Genetic predisposition, epigenetic changes, aging and accumulated life-long environmental exposures are known ALS risk factors. The complex and dynamic interplay between these pathological influences plays a role in disease onset and progression. Recently, the gut microbiome has also been implicated in ALS development. In addition, immune cell populations are differentially expanded and activated in ALS compared to healthy individuals. However, the temporal evolution of both the intestinal flora and the immune system relative to symptom onset in ALS is presently not fully understood. To better elucidate the timeline of the various potential pathological factors, we performed a longitudinal study to simultaneously assess the gut microbiome, immunophenotype and changes in ileum and brain epigenetic marks relative to motor behavior and muscle atrophy in the mutant superoxide dismutase 1 (SOD1G93A) familial ALS mouse model. We identified alterations in the gut microbial environment early in the life of SOD1G93A animals followed by motor dysfunction and muscle atrophy, and immune cell expansion and activation, particularly in the spinal cord. Global brain cytosine hydroxymethylation was also altered in SOD1G93A animals at disease end-stage compared to control mice. Correlation analysis confirmed interrelationships with the microbiome and immune system. This study serves as a starting point to more deeply comprehend the influence of gut microorganisms and the immune system on ALS onset and progression. Greater insight may help pinpoint novel biomarkers and therapeutic interventions to improve diagnosis and treatment for ALS patients. This article has an associated First Person interview with the joint first authors of the paper

Literature-based discovery of diabetes- and ROS-related targets

Abstract Background Reactive oxygen species (ROS) are known mediators of cellular damage in multiple diseases including diabetic complications. Despite its importance, no comprehensive database is currently available for the genes associated with ROS. Methods We present ROS- and diabetes-related targets (genes/proteins) collected from the biomedical literature through a text mining technology. A web-based literature mining tool, SciMiner, was applied to 1,154 biomedical papers indexed with diabetes and ROS by PubMed to identify relevant targets. Over-represented targets in the ROS-diabetes literature were obtained through comparisons against randomly selected literature. The expression levels of nine genes, selected from the top ranked ROS-diabetes set, were measured in the dorsal root ganglia (DRG) of diabetic and non-diabetic DBA/2J mice in order to evaluate the biological relevance of literature-derived targets in the pathogenesis of diabetic neuropathy. Results SciMiner identified 1,026 ROS- and diabetes-related targets from the 1,154 biomedical papers (http://jdrf.neurology.med.umich.edu/ROSDiabetes/). Fifty-three targets were significantly over-represented in the ROS-diabetes literature compared to randomly selected literature. These over-represented targets included well-known members of the oxidative stress response including catalase, the NADPH oxidase family, and the superoxide dismutase family of proteins. Eight of the nine selected genes exhibited significant differential expression between diabetic and non-diabetic mice. For six genes, the direction of expression change in diabetes paralleled enhanced oxidative stress in the DRG. Conclusions Literature mining compiled ROS-diabetes related targets from the biomedical literature and led us to evaluate the biological relevance of selected targets in the pathogenesis of diabetic neuropathy.http://deepblue.lib.umich.edu/bitstream/2027.42/78315/1/1755-8794-3-49.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/2/1755-8794-3-49-S7.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/3/1755-8794-3-49-S10.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/4/1755-8794-3-49-S8.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/5/1755-8794-3-49-S3.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/6/1755-8794-3-49-S1.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/7/1755-8794-3-49-S4.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/8/1755-8794-3-49-S2.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/9/1755-8794-3-49-S12.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/10/1755-8794-3-49-S11.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/11/1755-8794-3-49-S9.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/12/1755-8794-3-49-S5.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/13/1755-8794-3-49-S6.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/14/1755-8794-3-49.pdfPeer Reviewe