Homologous self-organising scale-invariant properties characterise long range species spread and cancer invasion

The invariance of some system properties over a range of temporal and/or spatial scales is an attribute of many processes in nature1, often characterised by power law functions and fractal geometry2. In particular, there is growing consensus in that fat-tailed functions like the power law adequately describe long-distance dispersal (LDD) spread of organisms 3,4. Here we show that the spatial spread of individuals governed by a power law dispersal function is represented by a clear and unique signature, characterised by two properties: A fractal geometry of the boundaries of patches generated by dispersal with a fractal dimension D displaying universal features, and a disrupted patch size distribution characterised by two different power laws. Analysing patterns obtained by simulations and real patterns from species dispersal and cell spread in cancer invasion we show that both pattern properties are a direct result of LDD and localised dispersal and recruitment, reflecting population self-organisation

Antibodies for the treatment of brain metastases, a dream or a reality?

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).The incidence of brain metastases (BM) in cancer patients is increasing. After diagnosis, overall survival (OS) is poor, elicited by the lack of an effective treatment. Monoclonal antibody (mAb)-based therapy has achieved remarkable success in treating both hematologic and non-central-nervous system (CNS) tumors due to their inherent targeting specificity. However, the use of mAbs in the treatment of CNS tumors is restricted by the blood-brain barrier (BBB) that hinders the delivery of either small-molecules drugs (sMDs) or therapeutic proteins (TPs). To overcome this limitation, active research is focused on the development of strategies to deliver TPs and increase their concentration in the brain. Yet, their molecular weight and hydrophilic nature turn this task into a challenge. The use of BBB peptide shuttles is an elegant strategy. They explore either receptor-mediated transcytosis (RMT) or adsorptive-mediated transcytosis (AMT) to cross the BBB. The latter is preferable since it avoids enzymatic degradation, receptor saturation, and competition with natural receptor substrates, which reduces adverse events. Therefore, the combination of mAbs properties (e.g., selectivity and long half-life) with BBB peptide shuttles (e.g., BBB translocation and delivery into the brain) turns the therapeutic conjugate in a valid approach to safely overcome the BBB and efficiently eliminate metastatic brain cells.This research was funded by the Portuguese Funding Agency, Fundação para a Ciência e Tecnologia, FCT IP, grants PD/BD/128281/2017, PTDC/BBB-BQB/1693/2014 and PTDC/BBB-NAN/1578/2014.info:eu-repo/semantics/publishedVersio

Phosphomannosylation and the functional analysis of the extended Candida albicans MNN4-like gene family

We thank Luz A. López-Ramírez (Universidad de Guanajuato) for technical assistance. This work was supported by Consejo Nacional de Ciencia y Tecnología (ref. CB2011/166860; PDCPN2014-247109, and FC 2015-02-834), Universidad de Guanajuato (ref. 000025/11; 0087/13; ref. 1025/2016; Convocatoria Institucional para Fortalecer la Excelencia Académica 2015; CIFOREA 89/2016), Programa de Mejoramiento de Profesorado (ref. UGTO-PTC-261), and Red Temática Glicociencia en Salud (CONACYT-México). NG acknowledges the Wellcome Trust (086827, 075470, 101873, and 200208) and MRC Centre for Medical Mycology for funding (N006364/1). KJ was supported by a research visitor grant to Aberdeen from China Scholarship Council (CSC No. 201406055024). The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmicb.2017.02156/full#supplementary-materialPeer reviewedPublisher PD

Predictors of a Healthy Eating Disorder Examination-Questionnaire (EDE-Q) Score 1 Year After Bariatric Surgery

BACKGROUND: Bariatric surgery (BS) has been shown to ameliorate health-related quality of life and eating disorder symptoms. However, the correlation of these changes with weight loss is not uniform, suggesting that additional factors have an impact on postoperative outcomes. OBJECTIVE: To assess the impact of BS on eating disorder symptoms at 1 year postoperatively and to generate predictive models for the achievement of optimal eating behavior. METHODS: Retrospective cohort study on a prospectively collected database of all consecutive patients who underwent primary BS in our academic center between January 2015 and March 2017. Eating Disorder Examination-Questionnaire (EDE-Q) was used to measure eating psychopathology. Logistic regression was used to estimate the odds ratio of achieving "healthy" EDE-Q at 1 year. Missing data was handled by multiple imputations for the regression model. RESULTS: Two-hundred thirty-four patients were included. A complete-case analysis in 135 cases showed a "healthy" EDE-Q in 27.4% at baseline and in 83.7% at 1 year (difference = 56.3%, P = 0.018). Only the baseline EDE-Q "healthy" status influenced significantly the odds of achieving "healthy" EDE-Q at 1 year (OR 6.7, 95% CI 1.18-38.14, P = 0.04). CONCLUSION: BS seems to promote successful treatment of self-reported eating disorder symptoms during the first postoperative year. The achievement of optimal results is independent of age, sex, weight loss, obesity-related comorbidity status, surgical technique, or 30-day surgical complications. Future studies, using validated questionnaires specifically designed to investigate eating behavior after BS and/or direct measurements of the eating behavior are needed to clarify the underlying neuropsychologic mechanisms that drive the observed postoperative changes

Salivary biomarkers for diagnosis of systemic diseases and malignant tumors. A systematic review

Saliva evaluation could be a possible alternative to blood and/or tissue analyses, for researching specific molecules associated to the presence of systemic diseases and malignancies. The present systematic review has been designed in order to answer to the question ?are there significant associations between specific salivary biomarkers and diagnosis of systemic diseases or malignancies??. The Preferred Reporting Item for Systematic Reviews and Meta-analysis (PRISMA) statement was used to guide the review. The combinations of ?saliva? and ?systemic diseases? or ?diagnosis? or ?biomarkers? or ?cancers? or ?carcinoma? or ?tumors?, were used to search Medline, Scopus and Web of Science databases. Endpoint of research has been set at May 2019. Studies were classified into 3 groups according to the type of disease investigated for diagnosis: 1) malignant tumors; 2) neurologic diseases and 3) inflammatory/metabolic/cardiovascular diseases. Assessment of quality has been assigned according to a series of questions proposed by the National Institute of Health. Level of evidence was assessed using the categories proposed in the Oxford Center for Evidence-Based medicine (CEMB) levels for diagnosis (2011). Seventy-nine studies met the inclusion and exclusion criteria. Fifty-one (64%) investigated malignant tumors, 14 (17.5%) neurologic and 14 (18.5%) inflammatory/cardiovascular/metabolic diseases. Among studies investigating malignant tumors, 12 (23.5%) were scored as ?good? and 11 of these reported statistically significant associations between salivary molecules and pathology. Two and 5 studies were found to have a good quality, among those evaluating the association between salivary biomarkers and neurologic and inflammatory/metabolic/cardiovascular diseases, respectively. The present systematic review confirms the existence of some ?good? quality evidence to support the role of peculiar salivary biomarkers for diagnosis of systemic diseases (e.g. lung cancer and EGFR)

Efflux Activity Differentially Modulates the Levels of Isoniazid and Rifampicin Resistance among Multidrug Resistant and Monoresistant Mycobacterium tuberculosis Strains

With the growing body of knowledge on the contribution of efflux activity to Mycobacterium tuberculosis drug resistance, increased attention has been given to the use of efflux inhibitors as adjuvants of tuberculosis therapy. Here, we investigated how efflux activity modulates the levels of efflux between monoresistant and multi- and extensively drug resistant (M/XDR) M. tuberculosis clinical isolates. The strains were characterized by antibiotic susceptibility testing in the presence/absence of efflux inhibitors, molecular typing, and genetic analysis of drug-resistance-associated genes. Efflux activity was quantified by real-time fluorometry. The results demonstrated that all the M. tuberculosis clinical strains, susceptible or resistant, presented a faster, rapid, and non-specific efflux-mediated short-term response to drugs. The synergism assays demonstrated that the efflux inhibitors were more effective in reducing the resistance levels in the M/XDR strains than in the monoresistant strains. This indicated that M/XDR strains presented a more prolonged response to drugs mediated by efflux compared to the monoresistant strains, but both maintain it as a long-term stress response. This work shows that efflux activity modulates the levels of drug resistance between monoresistant and M/XDR M. tuberculosis clinical strains, allowing the bacteria to survive in the presence of noxious compounds.publishersversionpublishe

Bilateral Transcranial Magnetic Stimulation of the Prefrontal Cortex Reduces Cocaine Intake: A Pilot Study

Background: Chronic cocaine consumption is associated with a decrease in mesolim- bic dopamine transmission that maintains drug intake. transcranial magnetic stimulation (TMS) is gaining reliability, a useful therapeutic tool in drug addiction, since it can modu- late cortico-limbic activity resulting in reduction of drug craving. Aims: In the present study, we investigated the therapeutic effect of bilateral TMS of prefrontal cortex (PFC) in reducing cocaine intake, in a sample of treatment-seeking patients with current cocaine use disorder (DSM-V). Methods: Ten cocaine addicts (DSM-V) were randomly assigned to the active or sham stimulation protocol in a double-blind experimental design. Twelve repetitive TMS (rTMS) sessions were administered three times a week for 4 weeks at 100% of motor threshold, over bilateral PFC. Cocaine intake (ng/mg) was assessed by hair analysis at baseline (before treatment, T0), after 1 month (end of treatment, T1), 3 (T2), and 6 (T3) months later. All subjects received psychological support weekly. Results: The two-way ANOVA for repeated measures did not show a signi cant effect of the interaction between time and treatment (F4,32 = 0.35; p = 0.87). Despite that result indicated no difference in the effect of the two conditions (active vs. sham) along time, a decreasing trend in cocaine consumption in active TMS group (F3,23 = 3.42; p = 0.04) vs. sham (F3,15 = 1.88; p = 0.20) was observed when we performed exploratory analysis with time as factor. Indeed, Post hoc comparisons showed a signi cant reduction in the amount of cocaine detected from the onset to 3 months later (T0–T2; p = 0.02) and to the end of treatment (T0–T3; p = 0.01) in addicts from the active group. Conclusion: Bilateral rTMS of PFC at 10 Hz did not show a signi cant effect on cocaine intake compared to sham. However, a long-term reduction on cocaine intake in active TMS-treated patients was observed when we considered the time as factor. Further studies are required to con rm these encouraging but preliminary ndings, in order to consolidate rTMS as a valid tool to treat cocaine addiction

Similar self-organizing scale-invariant properties characterize early cancer invasion and long range species spread

Occupancy of new habitats through dispersion is a central process in nature. In particular, long range dispersal is involved in the spread of species and epidemics, although it has not been previously related with cancer invasion, a process that involves spread to new tissues. We show that the early spread of cancer cells is similar to the species individuals spread and that both processes are represented by a common spatio-temporal signature, characterized by a particular fractal geometry of the boundaries of patches generated, and a power law-scaled, disrupted patch size distribution. We show that both properties are a direct result of long-distance dispersal, and that they reflect homologous ecological processes of population self-organization. Our results are significant for processes involving long-range dispersal like biological invasions, epidemics and cancer metastasis.Comment: 21 pages, 2 figure

Modeling methodology for defining a priori the hydrodynamics of a dynamic suspension bioreactor. Application to human induced pluripotent stem cell culture

Three-dimensional dynamic suspension is becoming an effective cell culture method for a wide range of bioprocesses, with an increasing number of bioreactors proposed for this purpose. The complex hydrodynamics establishing within these devices affects bioprocess outcomes and efficiency, and usually expensive in vitro trial-and-error experiments are needed to properly set the working parameters. Here we propose a methodology to define a priori the hydrodynamic working parameters of a dynamic suspension bioreactor, selected as a test case because of the complex hydrodynamics characterizing its operating condition. A combination of computational and analytical approaches was applied to generate operational guideline graphs for defining a priori specific working parameters. In detail, 43 simulations were performed under pulsed flow regime to characterize advective transport within the device depending on different operative conditions, i.e., culture medium flow rate and its duty cycle, cultured particle diameter, and initial particle suspension volume. The operational guideline graphs were then used to set specific hydrodynamic working parameters for an in vitro proof-of-principle test, where human induced pluripotent stem cell (hiPSC) aggregates were cultured for 24 h within the bioreactor. The in vitro findings showed that, under the selected pulsed flow regime, sedimentation was avoided, hiPSC aggregate circularity and viability were preserved, and culture heterogeneity was reduced, thus confirming the appropriateness of the a priori method. This methodology has the potential to be adaptable to other dynamic suspension devices to support experimental studies by providing in silico-based a priori knowledge, useful to limit costs and to optimize culture bioprocesses

Comparative metabolomics of leaves and stems of three Italian olive cultivars under drought stress

The Mediterranean will be one of the focal points of climate change. The predicted dry and hot summers will lead to water scarcity in agriculture, which may limit crop production and growth. The olive tree serves as a model woody plant for studying drought stress and improving water resource management; thus, it is critical to identify genotypes that are more drought tolerant and perform better under low irrigation or even rainfed conditions. In this study, the metabolomic approach was used to highlight variations in metabolites in stems and leaves of three Italian olive cultivars (previously characterized physiologically) under two and four weeks of drought stress. Phenolic and lipophilic profiles were obtained by gas chromatography-mass spectrometry and ultra-high performance liquid chromatography-mass spectrometry, respectively. The findings identified the leaf as the primary organ in which phenolic variations occurred. The Maurino cultivar exhibited a strong stress response in the form of phenolic compound accumulation, most likely to counteract oxidative stress. The phenolic compound content of ‘Giarraffa’ and ‘Leccino’ plants remained relatively stable whether they were exposed to drought or not. Variations in the lipid profile occurred in leaves and stems of all the cultivars. A high accumulation of compounds related to epicuticular wax components was observed in the leaf of ‘Giarraffa’, while a strong reduction of lipids and long-chain alkanes occurred in ‘Maurino’ when exposed to drought stress conditions