Anti-Plasmodium Activity of Angiotensin II and Related Synthetic Peptides

Plasmodium species are the causative agents of malaria, the most devastating insect-borne parasite of human populations. Finding and developing new drugs for malaria treatment and prevention is the goal of much research. Angiotensins I and II (ang I and ang II) and six synthetic related peptides designated Vaniceres 1-6 (VC1-VC6) were assayed in vivo and in vitro for their effects on the development of the avian parasite, Plasmodium gallinaceum. Ang II and VC5 injected into the thoraces of the insects reduced mean intensities of infection in the mosquito salivary glands by 88% and 76%, respectively. Although the mechanism(s) of action is not completely understood, we have demonstrated that these peptides disrupt selectively the P. gallinaceum cell membrane. Additionally, incubation in vitro of sporozoites with VC5 reduced the infectivity of the parasites to their vertebrate host. VC5 has no observable agonist effects on vertebrates, and this makes it a promising drug for malaria prevention and chemotherapy.

Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma

Background: Cancer shows a great diversity in its clinical behavior which cannot be easily predicted using the currently available clinical or pathological markers. The identification of pathways associated with lymph node metastasis (N+) and recurrent head and neck squamous cell carcinoma (HNSCC) may increase our understanding of the complex biology of this disease. Methods: Tumor samples were obtained from untreated HNSCC patients undergoing surgery. Patients were classified according to pathologic lymph node status (positive or negative) or tumor recurrence (recurrent or non-recurrent tumor) after treatment (surgery with neck dissection followed by radiotherapy). Using microarray gene expression, we screened tumor samples according to modules comprised by genes in the same pathway or functional category. Results: The most frequent alterations were the repression of modules in negative lymph node (N0) and in non-recurrent tumors rather than induction of modules in N+ or in recurrent tumors. N0 tumors showed repression of modules that contain cell survival genes and in non-recurrent tumors cell-cell signaling and extracellular region modules were repressed. Conclusions: The repression of modules that contain cell survival genes in N0 tumors reinforces the important role that apoptosis plays in the regulation of metastasis. In addition, because tumor samples used here were not microdissected, tumor gene expression data are represented together with the stroma, which may reveal signaling between the microenvironment and tumor cells. For instance, in non-recurrent tumors, extracellular region module was repressed, indicating that the stroma and tumor cells may have fewer interactions, which disable metastasis development. Finally, the genes highlighted in our analysis can be implicated in more than one pathway or characteristic, suggesting that therapeutic approaches to prevent tumor progression should target more than one gene or pathway, specially apoptosis and interactions between tumor cells and the stroma.

THE LOWER CENTRAL AND DERIVED SERIES OF THE BRAID GROUPS OF THE SPHERE

In this paper, we determine the lower central and derived series for the braid groups of the sphere. We are motivated in part by the study of Fadell-Neuwirth short exact sequences, but the problem is important in its own right. The braid groups of the 2-sphere S(2) were studied by Fadell, Van Buskirk and Gillette during the 1960s, and are of particular interest due to the fact that they have torsion elements (which were characterised by Murasugi). We first prove that for all n epsilon N, the lower central series of the n-string braid group B(n)(S(2)) is constant from the commutator subgroup onwards. We obtain a presentation of Gamma(2)(Bn(S(2))), from which we observe that Gamma(2)(B(4)(S(2))) is a semi-direct product of the quaternion group Q(8) of order 8 by a free group F(2) of rank 2. As for the derived series of Bn(S(2)), we show that for all n >= 5, it is constant from the derived subgroup onwards. The group Bn(S(2)) being finite and soluble for n <= 3, the critical case is n = 4 for which the derived subgroup is the above semi-direct product Q(8) (sic) F(2). By proving a general result concerning the structure of the derived subgroup of a semi-direct product, we are able to determine completely the derived series of B(4)(S(2)) which from (B(4)(S(2)))(4) onwards coincides with that of the free group of rank 2, as well as its successive derived series quotients.

COUNTABLE GROUPS OF ISOMETRIES ON BANACH SPACES

A group G is representable in a Banach space X if G is isomorphic to the group of isometrics on X in some equivalent norm. We prove that a countable group G is representable in a separable real Banach space X in several general cases, including when G similar or equal to {-1,1} x H, H finite and dim X >= vertical bar H vertical bar or when G contains a normal subgroup with two elements and X is of the form c(0)(Y) or l(p)(Y), 1 <= p < +infinity. This is a consequence of a result inspired by methods of S. Bellenot (1986) and stating that under rather general conditions on a separable real Banach space X and a countable bounded group G of isomorphisms on X containing -Id, there exists an equivalent norm on X for which G is equal to the group of isometrics on X. We also extend methods of K. Jarosz (1988) to prove that any complex Banach space of dimension at least 2 may be renormed with an equivalent complex norm to admit only trivial real isometries, and that any complexification of a Banach space may be renormed with an equivalent complex norm to admit only trivial and conjugation real isometrics. It follows that every real Banach space of dimension at least 4 and with a complex structure may be renormed to admit exactly two complex structures up to isometry, and that every real Cartesian square may be renormed to admit a unique complex structure up to isometry.

Dynamic light scattering and optical absorption spectroscopy study of pH and temperature stabilities of the extracellular hemoglobin of Glossoscolex paulistus

The extracellular hemoglobin of Glossoscolex paulistus (HbGp) is constituted of subunits containing heme groups, monomers and trimers, and nonheme structures, called linkers, and the whole protein has a minimum molecular mass near 3.1 x 10(6) Da. This and other proteins of the same family are useful model systems for developing blood substitutes due to their extracellular nature, large size, and resistance to oxidation. HbGp samples were studied by dynamic light scattering (DLS). In the pH range 6.0-8.0, HbGp is stable and has a monodisperse size distribution with a z-average hydrodynamic diameter (D-h) of 27 +/- 1 nm. A more alkaline pH induced an irreversible dissociation process, resulting in a smaller D-h of 10 +/- 1 nm. The decrease in D-h suggests a complete hemoglobin dissociation. Gel filtration chromatography was used to show unequivocally the oligomeric dissociation observed at alkaline pH. At pH 9.0, the dissociation kinetics is slow, taking a minimum of 24 h to be completed. Dissociation rate constants progressively increase at higher pH, becoming, at pH 10.5, not detectable by DILS. Protein temperature stability was also pH-dependent. Melting curves for HbGp showed oligomeric dissociation and protein denaturation as a function of pH. Dissociation temperatures were lower at higher pH. Kinetic studies were also performed using ultraviolet-visible absorption at the Soret band. Optical absorption monitors the hemoglobin autoxidation while DLS gives information regarding particle size changes in the process of protein dissociation. Absorption was analyzed at different pH values in the range 9.0-9.8 and at two temperatures, 25 degrees C and 38 degrees C. At 25 degrees C, for pH 9.0 and 9.3, the kinetics monitored by ultraviolet-visible absorption presents a monoexponential behavior, whereas for pH 9.6 and 9.8, a biexponential behavior was observed, consistent with heme heterogeneity at more alkaline pH. The kinetics at 38 degrees C is faster than that at 25 degrees C and is biexponential in the whole pH range. DLS dissociation rates are faster than the autoxidation dissociation rates at 25 degrees C. Autoxiclation and dissociation processes are intimately related, so that oligomeric protein dissociation promotes the increase of autoxidation rate and vice versa. The effect of dissociation is to change the kinetic character of the autoxidation of hemes from monoexponential to biexponential, whereas the reverse change is not as effective. This work shows that DLS can be used to follow, quantitatively and in real time, the kinetics of changes in the oligomerization of biologic complex supramolecular systems. Such information is relevant for the development of mimetic systems to be used as blood substitutes.

Anthelmintic effects of condensed tannins on Trichostrongylus colubriformis in experimentally infected sheep

Recent surveys have identified anthelmintic effects from many bioactive substances particularly from condensed tannin (CT) sources. The aims of the present study were to investigate the potential anthelmintic effects of condensed tannins (CT) on Trichostrongylus colubriformis in experimentally infected sheep and the nutritional consequences on animals. Twenty helminth-free lambs were divided into five groups of four animals. Groups I to IV were artificially infected with 6,000 third stage larvae (L3) of T. colubriformis. Group I was the infected control and group V was the uninfected control. Twenty-eight days post-infection (p.i.) lambs from GII were supplemented with tanniniferous sorghum (350 g/animal/day, during seven days); GIII were drenched with Acacia mearnsii extract (15% CT) for just one day and GIV during two days (1.6 g extract/kg BW). At day 36 p.i., animals from infected group (GI to GIV) were slaughtered. Faecal egg counts (FEC) values present a reduction on GII when compared with GI at day 29 p.i. (P < 0.05) and between GIII and GI at day 35 and 36 p.i. (P < 0.05). The values of egg hatchability and number of L3 recovered from the faeces were not statistical analyzed (there was no duplicate data), however there was a considerable reduction between the values from treated and control group. The use of CT on diet did not cause significant difference on blood parameters, body-weight and carcass-weight (P > 0.05). No difference was related on total worm burden between treatments; however, GIV presented lower number of females than GI (P < 0.05). The use of CT could be a promising alternative source to reduce the pasture contamination and to control T. colubriformis infection in sheep.

Effect of different resistance-training regimens on the WNT-signaling pathway

The purpose of the present study was to evaluate the effects of 8 weeks of strength and power training on the expression of genes related to the canonical WNT pathway and beta-catenin protein levels in physically active men. Twenty-five subjects (27.4 +/- A 4.6 years) were balanced based on their relative maximum strength in the squat exercise (squat 1RM/body mass) and randomly assigned to strength training (ST) (n = 10), power training (PT) (n = 10), and control (C) (n = 5) groups. The ST and the PT groups performed high and low intensity squats, respectively, thrice a week, for 8 weeks. Muscle biopsies from the vastus lateralis muscle were collected before and after the training period. Relative strength and power increased similarly in both ST and PT groups (P < 0.001). Fiber cross-sectional area also increased similarly in both ST and PT groups. Gene expression and beta-catenin protein expression levels were assessed by real-time PCR and Western blot. Certain genes were up-regulated in the ST group (WNT1: 6.4-fold, P < 0.0001; SFRP1: 3.3-fold, P < 0.0001 and LEF1: 7.3-fold, P < 0.0001) and also in the PT group (WNT1: 24.9-fold, P < 0.0001; SFRP1: 2.7-fold, P < 0.0001; LEF1: 34.1-fold, P < 0.0001 and Cyclin D1: 7.7-fold, P < 0.001). In addition, the expression of key WNT pathway genes was substantially more responsive to PT than to ST (WNT1: P < 0.0001; LEF1: P < 0.0001 and Cyclin D1: P < 0.001). Finally, the total beta-catenin protein content increased only in the PT group (P < 0.05). Our data indicate that a PT regimen triggers greater responses in key elements of the WNT pathway.

Forest-related partnerships in Brazilian Amazonia: There is more to sustainable forest management than reduced impact logging

There is more to sustainable forest management than reduced impact logging. Partnerships between multiple actors are needed in order to create the institutional context for good forest governance and sustainable forest management and stimulate the necessary local community involvement. The idea behind this is that the parties would be able to achieve more jointly than on their own by combining assets, knowledge, skills and political power of actors at different levels of scale. This article aims to demonstrate by example the nature and variety of forest-related partnerships in Brazilian Amazonia. Based on the lessons learned from these cases and the authors` experience, the principal characteristics of successful partnerships are described, with a focus on political and socioeconomic aspects. These characteristics include fairly negotiated partnership objectives, the active involvement of the public sector as well as impartial brokers, equitable and cost-effective institutional arrangements, sufficient and equitably shared benefits for all the parties involved, addressing socioeconomic drawbacks, and taking measures to maintain sustainable exploitation levels. The authors argue that, in addition to product-oriented partnerships which focus on sustainable forest management, there is also a need for politically oriented partnerships based on civil society coalitions. The watchdog function of these politically oriented partnerships, their awareness-raising campaigns regarding detrimental policies and practices, and advocacy for good forest governance are essential for the creation of the appropriate legal and political framework for sustainable forest management. (C) 2008 Elsevier B.V. All rights reserved.

Effect of Food Restriction and Intense Physical Training on Estrous Cyclicity and Plasma Leptin Concentrations in Rats

Intense physical training and dietary energy restriction have been associated with consequences such as nutritional amenorrhea. We investigated the effects of intense physical training, food restriction or the combination of both strategies on estrous cyclicity in female rats, and the relationship between leptin ad these effects. Twenty-seven female Wistar rats were distributed into four groups: SF: sedentary, fed ad libitum; SR: sedentary subjected to 50% food restriction (based on the food intake of their fed counterparts); TF: trained (physical training on a motor treadmill with a gradual increase in speed and time), fed ad libitum; TR; trained with 50% food restriction. We analysed estrous cyclicity, plasma leptin and estradiol as well as chemical composition of the carcass, body weight variation. and weight of ovaries and perirenal adipose tissue. Data demonstrate that physical training alone was not responsible for significant modifications in either carcass chemical composition or reproductive function. Food restriction reduced leptin levels in all animals and interrupted the estrous cyclicity in some animals, but only the combination of food restriction and physical training was capable of interrupting the estrous cyclicity in all animals. Leptin was not directly related to estrous cyclicity. From our findings, it may be concluded that there is an additive or synergistic effect of energy intake restriction and energy expenditure by intense physical training on estrous cyclicity. Leptin appears to be one among others factors related to estrous cycle, but it probably acts indirectly.

Enrollment in Physical Education Is Associated With Health-Related Behavior Among High School Students

METHODS: A total of 4210 students attending public high schools in Pernambuco (northeast of Brazil) were selected using random 2-stage cluster sampling. Data were collected by using the Global School-based Student Health Survey. The independent variable was the frequency of participation in PE classes, whereas physical activity, television viewing, smoking, and alcohol, fruit, vegetables and soda consumption were dependent variables. Logistic regressions were carried out to perform crude and adjusted analysis of the association between enrollment in PE classes and health-related behaviors. RESULTS: Sixty-five percent of students do not take part in PE classes, with a significantly higher proportion among females (67.8%). It was observed that enrollment in PE classes was positively associated with physical activity, TV viewing, and fruit consumption, but was negatively associated with soda drinking. The likelihood of reporting being active and eating fruit on a daily basis was 27% and 45% higher, respectively, among those who participate in at least 2 classes per week in comparison with those who do not. Students who participate in PE classes had 28-30% higher likelihood of reporting lower TV viewing during week days. CONCLUSIONS: Findings suggest that higher levels of enrollment in PE classes could play a role in the promotion of health-related behaviors among high school students.

EXPRESSION OF GENES RELATED TO MYOSTATIN SIGNALING DURING RAT SKELETAL MUSCLE LONGITUDINAL GROWTH

In this study we investigated the gene expression of proteins related to myostatin (MSTN) signaling during skeletal muscle longitudinal growth. To promote muscle growth, Wistar male rats were submitted to a stretching protocol for different durations (12, 24, 48, and 96 hours). Following this protocol, soleus weight and length and sarcomere number were determined. In addition, expression levels of the genes that encode MSTN, follistatin isoforms 288 and 315 (FLST288 and FLST315), follistatin-like 3 protein (FLST-L3), growth and differentiation factor-associated protein-1 (GASP-1), activin IIB receptor (ActIIB), and SMAD-7 were determined by real-time polymerase chain reaction. Prolonged stretching increased soleus weight, length, and sarcomere number. In addition, MSTN gene expression was increased at 12-24 hours, followed by a decrease at 96 hours when compared with baseline values. FLST isoforms, FLST-L3, and GASP-1 mRNA levels increased significantly over all time-points. ActIIB gene expression decreased quickly at 12-24 hours. SMAD-7 mRNA levels showed a late increase at 48 hours, which peaked at 96 hours. The gene expression pattern of inhibitory proteins related to MSTN signaling suggests a strong downregulation of this pathway in response to prolonged stretching. Muscle Nerve 40: 992-999, 2009

Nickel sorption capacity of ground xylem of Quercus ilex trees and effects of selected ligands present in the xylem sap

In this work the influence of four different ligands present in the xylem sap of Quercus ilex (histidine, citric, oxalic and aspartic acids) on Ni(II) adsorption by xylem was investigated. Grinded xylem was trapped in acrylic columns and solutions of Ni(II), in the absence and presence of the four ligands prepared in KNO(3) 0-1 mol L(-1) at pH 5.5, were percolated through the column. Aliquots of solutions were recovered in the column end for Ni determination by graphite furnace atomic absorption spectrometry (GFAAS). The experimental. data to describe Ni sorption by xylem in both the presence and absence of ligands was better explained by the Freundlich isotherm model. The decreasing affinity order of ligands for Ni was: oxalic acid > citric acid > histidine > aspartic acid. On the other hand, the Ni(II) adsorption by xylem increased following the inverse sequence of ligands. Potentiometric titrations of acidic groups were carried out to elucidate the sorption site groups available in Q. ilex xylem. The potentiometric titration has shown three sorption sites: pK(a) 2.6 (57.7% of the sorption sites), related to monobasic aliphatic carboxylic acids or nitrogen aromatic bases, pK(a) 8.1 (9.6%) and pK(a) 9.9 (32.7%), related to phenolic groups. (C) 2008 Elsevier GmbH. All rights reserved.

Improving Critical Thinking and Clinical Reasoning With a Continuing Education Course

Background: Continuing education courses related to critical thinking and clinical reasoning are needed to improve the accuracy of diagnosis. Method: This study evaluated a 4-day, 16-hour continuing education course conducted in Brazil. Thirty-nine nurses completed a pretest and a posttest consisting of two written case studies designed to measure the accuracy of nurses` diagnoses. Results: There were significant differences in accuracy from pretest to posttest for case 1 (p = .008) and case 2 (p = .042) and overall (p = .001). Conclusion: Continuing education courses should be implemented to improve the accuracy of nurses` diagnoses. J Contin Educ Nurs 2009;40(3):121-127.

Impact of cancer-related symptom synergisms on health-related quality of life and performance status

To identify the impact of multiple symptoms and their co-occurrence on health-related quality of life (HRQOL) dimensions and performance status (PS), 115 outpatients with cancer, who were not receiving active cancer treatment and were recruited from, a university hospital in Sao Paulo, Brazil completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, the Beck Depression Inventory, and the Brief Pain Inventory. Karnofsky Performance Status scores also were completed. Application of TwoStep Cluster analysis resulted in two distinct patient subgroups based on 113 patient experiences with pain, depression, fatigue, insomnia, constipation, lack of appetite, dyspnea, nausea, vomiting, and diarrhea. One group had multiple and severe symptom subgroup and another had Less symptoms and with lower severity. Multiple and severe symptoms had worse PS, role functioning, and physical, emotional, cognitive, social, and overall HRQOL. Multiple and severe symptom subgroup was also six times as likely as lower severity to have poor role functioning;five times more likely to have poor emotional;four times more likely to have poor PS, physical, and overall HRQOL, and three times as likely to have poor cognitive and social HRQOL, independent of gender, age, level of education, and economic condition. Classification and Regression Tree analyses were undertaken to identify which co-occurring symptoms would best determine reduction in HRQOL and PS. Pain and fatigue were identified as indicators of reduction on physical HRQOL and PS. Fatigue and insomnia were associated with reduction in cognitive; depression and pain in social; and fatigue and constipation in role functioning. Only depression was associated with reduction in overall HRQOL. These data demonstrate that there is a synergic effect among distinct cancer symptoms that result in reduction in HRQOL dimensions and PS.

Angiotensin receptor blockade improves the net balance of cardiac Ca(2+) handling-related proteins in sympathetic hyperactivity-induced heart failure

Aims: The clinical benefits of angiotensin II type 1 (AT1) receptor blockers (ARB) in heart failure (HF) include cardiac anti-remodeling and improved ventricular function. However, the cellular mechanisms underlying the benefits of ARB on ventricular function need to be better clarified. In the present manuscript, we evaluated the effects of AT1 receptor blockade on the net balance of Ca(2+) handling proteins in hearts of mice lacking alpha(2A) and alpha(2C) adrenoceptors (alpha(2A)/alpha(2C)ARKO), which develop sympathetic hyperactivity (SH) induced-HF. Main methods: A cohort of male wild-type (WT) and congenic alpha(2A)/alpha(2C)ARKO mice in a C57BL6/J genetic background (5-7 mo of age) was randomly assigned to receive either placebo or ARB (Losartan, 10 mg/kg for 8wks). Ventricular function (VF) was assessed by echocardiography, and cardiac myocyte width and ventricular fibrosis by a computer-assisted morphometric system. Sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), phospholamban (PLN), phospho-Ser(16)-PLN, phospho-Thr(17)-PLN, phosphatase 1 (PP1), Na(+)-Ca(2+) exchanger (NCX), Ca(2+)/calmodulin-dependent protein kinase 11 (CaMKII) and phospho-Thr(286)-CaMKII were analyzed by Western blot. Key findings: alpha(2A)/alpha(2C)ARKO mice displayed ventricular dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis paralleled by decreased SERCA2 and increased phospho-Thr(17)-PLN, CaMKII, phospho-Thr(286)-CaMKII and NCX levels. ARB induced anti-cardiac remodeling effect and improved VF in alpha(2A)/alpha(2C)ARKO associated with increased SERCA2 and phospho-Ser(16)-PLN levels, and SERCA2:NCX ratio. Additionally, ARB decreased phospho-Thr(17)-PLN levels as well as reestablished NCX, CaMKII and phospho-Thr(286)-CaMKII toward WT levels. Significance: Altogether, these data provide new insights on intracellular Ca(2+) regulatory mechanisms underlying improved ventricular function by ARB therapy in HF. (c) 2011 Elsevier Inc. All rights reserved.