Melanoma in the Eyes of Mechanobiology

Skin is the largest organ of the human body with several important functions that can be impaired by injury, genetic or chronic diseases. Among all skin diseases, melanoma is one of the most severe, which can lead to death, due to metastization. Mechanotransduction has a crucial role for motility, invasion, adhesion and metastization processes, since it deals with the response of cells to physical forces. Signaling pathways are important to understand how physical cues produced or mediated by the Extracellular Matrix (ECM), affect healthy and tumor cells. During these processes, several molecules in the nucleus and cytoplasm are activated. Melanocytes, keratinocytes, fibroblasts and the ECM, play a crucial role in melanoma formation. This manuscript will address the synergy among melanocytes, keratinocytes, fibroblasts cells and the ECM considering their mechanical contribution and relevance in this disease. Mechanical properties of melanoma cells can also be influenced by pigmentation, which can be associated with changes in stiffness. Mechanical changes can be related with the adhesion, migration, or invasiveness potential of melanoma cells promoting a high metastization capacity of this cancer. Mechanosensing, mechanotransduction, and mechanoresponse will be highlighted with respect to the motility, invasion, adhesion and metastization in melanoma cancer.The authors acknowledge to Ana Silva ([email protected]) for expert assistance with graphical design, and to Portuguese funds – FCT UID/BIM/04293/2019

Mechanobiology of Colorectal Cancer

In this review, the mechanobiology of colorectal cancer (CRC) are discussed. Mecha-notransduction of CRC is addressed considering the relationship of several biophysical cues and biochemical pathways. Mechanobiology is focused on considering how it may influence epithelial cells in terms of motility, morphometric changes, intravasation, circulation, extravasation, and metastization in CRC development. The roles of the tumor microenvironment, ECM, and stroma are also discussed, taking into account the influence of alterations and surface modifications on mechanical properties and their impact on epithelial cells and CRC progression. The role of cancer-associated fibroblasts and the impact of flow shear stress is addressed in terms of how it affects CRC metastization. Finally, some insights concerning how the knowledge of biophysical mechanisms may contribute to the development of new therapeutic strategies and targeting molecules and how mechanical changes of the microenvironment play a role in CRC disease are presented.The authors are grateful to Ana Silva ([email protected]) for expert assistance with graphical design and to Portuguese Fundação para a Ciência e a Tecnologia (FCT) for funds in the framework of the project Instituto de Investigação e Inovação em Saúde (i3S), ref. ID/BIM/04293/2020

Strategies to obtain designer polymers based on cyanobacterial extracellular polymeric substances (EPS)

Biopolymers derived from polysaccharides are a sustainable and environmentally friendly alternative to the synthetic counterparts available in the market. Due to their distinctive properties, the cyanobacterial extracellular polymeric substances (EPS), mainly composed of heteropolysaccharides, emerge as a valid alternative to address several biotechnological and biomedical challenges. Nevertheless, biotechnological/biomedical applications based on cyanobacterial EPS have only recently started to emerge. For the successful exploitation of cyanobacterial EPS, it is important to strategically design the polymers, either by genetic engineering of the producing strains or by chemical modification of the polymers. This requires a better understanding of the EPS biosynthetic pathways and their relationship with central metabolism, as well as to exploit the available polymer functionalization chemistries. Considering all this, we provide an overview of the characteristics and biological activities of cyanobacterial EPS, discuss the challenges and opportunities to improve the amount and/or characteristics of the polymers, and report the most relevant advances on the use of cyanobacterial EPS as scaffolds, coatings, and vehicles for drug delivery.This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-028779, contract DL57/2016/CP1327/CT0007 and fellowship SFRH/BD/119920/2016

Intellectual disability, unusual facial morphology and hand anomalies in sibs

Here we report on a Portuguese family with three sisters who shared moderate intellectual disability, unusual facial morphology (short palpebral fissures; broad nasal tip; thin upper and lower vermillion; broad and pointed chin) and hand anomalies in two of them (short left third and fifth right metacarpals in one case; marked syndactyly between the third and fourth fingers in another). One of the sisters had microcephaly and short stature, and the other two were obese. Obesity and somewhat similar facial features were also present in the otherwise healthy mother. Despite the overlap with several known syndromes (Albright osteodystrophy; Filippi syndrome; Rubinstein-Taybi syndrome; microdeletion 2q37), we suggest this condition is previously unreported, and most likely displays an autosomal recessive pattern of inheritance

Intellectual disability, coarse face, relative macrocephaly, and cerebellar hypotrophy in two sisters

We report on two Portuguese sisters with a very similar phenotype characterized by severe intellectual disability, absent speech, relative macrocephaly, coarse face, cerebellar hypotrophy, and severe ataxia. Additional common features include increased thickness of the cranial vault, delayed dental eruption, talipes equino-varus, clinodactyly, and camptodactyly of the fifth finger. The older sister has retinal dystrophy and the younger sister has short stature. Their parents are consanguineous. We suggest this condition constitutes a previously unreported autosomal recessive entity

Emergence of scale-free close-knit friendship structure in online social networks

Despite the structural properties of online social networks have attracted much attention, the properties of the close-knit friendship structures remain an important question. Here, we mainly focus on how these mesoscale structures are affected by the local and global structural properties. Analyzing the data of four large-scale online social networks reveals several common structural properties. It is found that not only the local structures given by the indegree, outdegree, and reciprocal degree distributions follow a similar scaling behavior, the mesoscale structures represented by the distributions of close-knit friendship structures also exhibit a similar scaling law. The degree correlation is very weak over a wide range of the degrees. We propose a simple directed network model that captures the observed properties. The model incorporates two mechanisms: reciprocation and preferential attachment. Through rate equation analysis of our model, the local-scale and mesoscale structural properties are derived. In the local-scale, the same scaling behavior of indegree and outdegree distributions stems from indegree and outdegree of nodes both growing as the same function of the introduction time, and the reciprocal degree distribution also shows the same power-law due to the linear relationship between the reciprocal degree and in/outdegree of nodes. In the mesoscale, the distributions of four closed triples representing close-knit friendship structures are found to exhibit identical power-laws, a behavior attributed to the negligible degree correlations. Intriguingly, all the power-law exponents of the distributions in the local-scale and mesoscale depend only on one global parameter -- the mean in/outdegree, while both the mean in/outdegree and the reciprocity together determine the ratio of the reciprocal degree of a node to its in/outdegree.Comment: 48 pages, 34 figure

Concentration-dependent diffusivity and anomalous diffusion: A magnetic resonance imaging study of water ingress in porous zeolite

Magnetic resonance imaging is employed to study water ingress in fine zeolite powders compacted by high pressure. The experimental conditions are chosen such that the applicability of Boltzmann's transformation of the one-dimensional diffusion equation is approximately satisfied. The measured moisture profiles indicate subdiffusive behavior with a spatiotemporal scaling variable eta=x/t(gamma/2) (0 <gamma < 1). A time-fractional diffusion equation model of anomalous diffusion is adopted to analyze the data, and an expression that yields the moisture dependence of the generalized diffusivity is derived and applied to our measured profiles. In spite of the differences between systems exhibiting different values of gamma a striking similarity in the moisture dependence of the diffusivity is apparent. This suggests that the model addresses the underlying physical processes involved in water transport.731

New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals

Enterococcus faecium as potential probiotic for ornamental neotropical cichlid fish, Pterophyllum scalare (Schultze, 1823).

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