Proteolytic Processing of OPA1 Links Mitochondrial Dysfunction to Alterations in Mitochondrial Morphology

Many muscular and neurological disorders are associated with mitochondrial dysfunction and are often accompanied by changes in mitochondrial morphology. Mutations in the gene encoding OPA1, a protein required for fusion of mitochondria, are associated with hereditary autosomal dominant optic atrophy type I. Here we show that mitochondrial fragmentation correlates with processing of large isoforms of OPA1 in cybrid cells from a patient with myoclonus epilepsy and ragged-red fibers syndrome and in mouse embryonic fibroblasts harboring an error-prone mitochondrial mtDNA polymerase {gamma}. Furthermore, processed OPA1 was observed in heart tissue derived from heart-specific TFAM knock-out mice suffering from mitochondrial cardiomyopathy and in skeletal muscles from patients suffering from mitochondrial myopathies such as myopathy encephalopathy lactic acidosis and stroke-like episodes. Dissipation of the mitochondrial membrane potential leads to fast induction of proteolytic processing of OPA1 and concomitant fragmentation of mitochondria. Recovery of mitochondrial fusion depended on protein synthesis and was accompanied by resynthesis of large isoforms of OPA1. Fragmentation of mitochondria was prevented by overexpressing OPA1. Taken together, our data indicate that proteolytic processing of OPA1 has a key role in inducing fragmentation of energetically compromised mitochondria. We present the hypothesis that this pathway regulates mitochondrial morphology and serves as an early response to prevent fusion of dysfunctional mitochondria with the functional mitochondrial network

Exploring EEG for object detection and retrieval

This paper explores the potential for using Brain Computer Interfaces (BCI) as a relevance feedback mechanism in contentbased image retrieval. Several experiments are performed using a rapid serial visual presentation (RSVP) of images at different rates (5Hz and 10Hz) on 8 users with different degrees of familiarization with BCI and the dataset. We compare the feedback from the BCI and mouse-based interfaces in a subset of TRECVid images, finding that, when users have limited time to annotate the images, both interfaces are comparable in performance. Comparing our best users in a retrieval task, we found that EEG-based relevance feedback can outperform mouse-based feedback

Reconstrucción de la articulación temporomandibular con prótesis personalizadas

La reconstrucción de la articulación temporomandibular (ATM) tras la resección de una anquilosis postraumática es un reto para el cirujano maxilofacial. Entre estas opciones reconstructivas se hallan las osteotomías deslizantes, los injertos autólogos y las prótesis (de stock o personalizadas). El objetivo de este trabajo es mostrar las ventajas de la reconstrucción de las ATM con prótesis personalizadas utilizando tecnología CAD/CAM, en el tratamiento de pacientes con deformidades anatómicas complejas. Presentamos 4 pacientes varones con una media de 54 años de edad (rango 48-70 años). Todos presentaban antecedente de traumatismo facial con afectación de las ATM, que cursaba con limitación de la apertura oral (media12.25 mm, rango 9mm-17 mm) y restricción dietética (media 6.75 puntos, rango 5.5-8 puntos) según escala analógica visual (EAV) siendo 0= función normal y 10= no función. El número de cirugías previas en todos los pacientes fue 2.75 de media (rango 1-4 cirugías) Se practicó una tomografía computerizada (TC) craneofacial a todos los pacientes, que sirvió de base para fabricar un modelo esterolitográfico a escala 1:1, sobre el cual se planeó la cirugía a realizar y las futuras prótesis articulares a medida o personalizadas, que posteriormente fueron fabricadas. Los resultados postquirúrgicos mostraron una mejoría de la apertura oral (media 31.5 mm, rango 29-34 mm) y de la función masticatoria (media 0.75 puntos en EAV, rango 0-1.5 puntos). No hubo complicaciones permanentes, y no se observó rechazo ni rotura al material implantado, así como tampoco infección, tras un seguimiento de 26.7 meses (rango 8- 46 meses). En conclusión, la reconstrucción de la ATM con prótesis a medida es una alternativa válida o, en ocasiones, la única para reconstruir pacientes con deformidades craneofaciales severas tras traumatismos.Temporomandibular joint (TMJ) reconstruction after postraumatic ankylosis resection is a challenge for maxillofacial surgeons. Sliding osteotomies, autogenous grafts and prostheses (stock o custom-made prostheses) are described among these reconstructive options. The purpose of this study is to evaluate the advantages of TMJ reconstruction by means of custom-made prostheses, performing CAD/CAM technology, in the treatment of severe craniofacial deformities. The sample included 4 males (average age at surgery 54 years, range 48-70 years). All of them had suffered severe facial trauma involving the TMJ complex, resulting in a limited mouth opening (average mouth opening 12.25 mm, range 9mm- 17 mm) and masticatory restrictions (average masticatory restriction 6.75 points, range 5.5-8 points), measured by means of a visual analogic scale (VAS), VAS=0 no function and VAS=10 normal function. The average number of previous surgical procedures that suffered the patients was 2.75 (range 1-4 procedures). As part of the presurgical workup, a craniofacial computed tomography (CT) was obtained at all the patients and a CAD/CAM model of the craniofacial skeleton was created (1:1 scale). The planned surgical procedures and the prostheses samples were executed on the model and after the definitive prosthetic devices were manufactured. The postsurgical results showed an improvement in mouth opening (average postsurgical mouth opening 31.5 mm, range 29-34 mm) and masticatory function (average postsurgical masticatory function,0.75 points, range 0-1.5 points). No permanent complications were found, and no failure neither infection of the alloplastic fitted components was observed, after a 26.7 months follow-up (range 8-46 months). In conclusion, TMJ reconstruction by means of custom made prostheses is a valid choice (or sometimes the only one) to treat patients with severe deformities after craniofacial trauma

Simultaneous removal of CO2, SO2, and NOx from flue gas by liquid phase dehumidification at cryogenic temperatures and low pressure

Published versio

The effect of potential supramolecular-bond promoters on the DNA-interacting abilities of copper-terpyridine compounds.

Three copper(II) coordination compounds have been prepared from three different 2,2′:6′,2′′-terpyridine-based ligands, which have been selected to investigate the potential role of supramolecular interactions on the DNA-interacting and cytotoxicity properties of the corresponding metal complexes. Hence, the ligands 4′-((naphthalen-2-yl)methoxy)-2,2′:6′,2′′-terpyridine (Naphtpy) and 4′-((1H-benzo[d]imidazol-2-yl)methoxy)-2,2′:6′,2′′-terpyridine (Bimztpy) have been synthesized from commercially-available 4′-chloro-2,2′:6′,2′′-terpyridine (Cltpy), and their copper(II) complexes have been obtained by reaction with copper(II) nitrate. The DNA-interacting abilities of the corresponding compounds [Cu(Cltpy)(H2O)(NO3)2] (1), [Cu(naphtpy)(NO3)(H2O)](NO3)(MeOH) (2) and [Cu(bimztpy)(NO3)(H2O)](NO3) (3) have been investigated using different techniques, and cytotoxicity assays with several cancer cell lines have revealed interesting features, viz. the more efficient complex is 2, which although it does not act as a DNA cleaver, displays the most effective DNA-interacting and cytotoxic properties, compared to 1 and 3

Recent advances in food allergy

Food allergy is a public health issue that has significantly increased worldwide in the past decade, affecting consumers’ quality of life and making increasing demands on health service resources. Despite recent advances in many areas of diagnosis and treatment, our general knowledge of the basic mechanisms of the disease remain limited i.e., not at pace with the exponential number of new cases and the explosion of new technologies. Many important key questions remain: What defines a major allergen? Why do some individuals develop food allergies and others do not? Which are the environmental factors? Could the environmental factors be monitored through epigenetics or modified by changes in the microbiome? Can tolerance to food be induced? Why are some foods more likely to trigger allergies than others? Does the route and timing of exposure have any role on sensitization? These and many other related questions remain unanswered. In this short review some of these topics are addressed in the light of recent advances in the area

Evaluating the role of quality assessment of primary studies in systematic reviews of cancer practice guidelines

BACKGROUND: The purpose of this study was to evaluate the role of study quality assessment of primary studies in cancer practice guidelines. METHODS: Reliable and valid study quality assessment scales were sought and applied to published reports of trials included in systematic reviews of cancer guidelines. Sensitivity analyses were performed to evaluate the relationship between quality scores and pooled odds ratios (OR) for mortality and need for blood transfusion. RESULTS: Results found that that whether trials were classified as high or low quality depended on the scale used to assess them. Although the results of the sensitivity analyses found some variation in the ORs observed, the confidence intervals (CIs) of the pooled effects from each of the analyses of high quality trials overlapped with the CI of the pooled odds of all trials. Quality score was not predictive of pooled ORs studied here. CONCLUSIONS: Had sensitivity analyses based on study quality been conducted prospectively, it is highly unlikely that different conclusions would have been found or that different clinical recommendations would have emerged in the guidelines

Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>In a previous report we have demonstrated that the chymotryptic-like serine protease kallikrein 7 (<it>KLK7</it>/hK7) is overexpressed in pancreatic cancer. In normal skin, hK7 is thought to participate in skin desquamation by contributing in the degradation of desmosomal components, such as desmogleins. Thus, the ability of hK7 to degrade desmogleins was assessed and the effect of hK7 expression on desmoglein 2 was examined in cultured pancreatic cancer cells.</p> <p>Methods</p> <p>The expression of Dsg1, Dsg2, and Dsg3 in pancreatic tissues was examined by immunohistochemistry and their expression in two pancreatic cancer cell lines, BxPC-3 and Panc-1, was determined by western blot analysis. The ability of hK7 to degrade Dsg1 and Dsg2 was investigated using <it>in vitro </it>degradation assays. BxPC-3 cells stably transfected to overexpress hK7 were used to examine the effect of hK7 on cell-surface resident Dsg2.</p> <p>Results</p> <p>The levels of immunoreactive Dsg1 and Dsg2 were reduced in pancreatic adenocarcinomas compared with both normal pancreatic and chronic pancreatitis tissues. Among the desmosomal proteins examined, Dsg2 exhibited robust expression on the surface of BxPC-3 cells. When hK7 was overexpressed in this cell line, there was a significant increase in the amount of soluble Dsg2 released into the culture medium compared with vector-transfected control cells.</p> <p>Conclusion</p> <p>A reduction in the amount of the cell adhesion components Dsg1 and Dsg2 in pancreatic tumors suggests that loss of these desmosomal proteins may play a role in pancreatic cancer invasion. Using <it>in vitro </it>degradation assays, both Dsg1 and Dsg2 could be readily proteolyzed by hK7, which is overexpressed in pancreatic adenocarcinomas. The enforced expression of hK7 in BxPC-3 cells that express significant amounts of Dsg2 resulted in a marked increase in the shedding of soluble Dsg2, which is consistent with the notion that aberrant expression of hK7 in pancreatic tumors may result in diminished cell-cell adhesion and facilitate tumor cell invasion.</p