Inspiratory threshold loading reduces lipoperoxidation in obese and normal-weight subjects

Obesity is related to increased oxidative stress. Although low-intensity physical exercise reduces oxidative stress, obese subjects may show exercise intolerance. For these subjects, inspiratory threshold loading could be an alternative tool to reduce oxidative stress. We investigated the effects of inspiratory threshold loading on biomarkers of oxidative stress in obese and normal-weight subjects. Twenty obese (31.4 ± 6 years old, 10 men and 10 women, 37.5 ± 4.7 kg/m2) and 20 normal-weight (29.4 ± 8 years old, 10 men and 10 women, 23.2 ± 1.5 kg/m2) subjects matched for age and gender participated in the study. Maximal inspiratory pressure (MIP) was assessed by a pressure transducer. Blood sampling was performed before and after loading and control protocols to assess thiobarbituric acid reactive substances (TBARS), protein carbonylation, and reduced glutathione. Inspiratory threshold loading was performed at 60% MIP and maintained until task failure. The 30-min control protocol was performed at 0 cmH2O. Our results demonstrated that inspiratory threshold loading reduced TBARS across time in obese (6.21 ± 2.03 to 4.91 ± 2.14 nmol MDA/ml) and normal-weight subjects (5.60 ± 3.58 to 4.69 ± 2.80 nmol MDA/ml; p = 0.007), but no change was observed in protein carbonyls and glutathione in both groups. The control protocol showed no significant changes in TBARS and protein carbonyls. However, reduced glutathione was increased across time in both groups (obese: from 0.50 ± 0.37 to 0.56 ± 0.35 μmol GSH/ml; normal-weight: from 0.61 ± 0.11 to 0.81 ± 0.23 μmol GSH/ml; p = 0.002). These findings suggest that inspiratory threshold loading could be potentially used as an alternative tool to reduce oxidative stress in both normal-weight and obese individuals

The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation

Peer reviewedPublisher PD

Z-extremization and F-theorem in Chern-Simons matter theories

The three dimensional exact R symmetry of N=2 SCFTs extremizes the partition function localized on a three sphere. Here we verify this statement at weak coupling. We give a detailed analysis for two classes of models. The first one is an SU(N)_k gauge theory at large k with both fundamental and adjoint matter fields, while the second is a flavored version of the ABJ theory, where the CS levels are large but they do not necessarily sum up to zero. We study in both cases superpotential deformations and compute the R charges at different fixed points. When these fixed points are connected by an RG flow we explicitly verify that the free energy decreases at the endpoints of the flow between the fixed points, corroborating the conjecture of an F-theorem in three dimensions.Comment: 28 pages, 3 figures, JHEP.cls, minor corrections, references adde

Fifty years of impact on liver pathology:a history of the Gnomes

Professional societies play a major role in medicine and science. The societies tend to be large with well-developed administrative structures. An additional model, however, is based on small groups of experts who meet regularly in an egalitarian model in order to discuss disease-specific scientific and medical problems. In order to illustrate the effectiveness of this model, the history and practices are examined of a long-standing successful example, the International Liver Pathology Group, better known as the Gnomes. The history shows that groups such as the Gnomes offer a number of important benefits not available in larger societies and nurturing such groups advances science and medicine in meaningful ways. The success of the Gnomes’ approach provides a road map for future small scientific groups

Identification of neural networks that contribute to motion sickness through principal components analysis of fos labeling induced by galvanic vestibular stimulation

Motion sickness is a complex condition that includes both overt signs (e.g., vomiting) and more covert symptoms (e.g., anxiety and foreboding). The neural pathways that mediate these signs and symptoms are yet to identified. This study mapped the distribution of c-fos protein (Fos)-like immunoreactivity elicited during a galvanic vestibular stimulation paradigm that is known to induce motion sickness in felines. A principal components analysis was used to identify networks of neurons activated during this stimulus paradigm from functional correlations between Fos labeling in different nuclei. This analysis identified five principal components (neural networks) that accounted for greater than 95% of the variance in Fos labeling. Two of the components were correlated with the severity of motion sickness symptoms, and likely participated in generating the overt signs of the condition. One of these networks included neurons in locus coeruleus, medial, inferior and lateral vestibular nuclei, lateral nucleus tractus solitarius, medial parabrachial nucleus and periaqueductal gray. The second included neurons in the superior vestibular nucleus, precerebellar nuclei, periaqueductal gray, and parabrachial nuclei, with weaker associations of raphe nuclei. Three additional components (networks) were also identified that were not correlated with the severity of motion sickness symptoms. These networks likely mediated the covert aspects of motion sickness, such as affective components. The identification of five statistically independent component networks associated with the development of motion sickness provides an opportunity to consider, in network activation dimensions, the complex progression of signs and symptoms that are precipitated in provocative environments. Similar methodology can be used to parse the neural networks that mediate other complex responses to environmental stimuli. © 2014 Balaban et al

Overexpression of hepatoma-derived growth factor in melanocytes does not lead to oncogenic transformation

<p>Abstract</p> <p>Background</p> <p>HDGF is a growth factor which is overexpressed in a wide range of tumors. Importantly, expression levels were identified as a prognostic marker in some types of cancer such as melanoma.</p> <p>Methods</p> <p>To investigate the presumed oncogenic/transforming capacity of HDGF, we generated transgenic mice overexpressing HDGF in melanocytes. These mice were bred with mice heterozygous for a defective copy of the Ink4a tumor suppressor gene and were exposed to UV light to increase the risk for tumor development both genetically and physiochemically. Mice were analyzed by immunohistochemistry and Western blotting. Furthermore, primary melanocytes were isolated from different strains created.</p> <p>Results</p> <p>Transgenic animals overexpressed HDGF in hair follicle melanocytes. Interestingly, primary melanocytes isolated from transgenic animals were not able to differentiate <it>in vitro </it>whereas cells isolated from wild type and HDGF-deficient animals were. Although, HDGF^-/-/Ink4a^+/-mice displayed an increased number of epidermoid cysts after exposure to UV light, no melanomas or premelanocytic alterations could be detected in this mouse model.</p> <p>Conclusions</p> <p>The results therefore provide no evidence that HDGF has a transforming capacity in tumor development. Our results in combination with previous findings point to a possible role in cell differentiation and suggest that HDGF promotes tumor progression after secondary upregulation and may represent another protein fitting into the concept of non-oncogene addiction of tumor tissue.</p

The role of cell death in the pathogenesis of autoimmune disease: HMGB1 and microparticles as intercellular mediators of inflammation

Cell death is critical to normal homeostasis, although this process, when increased aberrantly, can lead to the production of pro-inflammatory mediators promoting autoimmunity. Two novel intercellular mediators of inflammation generated during cell death are high mobility group box 1 (HMGB1) protein and microparticles (MPs). HMGB1 is a nuclear protein that functions in transcription when inside the nucleus but takes on pro-inflammatory properties when released during cell death. Microparticles are small, membrane-bound structures that extrude from cells when they die and contain cell surface proteins and nuclear material from their parent cells. MPs circulate widely throughout the vasculature and mediate long-distance communication between cells. Both MPs and HMGB1 have been implicated in the pathogenesis of a broad spectrum of inflammatory diseases, including the prototypic autoimmune conditions systemic lupus erythematosus and rheumatoid arthritis. Given their range of activity and association with active disease, both structures may prove to be targets for effective therapy in these and other disorders

Surface modification of Ti-6Al-4V alloy for biomineralization and specific biological response: Part II, Alkaline phosphatase grafting

Titanium and its alloys are the most widespread materials for the realization of orthopaedic and dental implants due to their good mechanical properties and biocompatibility. Surface functionalization of biomaterials aimed to improve and quicken implant integration and tissue regeneration is an active research field. The opportunity to confer biological activity (ability to directly stimulate cells with proper biological signals) to the Ti6Al4 V alloy, previously modified to be bioactive from the inorganic point of view (apatite precipitation), was explored in this research work. The alkaline phosphatase (ALP) enzyme was grafted to metal surface via tresyl chloride activation, maintaining its activity. A synergistic effect between biological functionalization and inorganic bioactivity was observed

Tracking Signals of Change in Mediterranean Fish Diversity Based on Local Ecological Knowledge

One of the expected effects of global change is increased variability in the abundance and distribution of living organisms, but information at the appropriate temporal and geographical scales is often lacking to observe these patterns. Here we use local knowledge as an alternative information source to study some emerging changes in Mediterranean fish diversity. A pilot study of thirty-two fishermen was conducted in 2009 from four Mediterranean locations along a south-north gradient. Semi-quantitative survey information on changes in species abundance was recorded by year and suggests that 59 fish species belonging to 35 families have experienced changes in their abundance. We distinguished species that increased from species that decreased or fluctuated. Multivariate analysis revealed significant differences between these three groups of species, as well as significant variation between the study locations. A trend for thermophilic taxa to increase was recorded at all the study locations. The Carangidae and the Sphyraenidae families typically were found to increase over time, while Scombridae and Clupeidae were generally identified as decreasing and Fistularidae and Scaridae appeared to fluctuate in abundance. Our initial findings strongly suggest the northward expansion of termophilic species whose occurrence in the northern Mediterranean has only been noted previously by occasional records in the scientific literature

Hyperon Photoproduction in the Nucleon Resonance Region

Cross-sections and recoil polarizations for the reactions gamma + p --> K^+ + Lambda and gamma + p --> K^+ + Sigma^0 have been measured with high statistics and with good angular coverage for center-of-mass energies between 1.6 and 2.3 GeV. In the K^+Lambda channel we confirm a structure near W=1.9 GeV at backward kaon angles, but our data shows a more complex s- and u- channel resonance structure than previously seen. This structure is present at forward and backward angles but not central angles, and its position and width change with angle, indicating that more than one resonance is playing a role. Rising back-angle cross sections at higher energies and large positive polarization at backward angles are consistent with sizable s- or u-channel contributions. None of the model calculations we present can consistently explain these aspects of the data.Comment: 5 pages, 3 figures, submitted to Physical Review Letter