Human Mitochondrial Hsp70 (mortalin): Shedding Light On Atpase Activity, Interaction With Adenosine Nucleotides, Solution Structure And Domain Organization.

The human mitochondrial Hsp70, also called mortalin, is of considerable importance for mitochondria biogenesis and the correct functioning of the cell machinery. In the mitochondrial matrix, mortalin acts in the importing and folding process of nucleus-encoded proteins. The in vivo deregulation of mortalin expression and/or function has been correlated with age-related diseases and certain cancers due to its interaction with the p53 protein. In spite of its critical biological roles, structural and functional studies on mortalin are limited by its insoluble recombinant production. This study provides the first report of the production of folded and soluble recombinant mortalin when co-expressed with the human Hsp70-escort protein 1, but it is still likely prone to self-association. The monomeric fraction of mortalin presented a slightly elongated shape and basal ATPase activity that is higher than that of its cytoplasmic counterpart Hsp70-1A, suggesting that it was obtained in the functional state. Through small angle X-ray scattering, we assessed the low-resolution structural model of monomeric mortalin that is characterized by an elongated shape. This model adequately accommodated high resolution structures of Hsp70 domains indicating its quality. We also observed that mortalin interacts with adenosine nucleotides with high affinity. Thermally induced unfolding experiments indicated that mortalin is formed by at least two domains and that the transition is sensitive to the presence of adenosine nucleotides and that this process is dependent on the presence of Mg2+ ions. Interestingly, the thermal-induced unfolding assays of mortalin suggested the presence of an aggregation/association event, which was not observed for human Hsp70-1A, and this finding may explain its natural tendency for in vivo aggregation. Our study may contribute to the structural understanding of mortalin as well as to contribute for its recombinant production for antitumor compound screenings.

Low-level Laser Therapy To The Mouse Femur Enhances The Fungicidal Response Of Neutrophils Against Paracoccidioides Brasiliensis.

Neutrophils (PMN) play a central role in host defense against the neglected fungal infection paracoccidioidomycosis (PCM), which is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb). PCM is of major importance, especially in Latin America, and its treatment relies on the use of antifungal drugs. However, the course of treatment is lengthy, leading to side effects and even development of fungal resistance. The goal of the study was to use low-level laser therapy (LLLT) to stimulate PMN to fight Pb in vivo. Swiss mice with subcutaneous air pouches were inoculated with a virulent strain of Pb or fungal cell wall components (Zymosan), and then received LLLT (780 nm; 50 mW; 12.5 J/cm2; 30 seconds per point, giving a total energy of 0.5 J per point) on alternate days at two points on each hind leg. The aim was to reach the bone marrow in the femur with light. Non-irradiated animals were used as controls. The number and viability of the PMN that migrated to the inoculation site was assessed, as well as their ability to synthesize proteins, produce reactive oxygen species (ROS) and their fungicidal activity. The highly pure PMN populations obtained after 10 days of infection were also subsequently cultured in the presence of Pb for trials of protein production, evaluation of mitochondrial activity, ROS production and quantification of viable fungi growth. PMN from mice that received LLLT were more active metabolically, had higher fungicidal activity against Pb in vivo and also in vitro. The kinetics of neutrophil protein production also correlated with a more activated state. LLLT may be a safe and non-invasive approach to deal with PCM infection.

Circulating Levels Of Chemokines In Psoriasis.

Chemokines may contribute to local and systemic inflammation in patients with psoriasis. Previous studies have demonstrated the importance of chemokine ligands and receptors in the recruitment of T cells into psoriatic lesional skin and synovial fluid. The aim of this study was to evaluate the levels of Th1-related chemokines in psoriasis and to investigate any association with disease severity. We quantified serum levels of CXCL9, CXCL10 and CXCL16 and the frequencies of CD4+CXCR3+ T lymphocytes through ELISA and flow cytometry, respectively. A total of 38 patients with psoriasis and 33 controls were included. There were no significant differences in chemokine levels between psoriasis and control groups. Patients with psoriatic arthritis had lower median level of CXCL10 when compared with controls (p=0.03). There were no significant correlations between serum chemokines analyzed and disease severity. Frequencies of CD4+CXCR3+ T cells were lower in patients with psoriasis than in controls (p<0.01). A sensitivity analysis excluding patients on systemic therapy yielded similar results. Serum concentrations of CXCL9, CXCL10 and CXCL16 were not increased in the psoriasis group or correlated with disease severity. Systemic levels of chemokine ligands do not seem to be sensitive biomarkers of disease activity or accurate parameters to predict response to therapy. Frequencies of CD4+CXCR3+ T cells were decreased in the peripheral blood of psoriasis patients, possibly due to recruitment to inflammatory lesions.

The Influence Of Body Weight On Sexual Function And Quality Of Life In Women With Polycystic Ovary Syndrome.

To assess sexual function (SF) and quality of life (QOL) in women with polycystic ovary syndrome (PCOS). A cross-sectional study was conducted to assess 56 women with PCOS and 102 control women with regular menstrual cycles. To assess SF and QOL in Brazilian women with PCOS with Female Sexual Function Index (FSFI) and the WHOQOL-bref questionnaires. Women with PCOS had a worse evaluation to arousal, lubrication, satisfaction, pain and total FSFI, and there was no difference in sexual desire and orgasm. Besides, they had a worse evaluation concerning health status than controls. The body mass index was inversely correlated to the QOL, especially to the physical, psychological, environment aspects and self-assessment of QOL, but it did not show correlation to the SF. Women with PCOS had a worse sexual function and self-assessment of health condition in comparison to controls. The body weight as isolated symptom was correlated to the worsening in quality of life, but not with the worsening of sexual function.

Encephalization And Diversification Of The Cranial Base In Platyrrhine Primates.

The cranial base, composed of the midline and lateral basicranium, is a structurally important region of the skull associated with several key traits, which has been extensively studied in anthropology and primatology. In particular, most studies have focused on the association between midline cranial base flexion and relative brain size, or encephalization. However, variation in lateral basicranial morphology has been studied less thoroughly. Platyrrhines are a group of primates that experienced a major evolutionary radiation accompanied by extensive morphological diversification in Central and South America over a large temporal scale. Previous studies have also suggested that they underwent several evolutionarily independent processes of encephalization. Given these characteristics, platyrrhines present an excellent opportunity to study, on a large phylogenetic scale, the morphological correlates of primate diversification in brain size. In this study we explore the pattern of variation in basicranial morphology and its relationship with phylogenetic branching and with encephalization in platyrrhines. We quantify variation in the 3D shape of the midline and lateral basicranium and endocranial volumes in a large sample of platyrrhine species, employing high-resolution CT-scans and geometric morphometric techniques. We investigate the relationship between basicranial shape and encephalization using phylogenetic regression methods and calculate a measure of phylogenetic signal in the datasets. The results showed that phylogenetic structure is the most important dimension for understanding platyrrhine cranial base diversification; only Aotus species do not show concordance with our molecular phylogeny. Encephalization was only correlated with midline basicranial flexion, and species that exhibit convergence in their relative brain size do not display convergence in lateral basicranial shape. The evolution of basicranial variation in primates is probably more complex than previously believed, and understanding it will require further studies exploring the complex interactions between encephalization, brain shape, cranial base morphology, and ecological dimensions acting along the species divergence process.

Sorghum Flour Fractions: Correlations Among Polysaccharides, Phenolic Compounds, Antioxidant Activity And Glycemic Index.

Nutrients composition, phenolic compounds, antioxidant activity and estimated glycemic index (EGI) were evaluated in sorghum bran (SB) and decorticated sorghum flour (DSF), obtained by a rice-polisher, as well as whole sorghum flour (WSF). Correlation between EGI and the studied parameters were determined. SB presented the highest protein, lipid, ash, β-glucan, total and insoluble dietary fiber contents; and the lowest non-resistant and total starch contents. The highest carbohydrate and resistant starch contents were in DSF and WSF, respectively. Phenolic compounds and antioxidant activities were concentrated in SB. The EGI values were: DSF 84.5±0.41; WSF 77.2±0.33; and SB 60.3±0.78. Phenolic compounds, specific flavonoids and antioxidant activities, as well as total, insoluble and soluble dietary fiber and β-glucans of sorghum flour samples were all negatively correlated to EGI. RS content was not correlated to EGI.

Explosive Synchronization With Partial Degree-frequency Correlation.

Networks of Kuramoto oscillators with a positive correlation between the oscillators frequencies and the degree of their corresponding vertices exhibit so-called explosive synchronization behavior, which is now under intensive investigation. Here we study and discuss explosive synchronization in a situation that has not yet been considered, namely when only a part, typically a small part, of the vertices is subjected to a degree-frequency correlation. Our results show that in order to have explosive synchronization, it suffices to have degree-frequency correlations only for the hubs, the vertices with the highest degrees. Moreover, we show that a partial degree-frequency correlation does not only promotes but also allows explosive synchronization to happen in networks for which a full degree-frequency correlation would not allow it. We perform a mean-field analysis and our conclusions were corroborated by exhaustive numerical experiments for synthetic networks and also for the undirected and unweighed version of a typical benchmark biological network, namely the neural network of the worm Caenorhabditis elegans. The latter is an explicit example where partial degree-frequency correlation leads to explosive synchronization with hysteresis, in contrast with the fully correlated case, for which no explosive synchronization is observed.

Key Endothelial Cell Angiogenic Mechanisms Are Stimulated By The Circulating Milieu In Sickle Cell Disease And Attenuated By Hydroxyurea.

As hypoxia-induced inflammatory angiogenesis may contribute to sickle cell disease manifestations, we compared the angiogenic molecular profiles of plasma from sickle cell disease individuals and correlated these with in vitro endothelial cell-mediated angiogenesis-stimulating activity and in vivo neovascularization. Bioplex demonstrated that plasma from steady-state sickle cell anemia patients presented elevated concentrations of pro-angiogenic factors (Angiopoietin-1, basic fibroblast growth factor, vascular endothelial growth factor, vascular endothelial growth factor-D and placental growth factor) and displayed potent pro-angiogenic activity, significantly augmenting endothelial cell proliferation, migration and capillary-like structure formation. In vivo neovascularization of Matrigel plugs was significantly greater in sickle cell disease mice, compared with non-sickle cell disease mice, consistent with an upregulation of angiogenesis in the disease. In plasma from patients with hemoglobin SC disease without proliferative retinopathy, anti-angiogenic endostatin and thrombospondin-2 were significantly elevated. In contrast, plasma from hemoglobin SC individuals with proliferative retinopathy displayed a pro-angiogenic profile and had more significant effects on endothelial cell proliferation and capillary formation than plasma of patients without retinopathy. Hydroxyurea therapy was associated with significant reductions in plasma angiogenic factor profile, in association with an inhibition of endothelial cell-mediated angiogenic mechanisms and neovascularization. Thus, sickle cell anemia and retinopathic hemoglobin SC individuals present a highly angiogenic circulating milieu, capable of stimulating key endothelial cell-mediated angiogenic mechanisms. Combination anti-angiogenic therapy for preventing progression of unregulated neovascularization and associated manifestations in sickle cell disease, such as pulmonary hypertension, may be indicated; furthermore, the benefits and drawbacks of the potent anti-angiogenic effects of hydroxyurea should be clarified.

Low Molecular Weight Protein Tyrosine Phosphatase (lmwptp) Upregulation Mediates Malignant Potential In Colorectal Cancer.

Phosphatases have long been regarded as tumor suppressors, however there is emerging evidence for a tumor initiating role for some phosphatases in several forms of cancer. Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP; acid phosphatase 1 [ACP1]) is an 18 kDa enzyme that influences the phosphorylation of signaling pathway mediators involved in cancer and is thus postulated to be a tumor-promoting enzyme, but neither unequivocal clinical evidence nor convincing mechanistic actions for a role of LMWPTP have been identified. In the present study, we show that LMWPTP expression is not only significantly increased in colorectal cancer (CRC), but also follows a step-wise increase in different levels of dysplasia. Chemical inhibition of LMWPTP significantly reduces CRC growth. Furthermore, downregulation of LMWPTP in CRC leads to a reduced migration ability in both 2D- and 3D-migration assays, and sensitizes tumor cells to the chemotherapeutic agent 5-FU. In conclusion, this study shows that LMWPTP is not only overexpressed in colorectal cancer, but it is correlated with the malignant potential of this cancer, suggesting that this phosphatase may act as a predictive biomaker of CRC stage and represents a rational novel target in the treatment of this disease.

Salivary Bpifa1 (splunc1) And Bpifa2 (splunc2 A) Are Modified By Head And Neck Cancer Radiotherapy.

To determine the effects of radiotherapy on salivary BPIFA expression and to investigate the role of BPIFA in the development of known radiotherapy side effects. Unstimulated whole-mouth saliva was collected from 45 cancer patients (1 week before treatment, during the treatment, and 1 week after completion of radiotherapy) and from 20 controls. BPIFA1 and BPIFA2 expression was detected by western blotting and analyzed along with clinicopathologic data and side effects from the radiotherapy. A facial radiation field was associated with lower salivary flow during and after radiotherapy and correlated with side effects, mainly mucositis. Salivary BPIFA1 expression levels were similar between the control group and the patient group before treatment. On the other hand, BPIFA2 levels were higher in the patient group before treatment compared with the control group. BPIFA concentration was modified by radiotherapy as BPIFA1 levels increased (P = .0081) and BPIFA2 decreased (P < .0001). Higher levels of BPIFA1 were associated with the presence of mucositis (P = .0363) and its severity (P = .0500). The present study found that levels of BPIFA1 and glycosylated forms of BPIFA2 are affected by radiotherapy, suggesting that these proteins may play a role in the oral microenvironment in irradiated patients with head and neck cancer.

Neuropsychological and phonological evaluation in the Apert's syndrome: study of two cases

This study evaluated two cases of Apert's syndrome, through phonological, cognitive, and neuropsychological instruments and correlated the results to complementary exams. In short, this study reveals the necessity of application of neuropsychological, cognitive and phonological evaluation and correlation of the results with complementary testings because significant differences can be present in the Apert's syndrome.

Modelos de regressão lineares para estimativa de produtividade da soja no oeste do Paraná, utilizando dados espectrais

The main objective of this work was to evaluate the linear regression between spectral response and soybean yield in regional scale. In this study were monitored 36 municipalities from the west region of the states of Parana using five images of Landsat 5/TM during 2004/05 season. The spectral response was converted in physical values, apparent and surface reflectances, by radiometric transformation and atmospheric corrections and both used to calculate NDVI and GVI vegetation indices. Those ones were compared by multiple and simple regression with government official yield values (IBGE). Diagnostic processing method to identify influents values or collinearity was applied to the data too. The results showed that the mean surface reflectance value from all images was more correlated with yield than individual dates. Further, the multiple regressions using all dates and both vegetation indices gave better results than simple regression.

Malpighiaceae: correlations between habit, fruit type and basic chromosome number

The family Malpighiaceae presents species with different habits, fruit types and cytological characters. Climbers are considered the most derived habit, followed, respectively, by the shrubby and arboreal ones. The present study examines the relationship between basic chromosome numbers and the derivation of climbing habit and fruit types in Malpighiaceae. A comparison of all the chromosome number reports for Malpighiaceae showed a predominance of chromosome numbers based on x=5 or 10 in the genera of sub-family Malpighioideae, mainly represented by climbers with winged fruits, whereas non-climbing species with non-winged fruits, which predominate in sub-family Byrsonimoideae, had counts based on x=6, which is considered the less derived basic number for the family. Based on such data, confirmed by statistic assays, and on the monophyletic origin of this family, we admit the hypothesis that morphological derivation of habit and fruit is correlated with chromosome basic number variation in the family Malpighiaceae.

Produção de serapilheira e decomposição do material foliar em um cerradão na Estação Ecológica de Jataí, município de Luiz Antônio, SP, Brasil

We estimate litter production and leaf decomposition rate in a cerradão area, physiognomy little studied and very threatened in São Paulo State. During the period of study, litter production was 5646.9 kg.ha-1.year-1, which the 'leaf' fraction corresponded to 4081.2 kg.ha¹.year¹; the 'branch' fraction, to 1066.1 kg.ha-1.year-1; the 'reproductive structures' fraction, to 434.1 kg.ha-1.year-1; and the 'miscellaneous' fraction to 65.5 kg.ha-1.year-1. Litter production was highly seasonal and negatively correlated with relative humidity and air temperature. Leaf production was negatively correlated with relative humidity, rainfall, and air temperature. There was no significant difference between litter production found in this study and those in two other sites with cerradão and semideciduous forest, but these physiognomies differed significantly from the cerrado sensu stricto. Leaf decomposition rate (K) was 0.56. Half-life of the decomposing material was 1.8 years and turnover time was 2.3 years.

Unidade Haugh como medida da qualidade de ovos de galinha armazenados sob refrigeração

Alterations in physical, chemical and functional characteristics of egg proteins occur during storage. These changes depend on the storage conditions, mainly duration, temperature and relative humidity. This study examined the fresh egg Haugh unit score and the storage egg Haugh unit score, at room temperature (25°C) and under refrigeration conditions (8°C), during 7, 14 and 21 days of storage. Haugh units and albumin height decreased considerably during storage at room temperature. At 8°C, there was no significant difference in the Haugh unit for different periods of storage, but their values were smaller as compared to fresh eggs. The weight of the eggs was not affected by both storage and temperature. For both temperatures, pH was positively correlated with Haugh units and negatively with the albumin height.