VCF/Plotein: visualization and prioritization of genomic variants from human exome sequencing projects.

MOTIVATION: Identifying disease-causing variants from exome sequencing projects remains a challenging task that often requires bioinformatics expertise. Here we describe a user-friendly graphical application that allows medical professionals and bench biologists to prioritize and visualize genetic variants from human exome sequencing data. RESULTS: We have implemented VCF/Plotein, a graphical, fully interactive web application able to display exome sequencing data in VCF format. Gene and variant information is extracted from Ensembl. Cross-referencing with external databases and application-based gene and variant filtering have also been implemented. All data processing is done locally by the user's CPU to ensure the security of patient data. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at https://vcfplotein.liigh.unam.mx. Website implemented in JavaScript using the Vue.js framework, with all major browsers supported. Source code freely available for download at https://github.com/raulossio/VCF-plotein. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Effects of the Morphology, Surface Modification and Application Methods of ZnO-NPs on the Growth and Biomass of Tomato Plants.

Benefits of nanotechnology in agriculture include reduced fertilizer loss, improved seed germination rate and increased crops quality and yield. The objective of this research was to evaluate the effects of zinc oxide nanoparticles (ZnO-NPs), at 1500 ppm, on tomato (Solanum lycopersicum L.) growth. ZnO-NPs were synthetized to produce either spherical or hexagonal morphologies. In this research, we also studied two application methods (foliar and drench) and nanoparticles' (NPs) surface modification with maltodextrin. The results obtained indicate that ZnO-NP-treated tomato plants significantly increased plant height, stem diameter and plant organs (leaves, stem and root) dry weight compared to plants without NP treatment.

A new automatic method for tracking rats in the Morris water maze.

Morris water maze (MWM) test is widely used to evaluate the learning and memory deficits in rodents. Image processing and pattern recognition can be used to analyse videos and recognize automatically the tracking in MWM. There are several commercial and free access software that allows analyzing the behavioral tasks although they also have limitations such as automation, cost, user intervention among other things. The aim of this paper was to develop a new image processing technique to automatically analyse the track of the rat in the MWM, which we called RatsTrack. The MWM test was performed with an animal model for Alzheimer, and the videos were recorded to measure the distance, time, and speed. The segmentation method based on the projection of the video frames was made for pool identification, eliminating the rat, while conserving the shape of the pool. Then, the Hough transformation was used to recognize the position and radius of the pool. Finally, the frame in which the rat is released into the pool was established automatically using mathematical morphology techniques and added as a plugin on free access ImageJ software. The new image processing technique, RatsTrack, successfully detected and located the pool and rat without user intervention, significantly decreasing operational time and providing results for distance, time, speed, and acceleration parameters of the MWM test. Alzheimer's rats compared with the control group presented significant data measured with the RatsTrack. RatsTrack is a plugin of ImageJ software and will be made freely available for public use.

Covered Rutile-TiO2 Nanoparticles Enhance Tomato Yield and Growth by Modulating Gas Exchange and Nutrient Status.

Nanotechnology has developed materials that can increase food production while reducing the use of conventional fertilizers. In this study, the effect of two forms of application (foliar and drench) as well as covering or non-covering of the surface of titanium dioxide nanoparticles (nTiO2) with maltodextrin (MDX) at 1500 ppm was investigated on tomato plants. The results show that treatment of tomato with nTiO2 increased yield (+21%), while covering the surface of the NPs resulted in a further yield increase (+27%). Similar trends were observed in the dry weight of vegetative plant parts. Fruit firmness (+33%) and total soluble solids (+36%) were enhanced by MDX-covered nTiO2. Application of nTiO2 resulted in enhanced SPAD index, photosynthesis rate, NO3-, K, and Ca concentration in the petiole sap, whereas in the fruits there was an increase in P and K in MDX-covered nTiO2. Considering the dilution effect due to the higher fruit yield, N, P, Mg, Cu, and B increased in plants treated with nTiO2. Covering the surface with MDX resulted in an enhanced response to nTiO2, as fruit yield and quality increased compared to plants treated with non-covered nTiO2.

PulmonDB: a curated lung disease gene expression database.

Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) have contrasting clinical and pathological characteristics and interesting whole-genome transcriptomic profiles. However, data from public repositories are difficult to reprocess and reanalyze. Here, we present PulmonDB, a web-based database (http://pulmondb.liigh.unam.mx/) and R library that facilitates exploration of gene expression profiles for these diseases by integrating transcriptomic data and curated annotation from different sources. We demonstrated the value of this resource by presenting the expression of already well-known genes of COPD and IPF across multiple experiments and the results of two differential expression analyses in which we successfully identified differences and similarities. With this first version of PulmonDB, we create a new hypothesis and compare the two diseases from a transcriptomics perspective.

Distribution of alpha-neoendorphin, ACTH (18-39) and beta-endorphin (1-27) in the alpaca brainstem.

Using an immunocytochemical technique, we have studied in the alpaca brainstem the distribution of immunoreactive structures containing prodynorphin (alpha-neoendorphin)- and pro-opiomelanocortin (adrenocorticotrophin hormone (18-39) (ACTH), beta-endorphin (1-27))-derived peptides. No peptidergic-immunoreactive cell body was observed. Immunoreactive fibres were widely distributed, although in most of the brainstem nuclei the density of the peptidergic fibres was low or very low. In general, the distribution of the immunoreactive fibres containing the peptides studied was very similar. A close anatomical relationship occurred among the fibres containing alpha-neoendorphin, ACTH or beta-endorphin (1-27), suggesting a functional interaction among the three peptides in many of the brainstem nuclei. The number of fibres belonging to the prodynorphin system was higher than that of the pro-opiomelanocortin system. A moderate/low density of immunoreactive fibres was observed in 65.11% (for alpha-neoendorphin (1-27)), 18.18% (for ACTH) and 13.95% (for beta-endorphin) of the brainstem nuclei/tracts. In the alpaca brainstem, a high density of immunoreactive fibres was not observed. The neuroanatomical distribution of the immunoreactive fibres suggests that the peptides studied are involved in auditory, motor, gastric, feeding, vigilance, stress, respiratory and cardiovascular mechanisms, taste response, sleep-waking cycle and the control of pain transmission.

The avian community of the Karen Mogensen Reserve, a wealth of biodiversity within the poorly investigated and threatened environments of northwestern Costa Rica.

Despite being characterized by some of the most threatened forest ecosystems of Mesoamerica, the Nicoya Peninsula is among the least known regions of neotropical Costa Rica in terms of its birdlife. Within this region, in the framework of an ongoing international cooperation program between Italy and Costa Rica, we had the opportunity to investigate the Karen Mogensen Reserve, a protected area distinguished by the presence of a variety of habitats, including tropical dry forest and moist forest. Species richness in the Reserve was relatively high compared with similar areas in northwestern Costa Rica. A series of surveys carried out over a 20-year period documented an avian community consisting of 207 species, of which 115 were breeding in the zone and another 14 were potentially breeding. We recorded five IUCN globally Vulnerable or Near-Threatened species, along with six species reported for the first time from the Nicoya Peninsula, each representing range extension of more than 100 km. Twenty-six species, mostly breeding in the area, are at their southernmost range borders, and are likely susceptible to global environmental alterations, such as the effects of climate change. Furthermore, our study revealed the presence of two species endemic to a restricted area of Central America and four subspecies endemic to Costa Rica, along with breeding populations of two species that are geographically isolated from the main ones. The present analysis led to the ecological characterization of the resident avian community, showing that 65% of the species are strictly associated with forested environments, and especially with the understory or middle tree level, hence more vulnerable to environmental change (climatic, anthropogenic, etc.) and susceptible to local extinction. These results underscore the importance of the Karen Mogensen Reserve for bird conservation within a vulnerable environmental context, and warrant the continuation of periodic bird surveys, taxonomic study of isolated populations or endemic taxa, and improvement of local conservation measures. The data collected will be an important tool for future studies aimed at evaluating the consequences of habitat fragmentation and to monitor the effects of climate change on the resident avifauna. We exhort the creation of programs that integrate bird monitoring, ecological research, conservation initiatives, and the involvement of the local communities, by promoting environmental education, capacity-building, and income generation. To this purpose, the Karen Mogensen Reserve may represent a convincing model and valuable example to apply in similar neotropical contexts.

Supplementary calcium ameliorates ammonium toxicity by improving water status in agriculturally important species.

Fertilization of agricultural plants with ammonium [Formula: see text] is often desirable because it is less susceptible to leaching than nitrate [Formula: see text] reducing environmental pollution, risk to human health and economic loss. However, a number of important agricultural species exhibit a reduction in growth when fertilized with [Formula: see text] and increasing the tolerance to [Formula: see text] may be of importance for the establishment of sustainable agricultural systems. The present study explored the feasibility of using calcium (Ca) to increase the tolerance of bell pepper (Capsicum annuum) to [Formula: see text] fertilization. Although [Formula: see text] at proportions ≥25 % of total nitrogen (N) decreased leaf dry mass (DM), supplementary Ca ameliorated this decrease. Increasing [Formula: see text] resulted in decreased root hydraulic conductance (Lo) and root water content (RWC), suggesting that water uptake by roots was impaired. The [Formula: see text]-induced reductions in Lo and RWC were mitigated by supplementary Ca. Ammonium induced increased damage to the cell membranes through lipid peroxidation, causing increased electrolyte leakage; Ca did not reduce lipid peroxidation and resulted in increased electrolyte leakage, suggesting that the beneficial effects of Ca on the tolerance to [Formula: see text] may be more of a reflection on its effect on the water status of the plant. Bell pepper plants that received [Formula: see text] had a low concentration of [Formula: see text] in the roots but a high concentration in the leaves, probably due to the high nitrate reductase activity observed. Ammonium nutrition depressed the uptake of potassium, Ca and magnesium, while increasing that of phosphorus. The results obtained in the present study indicate that [Formula: see text] caused growth reduction, nutrient imbalance, membrane integrity impairment, increased activity of antioxidant enzymes and affected water relations. Supplementary Ca partially restored growth of leaves by improving root Lo and water relations, and our results suggest that it may be used as a tool to increase the tolerance to [Formula: see text] fertilization.

Immunocytochemical distribution of Met-enkephalin-Arg6-Gly7-Leu8 (Met-8) in the auditory system of the rat.

Methionine-enkephalin-Arg(6)-Gly(7)-Leu(8) (Met(8)) is known to act as a neurotransmitter or neuromodulator and it has been implicated in pain, cardiovascular and motor mechanisms, but its role in audition is currently unknown. In the present study we have applied an immunocytochemical technique and describe the distribution of cell bodies and fibers containing Met(8) in the auditory pathway of the rat. The main finding is that we found either Met(8)-immunoreactive fibers or cell bodies or both in virtually all nuclei of the rat auditory system except for the medial superior olive and the ventral division of the medial geniculate body in which we did not find any immunoreactivity for Met(8). This suggests that the neuropeptide Met(8) is widely distributed throughout the auditory system of the rat. Our results suggest that Met(8) could play at least two roles in hearing. It seems to be involved in the processing of the descending auditory pathway, and it may be implicated in the multisensory integration of auditory information that takes place in the non-lemniscal auditory pathway.

In vitro osteoinductive effects of hydroxycholesterol on human adipose-derived stem cells are mediated through the hedgehog signaling pathway.

BACKGROUND: Human adipose-derived stem cells have been identified as a potential source of cells for use in bone tissue engineering because of their ready availability, ease of harvest, and susceptibility to osteogenic induction. The authors have previously demonstrated the ability of an osteogenic molecule called hydroxycholesterol, an oxidative derivative of cholesterol, to induce osteogenic differentiation in pluripotent murine and rabbit bone marrow stromal cells. In this study, the authors examine the ability of hydroxycholesterol to induce osteogenesis in human adipose-derived stem cells. METHODS: Human adipose-derived stem cells were isolated from raw human lipoaspirates through standard isolation and expansion of the stromal vascular fraction. Cells were plated onto tissue culture plates in control medium and harvested between passages 2 and 3, incubated with conventional osteogenic media, and treated with various concentrations (1, 5, and 10 µM) of the 20(S) analogue of hydroxycholesterol. Evaluation of cellular osteogenic activity was performed. The role of the hedgehog signaling pathway in hydroxycholesterol-mediated osteogenesis was evaluated by hedgehog inhibition assays. RESULTS: Alkaline phosphatase activity, bone-related gene expression, and mineralization were all significantly increased in cultures of human adipose-derived stem cells treated with 5 µM of 20(S)-hydroxycholesterol relative to controls. In addition, induction of hydroxycholesterol-mediated osteogenesis was mitigated by the addition of the hedgehog pathway inhibitor to cell cultures, implicating the hedgehog signaling pathway in the osteogenic mechanism on human adipose-derived stem cells by hydroxycholesterol. CONCLUSION: These in vitro studies demonstrate that hydroxycholesterol exerts an osteoinductive influence on human adipose-derived stem cells and that these effects are mediated at least in part through the hedgehog signaling pathway.

Fast and mechanistic ultrasound simulation using a point source/receiver approach.

Ultrasound simulators relying on impulse response methods are faithful to the mechanisms of image formation from the underlying radio-frequency signals, but as a result tend to be relatively slow. At the other extreme are fast techniques, often motivated by the development of teaching and training simulators, which approximate the image formation processes rather than rigorously modeling the underlying physics. Previously, we have shown that transmit field distributions from linear phased-array transducers can be modeled accurately and efficiently using arrays of point sources. This approach is now extended to point sources/receivers, which allows for simulation of the transmit/receive fields, and thus the physical processes underlying ultrasound image formation. Field distributions and fast-time signals are shown to compare favorably to those obtained using the impulse response method. Doppler spectrogram and B-mode images derived from these signals also show excellent agreement with the results obtained using the impulse response method, but with a computational savings of nearly two orders of magnitude. Because of the inherent simplicity of our Fast and Mechanistic Ultrasound Simulation (FAMUS) approach, CPU parallelization was readily achieved, and further orders of magnitude speed improvements, and thus real-time performance, can be anticipated via extension to modern graphics processing units.

On the synthesis of sample volumes for real-time spectral Doppler ultrasound simulation.

A variety of methods for simulating the ultrasound field produced by transducers are currently used in ultrasound imaging system design. However, simulations can be time-consuming, making them difficult to apply in real-time environments when the observation field changes rapidly with time. This is particularly true for interactive real-time Doppler and B-mode ultrasound simulators designed for use as training tools. In this paper, it is demonstrated that the use of a distribution of monopole sources can be used to simulate the field from a phased linear array and the accuracy should be sufficient for simulating pulsed spectral Doppler. Very good agreement can be achieved in comparison with that obtained by a more exact method and, because of the simplicity of the calculations, real-time simulations of flow in the arterial system becomes possible. Specifically, quantitative measurements were made and compared against an analytic solution for the case of a piston transducer and against Field II for the phased array. The root-mean-square error shows that it is possible to achieve 10% or less error for the latter case. For comparable conditions, the computational speed for the transmit field of phased array using the Field II method as compared with the monopole approach was found to be at least an order of magnitude faster. It is pointed out that the simplicity of the monopole approach provides the opportunity for a further order of magnitude gain. Our findings can have direct application on the simulation of spectral Doppler and other ultrasound techniques for the purpose of teaching and training.