A Mutational Hotspot and Strong Selection Contribute to the Order of Mutations Selected for during Escherichia coli Adaptation to the Gut

The relative role of drift versus selection underlying the evolution of bacterial species within the gut microbiota remains poorly understood. The large sizes of bacterial populations in this environment suggest that even adaptive mutations with weak effects, thought to be the most frequently occurring, could substantially contribute to a rapid pace of evolutionary change in the gut. We followed the emergence of intra-species diversity in a commensal Escherichia coli strain that previously acquired an adaptive mutation with strong effect during one week of colonization of the mouse gut. Following this first step, which consisted of inactivating a metabolic operon, one third of the subsequent adaptive mutations were found to have a selective effect as high as the first. Nevertheless, the order of the adaptive steps was strongly affected by a mutational hotspot with an exceptionally high mutation rate of 10-5. The pattern of polymorphism emerging in the populations evolving within different hosts was characterized by periodic selection, which reduced diversity, but also frequency-dependent selection, actively maintaining genetic diversity. Furthermore, the continuous emergence of similar phenotypes due to distinct mutations, known as clonal interference, was pervasive. Evolutionary change within the gut is therefore highly repeatable within and across hosts, with adaptive mutations of selection coefficients as strong as 12% accumulating without strong constraints on genetic background. In vivo competitive assays showed that one of the second steps (focA) exhibited positive epistasis with the first, while another (dcuB) exhibited negative epistasis. The data shows that strong effect adaptive mutations continuously recur in gut commensal bacterial species.

The effects of celebrity endorsement on the consumers’ perceptions towards global brands

Brands are those lifestyles which consumers chose to buy in order to gain the value offered by the company, in order to be part of the community created through the brand equity elements and validated in the purchase of the products. Companies have understood how important it is to build a strong brand and many of them spend millions on aligning the brand with the design and style of the products, projecting the face and values of the company into the advertising campaigns. One of the most popular methods is through endorsement, placing a renounced celebrity and leveraging on the positive feedback of those customers that also follow the activities of the star whose face is on the cover of the marcom campaign. Celebrities have been used for a very long time to promote brands, sell products and services. Research has shown that those spokesmen of a brand who are more attractive can improve the statistics of recall and appeal more interest to the promotion campaign, as well as influence more on customer’s intention of buying the product (Kahle and Homer, 1985). The main purpose of this research is to investigate how celebrity endorsements influence the brand equity dimensions (brand loyalty, brand awareness, perceived quality and brand associations) as well as stimulate consumers’ word-of-mouth through brand identification, growth in interest and the advertising memorability. The hypotheses were tested with the aid of Structural Equation Modelling (SEM) in the PLS (Partial Least Squares) software. The survey is comprised of a target group of 589 respondents, from three countries – Brazil, Moldova and Portugal. Results evidence that the Attitude towards the Celebrity influences different Brand Equity dimensions and affects brand identification, growth in advertisement interest and advertising memorability, generating positive word of mouth (or negative, depending on the type of advertisement and reputation). Based on these findings we suggest further investigation in this area with the possibility to gain more data about the different fields of marcom and the different types of CE which are more appropriate for the given type of business.

Effects of fibrosis morphology on reentrant ventricular tachycardia inducibility and simulation fidelity in patient-derived models

Myocardial fibrosis detected via delayed-enhanced magnetic resonance imaging (MRI) has been shown to be a strong indicator for ventricular tachycardia (VT) inducibility. However, little is known regarding how inducibility is affected by the details of the fibrosis extent, morphology, and border zone configuration. The objective of this article is to systematically study the arrhythmogenic effects of fibrosis geometry and extent, specifically on VT inducibility and maintenance. We present a set of methods for constructing patient-specific computational models of human ventricles using in vivo MRI data for patients suffering from hypertension, hypercholesterolemia, and chronic myocardial infarction. Additional synthesized models with morphologically varied extents of fibrosis and gray zone (GZ) distribution were derived to study the alterations in the arrhythmia induction and reentry patterns. Detailed electrophysiological simulations demonstrated that (1) VT morphology was highly dependent on the extent of fibrosis, which acts as a structural substrate, (2) reentry tended to be anchored to the fibrosis edges and showed transmural conduction of activations through narrow channels formed within fibrosis, and (3) increasing the extent of GZ within fibrosis tended to destabilize the structural reentry sites and aggravate the VT as compared to fibrotic regions of the same size and shape but with lower or no GZ. The approach and findings represent a significant step toward patient-specific cardiac modeling as a reliable tool for VT prediction and management of the patient. Sensitivities to approximation nuances in the modeling of structural pathology by image-based reconstruction techniques are also implicated.

The potential of symbolic approximation. Disentangling the effects of approximation vs. calculation demands in nonsymbolic and symbolic representations.

Mathematical skills that we acquire during formal education mostly entail exact numerical processing. Besides this specifically human faculty, an additional system exists to represent and manipulate quantities in an approximate manner. We share this innate approximate number system (ANS) with other nonhuman animals and are able to use it to process large numerosities long before we can master the formal algorithms taught in school. Dehaene´s (1992) Triple Code Model (TCM) states that also after the onset of formal education, approximate processing is carried out in this analogue magnitude code no matter if the original problem was presented nonsymbolically or symbolically. Despite the wide acceptance of the model, most research only uses nonsymbolic tasks to assess ANS acuity. Due to this silent assumption that genuine approximation can only be tested with nonsymbolic presentations, up to now important implications in research domains of high practical relevance remain unclear, and existing potential is not fully exploited. For instance, it has been found that nonsymbolic approximation can predict math achievement one year later (Gilmore, McCarthy, & Spelke, 2010), that it is robust against the detrimental influence of learners´ socioeconomic status (SES), and that it is suited to foster performance in exact arithmetic in the short-term (Hyde, Khanum, & Spelke, 2014). We provided evidence that symbolic approximation might be equally and in some cases even better suited to generate predictions and foster more formal math skills independently of SES. In two longitudinal studies, we realized exact and approximate arithmetic tasks in both a nonsymbolic and a symbolic format. With first graders, we demonstrated that performance in symbolic approximation at the beginning of term was the only measure consistently not varying according to children´s SES, and among both approximate tasks it was the better predictor for math achievement at the end of first grade. In part, the strong connection seems to come about from mediation through ordinal skills. In two further experiments, we tested the suitability of both approximation formats to induce an arithmetic principle in elementary school children. We found that symbolic approximation was equally effective in making children exploit the additive law of commutativity in a subsequent formal task as a direct instruction. Nonsymbolic approximation on the other hand had no beneficial effect. The positive influence of the symbolic approximate induction was strongest in children just starting school and decreased with age. However, even third graders still profited from the induction. The results show that also symbolic problems can be processed as genuine approximation, but that beyond that they have their own specific value with regard to didactic-educational concerns. Our findings furthermore demonstrate that the two often con-founded factors ꞌformatꞌ and ꞌdemanded accuracyꞌ cannot be disentangled easily in first graders numerical understanding, but that children´s SES also influences existing interrelations between the different abilities tested here.

Effects of radiation therapy on the structure and function of the pelvic floor muscles of patients with cancer in the pelvic area : a systematic review

Purpose Radiation therapy (RT) is often recommended in the treatment of pelvic cancers. Following RT, a high prevalence of pelvic floor dysfunctions (urinary incontinence, dyspareunia, and fecal incontinence) is reported. However, changes in pelvic floor muscles (PFMs) after RT remain unclear. The purpose of this review was to systematically document the effects of RT on the PFM structure and function in patients with cancer in the pelvic area. Methods An electronic literature search using Pubmed Central, CINAHL, Embase, and SCOPUS was performed from date of inception up to June 2014. The following keywords were used: radiotherapy, muscle tissue, and pelvic floor. Two reviewers selected the studies in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). Out of the 369 articles screened, 13 met all eligibility criteria. The methodological quality was assessed using the QualSyst scoring system, and standardized mean differences were calculated. Results Thirteen studies fulfilled all inclusion criteria, from which four were of good methodological quality. One presented strong evidence that RT affects PFM structure in men treated for prostate cancer. Four presented high-level evidence that RT affects PFM function in patients treated for rectal cancer. Meta-analysis was not possible due to heterogeneity and lack of descriptive statistics. Conclusion There is some evidence that RT has detrimental impacts on both PFMs’ structure and function. Implications for cancer survivors A better understanding of muscle damage and dysfunction following RT treatment will improve pelvic floor rehabilitation and, potentially, prevention of its detrimental impacts.

Effects of dry-land strength and conditioning programs in age group swimmers

Context: Even though dry-land S&C training is a common practice in swimming, there are countless uncertainties over it effects in performance of age group swimmers. Objective: To investigate the effects of dry-land S&C programs in swimming performance of age group swimmers. Participants: A total of 21 male competitive swimmers (12.7±0.7 years) were randomly assigned to the Control Group (n=7) and experimental GR1 and GR2 (n=7 for each group). Intervention: Control group performed a 10-week training period of swim training alone, GR1 followed a 6-week dry-land S&C program based on sets/repetitions plus a 4-week swim training program alone and GR2 followed a 6-week dry-land S&C program focused on explosiveness, plus a 4-week program of swim training alone. Results: For the dry-land tests a time effect was observed between week 0 and week 6 for vertical jump (p<0.01) in both experimental groups, and for the GR2 ball throwing (p<0.01), with moderate-strong effect sizes. The time*group analyses showed that for performance in 50 m, differences were significant, with the GR2 presenting higher improvements than their counterparts (F=4.156; ƿ=0.007; η2=0.316) at week 10. Conclusions: The results suggest that 6 weeks of a complementary dry-land S&C training may lead to improvements in dry-land strength. Furthermore, a 4-week adaptation period was mandatory to achieve beneficial transfer for aquatic performance. Additional benefits may occur if coaches plan the dry-land S&C training focusing on explosiveness.

Solar and thermal radiative effects during the 2011 extreme desert dust episode over Portugal

This paper analyses the influence of the extreme Saharan desert dust (DD) event on shortwave (SW) and longwave (LW) radiation at the EARLINET/AERONET Évora station (Southern Portugal) from 4 up to 7 April 2011. There was also some cloud occurrence in the period. In this context, it is essential to quantify the effect of cloud presence on aerosol radiative forcing. A radiative transfer model was initialized with aerosol optical properties, cloud vertical properties and meteorological atmospheric vertical profiles. The intercomparison between the instantaneous TOA shortwave and longwave fluxes derived using CERES and those calculated using SBDART, which was fed with aerosol extinction coefficients derived from the CALIPSO and lidar-PAOLI observations, varying OPAC dataset parameters, was reasonably acceptable within the standard deviations. The dust aerosol type that yields the best fit was found to be the mineral accumulation mode. Therefore, SBDART model constrained with the CERES observations can be used to reliably determine aerosol radiative forcing and heating rates. Aerosol radiative forcings and heating rates were derived in the SW (ARFSw, AHRSw) and LW (ARFLw, AHRLw) spectral ranges, considering a cloud-aerosol free reference atmosphere. We found that AOD at 440 nm increased by a factor of 5 on 6 April with respect to the lower dust load on 4 April. It was responsible by a strong cooling radiative effect pointed out by the ARFSw value (−99 W/m2 for a solar zenith angle of 60°) offset by a warming radiative effect according to ARFLw value (+21.9 W/m2) at the surface. Overall, about 24% and 12% of the dust solar radiative cooling effect is compensated by its longwave warming effect at the surface and at the top of the atmosphere, respectively. Hence, larger aerosol loads could enhance the response between the absorption and re-emission processes increasing the ARFLw with respect to those associated with moderate and low aerosol loads. The unprecedented results derived from this work complement the findings in other regions on the modifications of radiative energy budget by the dust aerosols, which could have relevant influences on the regional climate and will be topics for future investigations.

Anti-proliferative effects of novel hydroxyamides and triazoles

Chemotherapy is a major cancer treatment option. The synthesis of new compounds with anti-proliferative properties and specificity is a current challenge in drug-discovery today. Our goal was to develop compounds, either hydroxyamides derived from D-glucuronic acid or triazole-cinchone hybrids, and to evaluate their anti-proliferative properties. Anti-proliferative activity of the newly synthesized compounds was examined against human breast adenocarcinoma (MCF-7) and human colon carcinoma (MDST8) cell-lines. Cell growth and viability was analysed by the Cell-Counting Kit-8 method. The 5-fluoroacil was used as a positive control. The compounds were studied between 10-9-10-5M. Fifteen compounds from the hydroxyamide family and two triazole compounds were investigated. Most of the compounds from the hydroxyamide family revealed mild (~20%) to moderate (50%) anti-proliferative effects in both cell-lines, with the exception of Hydroxyamide B1 which did not affect MDST8 proliferation, and hydroxyamide B3 where proliferation of MDST8 was inhibited by 90%. Triazoles (A and B) evoked a strong (~100%) anti-proliferative effect of MDST8 cell-lines. Proliferation of MCF-7 was selectively and effectively (~98%) inhibited by triazole B while triazole A had a mild effect. In conclusion, when compared to hydroxyamides, triazoles evoked a stronger anti-proliferative effect and might be promising anti-tumoral drugs.

Non-specific transient mutualism between the plant parasitic nematode, Bursaphelenchus xylophilus , and the opportunistic bacterium Serratia quinivorans BXF1, a plant-growth promoting pine endophyte with antagonistic effects

The aim of this study is to understand the biological role of Serratia quinivorans BXF1, a bacterium commonly found associated with Bursaphelenchus xylophilus, the plant parasitic nematode responsible for pine wilt disease. Therefore, we studied strain BXF1 effect in pine wilt disease. We found that strain BXF1 promoted in vitro nematode reproduction. Moreover, the presence of bacteria led to the absence of nematode chitinase gene (Bxcht-1) expression, suggesting an effect for bacterial chitinase in nematode reproduction. Nevertheless, strain BXF1 was unable to colonize the nematode interior, bind to its cuticle with high affinity or protect the nematode from xenobiotic stress. Interestingly, strain BXF1 was able to promote tomato and pine plant-growth, as well as to colonize its interior, thus, acting like a plant-growth promoting endophyte. Consequently, strain BXF1 failed to induce wilting symptoms when inoculated in pine shoot artificial incisions. This bacterium also presented strong antagonistic activities against fungi and bacteria isolated from Pinus pinaster. Our results suggest that B. xylophilus does not possess a strict symbiotic community capable of inducing pine wilt disease symptoms as previously hypothesized. We show that bacteria like BXF1, which possess plant-growth promoting and antagonistic effects, may be opportunistically associated with B. xylophilus, possibly acquired from the bacterial endophytic community of the host pine.

One Step Forward: Contrasting The Effects Of Toe Clipping And Pit Tagging On Frog Survival And Recapture Probability.

Amphibians have been declining worldwide and the comprehension of the threats that they face could be improved by using mark-recapture models to estimate vital rates of natural populations. Recently, the consequences of marking amphibians have been under discussion and the effects of toe clipping on survival are debatable, although it is still the most common technique for individually identifying amphibians. The passive integrated transponder (PIT tag) is an alternative technique, but comparisons among marking techniques in free-ranging populations are still lacking. We compared these two marking techniques using mark-recapture models to estimate apparent survival and recapture probability of a neotropical population of the blacksmith tree frog, Hypsiboas faber. We tested the effects of marking technique and number of toe pads removed while controlling for sex. Survival was similar among groups, although slightly decreased from individuals with one toe pad removed, to individuals with two and three toe pads removed, and finally to PIT-tagged individuals. No sex differences were detected. Recapture probability slightly increased with the number of toe pads removed and was the lowest for PIT-tagged individuals. Sex was an important predictor for recapture probability, with males being nearly five times more likely to be recaptured. Potential negative effects of both techniques may include reduced locomotion and high stress levels. We recommend the use of covariates in models to better understand the effects of marking techniques on frogs. Accounting for the effect of the technique on the results should be considered, because most techniques may reduce survival. Based on our results, but also on logistical and cost issues associated with PIT tagging, we suggest the use of toe clipping with anurans like the blacksmith tree frog.

Impact Of Benign Prostatic Hyperplasia Pharmacological Treatment On Transrectal Prostate Biopsy Adverse Effects.

Background. Benign prostatic hyperplasia (BPH) pharmacological treatment may promote a decrease in prostate vascularization and bladder neck relaxation with theoretical improvement in prostate biopsy morbidity, though never explored in the literature. Methods. Among 242 consecutive unselected patients who underwent prostate biopsy, after excluding those with history of prostate biopsy/surgery or using medications not for BPH, we studied 190 patients. On the 15th day after procedure patients were questioned about symptoms lasting over a week and classified according to pharmacological BPH treatment. Results. Thirty-three patients (17%) were using alpha-blocker exclusively, five (3%) 5-alpha-reductase inhibitor exclusively, twelve (6%) patients used both medications, and 140 (74%) patients used none. There was no difference in regard to age among groups (P = 0.5). Postbiopsy adverse effects occurred as follows: hematuria 96 (50%), hematospermia 53 (28%), hematochezia 22 (12%), urethrorrhagia 19 (10%), fever 5 (3%), and pain 20 (10%). There was a significant negative correlation between postbiopsy hematuria and BPH pharmacological treatment with stronger correlation for combined use of 5-alpha-reductase inhibitor and alpha-blocker over 6 months (P = 0.0027). Conclusion. BPH pharmacological treatment, mainly combined for at least 6 months seems to protect against prostate biopsy adverse effects. Future studies are necessary to confirm our novel results.

Inhibitory Effects Of A Cured Antibacterial Bonding System On Viability And Metabolic Activity Of Oral Bacteria.

To evaluate the antimicrobial efficacy of Clearfil SE Protect (CP) and Clearfil SE Bond (CB) after curing and rinsed against five individual oral microorganisms as well as a mixture of bacterial culture prepared from the selected test organisms. Bacterial suspensions were prepared from single species of Streptococcus mutans, Streptococcus sobrinus, Streptococcus gordonii, Actinomyces viscosus and Lactobacillus lactis, as well as mixed bacterial suspensions from these organisms. Dentin bonding system discs (6 mm×2 mm) were prepared, cured, washed and placed on the bacterial suspension of single species or multispecies bacteria for 15, 30 and 60 min. MTT, Live/Dead bacterial viability (antibacterial effect), and XTT (metabolic activity) assays were used to test the two dentin system's antibacterial effect. All assays were done in triplicates and each experiment repeated at least three times. Data were submitted to ANOVA and Scheffe's f-test (5%). Greater than 40% bacteria killing was seen within 15 min, and the killing progressed with increasing time of incubation with CP discs. However, a longer (60 min) period of incubation was required by CP to achieve similar antimicrobial effect against mixed bacterial suspension. CB had no significant effect on the viability or metabolic activity of the test microorganisms when compared to the control bacterial culture. CP was significantly effective in reducing the viability and metabolic activity of the test organisms. The results demonstrated the antimicrobial efficacy of CP both on single and multispecies bacterial culture. CP may be beneficial in reducing bacterial infections in cavity preparations in clinical dentistry.

In Vitro And In Vivo Anti-angiogenic Effects Of Hydroxyurea.

Hydroxyurea (HU), or hydroxycarbamide, is used for the treatment of some myeloproliferative and neoplastic diseases, and is currently the only drug approved by the FDA for use in sickle cell disease (SCD). Despite the relative success of HU therapy for SCD, a genetic disorder of the hemoglobin β chain that results in red-cell sickling, hemolysis, vascular inflammation and recurrent vasoocclusion, the exact mechanisms by which HU actuates remain unclear. We hypothesized that HU may modulate endothelial angiogenic processes, with important consequences for vascular inflammation. The effects of HU (50-200 μM; 17-24 h) on endothelial cell functions associated with key steps of angiogenesis were evaluated using human umbilical vein endothelial cell (HUVEC) cultures. Expression profiles of the HIF1A gene and the miRNAs 221 and 222, involved in endothelial function, were also determined in HUVECs following HU administration and the direct in vivo antiangiogenic effects of HU were assessed using a mouse Matrigel-plug neovascularization assay. Following incubation with HU, HUVECs exhibited high cell viability, but displayed a significant 75% inhibition in the rate of capillary-like-structure formation, and significant decreases in proliferative and invasive capacities. Furthermore, HU significantly decreased HIF1A expression, and induced the expression of miRNA 221, while downregulating miRNA 222. In vivo, HU reduced vascular endothelial growth factor (VEGF)-induced vascular development in Matrigel implants over 7 days. Findings indicate that HU is able to inhibit vessel assembly, a crucial angiogenic process, both in vitro and in vivo, and suggest that some of HU's therapeutic effects may occur through novel vascular mechanisms.

Angiogenic Effects Of Cryosurgery With Liquid Nitrogen On The Normal Skin Of Rats, Through Morphometric Study.

Cryosurgery is an efficient therapeutic technique used to treat benign and malignant cutaneous diseases. The primary active mechanism of cryosurgery is related to vascular effects on treated tissue. After a cryosurgical procedure, exuberant granulation tissue is formed at the injection site, probably as a result of angiogenic stimulation of the cryogen and inflammatory response, particularly in endothelial cells. To evaluate the angiogenic effects of freezing, as part of the phenomenon of healing rat skin subjected to previous injury. Two incisions were made in each of the twenty rats, which were divided randomly into two groups of ten. After 3 days, cryosurgery with liquid nitrogen was performed in one of incisions. The rats' samples were then collected, cut and stained to conduct histopathological examination, to assess the local angiogenesis in differing moments and situations. It was possible to demonstrate that cryosurgery, in spite of promoting cell death and accentuated local inflammation soon after its application, induces quicker cell proliferation in the affected tissue and maintenance of this rate in a second phase, than in tissue healing without this procedure. These findings, together with the knowledge that there is a direct relationship between mononuclear cells and neovascularization (the development of a rich system of new vessels in injury caused by cold), suggest that cryosurgery possesses angiogenic stimulus, even though complete healing takes longer to occur. The significance level for statistical tests was 5% (p<0,05).

Core-valence Correlation Effects On Ir Calculations: The Bf3 And Bcl3 Cases.

The first theoretical results of core-valence correlation effects are presented for the infrared wavenumbers and intensities of the BF3 and BCl3 molecules, using (double- and triple-zeta) Dunning core-valence basis sets at the CCSD(T) level. The results are compared with those calculated in the frozen core approximation with standard Dunning basis sets at the same correlation level and with the experimental values. The general conclusion is that the effect of core-valence correlation is, for infrared wavenumbers and intensities, smaller than the effect of adding augmented diffuse functions to the basis set, e.g., cc-pVTZ to aug-cc-pVTZ. Moreover, the trends observed in the data are mainly related to the augmented functions rather than the core-valence functions added to the basis set. The results obtained here confirm previous studies pointing out the large descrepancy between the theoretical and experimental intensities of the stretching mode for BCl3.