Unique morphological characteristics of mitochondrial subtypes in the heart: the effect of ischemia and ischemic preconditioning.

RATIONALE: Three subsets of mitochondria have been described in adult cardiomyocytes - intermyofibrillar (IMF), subsarcolemmal (SSM), and perinuclear (PN). They have been shown to differ in physiology, but whether they also vary in morphological characteristics is unknown. Ischemic preconditioning (IPC) is known to prevent mitochondrial dysfunction induced by acute myocardial ischemia/reperfusion injury (IRI), but whether IPC can also modulate mitochondrial morphology is not known. AIMS: Morphological characteristics of three different subsets of adult cardiac mitochondria along with the effect of ischemia and IPC on mitochondrial morphology will be investigated. METHODS: Mouse hearts were subjected to the following treatments (N=6 for each group): stabilization only, IPC (3x5 min cycles of global ischemia and reperfusion), ischemia only (20 min global ischemia); and IPC and ischemia. Hearts were then processed for electron microscopy and mitochondrial morphology was assessed subsequently. RESULTS: In adult cardiomyocytes, IMF mitochondria were found to be more elongated and less spherical than PN and SSM mitochondria. PN mitochondria were smaller in size when compared to the other two subsets. SSM mitochondria had similar area to IMF mitochondria but their sphericity measures were similar to PN mitochondria. Ischemia was shown to increase the sphericity parameters of all 3 subsets of mitochondria; reduce the length of IMF mitochondria, and increase the size of PN mitochondria. IPC had no effect on mitochondrial morphology either at baseline or after ischemia. CONCLUSION: The three subsets of mitochondria in the adult heart are morphologically different. IPC does not appear to modulate mitochondrial morphology in adult cardiomyocytes

Diabetes Mellitus (DM) y Enfermedad Pulmonar Obstructiva Crónica (EPOC). Revisión no sistemática. Diabetes mellitus (DM) and Chronic Obstructive Pulmonary Disease (COPD). Non-systematic review

El envejecimiento de la población aumenta la prevalencia de enfermedades crónicas como la diabetes mellitus (DM) y la enfermedad pulmonar obstructiva crónica (EPOC). Diferentes estudios realizados con un diseño de casos y controles y de cohortes confirman la asociación existente entre DM y EPOC. Existen diferentes explicaciones plausibles que relacionan la EPOC y la DM (tabaco, menor actividad física, presencia de un estado pro-inflamatorio y el uso de corti- coides) y también que relacionan y explican el deterioro de la función pulmonar en pacientes con DM, tratándose de una complicación principalmente microvascular. La presente revisión bibliográfica, sin ser una revisión sistemática de la literatura, pretende aproximar la relación existente entre ambas patologías a todos los profesionales implicados en su manejo práctico y aporta una serie de consejos prácticos de manejo del paciente con ambas patologías

OTUB1 inhibits the ubiquitination and degradation of FOXM1 in breast cancer and epirubicin resistance

The forkhead transcription factor FOXM1 has a key role in DNA damage response, and its deregulated overexpression is associated with genotoxic drug resistance in breast cancer. However, little is known about the posttranslational mechanisms by which FOXM1 expression is regulated by genotoxic agents and how they are deregulated in resistant cells. Initial co-immunoprecipitation studies verified previous proteomic analysis finding that the OTUB1 is a novel FOXM1-interacting protein. Western blot analysis showed that both OTUB1 and FOXM1 expression reduced upon genotoxic agent treatment in MCF-7 cells, but remained relatively constant in resistant cells. FOXM1 expression reduced upon OTUB1 depletion by siRNA and increased with OTUB1 overexpression in MCF-7 cells, arguing that OTUB1 positively regulates FOXM1 expression. In agreement, co-immunoprecipitation experiments demonstrated that FOXM1 expression is associated with OTUB1 binding but inversely correlates with conjugation to the protein degradation-associated Lys-48-linked ubiquitin-chains. Overexpression of wild-type (WT) OTUB1, but not the OTUB1(C91S) mutant, disrupted the formation of Lys48-linked ubiquitin-conjugates on FOXM1. Importantly, knockdown of OTUB1 by siRNA resulted in an increase in turnover of FOXM1 in MCF-7 cells treated with the protein synthesis inhibitor cycloheximide, whereas overexpression of WT OTUB1, but not the OTUB1(C91S) mutant, significantly enhances the half-life of FOXM1. In addition, proliferative and clonogenic assays also show that OTUB1 can enhance the proliferative rate and epirubicin resistance through targeting FOXM1, as OTUB1 has little effect on FOXM1-deficient cells. The physiological relevance of the regulation of FOXM1 by OTUB1 is further underscored by the significant correlations between FOXM1 and OTUB1 expression in breast cancer patient samples. Cox-regression survival analysis indicates that OTUB1 overexpression is linked to poorer outcome in particular in patients treated with chemotherapy. Collectively, these data suggest that OTUB1 limits the ubiquitination and degradation of FOXM1 in breast cancer and has a key role in genotoxic agent resistance

Scale invariance of a diodelike tunnel junction

We measure the current vs voltage (I-V) characteristics of a diodelike tunnel junction consisting of a sharp metallic tip placed at a variable distance d from a planar collector and emitting electrons via electric-field assisted emission. All curves collapse onto one single graph when I is plotted as a function of the single scaling variable Vd^{-\lambda}, d being varied from a few mm to a few nm, i.e., by about six orders of magnitude. We provide an argument that finds the exponent {\lambda} within the singular behavior inherent to the electrostatics of a sharp tip. A simulation of the tunneling barrier for a realistic tip reproduces both the scaling behavior and the small but significant deviations from scaling observed experimentally.Comment: 6 pages, 6 figures. Accepted for publication in Physical Review

Increased tartrate-resistant acid phosphatase (TRAP) expression in malignant breast, ovarian and melanoma tissue: an investigational study

BACKGROUND: Tartrate-resistant acid phosphatase (TRAP) is a metalloprotein enzyme that belongs to the acid phosphatases and is known to be expressed by osteoclasts. It has already been investigated as a marker of bone metastases in cancer patients. In this study, which examined the value of serum TRAP concentrations as a marker of bone disease in breast cancer patients, we observed high concentrations of TRAP even in patients without bone metastases. To elucidate this phenomenon, we examined the expression of TRAP in breast cancer cells and the cells of several other malignancies. METHODS: TRAP concentrations in the serum of tumor patients were determined by ELISA. The expression of TRAP in breast, ovarian, and cervical cancer and malignant melanoma was analyzed by immunohistochemistry. RT-PCR and immunocytology were used to evaluate TRAP expression in cultured tumor cells. RESULTS: A marked increase in serum TRAP concentrations was observed in patients with breast and ovarian cancer, regardless of the presence or absence of bone disease. TRAP expression was found in breast and ovarian cancers and malignant melanoma, while cervical cancer showed only minimal expression of TRAP. Expression of TRAP was absent in benign tissue or was much less marked than in the corresponding malignant tissue. TRAP expression was also demonstrated in cultured primary cancer cells and in commercially available cell lines. CONCLUSION: Overexpression of TRAP was detected in the cells of various different tumors. TRAP might be useful as a marker of progression of malignant disease. It could also be a potential target for future cancer therapies

Female sex pheromone of the cone moth, dioryctria mendacella: Investigation of synergism between Type I and Type II pheromone components

Polyunsaturated hydrocarbons (Type II pheromone components) have been reported to be synergists for unsaturated acetates, alcohols or aldehydes (Type I components) in the sex pheromones of several species of Lepidoptera. However, there is some debate over whether the active components are the hydrocarbons themselves or more volatile degradation products. Extracts of pheromone glands of adult females of the cone moth, Dioryctria mendacella (Lepidoptera: Pyralidae), contain (Z,E)-9,11-tetradecadienyl acetate (ZE9,11-14:Ac) and at least ten times as much (Z,Z,Z,Z,Z)-3,6,9,12,15-pentacosapentaene (ZZZZZ3,6,9,12,15-25:H). The former elicits a strong electroantennogram response from males while no response could be recorded to the latter. In field trapping tests, both compounds were individually unattractive to male D. mendacella moths, but blends of the two compounds containing at least a 10:1 ratio of ZZZZZ3,6,9,12,15-25:H : ZE9,11-14:Ac were highly attractive. The relatively involatile hydrocarbon was shown to be released from the dispensers used and no significant degradation could be detected. Furthermore, blends of ZE9,11-14:Ac and analogs of ZZZZZ3,6,9,12,15-25:H with fewer carbons and/or double bonds that might be expected to produce similar degradation products to ZZZZZ3,6,9,12,15-25:H were unattractive. This indicated a specific response to the hydrocarbon itself, further substantiated by the observation that related hydrocarbons did not interfere with the activity of ZZZZZ3,6,9,12,15-25:H. Thus a three-step conversion of fish oil was used to produce a blend of unsaturated hydrocarbons containing ZZZZZ3,6,9,12,15-25:H as the major component, albeit only 30% of the total, and a blend of this material with ZE9,11-14:Ac was as attractive to male D. mendacella moths as blends with an equivalent amount of the purified material. This mixture of unsaturated hydrocarbons is much cheaper to produce than the pure pentaene, and may be useful in lures for other species using these compounds. Dioryctria mendacella is a major constraint to production of edible pine kernels throughout the Mediterranean region. Pheromone traps will provide a means to improve monitoring of seasonal flight patterns and changes in population abundance of this pest

Statistical Modeling of Single Target Cell Encapsulation

High throughput drop-on-demand systems for separation and encapsulation of individual target cells from heterogeneous mixtures of multiple cell types is an emerging method in biotechnology that has broad applications in tissue engineering and regenerative medicine, genomics, and cryobiology. However, cell encapsulation in droplets is a random process that is hard to control. Statistical models can provide an understanding of the underlying processes and estimation of the relevant parameters, and enable reliable and repeatable control over the encapsulation of cells in droplets during the isolation process with high confidence level. We have modeled and experimentally verified a microdroplet-based cell encapsulation process for various combinations of cell loading and target cell concentrations. Here, we explain theoretically and validate experimentally a model to isolate and pattern single target cells from heterogeneous mixtures without using complex peripheral systems.Wallace H. Coulter Foundation (Young Investigator in Bioengineering Award)National Institutes of Health (U.S.) (Grant R01AI081534)National Institutes of Health (U.S.) (Grant R21AI087107

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic

Reproductive medicine in northwest Argentina: traditional and institutional systems

<p>Abstract</p> <p>Background</p> <p>The state of conservation of the traditional cultures of Northwest Argentina is variable and somewhat problematic but to a lesser or a greater extent all the peoples are related to an hegemonic culture. We present a case study carried out in the rural communities of the Yungas biome (Salta) where the extent of isolation varies as does the type of access to public health services. The use of medicinal plants in the area is ordinary and widely spread.</p> <p>Methods</p> <p>The data can be organized in two categories, as medical systems public records (for the regional hospital at Los Toldos), and as ethnobotanical sets. A total of 59 surveys to 40 interviewees were undertaken using a semi structured questionnaire. We present an analysis of the relative importance of the medicinal herbs used in reproductive medicine considering the plants used in the traditional medical system and the factors that can affect the relationship between formal medicine and patients. We further analized how the degree of accessibility to the local hospital influences the diversity of use of plant species used to assist deliveries and to decrease infant mortality in children minor than one year of age.</p> <p>Results</p> <p>In reproductive medicine, 13 ailments and/or different physiological states are locally identified and treated. Local population uses 108 ethnospecies for this kind of illnesses. According to the local conception the hot/cold imbalance could be the principal cause for reproductive illnesses; pregnancy may have natural or supernatural origin, post partum and menstruation involve similar sanitary risks, and neonatal care has a strong magic connotation. In relation with the formal medicine, the more accessible is the health center the more women assist to it. We have not found a relation between accessibility and infant mortality.</p> <p>Conclusion</p> <p>In the local reproductive medicine, most of the practices are concerned with the hot/cold balance. According to their importance the factors involved are: the family medicine, the midwife, and the formal doctors. Plants have an important role; however there is a lack of total agreement among the families who use them. Reluctance to institutional deliveries may be due to the weak relationship between patients and doctors, and the lack of logistic assistance to delivering mothers coming from far away locations.</p

Investigating Tissue Optical Properties and Texture Descriptors of the Retina in Patients with Multiple Sclerosis

PURPOSE: To assess the differences in texture descriptors and optical properties of retinal tissue layers in patients with multiple sclerosis (MS) and to evaluate their usefulness in the detection of neurodegenerative changes using optical coherence tomography (OCT) image segmentation. PATIENTS AND METHODS: 38 patients with MS were examined using Stratus OCT. The raw macular OCT data were exported and processed using OCTRIMA software. The enrolled eyes were divided into two groups, based on the presence of optic neuritis (ON) in the history (MSON+ group, n = 36 and MSON- group, n = 31). Data of 29 eyes of 24 healthy subjects (H) were used as controls. A total of seven intraretinal layers were segmented and thickness as well as optical parameters such as contrast, fractal dimension, layer index and total reflectance were measured. Mixed-model ANOVA analysis was used for statistical comparisons. RESULTS: Significant thinning of the retinal nerve fiber layer (RNFL), ganglion cell/inner plexiform layer complex (GCL+IPL) and ganglion cell complex (GCC, RNFL+GCL+IPL) was observed between study groups in all comparisons. Significant difference was found in contrast in the RNFL, GCL+IPL, GCC, inner nuclear layer (INL) and outer plexiform layer when comparing MSON+ to the other groups. Higher fractal dimension values were observed in GCL+IPL and INL layers when comparing H vs. MSON+ groups. A significant difference was found in layer index in the RNFL, GCL+IPL and GCC layers in all comparisons. A significant difference was observed in total reflectance in the RNFL, GCL+IPL and GCC layers between the three examination groups. CONCLUSION: Texture and optical properties of the retinal tissue undergo pronounced changes in MS even without optic neuritis. Our results may help to further improve the diagnostic efficacy of OCT in MS and neurodegeneration