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We reviewed 33 original research studies assessing brain perfusion, using consensus guidelines from a "white paper" issued by the International Society for Magnetic Resonance in Medicine Perfusion Study Group and the European Cooperation in Science and Technology Action BM1103 ("Arterial Spin Labelling Initiative in Dementia"; https://www.cost.eu/actions/BM1103/). The studies were published between 2011 and 2023 and included participants with subjective cognitive decline plus; neurocognitive disorders, including mild cognitive impairment (MCI), Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies (DLB) and vascular cognitive impairment (VCI); as well as schizophrenia spectrum disorders, bipolar and major depressive disorders, autism spectrum disorder, attention-deficit/hyperactivity disorder, panic disorder and alcohol use disorder. Hypoperfusion associated with cognitive impairment was the major finding across the spectrum of cognitive decline. Regional hyperperfusion also was reported in MCI, AD, frontotemporal dementia phenocopy syndrome and VCI. Hypoperfused structures found to aid in diagnosing AD included the precunei and adjacent posterior cingulate cortices. Hypoperfused structures found to better diagnose patients with FTLD were the anterior cingulate cortices and frontal regions. Hypoperfusion in patients with DLB was found to relatively spare the temporal lobes, even after correction for partial volume effects. Hyperperfusion in the temporal cortices and hypoperfusion in the prefrontal and anterior cingulate cortices were found in patients with schizophrenia, most of whom were on medication and at the chronic stage of illness. Infratentorial structures were found to be abnormally perfused in patients with bipolar or major depressive disorders. Brain perfusion abnormalities were helpful in diagnosing most neurocognitive disorders. Abnormalities reported in VCI and the remaining mental disorders were heterogeneous and not generalisable. [ABSTRACT FROM AUTHOR]

The health benefits of exercise training in a cancer setting are increasingly acknowledged; however, the underlying molecular mechanisms remain poorly understood. It has been suggested that extracellular vesicles (EVs) released from contracting skeletal muscles play a key role in mediating the systemic benefits of exercise by transporting bioactive molecules, including myokines. Nevertheless, skeletal muscle-derived vesicles account for only about 5% of plasma EVs, with the immune cells making the largest contribution. Moreover, it remains unclear whether the contribution of skeletal muscle-derived EVs increases after physical exercise or how muscle contraction modulates the secretory activity of other tissues and thus influences the content and profile of circulating EVs. Furthermore, the destination of EVs after exercise is unknown, and it depends on their molecular composition, particularly adhesion proteins. The cargo of EVs is influenced by the training program, with acute training sessions having a greater impact than chronic adaptations. Indeed, there are numerous questions regarding the role of EVs in mediating the effects of exercise, the clarification of which is critical for tailoring exercise training prescriptions and designing exercise mimetics for patients unable to engage in exercise programs. This review critically analyzes the current knowledge on the effects of exercise on the content and molecular composition of circulating EVs and their impact on cancer progression. [ABSTRACT FROM AUTHOR]

This work aimed to understand how lifelong exercise training promotes the remodelling of the immune system and prostate signalome in a rat model of PCa. Fifty-five male Wistar rats were divided into four groups: control sedentary, control exercised, induced PCa sedentary and induced PCa exercised. Exercised animals were trained in a treadmill for 53 weeks. Pca induction consisted on the sequential administration of flutamide, N-methyl-N-nitrosourea and testosterone propionate implants. Serum concentrations of C-reactive protein (CRP) and tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) were not different among groups. Peripheral levels of γδ T cells were higher in Pca exercised group than in the PCa sedentary group (p < 0.05). Exercise training also induced Oestrogen Receptor (ESR1) upregulation and Mitogen-activated Protein Kinase 13 (MAPK13) downregulation, changed the content of the phosphorylated (at Ser-104) form of this receptor (coded by the gene ESR1) and seemed to increase Erα phosphorylation and activity in exercised PCa rats when compared with sedentary PCa rats. Our data highlight the exercise-induced remodelling of peripheral lymphocyte subpopulations and lymphocyte infiltration in prostate tissue. Moreover, exercise training promotes the remodelling prostate signalome in this rat model of prostate carcinogenesis. [ABSTRACT FROM AUTHOR]

The common bottlenose dolphin (Tursiops truncatus) is a top marine predator widely dispersed in coastal and pelagic habitats and with a generalist feeding behavior. Yet, information on the trophic ecology of animals inhabiting pelagic environments is still scarce. Using carbon (δ13C: 13C/12C) and nitrogen (δ15N: 15N/14N) stable isotope ratios, we identified and quantified the main groups of prey assimilated by bottlenose dolphins inhabiting an oceanic habitat (Madeira Island, East Atlantic). Bottlenose dolphins assimilated pelagic, schooling fish (such as blue jack mackerel, Trachurus picturatus) and mesopelagic and demersal squids, which reinforces the pelagic dietary composition of insular/oceanic dolphins. Also, intra-seasonal differences were found in their stable isotope ratios, which suggest intraspecific variability in the feeding behavior among individuals living in the same area. Sex was not the main factor contributing to these differences, suggesting the lack of trophic niche segregation between adult males and females in this offshore environment. Nonetheless, further studies including different life stages and information on the ecophysiological requirements are necessary to disclose the factors responsible for the observed variability. This study showed that insular dolphins fed primarily on economically important pelagic prey, highlighting the need of developing management strategies that integrate conservation in fisheries plans. [ABSTRACT FROM AUTHOR]

The radial surface coating layer of compression piston rings is used to improve their wear resistance during the internal combustion engine operation. However, at top dead centers, the friction coefficient of the piston ring-cylinder liner pair is detrimental to the engine's tribological performance. In this work, dimples with different texture dimensions and densities were tested in a home-developed tribometer. The friction coefficient was measured for all samples, and for those with the best results, their wear resistance was assessed. The texture with an aspect ratio of 0.25 and a density area of 15% reported the best tribological results. [ABSTRACT FROM AUTHOR]

We introduce a unified framework based on bi-level optimization schemes to deal with parameter learning in the context of image processing. The goal is to identify the optimal regularizer within a family depending on a parameter in a general topological space. Our focus lies on the situation with non-compact parameter domains, which is, for example, relevant when the commonly used box constraints are disposed of. To overcome this lack of compactness, we propose a natural extension of the upper-level functional to the closure of the parameter domain via Gamma-convergence, which captures possible structural changes in the reconstruction model at the edge of the domain. Under two main assumptions, namely, Mosco-convergence of the regularizers and uniqueness of minimizers of the lower-level problem, we prove that the extension coincides with the relaxation, thus admitting minimizers that relate to the parameter optimization problem of interest. We apply our abstract framework to investigate a quartet of practically relevant models in image denoising, all featuring nonlocality. The associated families of regularizers exhibit qualitatively different parameter dependence, describing a weight factor, an amount of nonlocality, an integrability exponent, and a fractional order, respectively. After the asymptotic analysis that determines the relaxation in each of the four settings, we finally establish theoretical conditions on the data that guarantee structural stability of the models and give examples of when stability is lost. [ABSTRACT FROM AUTHOR]

Background: Inflammation is widely recognized as the driving force of cachexia induced by chronic diseases; however, therapies targeting inflammation do not always reverse cachexia. Thus, whether inflammation per se plays an important role in the clinical course of cachectic patients is still a matter of debate. Aims: To give new insights into cachexia's pathogenesis and diagnosis, we performed a comprehensive literature search on the contribution of inflammatory markers to this syndrome, focusing on the noncommunicable diseases cancer and cardiovascular diseases. Methods: A systematic review was performed in PubMed using the keywords ("cancer" OR "cardiac" cachexia AND "human" OR "patient" AND "plasma" or "serum"). A total of 744 studies were retrieved and, from these, 206 were selected for full-text screening. In the end, 98 papers focusing on circulating biomarkers of cachexia were identified, which resulted in a list of 113 different mediators. Results: Data collected from the literature highlight the contribution of interleukin-6 (IL-6) and C-reactive protein (CRP) to cachexia, independently of the underlying condition. Despite not being specific, once the diagnosis of cachexia is established, CRP might help to monitor the effectiveness of anti-cachexia therapies. In cardiac diseases, B-type natriuretic peptide (BNP), renin, and obestatin might be putative markers of body wasting, whereas in cancer, growth differentiation factor (GDF) 15, transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) C seem to be better markers of this syndrome. Independently of the circulating mediators, NF-κB and JAK/STAT signaling pathways play a key role in bridging inflammation with muscle wasting; however, therapies targeting these pathways were not proven effective for all cachectic patients. Conclusion: The critical and integrative analysis performed herein will certainly feed future research focused on the better comprehension of cachexia pathogenesis toward the improvement of its diagnosis and the development of personalized therapies targeting specific cachexia phenotypes. [ABSTRACT FROM AUTHOR]

This study characterizes the plasma levels and composition of SDS-resistant aggregates (SRAs) in patients with heart failure with preserved ejection fraction (HFpEF) to infer molecular pathways associated with disease and/or proteostasis disruption. Twenty adults (ten with HFpEF and ten age-matched individuals) were included. Circulating SRAs were resolved by diagonal two-dimensional SDS-PAGE, and their protein content was identified by mass spectrometry. Protein carbonylation, ubiquitination and ficolin-3 were evaluated. Patients with HFpEF showed higher SRA/total (36.6 ± 4.9% vs 29.6 ± 2.2%, p = 0.009) and SRA/soluble levels (58.6 ± 12.7% vs 40.6 ± 5.8%, p = 0.008). SRAs were carbonylated and ubiquitinated, suggesting they are composed of dysfunctional proteins resistant to degradation. SRAs were enriched in proteins associated with cardiovascular function/disease and with proteostasis machinery. Total ficolin-3 levels were decreased (0.77 ± 0.22, p = 0.041) in HFpEF, suggesting a reduced proteostasis capacity to clear circulating SRA. Thus, the higher accumulation of SRA in HFpEF may result from a failure or overload of the protein clearance machinery. [ABSTRACT FROM AUTHOR]

A CuCoBe–diamond composite was used to reinforce a laser textured 410 stainless steel piston ring by hot-pressing. Different hot-pressing parameters were used to optimize the sintering process of the CuCoBe particles (P = 25 and 50 MPa, T = 820 and 980 °C, and t = 15 and 30 min). The results showed an increase in the hardness of the hot-pressed samples (50.5% and 48.5% for P = 25 and 50 MPa, respectively). Three textures with different track widths and distances between them were produced by laser on the compression piston rings' surface. The composite powders were used for the reinforcement of the textures by hot-pressing at the optimized sintering parameters (T = 980 °C, P = 25 and 50 MPa, and t = 15 min). The tribological results revealed that larger texture dimensions led to enhanced tribological performance. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is growing in prevalence, due to an increase in aging and comorbidities. Heart failure with reduced ejection fraction (HFrEF) is more common in men, whereas heart failure with preserved ejection fraction (HFpEF) has a higher prevalence in women. However, the reasons for these epidemiological trends are not clear yet. Since HFpEF affects mostly postmenopausal women, sex hormones should play a pivotal role in HFpEF development. Furthermore, for HFpEF, contrary to HFrEF, effective therapeutic approaches are missing. Interestingly, studies evidenced that some therapies can have better results in women than in HFpEF men, emphasizing the necessity of understanding these observations at a molecular level. Thus, herein, we review the molecular mechanisms of estrogen and androgen actions in the heart in physiological conditions and explain how its dysregulation can lead to disease development. This clarification is essential in the road for an effective personalized management of HF, particularly HFpEF, towards the development of sex-specific therapeutic approaches. [ABSTRACT FROM AUTHOR]

The escalation of life expectancy is accompanied by an increase in the prevalence of age-related conditions, such as sarcopenia. Sarcopenia, a muscle condition defined by low muscle strength, muscle quality or quantity, and physical performance, has a high prevalence among the elderly and is associated to increased mortality. The neuromuscular system has been emerging as a key contributor to sarcopenia pathogenesis. Indeed, the age-related degeneration of the neuromuscular junction (NMJ) function and structure may contribute to the loss of muscle strength and ultimately to the loss of muscle mass that characterize sarcopenia. The present mini-review discusses important signaling pathways involved in the function and maintenance of the NMJ, giving emphasis to the ones that might contribute to sarcopenia pathogenesis. Some conceivable biomarkers, such as C-terminal agrin fragment (CAF) and brain-derived neurotrophic factor (BDNF), and therapeutic targets, namely acetylcholine and calcitonin gene–related peptide (CGRP), can be retrieved, making way to future studies to validate their clinical use. [ABSTRACT FROM AUTHOR]

Mitoxantrone (MTX) is a topoisomerase II inhibitor used to treat a wide range of tumors and multiple sclerosis but associated with potential neurotoxic effects mediated by hitherto poorly understood mechanisms. In adult male CD-1 mice, the underlying neurotoxic pathways of a clinically relevant cumulative dose of 6 mg/kg MTX was evaluated after biweekly administration for 3 weeks and sacrifice 1 week after the last administration was undertaken. Oxidative stress, neuronal damage, apoptosis, and autophagy were analyzed in whole brain, while coronal brain sections were used for a closer look in the hippocampal formation (HF) and the prefrontal cortex (PFC), as these areas have been signaled out as the most affected in 'chemobrain'. In the whole brain, MTX-induced redox imbalance shown as increased endothelial nitric oxide synthase and reduced manganese superoxide dismutase expression, as well as a tendency to a decrease in glutathione levels. MTX also caused diminished ATP synthase β expression, increased autophagic protein LC3 II and tended to decrease p62 expression. Postsynaptic density protein 95 expression decreased in the whole brain, while hyperphosphorylation of Tau was seen in PFC. A reduction in volume was observed in the dentate gyrus (DG) and CA1 region of the HF, while GFAP-ir astrocytes increased in all regions of the HF except in the DG. Apoptotic marker Bax increased in the PFC and in the CA3 region, whereas p53 decreased in all brain areas evaluated. MTX causes damage in the brain of adult CD-1 mice in a clinically relevant cumulative dose in areas involved in memory and cognition. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction has been one of the most reported and studied adverse effects of cancer treatment, but, for many years, it was overlooked by the medical community. Nevertheless, the medical and scientific communities have now recognized that the cognitive deficits caused by chemotherapy have a strong impact on the morbidity of cancer treated patients. In fact, chemotherapy-induced cognitive dysfunction or 'chemobrain' (also named also chemofog) is at present a well-recognized effect of chemotherapy that could affect up to 78% of treated patients. Nonetheless, its underlying neurotoxic mechanism is still not fully elucidated. Therefore, this work aimed to provide a comprehensive review using PubMed as a database to assess the studies published on the field and, therefore, highlight the clinical manifestations of chemobrain and the putative neurotoxicity mechanisms. In the last two decades, a great number of papers was published on the topic, mainly with clinical observations. Chemotherapy-treated patients showed that the cognitive domains most often impaired were verbal memory, psychomotor function, visual memory, visuospatial and verbal learning, memory function and attention. Chemotherapy alters the brain's metabolism, white and grey matter and functional connectivity of brain areas. Several mechanisms have been proposed to cause chemobrain but increase of proinflammatory cytokines with oxidative stress seem more relevant, not excluding the action on neurotransmission and cellular death or impaired hippocampal neurogenesis. The interplay between these mechanisms and susceptible factors makes the clinical management of chemobrain even more difficult. New studies, mainly referring to the underlying mechanisms of chemobrain and protective measures, are important in the future, as it is expected that chemobrain will have more clinical impact in the coming years, since the number of cancer survivors is steadily increasing. [ABSTRACT FROM AUTHOR]

Sexual dimorphism greatly influences adipose tissue remodeling, which is characterized by changes in the activity, number, and/or size of adipocytes in response to distinct stimuli, including lifestyle and anti-obesity drugs. This sex dependence seems to be due to the anatomical and endocrine disparities between men and women. At the molecular level, sex hormones are believed to mediate such differences and involve estrogen and androgen receptor-induced gene expression. The signaling pathways that regulate adipose tissue metabolism and function include peroxisome proliferator-activated receptor gamma, uncoupling protein 1 (UCP1), 5' adenosine monophosphate-activated protein kinase (AMPK), and mitochondrial oxidative phosphorylation (OXPHOS), among other molecular players. Sex hormone-related pathways also interplay with adrenergic signaling, probably the most well-characterized molecular mechanism implicated in the remodeling of white adipose tissue. This review overviews and integrates the signaling pathways behind sexual dimorphism in adipose tissue remodeling, hoping to increase the knowledge on the pathogenesis of diseases, such as obesity and related comorbidities, and consequently, to drive future studies to investigate the regulation of this tissue homeostasis, either in men or women. [ABSTRACT FROM AUTHOR]

Aerobic exercise training induces a unique cardioprotective phenotype, but it is becoming clear that it does not promote the same structural, functional, and molecular adaptations in both ventricles. In the present study, we aimed to better characterize and compare the molecular pathways involved in the exercise-induced remodeling of both ventricles. Female Sprague-Dawley rats were randomly assigned to control and exercise groups. Animals in the exercise group were submitted to low-intensity treadmill exercise for 54 weeks. After the experimental period, biventricular hemodynamic analysis was performed and right and left ventricles were harvested for morphological and biochemical analyses. Data showed that long-term low-intensity exercise training improves cardiac function, especially left ventricular diastolic function; however, the expression of connexin-43, CCAAT-enhancer binding protein β, and c-kit did not change in none of the ventricles. In the right ventricle, long-term exercise training induced an increase of manganese superoxide dismutase and sirtuin 3 protein expression, suggestive of improved antioxidant capacity. Our results also support that long-term aerobic exercise training imposes greater metabolic remodeling to the right ventricle, mainly by increasing mitochondrial ability to produce ATP, with no association to estrogen-related receptor α regulation. [ABSTRACT FROM AUTHOR]

Muscle wasting is one of the major health problems in older adults and is traditionally associated to sarcopenia. Nonetheless, muscle loss may also occur in older adults in the presence of cancer, and in this case, it is associated to cancer cachexia. The clinical management of these conditions is a challenge due to, at least in part, the difficulties in their differential diagnosis. Thus, efforts have been made to better comprehend the pathogenesis of sarcopenia and cancer cachexia, envisioning the improvement of their clinical discrimination and treatment. To add insights on this topic, this review discusses the current knowledge on key molecular players underlying sarcopenia and cancer cachexia in a comparative perspective. Data retrieved from this analysis highlight that while sarcopenia is characterized by the atrophy of fast-twitch muscle fibers, in cancer cachexia an increase in the proportion of fast-twitch fibers appears to happen. The molecular drivers for these specificmuscle remodeling patterns are still unknown; however, among the predominant contributors to sarcopenia is the age-induced neuromuscular denervation, and in cancer cachexia, the muscle disuse experienced by cancer patients seems to play an important role. Moreover, inflammation appears to be more severe in cancer cachexia. Impairment of nutrition-related mediators may also contribute to sarcopenia and cancer cachexia, being distinctly modulated in each condition. [ABSTRACT FROM AUTHOR]

Exosomes are involved in a wide variety of biochemical processes in human body homeostasis. Exosomes also provide important information regarding communications among several organ systems. Additionally, they can serve as molecular vehicles to deliver drugs. Therefore, exosomes have received wide attention in current biomedical research for unraveling pathogenic mechanisms of diseases, searching for novel biomarkers, and discovering new drugs. This paper reviews and discusses the significance of urinary exosomes for a better understanding of human disease pathophysiology and their potential use as therapeutic targets. Isolation methods of exosomes and the latest technological advances are also discussed. Furthermore, novel urinary exosomal biomarkers are highlighted with special emphasis on their clinical applicability (particularly sensitivity, specificity, reliability, and other aspects). Finally, future trends for this field are analyzed and our perspectives are provided. [ABSTRACT FROM AUTHOR]

Purpose: Prostate cancer is a major cause of cancer-related death in males worldwide and, in addition to impairing prostate function, also causes testicular adaptations. In this study, we aim to investigate the preventive effect of exercise training on PCa-induced testicular dysfunction. Methods: As a model, we used fifty Wistar Unilever male rats, randomly divided in four experimental groups. Prostate cancer was chemically and hormonally induced in two groups of animals (PCa groups). One control group and one PCa group was submitted to moderate intensity treadmill exercise training. Fifty weeks after the start of the training the animals were sacrificed and sperm, prostate, testis and serum were collected and analyzed. Sperm concentration and morphology, and testosterone serum levels were determined. In addition, histological analyses of the testes were performed, and testis proteomes and metabolomes were characterized. Results: We found that prostate cancer negatively affected testicular function, manifested as an arrest of spermatogenesis. Oxidative stress-induced DNA damage, arising from reduced testis blood flow, may also contribute to apoptosis of germ cells and consequential spermatogenic impairment. Decreased utilization of the glycolytic pathway, increased metabolism of ketone bodies and the accumulation of branched chain amino acids were also evident in the PCa animals. Conversely, we found that the treadmill training regimen activated DNA repair mechanisms and counteracted several metabolic alterations caused by PCa without impact on oxidative stress. Conclusions: These findings confirm a negative impact of prostate cancer on testis function and suggest a beneficial role for exercise training in the prevention of prostate cancer-induced testis dysfunction. [ABSTRACT FROM AUTHOR]

In this paper, we study a priori estimates for a first-order mean-field planning problem with a potential. In the theory of mean-field games (MFGs), a priori estimates play a crucial role to prove the existence of classical solutions. In particular, uniform bounds for the density of players’ distribution and its inverse are of utmost importance. Here, we investigate a priori bounds for those quantities for a planning problem with a non-vanishing potential. The presence of a potential raises non-trivial difficulties, which we overcome by exploring a displacement-convexity property for the mean-field planning problem with a potential together with Moser’s iteration method. We show that if the potential satisfies a certain smallness condition, then a displacement-convexity property holds. This property enables L q bounds for the density. In the one-dimensional case, the displacement-convexity property also gives L q bounds for the inverse of the density. Finally, using these L q estimates and Moser’s iteration method, we obtain L ∞ estimates for the density of the distribution of the players and its inverse. We conclude with an application of our estimates to prove existence and uniqueness of solutions for a particular first-order mean-field planning problem with a potential. [ABSTRACT FROM AUTHOR]

Fertilization of grassland pastures may be a non-point pollution source in the Azores archipelago, despite the high phosphorus (P) retention of Andosols. To evaluate the risk of P desorption, representative Andosols samples (0–15 cm) were subdivided in five layers and different P pools were measured. The risk of P unloading into waters was assessed by the degree of phosphorus saturation (DPS), and by the P concentration in equilibrium solutions (0.01 M CaCl2). The higher contents in the superficial layers suggest P accumulation due to pasture overfertilization. The organic P represented about 54% of the total P, with an overall average of 2.66 g Pt/kg. Despite being above the agronomic threshold, the soil with the highest average mean values of extractable inorganic P, 77 mg POlsen/kg and and 73.7 mg PAL/kg, is still below environmental thresholds and none of the soils had DPS values above 25%, which is the critical value associated with eutrophication of surface waters. Similarly, all the P concentrations in the equilibrium CaCl2 solutions were below the critical limits. Therefore, P desorption from these soils did not seem to be the main process responsible for effective waterbodies eutrophication in the Azores. Since mineral fertilizers are applied superficially, the hypothesis of their direct runoff during rainfall events, even before their complete dissolution and interaction with the soil matrix, must be considered. Consequently, P fertilization with deep-banding systems may be the alternative to the interdiction of fertilizers in the most sensitive and hilly areas of the watersheds. [ABSTRACT FROM AUTHOR]

Purpose: The impact of exercise training on testicular function is relatively ill-defined. To gain new insights into this important topic, published data, deriving from both humans and animal studies, were critically analyzed.Results and Conclusions: The effects of exercise on the hypothalamus-pituitary-gonadal axis, influenced by the type, intensity and duration of the exercise program, can be evaluated in terms of total and free testosterone and/or luteinizing hormone and follicle-stimulating hormone serum levels and sperm parameters. High-intensity exercise promotes a common decrease in these parameters, and therefore, negatively impacts upon testicular function. However, published data for moderate-intensity exercise training are inconsistent. Conversely, there is consistent evidence to support the benefits of exercise training to prevent and/or counteract the impairment of testis function caused by aging, obesity and doxorubicin treatment. This positive effect is likely the consequence of decreased oxidative stress and inflammatory status. In the future, it will be important to clarify the molecular mechanisms which explain these reported discrepancies and to establish guidelines for an active lifestyle to promote healthy testicular function. [ABSTRACT FROM AUTHOR]

Purpose: ApneaLink is a portable device for the screening of sleep apnea, a prevalent and underdiagnosed comorbidity in heart failure patients. A prospective cross-sectional study in patients with chronic heart failure was carried out to assess the sensitivity and specificity of apnea-hypopnea index (AHI) measurements using ApneaLink against the standard polysomnography test.Methods: Adult patients with a prior hospitalization in an acute heart failure hospital unit were recruited for the study. All participants were tested for sleep apnea using ApneaLink and polysomnography simultaneously during an overnight stay at a sleep laboratory. Global sleep apnea was evaluated according to the AHI, which was analyzed and compared. Subpopulation comparison based on ejection fraction was not realized due to population size.Results: Thirty-five patients with stable chronic heart failure completed the study (mean age 70.9 ± 10.5 years and body mass index 30.0 ± 4.7 kg/m2). Two patients were excluded due to insufficient study duration. ApneaLink had a sensitivity greater than 80% for all AHI measurements, and a specificity greater than 80% for all AHI measurements, except for AHI ≥ 5 events/h (61.5%). The results showed higher sensitivities and specificities at AHI values of ≥ 10 events/h (sensitivity 81.3% and specificity 84.2%) and ≥ 15 events/h (sensitivity 83.3% and specificity 91.3%). Correlation analysis showed that AHI measurements using ApneaLink and polysomnography had a strong and significant correlation (r = 0.794; P < 0.001).Conclusions: Our results suggest that ApneaLink could be used in clinical practice to identify heart failure patients with high (AHI ≥ 15 events/h) and low (AHI < 5 events/h) probability of having sleep apnea, sparing the need for a diagnostic polysomnography and thus potentially impacting prognosis by providing a more cost-effective and timely diagnosis of this non-cardiac comorbidity. [ABSTRACT FROM AUTHOR]

Here, we consider numerical methods for stationary mean-field games (MFG) and investigate two classes of algorithms. The first one is a gradient-flow method based on the variational characterization of certain MFG. The second one uses monotonicity properties of MFG. We illustrate our methods with various examples, including one-dimensional periodic MFG, congestion problems, and higher-dimensional models. [ABSTRACT FROM AUTHOR]

A variational model for imaging segmentation and denoising color images is proposed. The model combines Meyer's 'u+v' decomposition with a chromaticity-brightness framework and is expressed by a minimization of energy integral functionals depending on a small parameter $$\varepsilon >0$$ . The asymptotic behavior as $$\varepsilon \rightarrow 0^+$$ is characterized, and convergence of infima, almost minimizers, and energies are established. In particular, an integral representation of the lower semicontinuous envelope, with respect to the $$L^1$$ -norm, of functionals with linear growth and defined for maps taking values on a certain compact manifold is provided. This study escapes the realm of previous results since the underlying manifold has boundary, and the integrand and its recession function fail to satisfy hypotheses commonly assumed in the literature. The main tools are $$\Gamma $$ -convergence and relaxation techniques. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignancy in women worldwide. Several studies have suggested that exercise training may decrease the risk of breast cancer development. This study aimed to evaluate the effects of long-term exercise training on mammary tumorigenesis in an animal model of mammary cancer. Fifty female Sprague-Dawley rats were randomly divided into four groups: MNU sedentary, MNU exercised, control sedentary and control exercised. Animals from MNU groups received an intraperitoneal administration of N-methyl- N-nitrosourea (MNU). Animals were exercised on a treadmill during 35 weeks. When animals were killed, blood samples were collected to determine the hematocrit and to perform the biochemical analysis. Mammary tumors were collected and histologically evaluated; the expression of ERs α and β was evaluated in tumor sections by immunohistochemistry. All survived animals from both MNU groups developed mammary tumors. The number of mammary tumors ( p > 0.05) and lesions ( p = 0.056) was lower in MNU exercised than in MNU sedentary animals. MNU exercised animals showed lower number of malignant lesions than MNU sedentary animals ( p = 0.020). C-reactive protein serum concentration was lower in exercised animals; however, the levels of 17-β estradiol were higher in exercised animals. Tumors from exercised animals exhibited higher expression of ER α than tumors from sedentary animals ( p < 0.05). This study analyzes the impact of the longest exercise training protocol on mammary tumorigenesis ever performed. We concluded that the lifelong endurance training has beneficial effects on mammary tumorigenesis in female rats (reduced the inflammation, the number of mammary tumors and lesions, and histological grade of malignancy). Additionally, the mammary tumors from MNU exercised group exhibited higher immunoexpression of ER α that is an indicator of well-differentiated tumors and better response to hormone therapy. [ABSTRACT FROM AUTHOR]

Infection due to Schistosoma haematobium is carcinogenic. However, the cellular and molecular mechanisms underlying urogenital schistosomiasis (UGS)-induced carcinogenesis have not been well defined. Conceptually, early molecular detection of this phenomenon, through non-invasive procedures, seems feasible and is desirable. Previous analysis of urine collected during UGS suggests that estrogen metabolites, including depurinating adducts, may be useful for this purpose. Here, a new direction was pursued: the identification of molecular pathways and potential biomarkers in S. haematobium-induced bladder cancer by analyzing the proteome profiling of urine samples from UGS patients. GeLC-MS/MS followed by protein-protein interaction analysis indicated oxidative stress and immune defense systems responsible for microbicide activity are the most representative clusters in UGS patients. Proteins involved in immunity, negative regulation of endopeptidase activity, and inflammation were more prevalent in UGS patients with bladder cancer, whereas proteins with roles in renal system process, sensory perception, and gas and oxygen transport were more abundant in subjects with urothelial carcinoma not associated with UGS. These findings highlighted a Th2-type immune response induced by S. haematobium, which seems to be further modulated by tumorigenesis, resulting in high-grade bladder cancer characterized by an inflammatory response and complement activation alternative pathway. These findings established a starting point for the development of multimarker strategies for the early detection of UGS-induced bladder cancer. [ABSTRACT FROM AUTHOR]

The administration of chemical carcinogens is one of the most commonly used methods to induce tumors in several organs in laboratory animals in order to study oncologic diseases of humans. The carcinogen agent N-methyl- N-nitrosourea (MNU) is the oldest member of the nitroso compounds that has the ability to alkylate DNA. MNU is classified as a complete, potent, and direct alkylating compound. Depending on the animals' species and strain, dose, route, and age at the administration, MNU may induce tumors' development in several organs. The aim of this manuscript was to review MNU as a carcinogenic agent, taking into account that this carcinogen agent has been frequently used in experimental protocols to study the carcinogenesis in several tissues, namely breast, ovary, uterus, prostate, liver, spleen, kidney, stomach, small intestine, colon, hematopoietic system, lung, skin, retina, and urinary bladder. In this paper, we also reviewed the experimental conditions to the chemical induction of tumors in different organs with this carcinogen agent, with a special emphasis in the mammary carcinogenesis. [ABSTRACT FROM AUTHOR]

Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease. [ABSTRACT FROM AUTHOR]

The dawn of a new Proteomics era, just over a decade ago, allowed for large-scale protein profiling studies that have been applied in the identification of distinctive molecular cell signatures. Proteomics provides a powerful approach for identifying and studying these multiple molecular markers in a vast array of biological systems, whether focusing on basic biological research, diagnosis, therapeutics, or systems biology. This is a continuously expanding field that relies on the combination of different methodologies and current advances, both technological and analytical, which have led to an explosion of protein signatures and biomarker candidates. But how are these biological markers obtained? And, most importantly, what can we learn from them? Herein, we briefly overview the currently available approaches for obtaining relevant information at the proteome level, while noting the current and future roles of both traditional and modern proteomics. Moreover, we provide some considerations on how the development of powerful and robust bioinformatics tools will greatly benefit high-throughput proteomics. Such strategies are of the utmost importance in the rapidly emerging field of immunoproteomics, which may play a key role in the identification of antigens with diagnostic and/or therapeutic potential and in the development of new vaccines. Finally, we consider the present limitations in the discovery of new signatures and biomarkers and speculate on how such hurdles may be overcome, while also offering a prospect for the next few years in what could be one of the most significant strategies in translational medicine research. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides are small molecules with activity against bacteria, yeasts, fungi, viruses, bacteria, and even tumor cells that make these molecules attractive as therapeutic agents. Due to the alarming increase of antimicrobial resistance, interest in alternative antimicrobial agents has led to the exploitation of antimicrobial peptides, both synthetic and from natural sources. Thus, many peptide-based drugs are currently commercially available for the treatment of numerous ailments, such as hepatitis C, myeloma, skin infections, and diabetes. Initial barriers are being increasingly overcome with the development of cost-effective, more stable peptides. Herein, we review the available strategies for their synthesis, bioinformatics tools for the rational design of antimicrobial peptides with enhanced therapeutic indices, hurdles and shortcomings limiting the large-scale production of AMPs, as well as the challenges that the pharmaceutical industry faces on their use as therapeutic agents. [ABSTRACT FROM AUTHOR]

Exercise training is a well-known non-pharmacological strategy for the prevention and treatment of cardiovascular diseases. Despite the established phenotypic knowledge, the molecular signature of exercise-induced cardiac remodeling remains poorly characterized. The great majority of studies dedicated to this topic use conventional reductionist methods, which only allow analyzing individual protein candidates. Nowadays, several methodologies based on mass spectrometry are available and have been successfully applied for the characterization of heart proteome, representing an attractive approach for the wide characterization of the complex molecular networks that underlie exercise-induced cardiac remodeling. Still, few studies have used these methodologies to understand the impact of exercise training on the remodeling of cardiac proteome. The present study analyzes the few available data obtained from mass spectrometry (MS)-based proteomic studies assessing the impact of distinct types of exercise training on the protein profile of heart (left ventricle and isolated mitochondria) and the potential cross-tolerance between exercise training and diseases as myocardial infarction and obesity. Network analysis was performed with bioinformatics to integrate data from distinct research papers, based on distinct exercise training protocols, animal models and methodological approaches applied in the characterization of heart proteome. The analysis revealed that exercise training confers a unique proteome signature characterized by the up-regulation of lipid and organic metabolic processes, vasculogenesis and tissue regeneration. Data retrieved from this analysis also suggested that cardiac mitochondrial proteome is highly dynamic in response to exercise training due, in part, to the action of specific kinases as PKA and PKG. Regarding to the type of exercise, treadmill training seems to have a greater effect on the modulation of cardiac proteome than swimming. Data from the present review will certainly open new perspectives on cardiac proteomics and will help to envisage future studies targeting the identification of the regulatory mechanisms underlying cardiac adaptive and maladaptive remodeling. [ABSTRACT FROM AUTHOR]

Mitoxantrone (MTX) is a chemotherapeutic agent, which presents late irreversible cardiotoxicity. This work aims to highlight the mechanisms involved in the MTX-induced cardiotoxicity, namely the effects toward mitochondria using in vivo and in vitro studies. Male Wistar rats were treated with 3 cycles of 2.5 mg/kg MTX at day 0, 10, and 20. One treated group was euthanized on day 22 (MTX22) to evaluate the early MTX cardiac toxic effects, while the other was euthanized on day 48 (MTX48), to allow the evaluation of MTX late cardiac effects. Cardiac mitochondria isolated from 4 adult untreated rats were also used to evaluate in vitro the MTX (10 nM, 100 nM, and 1 μM) direct effects upon mitochondria functionality. Two rats of MTX48 died on day 35, and MTX treatment caused a reduction in relative body weight gain in both treated groups with no significant changes in water and food intake. Decreased levels of plasma total creatine kinase and CK-MB were detected in the MTX22 group, and increased plasma levels of lactate were seen in MTX48. Increased cardiac relative mass and microscopic changes were evident in both treated groups. Considering mitochondrial effects, for the first time, it was evidenced that MTX induced an increase in the complex IV and complex V activities in MTX22 group, while a decrease in the complex V activity was accompanied by the reduction in ATP content in the MTX48 rats. No alterations in mitochondria transmembrane potential were found in isolated mitochondria from MTX48 rats or in isolated mitochondria directly incubated with MTX. This study highlights the relevance of the cumulative MTX-induced in vivo mitochondriopathy to the MTX cardiotoxicity. [ABSTRACT FROM AUTHOR]

l-glutamate plays a central role in nitrogen metabolism in all living organisms. In the genus Xanthomonas, the nitrogen nutrition is an important factor involved in the xanthan gum production, an important exopolysaccharide with various industrial and biotechnological applications. In this report, we demonstrate that the use of l-glutamate by the phytopathogen Xanthomonas axonopodis pv. citri as a nitrogen source in defined medium significantly increases the production of xanthan gum. This increase is dependent on the l-glutamate concentration. In addition, we have also characterized a glutamate transport system that is dependent on a proton gradient and on ATP and is modulated by amino acids that are structurally related to glutamate. This is the first biochemical characterization of an energy substrate transport system observed in a bacterial phytopathogen with a broad economic and industrial impact due to xanthan gum production. [ABSTRACT FROM AUTHOR]

Bacillus subtilis endospores have applications in different fields including their use as probiotics and antigen delivery vectors. Such specialized applications frequently require highly purified spore preparations. Nonetheless, quantitative data regarding both yields and purity of B. subtilis endospores after application of different growth conditions and purification methods are scarce or poorly reported. In the present study, we conducted several quantitative and qualitative analyses of growth conditions and purification procedures aiming generation of purified B. subtilis spores. Based on two growth media and different incubations conditions, sporulation frequencies up to 74.2 % and spore concentrations up to 7 × 10 spores/ml were achieved. Application of a simplified spore isolation method, in which samples were incubated with lysozyme and a detergent, resulted in preparations with highly purified spores at the highest yields. The present study represents, therefore, an important contribution for those working with B. subtilis endospores for different biotechnological purposes. [ABSTRACT FROM AUTHOR]

Bone strength depends on several material and structural properties, but findings concerning the best predictors of bone mechanical performance are conflicting. The aim of this study was to investigate how a broad set of bone properties in the proximal femur are influenced by age and hormonal status, and how these properties together determine bone strength. Twenty-five Wistar rats were ovariectomized (OVX, n = 13) or sham operated (SHAM, n = 12) at 5 months of age, and killed after 9 months. Another group of rats was killed at 5 months as baseline control (BSL, n = 7). At sacrifice, serum 17β-estradiol and bone turnover marker concentrations were determined in the serum. Both femurs were collected for assessment of trabecular microarchitecture, femoral neck geometry, radiographic absorptiometry, calcium and phosphate content, and biomechanical properties. While stiffness was mostly associated with proximal femur trabecular microarchitecture and mineralization degree, bone strength was mostly linked to bone size and femoral neck geometry, which predicted almost 50% of its variance. Despite the decrease in cortical and trabecular bone as well as in mineralization degree following estrogen loss, bone strength was not reduced in OVX animals compared to BSL or sham-operated rats. This was due to a change in femoral neck geometry as well as to an increase in femur size in OVX, which apparently compensated their lower bone volume and mineral content, thereby preserving bone strength. Estrogen loss leads to a deterioration of bone tissue quality, but bone strength was preserved at the expense of geometric adaptations. [ABSTRACT FROM AUTHOR]

This study investigated the influence of lifestyle on aging-related changes in cardiac proteins' oxidative modifications profile. Thirty C57BL/6 strain mice (2 months) were randomly divided into three groups (young Y, old sedentary S, and old active A). The S and A mice were individually placed into standard cages and in cages with running wheels, respectively, for 23 months. Upon killing, heart mitochondrial fractions were obtained for the evaluation of general proteins oxidative modifications profile, the identification of preferential protein targets, and oxidative phosphorylation (OXPHOS) activity. We observed age-related cardiac muscle impairment, evidenced by decreased OXPHOS activity, paralleled by an increased protein susceptibility to carbonylation and nitration. Among the main targets to these posttranslational modifications we found mitochondrial proteins, mainly from OXPHOS complexes, MnSOD and enzymes from lipid metabolism. Lifelong sedentary behavior exacerbated the nitrative damage of mitochondrial proteins, paralleled by a statistically significant decrease of respiratory chain complexes II and III activities. In overall, our results highlight the determinant role of aging in cardiac muscle impairment, which is worsened by a sedentary lifestyle. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the temporal involvement of different proteolytic systems and muscle proteome changes during experimental disuse atrophy (up to 1 week hindlimb suspension, HS) in murine gastrocnemius muscle. The results showed that proteolysis, cytoprotection mechanisms and signs of cellular infiltration occurred very early. After 1 day of HS, signals of lysosomal activation, rather than programmed cell death (apoptosis), seem to trigger protein breakdown in the whole skeletal muscle. Moreover, the ubiquitin-proteasome pathway remained elevated later whereas all other proteolytic parameters returned to control values when atrophy was fully established. Using proteomics, evidence is provided for metabolic alterations toward glycolysis and for cytoskeleton remodelling suggestive of reduced capacity for force generation. Overall, our data highlight an early and coordinated time-dependent activation of proteolysis, which explains the global proteome alterations observed in gastrocnemius under atrophic conditions. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to investigate the mechanisms of cell death (apoptosis vs. necrosis) during muscle atrophy induced by 1 week of hindlimb suspension. Biochemical and morphological parameters were examined in murine soleus and gastrocnemius muscles. A total of 70 male Charles River CD1 mice were randomly assigned to seven groups (n = 10/group): Cont (loading control conditions) and 6HS, 12HS, 24HS, 48HS, 72HS and 1wkHS with respect to the period of hindlimb suspension (HS). Compared to the Cont, skeletal muscle atrophy was confirmed by a significant decrease of 44 and of 17% in fiber cross-sectional areas in the gastrocnemius and soleus, respectively. A significant increase in caspase-3 activity was noticed in 6HS (196%, P < 0.05) and in 12HS (201%, P < 0.05), as well as the amount of cytosolic mono- and oligonucleosomes at 12HS (142%, P < 0.05) and 24HS (203%, P < 0.05) in the gastrocnemius and soleus, respectively. The profile of necrotic markers showed a peak of myeloperoxidase activity at 24HS (170%, P < 0.05) and at 72HS (114%, P < 0.05) in the gastrocnemius and soleus, respectively. The analysis of N-acetylglucosaminidase activity evidenced more increment in the soleus at 72HS (60%, P < 0.05). The analysis of the basal values of these parameters suggested that apoptosis prevailed in the slow-twitch muscle analyzed, whereas lysosomic activity seemed to be more pronounced in the gastrocnemius. The morphological data supported the biochemical results pointing towards a shift from apoptosis to necrosis, which seems to corroborate the aponecrosis theory. [ABSTRACT FROM AUTHOR]

Endurance training (ET) and adriamycin (ADR) treatment are two conditions that have been described as triggering metabolic alterations within the myocardium. ADR is an anti-neoplastic agent with notorious cardiotoxicity, most likely because it increases oxidative stress. ET and/or ADR treatment can induce metabolic and signaling alterations affording cross-tolerance against several insults such as ischemia and reperfusion. The objective of the present work was to investigate whether heart mitochondria isolated from rats submitted to ET with or without ADR treatment were more or less susceptible to in vitro anoxia-reoxygenation (AR) when compared with control rats. Twenty-four male Wistar rats were assigned into four groups ( n=6 each): control (C), ADR (20 mg-kg−1), 14 wk ET (T), and T+ADR. Respiratory parameters and oxidative damage were determined before and after 1 min anoxia followed by 4 min reoxygenation. Basal heat shock proteins (HSPs)60 and-70 and antioxidant enzymes' activity were measured. ADR by itself decreased state 3 and respiratory control ratio (RCR), as opposed to ET by itself, which improved state 3 and RCR. As expected, AR impaired state 3 and 4, RCR, and ADP/O in the C group ( p>0.05). In the ADR group, AR did not induce any alteration in RCR and in ADP/O values. ET in the absence of ADR treatment prevented the impairment in RCR and ADP/O and in state 4 induced by AR. Also, despite the fact that state 3 respiration after AR was lower in all groups, it was significantly higher in the T than in the C group. Increased mitochondrial carbonyls and malondialdehyde (MDA) after AR were only found in the C group. Also, following AR, both carbonyls and MDA levels were lower in the T and in the T+ADR than in C and ADR groups, respectively. HSP60 levels were higher in the ADR, T, and T+ADR than in the C group (2.5-fold, 2-fold, and 1.9-fold increase, respectively). HSP70 increased twofold in the T and T+ADR groups. ET augmented 1.5-fold the activity of superoxide dismutase. The present work demonstrates that both ET and ADR treatment induced myocardial alterations that interfere with in vitro mitochondrial responses to AR. [ABSTRACT FROM AUTHOR]

The comprehension of the cellular mechanisms underlying skeletal muscle atrophy has been the aim of several experimental studies. However, the majority of them focused on alterations of the myocytes induced by different experimental conditions yet disregarding the contribution of other cells such as endothelial cells and fibroblasts. In this sense, 70 Charles River CD1 male mice were randomly assigned to seven groups (n=10 per group): control and 6, 12, 24, 48, 72 h and 1 week with respect to the period of hindlimb suspension. Forty-eight hours before sacrifice, the animals were injected with bromodeoxyuridine (BrdU) in order to identify proliferating cells. Immunohistochemistry and south-western blotting techniques were used to evaluate across the whole gastrocnemius muscle BrdU incorporation into the different proliferating cells. The contribution of the apoptotic response was also measured in order to ascertain whether the balance between cell survival and death was preserved. The results observed during 1 week of unloading-induced atrophy evidenced an intense peak of proliferating activity only after 6 h, mainly due to the duplication of satellite cells. Consequently to this unexpected activation of satellite cells, the addition of nuclei to the fibre syncytium was recognized at 12 h of unloading. After 48 h of weightlessness, the proliferating activity observed was largely due to an interstitial fibrosis. According to the apoptotic index profile observed during the analysed unloading period, this general proliferative activity was balanced by apoptosis, which strongly suggests the existence of a regulatory feedback response between anabolic and catabolic events in unloading-induced skeletal muscle atrophy. [ABSTRACT FROM AUTHOR]

The effects of a high-altitude exposure were studied in six mountaineers who spent 3 weeks at an altitude range between 5,250 and 7,161 m after 1 week in an acclimatization trek (2,800-5,250 m). Blood drawn from the antecubital vein was collected at sea level 1 day before and 1 day after the expedition to analyse some haematological variables [haemoglobin (Hb), haematocrit (Htc) and red blood cell (RBC) count], erythrocyte antioxidant enzyme activity [superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (Gr)] and membrane fatty acid profile [mono-unsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), saturated fatty acids (SFA), trans fatty acids (TRANS)]. Moreover, total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), thiol protein groups (SH), SOD, GPx and Gr were measured in plasma. High-altitude exposure induced polycythaemia, with significant increases in RBC count (5.26%), Hb concentration (4.83%) and Htc (6.26%). Furthermore, a significant increase in plasma TBARS, SOD and Gr was observed after the expedition, whereas SH, TAS and GPx decreased. Erythrocyte glutathione-cycle-related antioxidant enzyme activity was upregulated, whereas SOD activity was maintained after the expedition. In addition, despite the unchanged (MUFA+PUFA)/SFA ratio, the membrane erythrocyte fatty acid content showed a significant increase in PUFAs and a decrease in TRANS, suggesting enhanced membrane fluidity. In conclusion, it seems that high-altitude exposure, besides quantitative variations in RBC expression, induced plasma oxidative stress and damage, and significant changes in erythrocyte components, namely in antioxidant enzyme activity and membrane fatty acid profile that might modify RBC functionality. [ABSTRACT FROM AUTHOR]

The oligopeptide permease (Opp), a protein-dependent ABC transporter, has been found in the genome of Xanthomonas axonopodis pv. citri (Xac), but not in Xanthomonas campestris pv. campestris (Xcc). Sequence analysis indicated that 4 opp genes (oppA, oppB, oppC, oppD/F), located in a 33.8-kbp DNA fragment present only in the Xac genome, are arranged in an operon-like structure and share highest sequence similarities with Streptomyces roseofulvus orthologs. Nonetheless, analyses of the GC content, codon usage, and transposon positioning suggested that the Xac opp operon does not have an exogenous origin. The presence of a stop codon at one of the ATP-binding domains of OppD/F would render the uptake system nonfunctional, but detection of a single polycistronic mRNA and periplasmic OppA in actively growing bacteria suggests that the Opp permease is active and could contribute to the distinct nutritional requirements and host specificities of the two Xanthomonas species. [ABSTRACT FROM AUTHOR]

This study intended to analyze: (1) the effects of acute and severe hypoxia exposure on skeletal muscle oxidative stress and oxidative damage markers; (2) the protective role of the antioxidant glutathione against oxidative damage; and (3) the expression of heat shock protein 70 kDa (HSP70) induced by this hypoxic insult. Forty mice were divided into four groups: control + placebo (C+P), hypoxia + placebo (H+P), control + l-buthionine-[S,R]-sulfoximine (BSO, a GSH-depleting compound) (C+BSO) and hypoxia + BSO (H+BSO). Hypoxia groups were continuously exposed for 24 h to a hypobaric hypoxic environment equivalent to an altitude of 7000 m and sacrificed immediately after. Control groups were maintained at sea level during the experimental protocol. Analyzed biochemical parameters were: reduced (GSH) and oxidized (GSSG) glutathione, thiobarbituric acid reactive substances (TBARS), sulfhydryl protein groups (SH), N-acetyl-β-d-glucosaminidase (NAG) and HSP70 protein. Hypoxia (H+P) per se, compared to C+P, induced a significant increase in %GSSG (5.68 vs. 1.14%), TBARS (436.7 vs. 227.9 nM), NAG (4.49 vs. 3.35 U/mg) and HSP70 (178.7 vs. 100%). Compared with H+P, H+BSO showed a significant decrease in total glutathione (19.30 vs. 6.13 nmol/mg) and an additional increase in %GSSG (5.68 vs. 11.33%) and in HSP70 expression (178.7 vs. 202.2%). However, no further oxidative damage was observed in H+BSO. These data suggest that acute hypoxia per se might enhance oxidative stress; however, the glutathione system seems to have a modest role in skeletal muscle protection against hypoxia-induced oxidative stress. Moreover, hypoxia and BSO treatment is a sufficient stimulus to promote HSP70 overexpression. [ABSTRACT FROM AUTHOR]