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Random energy models (REMs) provide a simple description of the energy landscapes that guide protein folding and evolution. The requirement of a large energy gap between the native structure and unfolded conformations, considered necessary for cooperative, protein-like, folding behavior, indicates that proteins differ markedly from random heteropolymers. It has been suggested, therefore, that natural selection might have acted to choose nonrandom amino acid sequences satisfying this particular condition, implying that a large fraction of possible, unselected random sequences, would not fold to any structure. From an informational perspective, however, this scenario could indicate that protein structures, regarded as messages to be transmitted through a communication channel, would not be efficiently encoded in amino acid sequences, regarded as the communication channel for this transmission, since a large fraction of possible channel states would not be used. Here, we use a combined REM for conformations and sequences, with previously estimated parameters for natural proteins, to explore an alternative possibility in which the appropriate shape of the landscape results mainly from the deviation from randomness of possible native structures instead of sequences. We observe that this situation emerges naturally if the distribution of conformational energies happens to arise from two independent contributions corresponding to sequence-dependent and -independent terms. This construction is consistent with the hypothesis of a protein burial folding code, with native structures being determined by a modest amount of sequence-dependent atomic burial information with sequence-independent constraints imposed by unspecific hydrogen bond formation. More generally, an appropriate combination of sequence-dependent and -independent information accommodates the possibility of an efficient structural encoding with the main physical requirement for folding, providing possible insight not only on the folding process but also on several aspects sequence evolution such as neutral networks, conformational coverage, and de novo gene emergence., (© 2023 Wiley Periodicals LLC.)

The connection between protein sequences and tertiary structures has intrigued investigators for decades. A plausible hypothesis for the coding scheme postulates that atomic burial information obtainable from the sequence could be sufficient for structural determination when combined to sequence-independent constraints. Accordingly, folding simulations using native burial information expressed by atomic central distances, discretized into a small number L of equiprobable burial layers, have indeed been successful in reaching and distinguishing the native structure of several globular proteins. Attempted predictions of layers from sequence, however, turned out to be insufficiently accurate for most proteins. Here we explore the possibility that a nonuniform assignment of layers, which is intended to account for constraints imposed by chain connectivity, might provide a more efficient burial encoding of tertiary structures. We consider the condition that adjacent C α -atoms along the sequence cannot occupy nonadjacent layers, in which case the information required to specify sequences of burials would be smaller. It is shown that appropriate folding behavior can still be observed in this explicitly more constrained scenario with a structure-dependent assignment intended to produce the thinnest possible layers still compatible with the imposed burial constraint. This thinnest assignment turns out to be sufficiently restrictive for the observed examples and provides appropriately thinner layers or, equivalently, a larger number of layers, for examples previously observed to indeed require more restrictive constraints when compared to counterparts of similar size, as well as the appropriate increase in number of layers for larger proteins. Implications for the general understanding of the protein folding code are discussed.

Opinion mining for app reviews aims to analyze people's comments from app stores to support data-driven requirements engineering activities, such as bug report classification, new feature requests, and usage experience. However, due to a large amount of textual data, manually analyzing these comments is challenging, and machine-learning-based methods have been used to automate opinion mining. Although recent methods have obtained promising results for extracting and categorizing requirements from users' opinions, the main focus of existing studies is to help software engineers to explore historical user behavior regarding software requirements. Thus, existing models are used to support corrective maintenance from app reviews, while we argue that this valuable user knowledge can be used for preventive software maintenance. This paper introduces the temporal dynamics of requirements analysis to answer the following question: how to predict initial trends on defective requirements from users' opinions before negatively impacting the overall app's evaluation? We present the MAPP-Reviews (Monitoring App Reviews) method, which (i) extracts requirements with negative evaluation from app reviews, (ii) generates time series based on the frequency of negative evaluation, and (iii) trains predictive models to identify requirements with higher trends of negative evaluation. The experimental results from approximately 85,000 reviews show that opinions extracted from user reviews provide information about the future behavior of an app requirement, thereby allowing software engineers to anticipate the identification of requirements that may affect the future app's ratings., Competing Interests: The authors declare that they have no competing interests., (© 2022 Alves de Lima et al.)

Objectives: to understand, from the vocabulary universe of young students, the knowledge and statements on cyberbullying via Web Radio Associação de Jovens de Irajá., Methods: a qualitative research. Students' speech questions were used on the web radio's message board and on the station's social networks; 35 students participated. The analysis was based on Paulo Freire's Culture Circle and Thematic Analysis., Results: the following categories emerged: "Cyberbullying: Reading the World Youth School", which describes the vocabulary universe of youths: social networks, bullying, internet, cyberbullying, violence, fakes and anonymity; and "Is Cyberbullying a Joke or Virtual Violence?", which points to the health consequences, therapeutic alternatives of treatment and punitive laws. Final Considerations: nursing educational care with schoolchildren via web radio brought contributions on cyberbullying, since the youths adopted reflective postures in the face of the problem.

Background: Fatigue is a common symptom in patients with inflammatory bowel diseases (IBD). A translated and culturally adapted, instrument with robust psychometric for measuring fatigue in Brazilian patients with IBD is needed., Objective: To translate and cross-culturally adapt the inflammatory Bowel Disease Fatigue Scale (IBD-F) into Brazilian-Portuguese and to test its measurement properties in Brazilian patients with IBD., Methods: Data from 123 patients with IBD were collected. In addition to IBD-F, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) was used. The measurement properties tested were: internal consistency, reproducibility (reliability and agreement), construct validity, internal and external responsiveness, and ceiling and floor effects., Results: The Brazilian-Portuguese version of the IBD-F showed excellent internal consistency (Cronbach's alpha of 0.95), excellent reproducibility (ICC=0.97) and a minimal detectable change of 6.0 points. The construct validity was demonstrated with a good correlation between the IBD-F and FACIT-F (r=- 0.46). Effect sizes used for measuring internal responsiveness were moderate among those with Crohn's (0.66) disease and low in patients with ulcerative colitis (0.24). The Brazilian-Portuguese version of the IBD-F presented with high external responsiveness for Crohn's disease (0.84) and with low external responsiveness for ulcerative colitis (0.33). The area under the curve considered for responsiveness was 0.84. Twenty-five percent of floor effects and no ceiling effect were recorded., Conclusion: The Brazilian-Portuguese version of IBD-F has adequate measurement properties and its use can be recommended in clinical practice and research.

Objective: To evaluate stress, and to associate it with sociodemographic and clinical aspects of nurses from the Mobile Emergency Care Service., Method: This is an observational, cross-sectional and quantitative study conducted with 123 nurses, who answered a questionnaire to assess sociodemographic and clinical variables, and the Job Stress Scale, which evaluates stress in the workplace., Results: The results indicated that most of them were women, 20 to 40 years old, married, without another employment bond and with specialization course. They had low control and low demand at work and performed a passive work. Women reported passive work and high stress levels, while men were equally divided in active and passive work with low stress levels., Conclusion: Passive work is harmful to health and it is related to lack of autonomy, decision-making, and social support. It may lead to reduced ability to solve problems faced in daily work routine.

Introduction: The challenges related to the diagnosis of sexually transmitted infections present more complex factors in remote and hard-to-reach areas. The use of self-collection devices that facilitate the obtaining of a biological sample with high quality for sensitive molecular tests have been examined. This study aimed to evaluate the performance and acceptance of the Evalyn® Brush (Rovers® Medical Devices) for detection of T. vaginalis among women living in the riverside communities of Amazonas, Brazil., Methodology: The study included 300 riverside women. They received instructions for self-collection, carried out the task, and then answered a questionnaire on the use of the device. T. vaginalis was detected by Polymerase Chain Reaction, using primers TVK3/TVK7., Results: The mean age of the women was 35.8 years, and most of them presented low schooling, low income, agricultural activity and lived in a marital union. All samples were positive for human genomic DNA (100%) and the prevalence of T. vaginalis infection was 5.6% (n = 17). Of the 300 women, 293 (97.7%) indicated that they liked the use of the device, 287 (95.7%) reported having had no difficulty in handling it, 265 (88.3%) did not feel any type of discomfort and 228 (76%) said they preferred the self-collection to the collection made by the professional, mainly due to privacy and comfort., Conclusions: The Evalyn® Brush proved reliable as a device for the collection of biological samples for molecular analysis and was well-accepted by women. Its use can be indicated in remote and hard to reach places., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2019 Danielle Albuquerque Rocha, Maria Joana Nunes Azevedo, Savio Jose Silva Batista, Emille Santos Beltrao, Adriene Fernandes Araujo, Cassia Oliveira Moraes, Renato Santos Reis, Katia Luz Torres, Jose Eduardo Levi, Josiane Montanho Marino.)

Concerns with health and wellness are currently a global trend. Consequently, people have increasingly been engaging in some form of regular sports practice in their adult lives. This is evidenced by the rise of markets that are related to the sports sector. One of those market trends is active tourism, which refers to the practice of physical activities in natural environments within a tourist destination. In this context, people travel to certain places, typically with friends or as couples, to engage in sports activities of greater or lesser intensities. This allows for them to disconnect with their daily routines and provides them all of the positive health-related outcomes that are associated with exercising. Therefore, health tourism is also an efficient tool against sedentariness. The present study explores which sports are currently the most popular amongst active tourists, which attributes they value the most when choosing a destination, and what is their expenditure pattern. To this end, a sample of 60 individuals who have engaged in some form of active tourism in Galicia is surveyed. The findings suggest that active tourists are particularly interested in dedicating their discretionary time to travelling and they have a higher daily expenditure within the destination than the average tourist.

Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection among women. In Brazil, there is no organized screening program for C. trachomatis, and the actual prevalence of infection is unknown. This study aimed to determine the prevalence of C. trachomatis infection in women living in riverside communities in the Amazon, using self-collection employing the Evalyn® Brush and polymerase chain reaction. A total of 299 riverine women aged 18-81 years, mean age 35.7 (±12.8) years, predominantly agricultural workers, with low schooling and living with a partner, participated in this study. The prevalence of C. trachomatis infection was found to be 3.7% (95% CI 1.8-6.5), most of them being symptomatic. The mean age of the first sexual intercourse reported by women was 15.2 (±2.3) years, and the majority reported having had none or only one partner in the last 12 months, with very low adherence to consistent condom use (15.4%). Most women (98.3%) reported having approved using the vaginal self-collecting brush, and only 4.7% reported having difficulty in handling the brush. We consider that a vaginal self-collecting device is adequate for diagnosing C. trachomatis infection in women living in remote, hard-to-reach areas.

This work presents an alternative method for arsenic speciation using the nano-TiO 2 hydride generation photocatalytic hydride generation (PCHG) system, which is easily separated from the medium. Nano-TiO 2 was studied as photocatalyst to reduction of arsenic species by UV-induced with formic acid and atomic absorption detection of different forms of arsenic [As (III), As (V), dimethylarsinic acid (DMA)] in environmental samples (water, sediment and plant). The effect of the average pH, the organic acid concentration, the ultraviolet irradiation time and their amount were investigated. With the presence of formic acid, the process was more effective in the reduction of arsenic when compared to other organic acids, mainly acetic acid. In addition, the photocatalytic hydride generation and flame atomic absorption spectrometry (nano-TiO 2 /PCHG-FAAS) increased the identification and quantification of different arsenic species. The ultrasound extraction procedure was used as a method to prepare samples with solutions of 1.0 mol L -1 phosphoric acid. The accuracy of the measurements (n = 12), calculated as relative standard deviation, was less than 8.6%. The detection limits for As (III) and As (total) in samples were 0.418 and 0.574 μg g -1 , respectively.

Mesenchymal stromal cells (MSCs) from different sources have differential effects on lung injury. To compare the effects of murine MSCs from bone marrow (BM), adipose tissue (AD), and lung tissue (LUNG) on inflammatory and remodeling processes in experimental allergic asthma, female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) or saline (C). Twenty-four hours after the last challenge, mice received either saline (50 µl, SAL), BM-MSCs, AD-MSCs, or LUNG-MSCs (10 5 cells per mouse in 50 µl total volume) intratracheally. At 1 week, BM-MSCs produced significantly greater reductions in resistive and viscoelastic pressures, bronchoconstriction index, collagen fiber content in lung parenchyma (but not airways), eosinophil infiltration, and levels of interleukin (IL)-4, IL-13, transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF) in lung homogenates compared to AD-MSCs and LUNG-MSCs. Only BM-MSCs increased IL-10 and interferon (IFN)-γ in lung tissue. In parallel in vitro experiments, BM-MSCs increased M2 macrophage polarization, whereas AD-MSCs and LUNG-MSCs had higher baseline levels of IL-4, insulin-like growth factor (IGF), and VEGF secretion. Exposure of MSCs to serum specimens obtained from asthmatic mice promoted reductions in secretion of these mediators, particularly in BM-MSCs. Intratracheally administered BM-MSCs, AD-MSCs, and LUNG-MSCs were differentially effective at reducing airway inflammation and remodeling and improving lung function in the current model of allergic asthma. In conclusion, intratracheal administration of MSCs from BM, AD, and LUNG were differentially effective at reducing airway inflammation and remodeling and improving lung function comparably reduced inflammation and fibrogenesis in this asthma model. However, altered lung mechanics and lung remodeling responded better to BM-MSCs than to AD-MSCs or LUNG-MSCs. Moreover, each type of MSC was differentially affected in a surrogate in vitro model of the in vivo lung environment. Stem Cells Translational Medicine 2017;6:1557-1567., (© 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

The aim of this integrative review was to compare Latin American literature about risk and knowledge on breast cancer. Of 47 studies selected, 20 were about knowledge or awareness and 27 about risk of breast cancer. English was the dominant language in studies about risk, whereas studies about knowledge were mainly written in Spanish or Portuguese. Studies about knowledge were all cross- sectional, whereas case- control studies dominated authors' interest about risk of breast cancer. Studies about knowledge were mainly focused on early detection of the disease and the most common study objective was breast self- examination (N = 14). In contrast, few studies about risk of breast cancer focused on early detection (N = 5). Obesity and overweight (N = 14), family history (N = 13), decreased parity (N = 12), and short breastfeeding duration (N = 10) were among the most frequent identified risk factors. Socio- economic factors such as income and educational level had variable effects on breast cancer risk and affected also knowledge of women about risk factors and early detection. Present results indicated that studies about risk of breast cancer were more often based on a better sound analytical background, compared to studies about knowledge, which were mostly descriptive.

Atrazine is an herbicide widely used in crops and has drawn attention due to potential pollution present in soil, sediment, water, and food. Since conventional methods are not potentially efficient to persistent degradation of organic compounds, new technology has been developed to remove them, especially practices utilizing advanced oxidation processes (AOPs). This work aims to evaluate the use of different energies (ultraviolet (UV), microwaves (MW), and radiations (MW-UV)) to the herbicide atrazine through the process of photo-oxidation. These systems found degradation rates of around 12 % (UV), 28 % (MW), and 83 % (MW-UV), respectively, with time intervals of 120 s. After the photolytic processes, the samples were analyzed at a wavelength scanning the range of 190 to 300 nm, where the spectral analysis of the signal was used to evaluate the degradation of atrazine and the appearance of some other peaks (degradation products). The spectrum evaluation resulting from photolytic processes gave rise to a new signal which was confirmed by chromatography. This spectrum indicated the possible pathway of atrazine degradation by the process of photolytic MW-UV, generating atrazine-2-hydroxy, atrazine-desethyl-2-hidroxy, and atrazine-desisopropyl-2-hydroxy. The process indicated that in all situations, chloride was present in the analytic structure and was substituted by a hydroxyl group, which lowered the toxicity of the compound through the photolytic process MW-UV. Chromatographic analysis ascertained these preliminary assessments using spectrophotometry. It was also significantly observed that the process can be optimized by adjusting the pH of the solution, which was evident by an improvement of 10 % in the rate of degradation when subjected to a pH solution equal to 8.37.

Recent ab initio folding simulations for a limited number of small proteins have corroborated a previous suggestion that atomic burial information obtainable from sequence could be sufficient for tertiary structure determination when combined to sequence-independent geometrical constraints. Here, we use simulations parameterized by native burials to investigate the required amount of information in a diverse set of globular proteins comprising different structural classes and a wide size range. Burial information is provided by a potential term pushing each atom towards one among a small number L of equiprobable concentric layers. An upper bound for the required information is provided by the minimal number of layers L(min) still compatible with correct folding behavior. We obtain L(min) between 3 and 5 for seven small to medium proteins with 50 ≤ Nr ≤ 110 residues while for a larger protein with Nr = 141 we find that L ≥ 6 is required to maintain native stability. We additionally estimate the usable redundancy for a given L ≥ L(min) from the burial entropy associated to the largest folding-compatible fraction of "superfluous" atoms, for which the burial term can be turned off or target layers can be chosen randomly. The estimated redundancy for small proteins with L = 4 is close to 0.8. Our results are consistent with the above-average quality of burial predictions used in previous simulations and indicate that the fraction of approachable proteins could increase significantly with even a mild, plausible, improvement on sequence-dependent burial prediction or on sequence-independent constraints that augment the detectable redundancy during simulations., (© 2016 Wiley Periodicals, Inc.)

Unlabelled: Since its identification as the causative agent of plague in 1894, thousands of Yersinia pestis strains have been isolated and stored. Here, we report the ability of Y. pestis to survive up to 47 years in agar stabs, in rubber-stoppered tubes, under refrigeration (+4 to +10°C), although overall subculture recovery rates were poor and inversely related to the length of time stored. Genetic characterization of virulence gene presence among these subcultures was suggestive of significant variation in the genomic stability of Y. pestis subcultures stored under these conditions. Specifically, we found variation in the presence of plasmid and chromosomal virulence markers (genes pla, lcrV, caf1 and irp2) among multiple subcultures of Y. pestis strains in the 'Collection of Yersinia pestis' (Fiocruz-CYP) maintained by the SRP of FIOCRUZ-PE in Brazil. This variation, together with all of the inherent temporal, geographic and other genetic variation represented by all of the recoverable strains in this historical collection was preserved in new frozen culture stocks stored at -70°C as a result of this study. These frozen culture stocks represent a valuable resource for future comparative studies of Y. pestis., Significance and Impact of the Study: We report the ability of Yersinia pestis to survive up to 47 years in agar stabs, in rubber-stoppered tubes, under refrigeration (+4 to +10°C), although overall subculture recovery rates were poor and inversely related to the length of time stored. Genetic characterization of virulence gene presence among these subcultures was suggestive of significant variation in the genomic stability of Y. pestis subcultures stored under these conditions. This variation, together with all of the inherent temporal, geographic and other genetic variation represented by all of the recoverable strains in the historical 'Collection of Yersinia pestis' (Fiocruz-CYP) maintained by the SRP of FIOCRUZ-PE in Brazil was preserved in new frozen culture stocks stored at -70°C as a result of this study. These frozen culture stocks represent a valuable resource for future comparative studies of Y. pestis., (© 2015 The Society for Applied Microbiology.)

The present study aimed to investigate the antinociceptive and anti-inflammatory effects of the cyclic dipeptide cyclo-Gly-Pro (CGP) in mice. Antinociceptive activity was assessed by employing different pain models, such as formalin test, acetic acid-induced writhing, hot plate test, and carrageenan-induced hyperalgesia, in mice. The number of c-Fos-immunoreactive cells in the periaqueductal gray (PAG) was evaluated in CGP-treated mice. Anti-inflammatory activity was evaluated using paw oedema induced by carrageenan, compound 48/80, serotonin, and prostaglandin E2 (PGE2) and analyzed by plethysmometry. Quantitation of myeloperoxidase (MPO) in the paw was carried out to analyze the presence of neutrophils in the tissue. Intraperitoneal injection of CGP produced a significant inhibition in both neurogenic and inflammatory phases of formalin-induced pain. The antinociceptive effect of CGP, evaluated in the acetic acid-induced writhing test, was detected for up to 6 h after treatment. Further, in the hot plate test, antinociceptive behaviour was evoked by CGP, and this response was inhibited by naloxone. Animals treated with CGP did not present changes in motor performance. In CGP-treated mice there was an increase in the number of c-Fos-positive neurons in the periaqueductal gray. In another set of experiments, CGP attenuated the hyperalgesic response induced by carrageenan. Furthermore, CGP also reduced the carrageenan-increased MPO activity in paws. In addition, CGP also reduced the paw oedema evoked by compound 48/80, serotonin, and PGE2 . Taken together, these results may support a possible therapeutic application of the cyclic dipeptide cyclo-Gly-Pro toward alleviating nociception and damage caused by inflammation conditions., (© 2015 Wiley Publishing Asia Pty Ltd.)

Background: Both exaggerated and diminished reactivity to stress can be maladaptive. Previous studies have shown that performing increasingly difficult tasks leads first to increased reactivity and then to a blunted response when success is impossible. Our aim was to investigate the influence of trait anxiety on cardiac and cortisol response to and recovery from a standardized psychosocial stress task (Trier Social Stress Task) in a homogeneous sample of healthy peacekeepers. We hypothesized that participants with higher trait anxiety would show blunted reactivity during the performance of an overwhelmingly difficult and stressful task. Participants (N = 50) delivered a speech and performed an arithmetic task in the presence of critical evaluators. Cortisol samples and electrocardiogram data were collected. Participants completed the State-Trait Anxiety Inventory-Trait version, the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C) and the Military Peace Force Stressor Inventory., Results: For heart rate, the findings showed that peacekeepers with higher trait anxiety reacted less to the speech task (p = 0.03) and to the arithmetic task (p = 0.008) than those with lower trait anxiety. Trait anxiety did not modulate cortisol responses to the task. Despite the high trait anxiety group having higher PCL-C scores than the low trait anxiety group (p < 0.0001), this did not influence the cardiac results., Conclusions: We concluded that individuals with higher trait anxiety had less tachycardia in response to acute psychological stress than those with lower trait anxiety. The present results point to a higher risk for more anxious individuals of a maladaptive reaction to stressful events.

In the present study, siaresinolic acid (siaresinol, SA) was isolated from the leaves of Sabicea grisea and studied to evaluate its antinociceptive and anti-inflammatory activity. The antinociceptive effect of SA was investigated in mice using different animal models to study pain. In the acetic acid-induced writhing test, intraperitoneal (i.p.) injection of SA (0.1, 1, and 10 mg/kg, i.p.) 1 h before a pain stimulus significantly reduced the nociceptive response (by 42.3, 68.2, and 70.9 %, respectively). Pretreatment with glibenclamide, but not with yohimbine, metoclopramide, ketanserin, or naloxone, restored the antinociceptive effect induced by SA in the writhing test, suggesting that the K(+)ATP channel pathway might be involved in its mechanism of action. In the formalin test, SA (1 mg/kg, i.p.) decreased licking time in the second phase only, thereby indicating an anti-inflammatory effect. In the hot plate test, there was no significant difference in nociceptive behavior. In the rota-rod test, it was verified that a high dose of SA (10 mg/kg, i.p.) did not affect the locomotor activity of mice. In the pleurisy model, induced by carrageenan, treatment with SA inhibited important events involved in inflammatory responses, namely leukocyte influx, plasma leakage, and increased inflammatory mediators (TNF-α, IL-1β, and chemokine CXCL1), in the pleural exudate. Additionally, SA itself was not cytotoxic when evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in macrophages cultured for 24 h at concentrations ranging from 1 to 200 μg/mL. These results suggest, for the first time, that SA attenuates nociceptive behavior through mechanisms involving receptors for ATP-dependent potassium channels, in addition to suppressing acute inflammatory responses.

The three-dimensional structure of proteins is determined by their linear amino acid sequences but decipherment of the underlying protein folding code has remained elusive. Recent studies have suggested that burials, as expressed by atomic distances to the molecular center, are sufficiently informative for structural determination while potentially obtainable from sequences. Here we provide direct evidence for this distinctive role of burials in the folding code, demonstrating that burial propensities estimated from local sequence can indeed be used to fold globular proteins in ab initio simulations. We have used a statistical scheme based on a Hidden Markov Model (HMM) to classify all heavy atoms of a protein into a small number of burial atomic types depending on sequence context. Molecular dynamics simulations were then performed with a potential that forces all atoms of each type towards their predicted burial level, while simple geometric constraints were imposed on covalent structure and hydrogen bond formation. The correct folded conformation was obtained and distinguished in simulations that started from extended chains for a selection of structures comprising all three folding classes and high burial prediction quality. These results demonstrate that atomic burials can act as informational intermediates between sequence and structure, providing a new conceptual framework for improving structural prediction and understanding the fundamentals of protein folding., (© 2013 Wiley Periodicals, Inc.)

Introduction: Among the plethora of cells under investigation to restore a functional myocardium, mesenchymal stromal cells (MSCs) have been granted considerable interest. However, whereas the beneficial effects of bone marrow MSCs (BM-MSCs) in the context of the diseased heart are widely reported, data are still scarce on MSCs from the umbilical cord matrix (UCM-MSCs). Herein we report on the effect of UCM-MSC transplantation to the infarcted murine heart, seconded by the dissection of the molecular mechanisms at play., Methods: Human umbilical cord tissue-derived MSCs (UCX®), obtained by using a proprietary technology developed by ECBio, were delivered via intramyocardial injection to C57BL/6 females subjected to permanent ligation of the left descending coronary artery. Moreover, medium produced by cultured UCX® preconditioned under normoxia (CM) or hypoxia (CMH) was collected for subsequent in vitro assays., Results: Evaluation of the effects upon intramyocardial transplantation shows that UCX® preserved cardiac function and attenuated cardiac remodeling subsequent to myocardial infarction (MI). UCX® further led to increased capillary density and decreased apoptosis in the injured tissue. In vitro, UCX®-conditioned medium displayed (a) proangiogenic activity by promoting the formation of capillary-like structures by human umbilical vein endothelial cells (HUVECs), and (b) antiapoptotic activity in HL-1 cardiomyocytes subjected to hypoxia. Moreover, in adult murine cardiac Sca-1+ progenitor cells (CPCs), conditioned medium enhanced mitogenic activity while activating a gene program characteristic of cardiomyogenic differentiation., Conclusions: UCX® preserve cardiac function after intramyocardial transplantation in a MI murine model. The cardioprotective effects of UCX® were attributed to paracrine mechanisms that appear to enhance angiogenesis, limit the extent of the apoptosis, augment proliferation, and activate a pool of resident CPCs. Overall, these results suggest that UCX® should be considered an alternative cell source when designing new therapeutic approaches to treat MI.

In earlier studies, we reported that a heterologous prime-boost regimen using recombinant plasmid DNA followed by replication-defective adenovirus vector, both containing Trypanosoma cruzi genes encoding trans-sialidase (TS) and amastigote surface protein (ASP) 2, provided protective immunity against experimental infection with a reticulotropic strain of this human protozoan parasite. Herein, we tested the outcome of genetic vaccination of F1 (CB10XBALB/c) mice challenged with myotropic parasite strains (Brazil and Colombian). Initially, we determined that the coadministration during priming of a DNA plasmid containing the murine IL-12 gene improved the immune response and was essential for protective immunity elicited by the heterologous prime-boost regimen in susceptible male mice against acute lethal infections with these parasites. The prophylactic or therapeutic vaccination of resistant female mice led to a drastic reduction in the number of inflammatory infiltrates in cardiac and skeletal muscles during the chronic phase of infection with either strain. Analysis of the electrocardiographic parameters showed that prophylactic vaccination reduced the frequencies of sinus arrhythmia and atrioventricular block. Our results confirmed that prophylactic vaccination using the TS and ASP-2 genes benefits the host against acute and chronic pathologies caused by T. cruzi and should be further evaluated for the development of a veterinary or human vaccine against Chagas disease.

Owing to the importance of major histocompatibility complex class Ia-restricted CD8(+) T cells for host survival following viral, bacterial, fungal, or parasitic infection, it has become largely accepted that these cells should be considered in the design of a new generation of vaccines. For the past 20 years, solid evidence has been provided that the heterologous prime-boost regimen achieves the best results in terms of induction of long-lived protective CD8(+) T cells against a variety of experimental infections. Although this regimen has often been used experimentally, as is the case for many vaccines, the mechanism behind the efficacy of this vaccination regimen is still largely unknown. The main purpose of this review is to examine the characteristics of the protective CD8(+) T cells generated by this vaccination regimen. Part of its efficacy certainly relies on the generation and maintenance of large numbers of specific lymphocytes. Other specific characteristics may also be important, and studies on this direction have only recently been initiated. So far, the characterization of these protective, long-lived T cell populations suggests that there is a high frequency of polyfunctional T cells; these cells cover a large breadth and display a T effector memory (TEM) phenotype. These TEM cells are capable of proliferating after an infectious challenge and are highly refractory to apoptosis due to a control of the expression of pro-apoptotic receptors such as CD95. Also, they do not undergo significant long-term immunological erosion. Understanding the mechanisms that control the generation and maintenance of the protective activity of these long-lived TEM cells will certainly provide important insights into the physiology of CD8(+) T cells and pave the way for the design of new or improved vaccines.

Motivation: It has been recently suggested that atomic burials, as expressed by molecular central distances, contain sufficient information to determine the tertiary structure of small globular proteins. A possible approach to structural determination from sequence could therefore involve a sequence-to-burial intermediate prediction step whose accuracy, however, is theoretically limited by the mutual information between these two variables. We use a non-redundant set of globular protein structures to estimate the mutual information between local amino acid sequence and atomic burials. Discretizing central distances of or atoms in equiprobable burial levels, we estimate relevant mutual information measures that are compared with actual predictions obtained from a Naive Bayesian Classifier (NBC) and a Hidden Markov Model (HMM)., Results: Mutual information density for 20 amino acids and two or three burial levels were estimated to be roughly 15% of the unconditional burial entropy density. Lower estimates for the mutual information between local amino acid sequence and burial of a single residue indicated an increase in mutual information with the number of burial levels up to at least five or six levels. Prediction schemes were found to efficiently extract the available burial information from local sequence. Lower estimates for the mutual information involving single burials are consistently approached by predictions from the NBC and actually surpassed by predictions from the HMM. Near-optimal prediction for the HMM is indicated by the agreement between its density of prediction information and the corresponding density of mutual information between input and output representations., Availability: The dataset of protein structures and the prediction implementations are available at http://www.btc.unb.br/ (in 'Software').

MHC class Ia-restricted CD8(+) T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector CD8(+) T cells can clear infection caused by intracellular pathogens, in some circumstances, the immune response is suboptimal and the microorganisms survive, causing host death or chronic infection. Here, we explored the cellular and molecular mechanisms that could explain why CD8(+) T cell-mediated immunity during infection with the human protozoan parasite Trypanosoma cruzi is not optimal. For that purpose, we compared the CD8(+) T-cell mediated immune responses in mice infected with T. cruzi or vaccinated with a recombinant adenovirus expressing an immunodominant parasite antigen. Several functional and phenotypic characteristics of specific CD8(+) T cells overlapped. Among few exceptions was an accelerated expansion of the immune response in adenoviral vaccinated mice when compared to infected ones. Also, there was an upregulated expression of the apoptotic-signaling receptor CD95 on the surface of specific T cells from infected mice, which was not observed in the case of adenoviral-vaccinated mice. Most importantly, adenoviral vaccine provided at the time of infection significantly reduced the upregulation of CD95 expression and the proapoptotic phenotype of pathogen-specific CD8(+) cells expanded during infection. In parallel, infected adenovirus-vaccinated mice had a stronger CD8 T-cell mediated immune response and survived an otherwise lethal infection. We concluded that a suboptimal CD8(+) T-cell response is associated with an upregulation of CD95 expression and a proapoptotic phenotype. Both can be blocked by adenoviral vaccination.

The prime objective in the surgical treatment of basilar impression (BI), Chiari malformation (CM) and/or syringomyelia (SM) is based on the restoration of the normal cerebrospinal fluid (CSF) dynamics at the craniovertebral junction through the creation of a large artificial cisterna magna. A small suboccipital craniectomy has been emphasized to avoid caudal migration of the hindbrain structures into the vertebral canal. Nevertheless, the results showed downward migration of the hindbrain related to that type of craniectomy. The authors present, otherwise, the results of 104 cases of BI, CM and/or SM, whose surgical treatment was characterized by a large craniectomy with the patient in the sitting position, tonsillectomy, large opening of the fourth ventricle and duraplasty with creation of a large artificial cisterna magna. A significant upward migration of the posterior fossa structures was detected by postoperative magnetic resonance imaging.

Recently, we described a heterologous prime-boost strategy using plasmid DNA followed by replication-defective human recombinant adenovirus type 5 as a powerful strategy to elicit long-lived CD8(+) T-cell-mediated protective immunity against experimental systemic infection of mice with a human intracellular protozoan parasite, Trypanosoma cruzi. In the present study, we further characterized the protective long-lived CD8(+) T cells. We compared several functional and phenotypic aspects of specific CD8(+) T cells present 14 or 98 days after the last immunizing dose and found the following: (i) the numbers of specific cells were similar, as determined by multimer staining or by determining the number of gamma interferon (IFN-γ)-secreting cells by enzyme-linked immunospot (ELISPOT) assay; (ii) these cells were equally cytotoxic in vivo; (iii) following in vitro stimulation, a slight decline in the frequency of multifunctional cells (CD107a(+) IFN-γ(+) or CD107a(+) IFN-γ(+) tumor necrosis factor alpha positive [TNF-α(+)]) was paralleled by a significant increase of CD107a singly positive cells after 98 days; (iv) the expression of several surface markers was identical, except for the reexpression of CD127 after 98 days; (v) the use of genetically deficient mice revealed a role for interleukin-12 (IL-12)/IL-23, but not IFN-γ, in the maintenance of these memory cells; and (vi) subsequent immunizations with an unrelated virus or a plasmid vaccine or the depletion of CD4(+) T cells did not significantly erode the number or function of these CD8(+) T cells during the 15-week period. From these results, we concluded that heterologous plasmid DNA prime-adenovirus boost vaccination generated a stable pool of functional protective long-lived CD8(+) T cells with an effector memory phenotype.

In social insects, the superposition of simple individual behavioral rules leads to the emergence of complex collective patterns and helps solve difficult problems inherent to surviving in hostile habitats. Modelling ant colony foraging reveals strategies arising from the insects' self-organization and helps develop of new computational strategies in order to solve complex problems. This paper presents advances in modelling ants' behavior when foraging in a confined and dynamic environment, based on experiments with the Argentine ant Linepithema humile in a relatively complex artificial network. We propose a model which overcomes the problem of stagnation observed in earlier models by taking into account additional biological aspects, by using non-linear functions for the deposit, perception and evaporation of pheromone, and by introducing new mechanisms to represent randomness and the exploratory behavior of the ants., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Amifostine has been widely tested as a cytoprotective agent against a number of aggressors in different organs. Recently, a gastroprotective effect was observed for this drug in a model of indomethacin-induced gastric injury. Our objective was to investigate the effect of amifostine on ethanol-induced gastric injury and the role played in this mechanism by afferent sensory neurons, non-protein sulfhydryl groups, nitric oxide, ATP-sensitive potassium channels, and cyclooxygenase-2., Methods: Rats were treated with amifostine (22.5, 45, 90, or 180 mg/kg, PO or SC). After 30 min, the rats received absolute ethanol (5 ml kg(-1), PO). One hour later, gastric damage was quantified with a planimeter. Samples from the stomach were also taken for histopathological assessment and for assays of non-protein sulfhydryl groups. The other groups were pretreated with L-NAME (10 mg kg(-1), IP), glibenclamide (10 mg kg(-1), PO), or celecoxib (10 mg kg(-1), PO). After 30 min, the animals were given amifostine (90 mg kg(-1), PO or SC), followed 30 min later by gavage with absolute ethanol (5 ml kg(-1)). Other rats were desensitized with capsaicin (125 mg kg(-1), SC) 8 days prior to amifostine treatment., Results: Amifostine administration PO and SC significantly and dose-dependently reduced ethanol-induced macroscopic and microscopic gastric damage by restoring glutathione levels in the stomach mucosa. Amifostine-promoted gastroprotection against ethanol-induced stomach injury was reversed by pretreatment with neurotoxic doses of capsaicin, but not by L-NAME, glibenclamide, or celecoxib., Conclusions: Amifostine protects against ethanol-induced gastric injury by increasing glutathione levels and stimulating the afferent sensory neurons in the stomach.

The authors describe ten cases of syringomyelia without hindbrain herniation depicted by preoperative magnetic resonance imaging (MRI) in supine position. However, the herniation was observed in all cases during the operation with the patient in sitting position. The postoperative MRI revealed an intense reduction of the syrinx in all patients, as well as it was also observed a clinical amelioration in all cases. The surgical treatment was based on a large craniectomy with the patient in sitting position, tonsillectomy, large opening of the fourth ventricle and duraplasty with creation of a large cisterna magna.

The growing self-organizing surface map (GSOSM) is a novel map model that learns a folded surface immersed in a 3D space. Starting from a dense point cloud, the surface is reconstructed through an incremental mesh composed of approximately equilateral triangles. Unlike other models such as neural meshes (NM), the GSOSM builds a surface topology while accepting any sequence of sample presentation. The GSOSM model introduces a novel connection learning rule called competitive connection Hebbian learning (CCHL), which produces a complete triangulation. GSOSM reconstructions are accurate and often free of false or overlapping faces. This letter presents and discusses the GSOSM model. It also presents and analyzes a set of results and compares GSOSM with some other models.

In this paper, we propose a new method for surface reconstruction based on growing self-organizing maps (SOMs), called growing self-reconstruction maps (GSRMs). GSRM is an extension of growing neural gas (GNG) that includes the concept of triangular faces in the learning algorithm and additional conditions in order to include and remove connections, so that it can produce a triangular two-manifold mesh representation of a target object given an unstructured point cloud of its surface. The main modifications concern competitive Hebbian learning (CHL), the vertex insertion operation, and the edge removal mechanism. The method proposed is able to learn the geometry and topology of the surface represented in the point cloud and to generate meshes with different resolutions. Experimental results show that the proposed method can produce models that approximate the shape of an object, including its concave regions, boundaries, and holes, if any.

Purpose: to describe the genetic diversity of HIV-1 isolates from serum positive women followed up at a reference center., Methods: transversal study, including 96 women with two ELISA serological tests and a Western Blot confirmatory test. The viral charge was determined by the b-DNA kit, and the counting of T CD4 and T CD8 lymphocytes, by the Excalibur flow cytometry, from the samples of peripheral blood. The extraction and purification of pro-viral DNA was performed by the polymerase (PCR) chain reaction, using the QIAamp Blood kit (Qiagen Inc., Chatsworth, CA, U.S.A.). Sequencing of the pol region was done in 52 isolates with the 3100 Genetic Analyzer (Applied Biosystems Inc., Foster City, CA), and the genotyping was assessed by the Rega Subtyping Tool. The resistance pattern to anti-retrovirals (ARV) was inferred by the algorithm from the Stanford HIV Resistance data bank. Participants' clinical stages were defined as A, B or C, according to the criteria established by the Center for Diseases Control (CDC). For statistical analysis, the chi(2) test was used for the categorical variables and the Student's t test, for the numerical variables., Results: The average age of the sample, the disease and treatment average duration were respectively: 33.7 years old, 3.8 and 2.5 years. The viral charge average was log(10) 2.3 copies/mL; the T CD4 e T CD8 lymphocytes, 494.9 cells/microL and 1126.4 cells/microL. Concerning the clinical stage, 30 women were in stage A, 47 in B and 19 in C. Sequencing from the 52 isolates found 33 of B subtype, 4 of F, 1 of C and 14 of BF recombinant. The analysis of resistance to ARV has shown 39 (75.0%) susceptible isolates, 13 (25.0%) resistant to reversal transcriptase inhibitors (RTIN), and 3 (5.7%) resistant to protease inhibitor (PI)., Conclusions: There has been a large variety of HIV-1 and a high percentage of isolates resistant to ARV in the studied sample.

Objectives: This research has appraised the quality of life (QL) of diabetics type 1 member of Associação dos Diabéticos de Itabuna (ASDITA) and has verified their correlation between clinic variable and social-demographic situation of this group., Research Design and Methods: Thirty-four patients (gamma = 88%, epsilon = 5%; 53% female, age 20.4 +/- 8.4 years, diagnostic time 5.7 +/- 4.9 year) have participated in this research, data showed weight and height after the interview and measuring., Results: The social-demographic profiles of this group revealed family income of 0.7 +/- 0.56 of minimal salary, 53% had elementary school level and 64.7% were students. In avarage, the QL was regular (58.8%). QL has not been influenced by the level of education, ethnology, occupation, BMI, daily shot of insulin, or glicemic monitorization profile but woman, adult, diagnostic time more than ten years, little family income have had the worst QL., Conclusions: The QL of the searched patients has been less than what several publications have showed, but additional researches are necessary to have better comparisons between diabetics with socio-economical and cultural conditions similar to the ones observed in this research.

We investigate the possibility that atomic burials, as measured by their distances from the structural geometrical center, contain sufficient information to determine the tertiary structure of globular proteins. We report Monte Carlo simulated annealing results of all-atom hard-sphere models in continuous space for four small proteins: the all-beta WW-domain 1E0L, the alpha/beta protein-G 1IGD, the all-alpha engrailed homeo-domain 1ENH, and the alpha + beta engineered monomeric form of the Cro protein 1ORC. We used as energy function the sum over all atoms, labeled by i, of |R(i) - R(i) (*)|, where R(i) is the atomic distance from the center of coordinates, or central distance, and R(i) (*) is the "ideal" central distance obtained from the native structure. Hydrogen bonds were taken into consideration by the assignment of two ideal distances for backbone atoms forming hydrogen bonds in the native structure depending on the formation of a geometrically defined bond, independently of bond partner. Lowest energy final conformations turned out to be very similar to the native structure for the four proteins under investigation and a strong correlation was observed between energy and distance root mean square deviation (DRMS) from the native in the case of all-beta 1E0L and alpha/beta 1IGD. For all alpha 1ENH and alpha + beta 1ORC the overall correlation between energy and DRMS among final conformations was not as high because some trajectories resulted in high DRMS but low energy final conformations in which alpha-helices adopted a non-native mutual orientation. Comparison between central distances and actual accessible surface areas corroborated the implicit assumption of correlation between these two quantities. The Z-score obtained with this native-centric potential in the discrimination of native 1ORC from a set of random compact structures confirmed that it contains a much smaller amount of native information when compared to a traditional contact Go potential but indicated that simple sequence-dependent burial potentials still need some improvement in order to attain a similar discriminability. Taken together, our results suggest that central distances, in conjunction to physically motivated hydrogen bond constraints, contain sufficient information to determine the native conformation of these small proteins and that a solution to the folding problem for globular proteins could arise from sufficiently accurate burial predictions from sequence followed by minimization of a burial-dependent energy function.

A 29-year-old woman with acute lancinating headache, throbbed nuchal pain and subacute paraparesis underwent brain MRI in supine position that depicted: the absence of the cisterna magna, filled by non herniated cerebellar tonsils and compression of the brain stem and cisternae of the posterior fossa, which are aspects of the impacted cisterna magna without syringomyelia and without hydrocephalus. During eight days, pain was constant and resistant to drug treatment. Osteodural-neural decompression of the posterior fossa, performed with the patient in sitting position, revealed: compression of the brainstem, fourth ventricle and foramen of Magendie by herniated cerebellar tonsils, which were aspirated. Immediately after surgery, the headache and nuchal pain remmited. MRI depicted the large created cisterna magna and also that the cerebellar tonsils did not compress the fourth ventricle, the foramen of Magendie and the brainstem, besides the enlargement of posterior fossa cisternae. Four months after surgery, headache, nuchal pain and paraparesis had disappeared but hyperactive patellar and Achilles reflexes remained.

We use complete enumeration of self-avoiding chains of up to N=26 monomers in two-dimensional lattices to investigate the effect of alternative implementations of backbone hydrogen bonds on the cooperativity of homopolypeptide collapse. Following a recent study on protein folding models, we use the square lattice with z=3 local conformations per monomer and lattice extensions containing diagonal steps which result in z=5 or z=7 and assume that only a subset of zh

We recently described that vaccination of mice with a glutathione S transferase fusion protein representing amino acids 261-500 of the Amastigote Surface Protein-2 efficiently cross-primed protective CD8+ T cells against a lethal challenge with the human protozoan parasite Trypanosoma cruzi. In this study, we initially established that this protective immunity was long lived. Subsequently, we studied the importance of TLR9 agonist CpG ODN 1826, TLR4 and CD4+ T cells for the generation of these protective CD8+ T cells. We found that: (i) the TLR9 agonist CpG ODN 1826 improved the efficiency of protective immunity; (ii) TLR4 is not relevant for priming of specific CD8+ T cells; (iii) CD4+ T cells are critical for priming of memory/protective CD8+ T cells.

Objectives: The aortopulmonary window (APW) is a communication between the pulmonary artery (PA) and the ascending aorta in the presence of two separate semilunar valves. This review describes the natural history of the APW and the impact of associated defects on surgical results in patients treated at our institution., Methods: Retrospective longitudinal study, based on the review of medical files of patients diagnosed between 1995 and 2005., Results: Of nine patients diagnosed as having APW, six had associated lesions. Seven patients were submitted to surgical treatment with two deaths. One patient was not submitted to surgery due to pulmonary hypertension and another one died before the surgery due to a respiratory infection complication., Conclusion: The surgical results are satisfactory when the APW presents as an isolated defect and when surgery is performed early, preventing the development of irreversible arterial pulmonary hypertension (APH). The presence of associated complex congenital heart disease is a bad prognostic factor in our series.

We perform a statistical analysis of atomic distributions as a function of the distance R from the molecular geometrical center in a nonredundant set of compact globular proteins. The number of atoms increases quadratically for small R, indicating a constant average density inside the core, reaches a maximum at a size-dependent distance R(max), and falls rapidly for larger R. The empirical curves turn out to be consistent with the volume increase of spherical concentric solid shells and a Fermi-Dirac distribution in which the distance R plays the role of an effective atomic energy epsilon(R) = R. The effective chemical potential mu governing the distribution increases with the number of residues, reflecting the size of the protein globule, while the temperature parameter beta decreases. Interestingly, betamu is not as strongly dependent on protein size and appears to be tuned to maintain approximately half of the atoms in the high density interior and the other half in the exterior region of rapidly decreasing density. A normalized size-independent distribution was obtained for the atomic probability as a function of the reduced distance, r = R/R(g), where R(g) is the radius of gyration. The global normalized Fermi distribution, F(r), can be reasonably decomposed in Fermi-like subdistributions for different atomic types tau, F(tau)(r), with Sigma(tau)F(tau)(r) = F(r), which depend on two additional parameters mu(tau) and h(tau). The chemical potential mu(tau) affects a scaling prefactor and depends on the overall frequency of the corresponding atomic type, while the maximum position of the subdistribution is determined by h(tau), which appears in a type-dependent atomic effective energy, epsilon(tau)(r) = h(tau)r, and is strongly correlated to available hydrophobicity scales. Better adjustments are obtained when the effective energy is not assumed to be necessarily linear, or epsilon(tau)*(r) = h(tau)*r(alpha,), in which case a correlation with hydrophobicity scales is found for the product alpha(tau)h(tau)*. These results indicate that compact globular proteins are consistent with a thermodynamic system governed by hydrophobic-like energy functions, with reduced distances from the geometrical center, reflecting atomic burials, and provide a conceptual framework for the eventual prediction from sequence of a few parameters from which whole atomic probability distributions and potentials of mean force can be reconstructed., (Copyright 2006 Wiley-Liss, Inc.)

The main factors that structure Neotropical animal communities have been the subject of discussion in ecology communities. We used a set of null models to investigate the existence of structure in snake communities from the Cerrado in Central Brazil in relation to the co-occurrence of species and guilds concerning specific resources. We used fragments (conservation units) inside the Distrito Federal and neighbor municipalities. In spite of recent human colonization in the region from the end of the 1950s, intense habitat modification and fragmentation has taken place. Sixty three snake species are present in the Distrito Federal. Co-occurrence analysis of species and guilds associated to snake diets and habitats suggested a lack of organization. The homogeneity of habitats in Central Brazil and the minor importance of ecological effects can lead to random arrangement.

We report on a 48 years-old man with basilar impression without syringohydromyelia, in which the cisterna magna was impacted by the cerebellar tonsils. Six months after posterior fossa decompression there was the disappearance of nuchal rigidity, vertigo, spastic paraparesis and improvement of balance. Nevertheless hyperreflexia and diminished pallesthesia of the lower limbs persisted.

We report on a 49 year old man with impacted cisterna magna without the presence of syringohydromyelie (SM). The clinical picture was characterized by spastic paraparesis. Magnetic resonance imaging depicted a cisterna magna filled by the cerebellar tonsils. Six months after osteodural-neural decompression of the posterior fossa there was resolution of neurological symptoms and signs with the exception of hyperactive patellar and Achilles reflexes.

In this paper we present an individual-based model describing the foraging behavior of ants moving in an artificial network of tunnels in which several interconnected paths can be used to reach a single food source. Ants lay a trail pheromone while moving in the network and this pheromone acts as a system of mass recruitment that attracts other ants in the network. The rules implemented in the model are based on measures of the decisions taken by ants at tunnel bifurcations during real experiments. The collective choice of the ants is estimated by measuring their probability to take a given path in the network. Overall, we found a good agreement between the results of the simulations and those of the experiments, showing that simple behavioral rules can lead ants to find the shortest paths in the network. The match between the experiments and the model, however, was better for nestbound than for outbound ants. A sensitivity study of the model suggests that the bias observed in the choice of the ants at asymmetrical bifurcations is a key behavior to reproduce the collective choice observed in the experiments.

Monte Carlo simulations of a hydrophobic protein model of 40 monomers in the cubic lattice are used to explore the effect of energetic frustration and interaction heterogeneity on its folding pathway. The folding pathway is described by the dependence of relevant conformational averages on an appropriate reaction coordinate, pfold, defined as the probability for a given conformation to reach the native structure before unfolding. We compare the energetically frustrated and heterogeneous hydrophobic potential, according to which individual monomers have a higher or lower tendency to form contacts unspecifically depending on their hydrophobicities, to an unfrustrated homogeneous Go-type potential with uniformly attractive native interactions and neutral non-native interactions (called Go1 in this study), and to an unfrustrated heterogeneous potential with neutral non-native interactions and native interactions having the same energy as the hydrophobic potential (called Go2 in this study). Folding kinetics are slowed down dramatically when energetic frustration increases, as expected and previously observed in a two-dimensional model. Contrary to our previous results in two dimensions, however, it appears that the folding pathway and transition state ensemble can be significantly dependent on the energy function used to stabilize the native structure. The sequence of events along the reaction coordinate, or the order along this coordinate in which different regions of the native conformation become structured, turns out to be similar for the hydrophobic and Go2 potentials, but with analogous events tending to occur at lower pfold values in the first case. In particular, the transition state obtained from the ensemble around pfold = 0.5 is more structured for the hydrophobic potential. For Go1, not only the transition state ensemble but the order of events itself is modified, suggesting that interaction heterogeneity, in addition to energetic frustration, can have significant effects on the folding mechanism, most likely by modifying the probability of different contacts in the unfolded state, the starting point for the folding reaction. Although based on a simple model, these results provide interesting insight into how sequence-dependent switching between folding pathways might occur in real proteins., (2005 Wiley-Liss, Inc.)