COmplexome Profiling ALignment (COPAL) reveals remodeling of mitochondrial protein complexes in Barth syndrome

Item does not contain fulltextMOTIVATION: Complexome profiling combines native gel electrophoresis with mass spectrometry to obtain the inventory, composition and abundance of multiprotein assemblies in an organelle. Applying complexome profiling to determine the effect of a mutation on protein complexes requires separating technical and biological variations from the variations caused by that mutation. RESULTS: We have developed the COmplexome Profiling ALignment (COPAL) tool that aligns multiple complexome profiles with each other. It includes the abundance profiles of all proteins on two gels, using a multi-dimensional implementation of the dynamic time warping algorithm to align the gels. Subsequent progressive alignment allows us to align multiple profiles with each other. We tested COPAL on complexome profiles from control mitochondria and from Barth syndrome (BTHS) mitochondria, which have a mutation in tafazzin gene that is involved in remodeling the inner mitochondrial membrane phospholipid cardiolipin. By comparing the variation between BTHS mitochondria and controls with the variation among either, we assessed the effects of BTHS on the abundance profiles of individual proteins. Combining those profiles with gene set enrichment analysis allows detecting significantly affected protein complexes. Most of the significantly affected protein complexes are located in the inner mitochondrial membrane (mitochondrial contact site and cristae organizing system, prohibitins), or are attached to it (the large ribosomal subunit). AVAILABILITY AND IMPLEMENTATION: COPAL is written in python and is available from http://github.com/cmbi/copal. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Complexome analysis of the nitrite - dependent methanotroph Methylomirabilis lanthanidiphila

The atmospheric concentration of the potent greenhouse gases methane and nitrous oxide (N2O) has increased drastically during the last century. Methylomirabilis bacteria can play an import role in controlling the emission of these two gases from natural ecosystems, by oxidizing methane to CO2 and reducing nitrite to N2 without producing N2O. These bacteria have an anaerobic metabolism, but are proposed to possess an oxygen-dependent pathway for the activation of methane. Methylomirabilis bacteria reduce nitrite to NO, and are proposed to dismutate NO into O2 and N2 by a putative NO dismutase (NO-D). The O2 produced in the cell can then be used for the activation of methane by a particulate methane monooxygenase. So far, the metabolic model of Methylomirabilis bacteria was based mainly on (meta)genomics and physiological experiments. Here we applied a complexome profiling approach to determine which of the proposed enzymes are actually expressed in Methylomirabilis lanthanidiphila. To validate the metabolic model, we focused on enzymes involved in respiration, and nitrogen and C1 transformation. All complexes proposed to be involved in nitrite-dependent methane oxidation, were identified in M. lanthanidiphila, including the putative NO-D. Furthermore, several complexes involved in nitrate reduction/nitrite oxidation and NO reduction were detected, which likely play a role in detoxification and redox homeostasis. In conclusion, complexome profiling validated the expression and composition of enzymes proposed to be involved in the energy, methane and nitrogen metabolism of M. lanthanidiphila, thereby further corroborating the metabolically unique and environmentally relevant process of nitrite-dependent methane oxidation

Virtual environment for local and remote control of a robot arm for support in engineering teaching

En este artículo se presenta el diseño e implementación de una plataforma virtual, que permite la simulación y mando local y remoto del brazo robot tipo SCARA llamado UV-CERMA, presente en el Laboratorio de Robótica de la Escuela de Ingeniería Eléctrica y Electrónica de la Facultad de Ingeniería de la Universidad del Valle, el robot UV-CERMA ha estado subutilizado desde hace algunos años debido a lo obsoleto de su sistema de control. La plataforma, enfocada con los lineamientos de educación en ingeniería está compuesta por dos aplicaciones que permiten la simulación y el mando y control locales y remotos para el robot, una de las aplicaciones se programó haciendo uso del paquete de National Instruments LabVIEW y la otra aplicación se realizó por medio de software libre, por medio del lenguaje de código abierto Java, ambos desarrollos implementan los modelos cinemático directo y cinemático inverso, un módulo para la planificación y ejecución de trayectorias, otro módulo para el monitoreo de variables y un modelo 3D del robot. Para la manipulación del robot se tiene una interfaz con un joystick, que lo hace más versátil. Las aplicaciones se comunican al robot real mediante una tarjeta de adquisición de datos de National Instruments NI USB-6211, y para el mando remoto la plataforma cuenta con una arquitectura cliente/servidor usando sockets TCP/IP.This paper presents the design and implementation of a virtual platform that allows simulation and local and remote command and control of the SCARA robot arm called UV-CERMA, which is installed at the Robotics Laboratory of the Escuela de Ingeniería Eléctrica y Electrónica, Facultad de Ingeniería, Universidad del Valle. The robot has been underutilized for some years due to the obsolete control system. The platform, focused on the engineering education methodology, consists of two applications which simulate the robot and permit its remote and local command and control. One of the applications was implemented on LabVIEW software of National Instruments and the other application was programmed on free software using the open source language Java. Both applications implement forward kinematics and inverse kinematics, have a module for trajectories planning and operation, a module for monitoring the values of the variables and a three dimensional model of the robot. To manipulate the robot, an interface with a joystick was developed, enhancing the versatility of the platform. The applications communicate with the real robot using the National Instruments data acquisition card NI USB-6211, and for the remote connection they have a client-server architecture using TCP/IP sockets

Nicotianamine Synthase 2 Is Required for Symbiotic Nitrogen Fixation in Medicago truncatula Nodules

Symbiotic nitrogen fixation carried out by the interaction between legumes and diazotrophic bacteria known as rhizobia requires relatively large levels of transition metals. These elements are cofactors of many key enzymes involved in this process. Metallic micronutrients are obtained from soil by the roots and directed to sink organs by the vasculature, in a process mediated by a number of metal transporters and small organic molecules that facilitate metal delivery in the plant fluids. Among the later, nicotianamine is one of the most important. Synthesized by nicotianamine synthases (NAS), this molecule forms metal complexes participating in intracellular metal homeostasis and long-distance metal trafficking. Here we characterized the NAS2 gene from model legume Medicago truncatula. MtNAS2 is located in the root vasculature and in all nodule tissues in the infection and fixation zones. Symbiotic nitrogen fixation requires of MtNAS2 function, as indicated by the loss of nitrogenase activity in the insertional mutant nas2-1, phenotype reverted by reintroduction of a wild-type copy of MtNAS2. This would result from the altered iron distribution in nas2-1 nodules shown with X-ray fluorescence. Moreover, iron speciation is also affected in these nodules. These data suggest a role of nicotianamine in iron delivery for symbiotic nitrogen fixation

Epidemiological characterization of ischemic heart disease at different altitudes: a nationwide population-based analysis from 2011 to 2021 in Ecuador

Background Cardiovascular diseases, including ischemic heart disease, are the leading cause of prema- ture death and disability worldwide. While traditional risk factors such as smoking, obesity, and diabetes have been thoroughly investigated, non-traditional risk factors like high-alti- tude exposure remain underexplored. This study aims to examine the incidence and mortal- ity rates of ischemic heart disease over the past decade in Ecuador, a country with a diverse altitude profile spanning from 0 to 4,300 meters. Methods We conducted a geographic distribution analysis of ischemic heart disease in Ecuador, uti- lizing hospital discharge and mortality data from the National Institute of Census and Statis- tics for the years 2011–2021. Altitude exposure was categorized according to two distinct classifications: the traditional division into low ( 2,500 m) altitudes, as well as the classification proposed by the International Society of Mountain Medicine, which delineates low (2500 m. Men had more pronounced rates across altitudes, exhibiting 138.7% and 150.0% higher incidence at low and high altitudes respectively, and mortality rates increased by 48.3% at low altitudes and 23.2% at high altitudes relative to women. Conclusion Ecuador bears a significant burden of ischemic heart disease (IHD), with men being more affected than women in terms of incidence. However, women have a higher percentage of mortality post-hospital admission. Regarding elevation, our analysis, using two different alti- tude cutoff points, reveals higher mortality rates in low-altitude regions compared to high- altitude areas, suggesting a potential protective effect of high elevation on IHD risk. Never- theless, a definitive dose-response relationship between high altitude and reduced IHD risk could not be conclusively established

A prognostic index predicting survival in transformed Waldenström macroglobulinemia

Histological transformation into diffuse large B-cell lymphoma is a rare complication in patients with Waldenström macroglobulinemia (WM) usually associated with a poor prognosis. The objective of this study was to develop and validate a prognostic index for survival in transformed WM patients. Through this multicenter, international collaborative effort, we developed a scoring system based on data from 133 patients with transformed WM who were evaluated between 1995 and 2016 (training cohort). Univariate and multivariate analyses were used to propose a prognostic index with 2-year survival after transformation as an end-point. For external validation, a data set of 67 patients was used to evaluate the performance of the model (validation cohort). By multivariate analysis, three adverse covariates were identified as independent predictors of 2-year survival after transformation: elevated serum LDH (2 points), platelet count < 100 x 109/L (1 point) and any previous treatment for WM (1 point). Three risk groups were defined: low-risk (0-1 point, 24% of patients), intermediate-risk (2-3 points, 59%, hazard ratio (HR) = 3.4) and high-risk (4 points, 17%, HR = 7.5). Two-year survival rates were 81%, 47%, and 21%, respectively (P < 0.0001). This model appeared to be a better discriminant than the International Prognostic Index (IPI) and the revised IPI (R-IPI). We validated this model in an independent cohort. This easy-to-compute scoring index is a robust tool that may allow identification of groups of transformed WM patients with different outcomes and could be used for improving the development of risk-adapted treatment strategies

CEDAR, an online resource for the reporting and exploration of complexome profiling data

Complexome profiling is an emerging ‘omics’ approach that systematically interrogates the composition of protein complexes (the complexome) of a sample, by combining biochemical separation of native protein complexes with mass-spectrometry based quantitation proteomics. The resulting fractionation profiles hold comprehensive information on the abundance and composition of the complexome, and have a high potential for reuse by experimental and computational researchers. However, the lack of a central resource that provides access to these data, reported with adequate descriptions and an analysis tool, has limited their reuse. Therefore, we established the ComplexomE profiling DAta Resource (CEDAR, www3.cmbi.umcn.nl/cedar/), an openly accessible database for depositing and exploring mass spectrometry data from complexome profiling studies. Compatibility and reusability of the data is ensured by a standardized data and reporting format containing the “minimum information required for a complexome profiling experiment” (MIACE). The data can be accessed through a user-friendly web interface, as well as programmatically using the REST API portal. Additionally, all complexome profiles available on CEDAR can be inspected directly on the website with the profile viewer tool that allows the detection of correlated profiles and inference of potential complexes. In conclusion, CEDAR is a unique, growing and invaluable resource for the study of protein complex composition and dynamics across biological systems

Sexual Size Dimorphism and Body Condition in the Australasian Gannet

Funding: The research was financially supported by the Holsworth Wildlife Research Endowment. Acknowledgments We thank the Victorian Marine Science Consortium, Sea All Dolphin Swim, Parks Victoria, and the Point Danger Management Committee for logistical support. We are grateful for the assistance of the many field volunteers involved in the study.Peer reviewedPublisher PD

HPV types and cofactors causing cervical cancer in Peru

We conducted a hospital-based case-control study in Peru of 198 women with histologically confirmed cervical cancer (173 squamous cell carcinomas and 25 cases of adenocarcinoma/adenosquamous carcinoma) and 196 control women. Information on risk factors was obtained by personal interview. Using PCR-based assays on exfoliated cervical cells and biopsy specimens, HPV DNA was detected in 95.3% of women with squamous cell carcinoma and in 92.0% of women with adenocarcinoma/adenosquamous carcinoma compared with 17.7% in control women. The age-adjusted odds ratio was 116.0 (95% Cl = 48.6–276.0) for squamous cell carcinoma and 51.4 (95% Cl = 11.4–232.0) for adenocarcinoma/adenosquamous carcinoma. The commonest types in women with cervical cancer were HPV 16, 18, 31, 52 and 35. The association with the various HPV types was equally strong for the two most common types (HPV 16 and 18) as for the other less common types. In addition to HPV, long-term use of oral contraceptives and smoking were associated with an increased risk. HPV is the main cause of both squamous cell carcinoma and adenocarcinoma in Peruvian women. © 2001 Cancer Research Campaignhttp://www.bjcancer.co