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In this work, we deal with a micro electromechanical system (MEMS), represented by a micro-accelerometer. Through numerical simulations, it was found that for certain parameters, the system has a chaotic behavior. The chaotic behaviors in a fractional order are also studied numerically, by historical time and phase portraits, and the results are validated by the existence of positive maximal Lyapunov exponent. Three control strategies are used for controlling the trajectory of the system: State Dependent Riccati Equation (SDRE) Control, Optimal Linear Feedback Control, and Fuzzy Sliding Mode Control. The controls proved effective in controlling the trajectory of the system studied and robust in the presence of parametric errors. [ABSTRACT FROM AUTHOR]

In this paper we consider a self-excited mechanical system by dry friction in order to study the bifurcational behavior of the arisen vibrations. The oscillating system consists of a mass block-belt-system which is self-excited by static and Coulomb friction. We analyze the system behavior numerically through bifurcation diagrams, phase portraits, frequency spectra and Poincaré maps, which show the existence of nonhomoclinic and homoclinic chaos and a route to homoclinic chaos. The homoclinic chaos is also analyzed analytically via the Melnikov prediction method. The system dynamic is characterized by the existence of two potential wells in the phase plane which exhibit rich bifurcational and chaotic behavior. [ABSTRACT FROM AUTHOR]

This work, considers a vibrating system, which consists of a snap-through truss absorber (STTA) coupled to an oscillator, under excitation of an DC motor, with an eccentricity and limited power, characterizing a non-ideal oscillator (NIO). It is aimed to use the absorber STTA, to establish the conditions, that we have the maxim attenuation of the jumpphenomenon (Sommerfeld Effect). Here, weare interestedin determining the conditions of the vibrating system, in which there arereduced amplitudes of the oscillator, when it passes through the region of resonance.

In this paper, we deal with the research of a vibrating model of an energy harvester device, including the nonlinearities in the model of the piezoelectric coupling and the non-ideal excitation. We show, using numerical simulations, in the analysis of the dynamic responses, that the harvested power is influenced by non-linear vibrations of the structure. Chaotic behavior was also observed, causing of the loss of energy throughout the simulation time. Using a perturbation technique, we find an approximate analytical solution for the non-ideal system. Then, we apply both two control techniques, to keep the considered system, into a stable condition. Both the State Dependent Ricatti Equation (SDRE) control as the feedback control by changing the energy of the oscillator, were efficient in controlling of the considered non-ideal system.

Background: Giant viruses have brought new insights into different aspects of virus-cell interactions. The resulting cytopathic effects from these interactions are one of the main aspects of infection assessment in a laboratory routine, mainly reflecting on the morphological features of an infected cell., Objectives: In this work, we follow the entire kinetics of the cytopathic effect in cells infected by viruses of the Mimiviridae family, spatiotemporally quantifying typical features such as cell roundness, loss of motility, decrease in cell area and cell lysis., Methods: Infections by Acanthamoeba polyphaga mimivirus (APMV), Tupanvirus (TPV) and M4 were carried out at multiplicity of infection (MOI) 1 and MOI 10 in Acanthamoeba castellanii. Monitoring of infections was carried out using time lapse microscopy for up to 72 hours. The images were analyzed using ImageJ software., Findings: The data obtained indicate that APMV is the slowest virus in inducing the cytopathic effects of rounding, decrease in cell area, mobility and cell lysis. However, it is the only virus whose MOI increase accelerates the lysis process of infected cells. In turn, TPV and M4 rapidly induce morphological and behavioral changes., Main Conclusions: Our results indicate that mimiviruses induce different temporal responses within the host cell and that it is possible to use these kinetic data to facilitate the understanding of infection by these viruses.

Background: Oral squamous cell carcinoma (OSCC) represents the primary form of oral cancer, posing a significant global health threat. The existing chemotherapy options are accompanied by notable side effects impacting patient treatment adherence. Consequently, the exploration and development of novel substances with enhanced anticancer effects and fewer side effects have become pivotal in the realms of biological and chemical science., Objective: This work presents the pioneering examples of naphthoquinone-coumarin hybrids as a new category of highly effective cytotoxic substances targeting oral squamous cell carcinoma (OSCC)., Methods: Given the significance of both naphthoquinones and coumarins as essential pharmacophores/ privileged structures in the quest for anticancer compounds, this study focused on the synthesis and evaluation of novel naphthoquinones/coumarin hybrids against oral squamous cell carcinoma., Results: By several in vitro, in silico, and in vivo approaches, we demonstrated that compound 6e was highly cytotoxic against OSCC cells and several other cancer cell types and was more selective than current chemotherapeutic drugs (carboplatin) and the naphthoquinone lapachol. Furthermore, compound 6e was non-hemolytic and tolerated in vivo at 50 mg/kg with an LD50 of 62.5 mg/kg. Furthermore, compound 6e did not induce apoptosis and cell cycle arrest but led to intracellular vesicle formation with LC3 aggregation in autophagosomes, suggesting an autophagic cell death. Additionally, 6e had a high-affinity potential for PKM2 protein, higher than the known ligands, such as lapachol or shikonin, and was able to inhibit this enzyme activity in vitro., Conclusion: We assert that compound 6e shows promise as a potential lead for a novel chemotherapeutic drug targeting OSCC, with potential applicability to other cancer types., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The incidence of invasive fungal infections caused by Candida species is increasing, particularly in immunocompromised individuals. This increasing incidence poses a dual challenge, comprising escalating antifungal resistance and the necessity for accurate fungal identification. The Candida haemulonii complex further complicates these challenges due to limited identification tools. Like some other Candida species, infections involving this complex show resistance to multiple antifungals, requiring innovative therapeutic approaches. Rapamycin, known for its antifungal properties and immunosuppressive characteristics, was investigated against the C. haemulonii complex species. Results revealed a rapamycin minimal inhibitory concentration (MIC) range of 0.07 to >20 µM, with fungicidal effects in most strains. In vitro analyses using the rapamycin maximum plasma concentration (0.016 µM) showed reduced surface properties and decreased production of extracellular enzymes. Rapamycin also hindered biofilm formation by some strains. Even when treated at the human therapeutic dose, which is lower than the MIC, phenotypic variations in C. haemulonii were detected, hinting at the possible attenuation of some virulence factors when exposed to rapamycin., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Susana Frases reports financial support and equipment, drugs, or supplies were provided by National Council for Scientific and Technological Development. Susana Frases reports financial support and equipment, drugs, or supplies were provided by Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Directional motility is an essential property of cells. Despite its enormous relevance in many fundamental physiological and pathological processes, how cells control their locomotion movements remains an unresolved question. Here, we have addressed the systemic processes driving the directed locomotion of cells. Specifically, we have performed an exhaustive study analyzing the trajectories of 700 individual cells belonging to three different species ( Amoeba proteus , Metamoeba leningradensis , and Amoeba borokensis ) in four different scenarios: in absence of stimuli, under an electric field (galvanotaxis), in a chemotactic gradient (chemotaxis), and under simultaneous galvanotactic and chemotactic stimuli. All movements were analyzed using advanced quantitative tools. The results show that the trajectories are mainly characterized by coherent integrative responses that operate at the global cellular scale. These systemic migratory movements depend on the cooperative nonlinear interaction of most, if not all, molecular components of cells., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

In this study, we conducted an in-depth analysis to characterize potential Acanthamoeba castellanii ( Ac ) proteins capable of recognizing fungal β-1,3-glucans. Ac specifically anchors curdlan or laminarin, indicating the presence of surface β-1,3-glucan-binding molecules. Using optical tweezers, strong adhesion of laminarin- or curdlan-coated beads to Ac was observed, highlighting their adhesive properties compared to controls (characteristic time τ of 46.9 and 43.9 s, respectively). Furthermore, Histoplasma capsulatum ( Hc ) G217B, possessing a β-1,3-glucan outer layer, showed significant adhesion to Ac compared to a Hc G186 strain with an α-1,3-glucan outer layer (τ of 5.3 s vs τ 83.6 s). The addition of soluble β-1,3-glucan substantially inhibited this adhesion, indicating the involvement of β-1,3-glucan recognition. Biotinylated β-1,3-glucan-binding proteins from Ac exhibited higher binding to Hc G217B, suggesting distinct recognition mechanisms for laminarin and curdlan, akin to macrophages. These observations hinted at the β-1,3-glucan recognition pathway's role in fungal entrance and survival within phagocytes, supported by decreased fungal viability upon laminarin or curdlan addition in both phagocytes. Proteomic analysis identified several Ac proteins capable of binding β-1,3-glucans, including those with lectin/glucanase superfamily domains, carbohydrate-binding domains, and glycosyl transferase and glycosyl hydrolase domains. Notably, some identified proteins were overexpressed upon curdlan/laminarin challenge and also demonstrated high affinity to β-1,3-glucans. These findings underscore the complexity of binding via β-1,3-glucan and suggest the existence of alternative fungal recognition pathways in Ac .IMPORTANCE Acanthamoeba castellanii ( Ac ) and macrophages both exhibit the remarkable ability to phagocytose various extracellular microorganisms in their respective environments. While substantial knowledge exists on this phenomenon for macrophages, the understanding of Ac 's phagocytic mechanisms remains elusive. Recently, our group identified mannose-binding receptors on the surface of Ac that exhibit the capacity to bind/recognize fungi. However, the process was not entirely inhibited by soluble mannose, suggesting the possibility of other interactions. Herein, we describe the mechanism of β-1,3-glucan binding by A. castellanii and its role in fungal phagocytosis and survival within trophozoites, also using macrophages as a model for comparison, as they possess a well-established mechanism involving the Dectin-1 receptor for β-1,3-glucan recognition. These shed light on a potential parallel evolution of pathways involved in the recognition of fungal surface polysaccharides., Competing Interests: The authors declare no conflict of interest.

The global surge in energy demand, driven by technological advances and population growth, underscores the critical need for effective management of electricity supply and demand. In certain developing nations, a significant challenge arises because the energy demand of their population exceeds their capacity to generate, as is the case in Iraq. This study focuses on energy forecasting in Iraq, using a previously unstudied dataset from 2019 to 2021, sourced from the Iraqi Ministry of Electricity. The study employs a diverse set of advanced forecasting models, including Linear Regression, XGBoost, Random Forest, Long Short-Term Memory, Temporal Convolutional Networks, and Multi-Layer Perceptron, evaluating their performance across four distinct forecast horizons (24, 48, 72, and 168 hours ahead). Key findings reveal that Linear Regression is a consistent top performer in demand forecasting, while XGBoost excels in supply forecasting. Statistical analysis detects differences in models performances for both datasets, although no significant differences are found in pairwise comparisons for the supply dataset. This study emphasizes the importance of accurate energy forecasting for energy security, resource allocation, and policy-making in Iraq. It provides tools for decision-makers to address energy challenges, mitigate power shortages, and stimulate economic growth. It also encourages innovative forecasting methods, the use of external variables like weather and economic data, and region-specific models tailored to Iraq's energy landscape. The research contributes valuable insights into the dynamics of electricity supply and demand in Iraq and offers performance evaluations for better energy planning and management, ultimately promoting sustainable development and improving the quality of life for the Iraqi population., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

This chapter describes methodological details for preparing specimens of Cryptococcus neoformans (although it can be applied to any species of the genus) and their subsequent analysis by scanning and transmission electron microscopy. Adaptations to conventional protocols for better preservation of the sample, as well as to avoid artifacts, are presented. The protocols may be used to examine both the surface ultrastructure and the interior of this pathogenic fungus in detail., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Glioblastoma is a highly aggressive brain tumor with a poor prognosis. Recent studies have suggested that mechanobiology, the study of how physical forces influence cellular behavior, plays an important role in glioblastoma progression. Several signaling pathways, molecules, and effectors, such as focal adhesions, stretch-activated ion channels, or membrane tension variations, have been studied in this regard. Also investigated are YAP/TAZ, downstream effectors of the Hippo pathway, which is a key regulator of cell proliferation and differentiation. In glioblastoma, YAP/TAZ have been shown to promote tumor growth and invasion by regulating genes involved in cell adhesion, migration, and extracellular matrix remodeling. YAP/TAZ can be activated by mechanical cues such as cell stiffness, matrix rigidity, and cell shape changes, which are all altered in the tumor microenvironment. Furthermore, YAP/TAZ have been shown to crosstalk with other signaling pathways, such as AKT, mTOR, and WNT, which are dysregulated in glioblastoma. Thus, understanding the role of mechanobiology and YAP/TAZ in glioblastoma progression could provide new insights into the development of novel therapeutic strategies. Targeting YAP/TAZ and mechanotransduction pathways in glioblastoma may offer a promising approach to treating this deadly disease.

Clinical evidence based on real-world data (RWD) is accumulating exponentially providing larger sample sizes available, which demand novel methods to deal with the enhanced heterogeneity of the data. Here, we used RWD to assess the prediction of cognitive decline in a large heterogeneous sample of participants being enrolled with cognitive stimulation, a phenomenon that is of great interest to clinicians but that is riddled with difficulties and limitations. More precisely, from a multitude of neuropsychological Training Materials (TMs), we asked whether was possible to accurately predict an individual's cognitive decline one year after being tested. In particular, we performed longitudinal modelling of the scores obtained from 215 different tests, grouped into 29 cognitive domains, a total of 124,610 instances from 7902 participants (40% male, 46% female, 14% not indicated), each performing an average of 16 tests. Employing a machine learning approach based on ROC analysis and cross-validation techniques to overcome overfitting, we show that different TMs belonging to several cognitive domains can accurately predict cognitive decline, while other domains perform poorly, suggesting that the ability to predict decline one year later is not specific to any particular domain, but is rather widely distributed across domains. Moreover, when addressing the same problem between individuals with a common diagnosed label, we found that some domains had more accurate classification for conditions such as Parkinson's disease and Down syndrome, whereas they are less accurate for Alzheimer's disease or multiple sclerosis. Future research should combine similar approaches to ours with standard neuropsychological measurements to enhance interpretability and the possibility of generalizing across different cohorts., (© 2023 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Oral squamous cell carcinoma (OSCC) is a worldwide public health problem, accounting for approximately 90% of all oral cancers, and is the eighth most common cancer in men. Cisplatin and carboplatin are the main chemotherapy drugs used in the clinic. However, in addition to their serious side effects, such as damage to the nervous system and kidneys, there is also drug resistance. Thus, the development of new drugs becomes of great importance. Naphthoquinones have been described with antitumor activity. Some of them are found in nature, but semi synthesis has been used as strategy to find new chemical entities for the treatment of cancer. In the present study, we promote a multiple component reaction (MCR) among lawsone, arylaldehydes, and benzylamine to produce sixteen chemoselectively derivated Mannich adducts of 1,4-naphthoquinones in good yield (up to 97%). The antitumor activities and molecular mechanisms of action of these compounds were investigated in OSCC models and the compound 6a induced cytotoxicity in three different tumor cell lines (OSCC4, OSCC9, and OSCC25) and was more selective (IS > 2) for tumor cells than the chemotropic drug carboplatin and the controls lapachol and shikonin, which are chemically similar compounds with cytotoxic effects. The 6a selectively and significantly reduced the amount of cell colony growth, was not hemolytic, and tolerable in mice with no serious side effects at a concentration of 100 mg/kg with a LD50 of 150 mg/kg. The new compound is biologically stable with a profile similar to carboplatin. Morphologically, 6a does not induce cell retraction or membrane blebs, but it does induce intense vesicle formation and late emergence of membrane bubbles. Exploring the mechanism of cell death induction, compound 6a does not induce ROS formation, and cell viability was not affected by inhibitors of apoptosis (ZVAD) and necroptosis (necrostatin 1). Autophagy followed by a late apoptosis process appears to be the death-inducing pathway of 6a, as observed by increased viability by the autophagy inhibitor (3-MA) and by the appearance of autophagosomes, later triggering a process of late apoptosis with the presence of caspase 3/7 and DNA fragmentation. Molecular modeling suggests the ability of the compound to bind to topoisomerase I and II and with greater affinity to hPKM2 enzyme than controls, which could explain the mechanism of cell death by autophagy. Finally, the in-silico prediction of drug-relevant properties showed that compound 6a has a good pharmacokinetic profile when compared to carboplatin and doxorubicin. Among the sixteen naphthoquinones tested, compound 6a was the most effective and is highly selective and well tolerated in animals. The induction of cell death in OSCC through autophagy followed by late apoptosis possibly via inhibition of the PKM2 enzyme points to a promising potential of 6a as a new preclinical anticancer candidate.

Background: Current drugs for the treatment of endometriosis are not able to completely cure the condition, and significant side effects hinder the continuation of treatment. Therefore, it is necessary to search for new drug candidates. In the present paper, the use of plant extracts is highlighted. Babassu oil and Copaiba oil resin have several therapeutic properties. We investigated the in vitro effects of two nanoemulsions containing oil extracted from Babassu ( Orbignya speciosa ) nuts (called SNEDDS-18) and/or oil resin extracted from Copaiba trunk ( Copaifera langsdorffii ) (called SNEDDS-18/COPA) on cultured human eutopic endometrium stromal cells from endometrial biopsies of patients without (CESC) and with (EuESC) endometriosis as well as human stromal cells from biopsies of endometriotic lesions (EctESC)., Methods: CESC, EuESC, and EctESC were taken and treated with SNEDDS-18 and SNEDDS-18/COPA to evaluate their effects on cytotoxicity, cell morphology, proliferation, and signaling pathways., Results: After 48 h of incubation with SNEDDS-18 and SNEDDS-18/COPA, cell viability and proliferation were inhibited, especially in EctESC. The lowest concentration of both nanoemulsions reduced cell viability and proliferation and broke down the cytoskeleton in EctESCs. After 24 h of treatment a decrease in IL-1, TNF-α, and MCP-1 was observed, as well as an increase in IL-10 production., Conclusions: Both nanoemulsions can affect endometriotic stromal cell behaviors, thus revealing two potential candidates for new phytotherapeutic agents for the management of endometriosis.

To our knowledge, this is the first study reported in the literature that has validated the Norma Latina Battery in a population of people with Alzheimer's disease (AD) in Mexico. The objective of the study was to determine the discriminant validity of the Norma Latina Battery in a group of Mexican individuals with AD and a group of heathy controls (HC). The Norma Latina Battery was administered to 234 Mexican participants (117 HC and 117 individuals with AD). Results show that: (1) the Norma Latina Battery has high discriminative capacity between groups in all domains; (2) participants with AD presented worse scores in each of the cognitive domains compared to the HC and a greater number of low scores in each of the established thresholds or cut-off points; and finally, (3) the Norma Latina Battery had optimal sensitivity and specificity, especially when a set was observed ≥5 scores below the 10th percentile or ≥4 scores below the 5th percentile. In conclusion, it is recommended that both clinicians and researchers use this battery in the evaluation of Mexican people with AD to better understand the prognosis of the disease and its subsequent treatment.

Glioblastoma is the most common and malignant type of primary brain tumor. Previous studies have shown that alterations in centrosome amplification and its components are frequently found in treatment-resistant tumors and may be associated with tumor progression. A centrosome protein essential for centrosome biogenesis is the centromere protein J (CENPJ), known to control the proliferation of neural progenitors and hepatocarcinoma cells, and also neuronal migration. However, it remains unknown the role of CENPJ in glioblastoma. Here we show that CENPJ is overexpressed in human glioblastoma cell lines in comparison to human astrocytes. Using bioinformatics analysis, we find that high Cenpj expression is associated with poor prognosis in glioma patients. Examining Cenpj loss of function in glioblastoma by siRNA transfection, we find impairments in cell proliferation and migration. Using a Cenpj mutant version with the deleted PN2-3 or TCP domain, we found that a conserved PN2-3 region is required for glioblastoma migration. Moreover, Cenpj downregulation modulates glioblastoma morphology resulting in microtubules stabilization and actin filaments depolymerization. Altogether, our findings indicate that CENPJ controls relevant aspects of glioblastoma progression and might be a target for therapeutic intervention and a biomarker for glioma malignancy., (© 2022 International Society for Neurochemistry.)

Oral squamous cell carcinoma (OSCC) is a global public health problem with high incidence and mortality. The chemotherapeutic agents used in the clinic, alone or in combination, usually lead to important side effects. Thus, the discovery and development of new antineoplastic drugs are essential to improve disease prognosis and reduce toxicity. In the present study, acridine-core naphthoquinone compounds were synthesized and evaluated for their antitumor activity in OSCC cells. The mechanism of action, pharmacokinetics, and toxicity parameters of the most promising compound was further analyzed using in silico, in vitro, and in vivo methods. Among the derivatives, compound 4e was highly cytotoxic (29.99 µM) and selective (SI 2.9) at levels comparable and generally superior to chemotherapeutic controls. Besides, compound 4e proved to be non-hemolytic, stable, and well tolerated in animals at all doses tested. Mechanistically, compound 4e promoted cell death by apoptosis in the OSCC cell, and molecular docking studies suggested this compound possibly targets enzymes important for tumor progression, such as RSK2, PKM2, and topoisomerase IIα. Importantly, compound 4e presented a pharmacological profile within desirable parameters for drug development, showing promise for future preclinical trials.

Glioblastomas are considered the most common and aggressive primary brain tumor in adults, with an average of 15 months' survival rate. The treatment is surgery resection, followed by chemotherapy with temozolomide, and/or radiotherapy. Glioblastoma must have wild-type IDH gene and some characteristics, such as TERT promoter mutation, EGFR gene amplification, microvascular proliferation, among others. Glioblastomas have great heterogeneity at cellular and molecular levels, presenting distinct phenotypes and diversified molecular signatures in each tumor mass, making it difficult to define a specific therapeutic target. It is believed that the main responsibility for the emerge of these distinct patterns lies in subcellular populations of tumor stem cells, capable of tumor initiation and asymmetric division. Studies are now focused on understanding molecular mechanisms of chemoresistance, the tumor microenvironment, due to hypoxic and necrotic areas, cytoskeleton and extracellular matrix remodeling, and in controlling blood brain barrier permeabilization to improve drug delivery. Another promising therapeutic approach is the use of oncolytic viruses that are able to destroy specifically glioblastoma cells, preserving the neural tissue around the tumor. In this review, we summarize the main biological characteristics of glioblastoma and the cutting-edge therapeutic targets that are currently under study for promising new clinical trials.

In this study, we investigated the influence of fungal extracellular vesicles (EVs) during biofilm formation and morphogenesis in Candida albicans. Using crystal violet staining and scanning electron microscopy (SEM), we demonstrated that C. albicans EVs inhibited biofilm formation in vitro . By time-lapse microscopy and SEM, we showed that C. albicans EV treatment stopped filamentation and promoted pseudohyphae formation with multiple budding sites. The ability of C. albicans EVs to regulate dimorphism was further compared to EVs isolated from different C. albicans strains, Saccharomyces cerevisiae, and Histoplasma capsulatum. C. albicans EVs from distinct strains inhibited yeast-to-hyphae differentiation with morphological changes occurring in less than 4 h. EVs from S. cerevisiae and H. capsulatum modestly reduced morphogenesis, and the effect was evident after 24 h of incubation. The inhibitory activity of C. albicans EVs on phase transition was promoted by a combination of lipid compounds, which were identified by gas chromatography-tandem mass spectrometry analysis as sesquiterpenes, diterpenes, and fatty acids. Remarkably, C. albicans EVs were also able to reverse filamentation. Finally, C. albicans cells treated with C. albicans EVs for 24 h lost their capacity to penetrate agar and were avirulent when inoculated into Galleria mellonella. Our results indicate that fungal EVs can regulate yeast-to-hypha differentiation, thereby inhibiting biofilm formation and attenuating virulence. IMPORTANCE The ability to undergo morphological changes during adaptation to distinct environments is exploited by Candida albicans and has a direct impact on biofilm formation and virulence. Morphogenesis is controlled by a diversity of stimuli, including osmotic stress, pH, starvation, presence of serum, and microbial components, among others. Apart from external inducers, C. albicans also produces autoregulatory substances. Farnesol and tyrosol are examples of quorum-sensing molecules (QSM) released by C. albicans to regulate yeast-to-hypha conversion. Here, we demonstrate that fungal EVs are messengers impacting biofilm formation, morphogenesis, and virulence in C. albicans. The major players exported in C. albicans EVs included sesquiterpenes, diterpenes, and fatty acids. The understanding of how C. albicans cells communicate to regulate physiology and pathogenesis can lead to novel therapeutic tools to combat candidiasis.

The viscoelastic properties of erythrocytes have been investigated by a range of techniques. However, the reported experimental data vary. This is not only attributed to the normal variability of cells, but also to the differences in methods and models of cell response. Here, an integrated protocol using optical tweezers and defocusing microscopy is employed to obtain the rheological features of red blood cells in the frequency range of 1 Hz to 35 Hz. While optical tweezers are utilized to measure the erythrocyte-complex elastic constant, defocusing microscopy is able to obtain the cell height profile, volume, and its form factor a parameter that allows conversion of complex elastic constant into complex shear modulus. Moreover, applying a soft glassy rheology model, the scaling exponent for both moduli can be obtained. The developed methodology allows to explore the mechanical behavior of red blood cells, characterizing their viscoelastic parameters, obtained under well-defined experimental conditions, for several physiological and pathological conditions.

Several studies have proved that glial cells, as well as neurons, play a role in pain pathophysiology. Most of these studies have focused on the contribution of central glial cells (e.g., microglia and astrocytes) to neuropathic pain. Likewise, some works have suggested that peripheral glial cells, particularly satellite glial cells (SGCs), and the crosstalk between these cells and the sensory neurons located in the peripheral ganglia, play a role in the phenomenon that leads to pain. Nonetheless, the study of SGCs may be challenging, as the validity of studying those cells in vitro is still controversial. In this study, a research protocol was developed to examine the potential use of primary mixed neuronal-glia cell cultures obtained from the trigeminal ganglion cells (TGCs) of neonate mice (P10-P12). Primary cultures were established and analyzed at 4 h, 24 h, and 48 h. To this purpose, phase contrast microscopy, immunocytochemistry with antibodies against anti-βIII-tubulin and Sk3, scanning electron microscopy, and time-lapse photography were used. The results indicated the presence of morphological changes in the cultured SGCs obtained from the TGCs. The SGCs exhibited a close relationship with neurons. They presented a round shape in the first 4 h, and a more fusiform shape at 24 h and 48 h of culture. On the other hand, neurons changed from a round shape to a more ramified shape from 4 h to 48 h. Intriguingly, the expression of SK3, a marker of the SGCs, was high in all samples at 4 h, with some cells double-staining for SK3 and βIII-tubulin. The expression of SK3 decreased at 24 h and increased again at 48 h in vitro. These results confirm the high plasticity that the SGCs may acquire in vitro. In this scenario, the authors hypothesize that, at 4 h, a group of the analyzed cells remained undifferentiated and, therefore, were double-stained for SK3 and βIII-tubulin. After 24 h, these cells started to differentiate into SCGs, which was clearer at 48 h in the culture. Mixed neuronal-glial TGC cultures might be implemented as a platform to study the plasticity and crosstalk between primary sensory neurons and SGCs, as well as its implications in the development of chronic orofacial pain.

Background: A clinical decision support system (CDSS ) has been designed to predict the outcome (overall survival) by extracting and analyzing information from routine clinical activity as a complement to clinical guidelines in lung cancer patients., Materials and Methods: Prospective multicenter data from 543 consecutive (2013-2017) lung cancer patients with 1167 variables were used for development of the CDSS. Data Mining analyses were based on the XGBoost and Generalized Linear Models algorithms. The predictions from guidelines and the CDSS proposed were compared., Results: Overall, the highest (> 0.90) areas under the receiver-operating characteristics curve AUCs for predicting survival were obtained for small cell lung cancer patients. The AUCs for predicting survival using basic items included in the guidelines were mostly below 0.70 while those obtained using the CDSS were mostly above 0.70. The vast majority of comparisons between the guideline and CDSS AUCs were statistically significant (p < 0.05). For instance, using the guidelines, the AUC for predicting survival was 0.60 while the predictive power of the CDSS enhanced the AUC up to 0.84 (p = 0.0009). In terms of histology, there was only a statistically significant difference when comparing the AUCs of small cell lung cancer patients (0.96) and all lung cancer patients with longer (≥ 18 months) follow up (0.80; p < 0.001)., Conclusions: The CDSS successfully showed potential for enhancing prediction of survival. The CDSS could assist physicians in formulating evidence-based management advice in patients with lung cancer, guiding an individualized discussion according to prognosis., Competing Interests: Conflict of interests The authors report no conflict of interest., (© 2021 Greater Poland Cancer Centre.)

The oral squamous cell carcinoma (OSCC) is the eighth more common cancer in men. The development of new and more efficient drugs is needed. Plants of the genus Piper are popularly used in the treatment of many diseases. This study evaluated the antitumor effect of extract, fraction and isolated compounds from leaves of P. rivinoides in oral cancer. The isolated compounds (conocarpan, eupomatenoid-5 and eupomatenoid-6) were effective in inducing cell death in OSCC cell lines (SCC4, SCC9 and SCC25) compared to the standard chemotherapeutic agent carboplatin, and this effect was time-dependent. Conocarpan was more selective and stable than eupomatenoid-5 and eupomatenoid-6, resembling the stability of carboplatin. There was a significant presence of pyknotic nuclei and active caspase-3 expression under conocarpan treatment, suggesting cell death through apoptosis. In conclusion, conocarpan was the most effective compound against OSCC cells and might be considered for future cancer studies.

Objective: To develop a new device for identifying physiological markers of pain perception by reading the brain's electrical activity and hemodynamic interactions while applying thermoalgesic stimulation., Methods: We designed a compact prototype that generates well-controlled thermal stimuli using a computer-driven Peltier cell while simultaneously capturing electroencephalography (EEG) and photoplethysmography (PPG) signals. The study was performed on 35 healthy subjects (mean age 30.46 years, SD 4.93 years; 20 males, 15 females). We first determined the heat pain threshold (HPT) for each subject, defined as the maximum temperature that the subject can withstand when the Peltier cell gradually increased the temperature. Next, we defined the painful condition as the one occurring at temperature equal to 90% of the HPT, comparing this to the no-pain state (control) in the absence of thermoalgesic stimulation., Results: Both the one-dimensional and the two-dimensional spectral entropy (SE) obtained from both the EEG and PPG signals differentiated the condition of pain. In particular, the SE for PPG was significantly reduced in association with pain, while the SE for EEG increased slightly. Moreover, significant discrimination occurred within a specific range of frequencies, 26-30 Hz for EEG and about 5-10 Hz for PPG., Conclusion: Hemodynamics, brain dynamics and their interactions can discriminate thermal pain perception., Significance: The possibility of monitoring on-line variations in thermal pain perception using a similar device and algorithms may be of interest to study different pathologies that affect the peripheral nervous system, such as small fiber neuropathies, fibromyalgia or painful diabetic neuropathy.

Despite advances in treatment of lethal prostate cancer, the incidence of prostate cancer brain metastases is increasing. In this sense, we analyzed the molecular profile, as well as the functional consequences involved in the reciprocal interactions between prostate tumor cells and human astrocytes. We observed that the DU145 cells, but not the LNCaP cells or the RWPE-1 cells, exhibited more pronounced, malignant and invasive phenotypes along their interactions with astrocytes. Moreover, global gene expression analysis revealed several genes that were differently expressed in our co-culture models with the overexpression of GLIPR1 and SPARC potentially representing a molecular signature associated with the invasion of central nervous system by prostate malignant cells. Further, these results were corroborated by immunohistochemistry and in silico analysis. Thus, we conjecture that the data here presented may increase the knowledge about the molecular mechanisms associated with the invasion of CNS by prostate malignant cells., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Head and neck squamous cell carcinomas (HNSCC) are among the most common and lethal tumors worldwide, occurring mostly in oral cavity, pharynx, and larynx tissues. The squamous epithelia homeostasis is supported by the extracellular matrix (ECM), and alterations in this compartment are crucial for cancer development and progression. Laminin is a fundamental component of ECM, where it represents one of the main components of basement membrane (BM), and data supporting its contribution to HNSCC genesis and progression has been vastly explored in oral cavity squamous cell carcinoma. Laminin subtypes 111 (LN-111) and 332 (LN-332) are the main isoforms associated with malignant transformation, contributing to proliferation, adhesion, migration, invasion, and metastasis, due to its involvement in the regulation of several pathways associated with HNSCC carcinogenesis, including the activation of the EGFR/MAPK signaling pathway. Therefore, it draws attention to the possibility that laminin may represent a convergence point in HNSCC natural history, and an attractive potential therapeutic target for these tumors.

Cryptococcus neoformans is a fungal pathogen that causes life-threatening infections in immunocompromised individuals. It is surrounded by three concentric structures that separate the cell from the extracellular space: the plasma membrane, the cell wall and the polysaccharide (PS) capsule. Although several studies have revealed the chemical composition of these structures, little is known about their ultrastructural organization and remodeling during C. neoformans budding events. Here, by combining the latest and most accurate light and electron microscopy techniques, we describe the morphological remodeling that occurs among the capsule, cell wall and plasma membrane during budding in C. neoformans . Our results show that the cell wall deforms to generate a specialized region at one of the cell's poles. This region subsequently begins to break into layers that are slightly separated from each other and with thick tips. We also observe a reorganization of the capsular PS around the specialized regions. While daughter cells present their PS fibers aligned in the direction of budding, mother cells show a similar pattern but in the opposite direction. Also, daughter cells form multilamellar membrane structures covering the continuous opening between both cells. Together, our findings provide compelling ultrastructural evidence for C. neoformans surface remodeling during budding, which may have important implications for future studies exploring these remodeled specialized regions as drug-targets against cryptococcosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Araújo, Alcantara, Rodrigues, de Souza, Pontes and Frases.)

Cryptococcus neoformans is a fungal pathogen that causes life-threatening infections in immunocompromised individuals, who often have some inflammatory condition and, therefore, end up using glucocorticoids, such as dexamethasone and methylprednisolone. Although the effects of this class of molecules during cryptococcosis have been investigated, their consequences for the biology of C. neoformans is less explored. Here, we studied the effects of dexamethasone and methylprednisolone on the metabolism and on the induction of virulence factors in C. neoformans . Our results showed that both glucocorticoids increased fungal cell proliferation and surface electronegativity but reduced capsule and secreted polysaccharide sizes, as well as capsule compaction, by decreasing the density of polysaccharide fibers. We also tested whether glucocorticoids could affect the fungal virulence in Galleria mellonella and mice. Although the survival rate of Galleria larvae increased, those from mice showed a tendency to decrease, with infected animals dying earlier after glucocorticoid treatments. The pathogenesis of spread of cryptococcosis and the interleukin secretion pattern were also assessed for lungs and brains of infected mice. While increases in the spread of the fungus to lungs were observed after treatment with glucocorticoids, a significant difference in brain was observed only for methylprednisolone, although a trend toward increasing was also observed for dexamethasone. Moreover, increases in both pulmonary and cerebral IL-10 production, reduction of IL-6 production but no changes in IL-4, IL-17, and INF-γ were also observed after glucocorticoid treatments. Finally, histopathological analysis confirmed the increase in number of fungal cells in lung and brain tissues of mice previously subjected to dexamethasone or methylprednisolone treatments. Together, our results provide compelling evidence for the effects of dexamethasone and methylprednisolone on the biology of C. neoformans and may have important implications for future clinical treatments, calling attention to the risks of using these glucocorticoids against cryptococcosis or in immunocompromised individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Araújo, Alves, Martins-de-Souza, Guimarães, Honorato, Nimrichter, Takiya, Pontes and Frases.)

The elastic properties of cell membranes, particularly the membrane tension and bending modulus, are known to be key regulators of cellular functions. Here, we present a correlative and integrated tool based on optical tweezers and scanning electron microscopy to accurately determine these properties in a variety of cell types. Although there are intrinsic difficulties associated with correlative experiments, we believe that the methods presented can be considered a suitable protocol for determining the elastic properties of cell membranes. For complete details on the use and execution of this protocol, please refer to Soares et al. (2020)., Competing Interests: The authors declare no competing interests., (© 2020 The Author(s).)

The mechanical properties of erythrocytes have been investigated by different techniques. However, there are few reports on how the viscoelasticity of these cells varies during malaria disease. Here, we quantitatively map the viscoelastic properties of Plasmodium falciparum-parasitized human erythrocytes. We apply new methodologies based on optical tweezers to measure the viscoelastic properties and defocusing microscopy to measure the erythrocyte height profile, the overall cell volume, and its form factor, a crucial parameter to convert the complex elastic constant into complex shear modulus. The storage and loss shear moduli are obtained for each stage of parasite maturation inside red blood cells, while the former increase, the latter decrease. Employing a soft glassy rheology model, we obtain the power-law exponent for the storage and loss shear moduli, characterizing the soft glassy features of red blood cells in each parasite maturation stage. Ring forms present a liquid-like behavior, with a slightly lower power-law exponent than healthy erythrocytes, whereas trophozoite and schizont stages exhibit increasingly solid-like behaviors. Finally, the surface elastic shear moduli, low-frequency surface viscosities, and shape recovery relaxation times all increase not only in a stage-dependent manner but also when compared to healthy red blood cells. Overall, the results call attention to the soft glassy characteristics of Plasmodium falciparum-parasitized erythrocyte membrane and may provide a basis for future studies to better understand malaria disease from a mechanobiological perspective., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The oral squamous cell carcinoma (OSCC) stands out as a public health problem due to its high incidence and low survival rate, despite advances in diagnosis and treatment. Moreover, the most commonly chemotherapeutic agents for OSCC, such as carboplatin and cisplatin, generate important side effects, evidencing the urgency in developing new drugs. Naphthoquinones are an important class of natural products or synthetic compounds with cytotoxic effect demonstrated on different cancer types. In the present study, thirty-five 1,4-naphthoquinones tethered to 1,2,3-1H-triazoles were synthesized and the antitumor activity and molecular mechanisms were evaluated in several assays including in vitro and in vivo models of OSCC and normal oral human cells. Compounds 16a, 16b and 16 g were able to induce cytotoxicity in three different tumor cell lines of human OSCC (SCC4, SCC9 and SCC25) and were more toxic and selective to tumor cells (Selective Index, SI > 2) than classical and chemically similar controls (Carboplatin and Lapachol). Compound 16 g showed the higher SI value. Besides, compounds 16a, 16b and 16 g significantly reduced colony formation of SCC9 cells in the tested concentrations. Hemolytic assay using compounds 16a, 16b and 16 g at high concentrations showed no compound exhibited hemolysis higher than 5%, similar to controls. In vivo acute toxicity study showed that 16 g was the only one, among the three compounds, with no apparent limiting toxic effects on mice in the tested concentrations. Thus, the investigation of cell death mechanisms was conducted with this compound. 16 g does not trigger ROS production nor binds to DNA. On the other hand, compound 16 g induced microtubule disorganization, and molecular modeling studies suggests a potential mechanism of action related to inhibition of topoisomerases and/or hPKM2 activities. Cell morphology, pyknotic nuclei presence, cleaved caspase-3 staining and viability assays using caspase-3 inhibitors demonstrate compound 16 g induced cell death through apoptosis. Among the 35 synthesized triazole naphthoquinones, compound 16 g was the most effective compound against OSCC cells, presenting high cytotoxicity (~35 µM), selectivity (SI ~ 6) and low acute toxicity on animals, and therefore might be considered for future cancer therapy., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The red blood cell membrane-cytoskeleton is a complex structure mainly responsible for giving the cell rigidity and shape. It also provides the erythrocyte with the ability to pass through narrow capillaries of the vertebrate blood circulatory system. Although the red blood cell viscoelastic properties have been extensively studied, reported experimental data differ by up to three orders of magnitude. This could be attributed to the natural cell variability, to the different techniques employed, and also to the models used for the cell response, which are highly dependent on cell geometry. Here, we use two methodologies based on optical tweezers to investigate the viscoelastic behavior of healthy human red blood cells, one applying small cell deformations (microrheology) and another imposing large deformations (tether extraction). We also establish a defocusing microscopy-based method to characterize the cell geometry and thus the erythrocyte form factor, an essential parameter that allows comparisons among the viscoelastic properties at different conditions. Moreover, for small deformations, a soft glassy rheology model is used to discuss the results, while for large deformations two surface shear moduli and one surface viscosity are determined, together with the surface tension and bending modulus of the erythrocyte membrane lipid component. We also show that F-actin is not detected in tethers, although the erythrocyte membrane has physical properties like those of other adherent cells, known to have tethers containing F-actin inside. Altogether, our results show good agreement with the reported literature and we argue that, to properly compare the viscoelastic properties of red blood cells in different situations, the task of cell geometry characterization must be accomplished. This may be especially important when the influence of agents, like the malaria parasite, induces changes in both the geometry and chemical constituents of the erythrocyte membrane. Together, the new methodologies and procedures used in this study would allow the erythrocyte community to better explore the mechanical behavior of red blood cells and may be useful to characterize erythrocyte viscoelasticity changes in several blood diseases.

Neural precursor cells differentiate into several cell types that display distinct functions. However, little is known about how cell surface mechanics vary during the differentiation process. Here, by precisely measuring membrane tension and bending modulus, we map their variations and correlate them with changes in neural precursor cell morphology along their distinct differentiation fates. Both cells maintained in culture as neural precursors as well as those plated in neurobasal medium reveal a decrease in membrane tension over the first hours of culture followed by stabilization, with no change in bending modulus. During astrocyte differentiation, membrane tension initially decreases and then increases after 72 h, accompanied by consolidation of glial fibrillary acidic protein expression and striking actin reorganization, while bending modulus increases following observed alterations. For oligodendrocytes, the changes in membrane tension are less abrupt over the first hours, but their values subsequently decrease, correlating with a shift from oligodendrocyte marker O4 to myelin basic protein expressions and a remarkable actin reorganization, while bending modulus remains constant. Oligodendrocytes at later differentiation stages show membrane vesicles with similar membrane tension but higher bending modulus as compared to the cell surface. Altogether, our results display an entire spectrum of how membrane elastic properties are varying, thus contributing to a better understanding of neural differentiation from a mechanobiological perspective., Competing Interests: The authors declare that they have no conflict of interest and no competing financial interest.

In the last years, the extracellular matrix (ECM) has been reported as playing a relevant role in esophageal cancer (EC) development, with this compartment being related to several aspects of EC genesis and progression. This sounds very interesting due to the complexity of this highly incident and lethal tumor, which takes the sixth position in mortality among all tumor types worldwide. The well-established increase in ECM stiffness, which is able to trigger mechanotransduction signaling, is capable of regulating several malignant behaviors by converting alteration in ECM mechanics into cytoplasmatic biochemical signals. In this sense, it has been shown that some molecules play a key role in these events, particularly the different collagen isoforms, as well as enzymes related to its turnover, such as lysyl oxidase (LOX) and matrix metalloproteinases (MMPs). In fact, MMPs are not only involved in ECM stiffness, but also in other events related to ECM homeostasis, which includes ECM remodeling. Therefore, the crucial role of distinct MMPs isoform has already been reported, especially MMP-2, -3, -7, and -9, along EC development, thus strongly associating these proteins with the control of important cellular events during tumor progression, particularly in the process of invasion during metastasis establishment. In addition, by distinct mechanisms, a vast diversity of glycoproteins and proteoglycans, such as laminin, fibronectin, tenascin C, galectin, dermatan sulfate, and hyaluronic acid exert remarkable effects in esophageal malignant cells due to the activation of oncogenic signaling pathways mainly involved in cytoskeleton alterations during adhesion and migration processes. Finally, the wide spectrum of interactions potentially mediated by ECM may represent a singular intervention scenario in esophageal carcinogenesis natural history and, due to the scarce knowledge on the cellular and molecular mechanisms involved in EC development, the growing body of evidence on ECM's role along esophageal carcinogenesis might provide a solid base to improve its management in the future.

Glioblastoma (GBM) is the most aggressive tumor of the central nervous system, and the identification of the mechanisms underlying the biological basis of GBM aggressiveness is essential to develop new therapies. Due to the low prognosis of GBM treatment, different clinical studies are in course to test the use of histone deacetylase inhibitors (iHDACs) in anticancer cocktails. Here, we seek to investigate the impact of HDAC activity on GBM cell behavior and plasticity by live cell imaging. We pharmacologically knock down HDAC activity using two different inhibitors (TSA and SAHA) in two different tumor cell types: a commercial GBM cell line (U87-MG) and primary tumor (GBM011). Upon 72 hours of in vitro iHDAC treatment, GBM cells presented a very unusual elongated cell shape due to tunneling tube formation and independent on TGF- β signaling epithelial to mesenchymal transition. Live cell imaging revealed that voltage-sensitive Ca ++ signaling was disrupted upon HDAC activity blockade. This behavior was coupled to vimentin and connexin 43 gene expression downregulation, suggesting that HDAC activity blockade downgrades GBM aggressiveness mostly due to tumor cell competence and plasticity modulation in vitro . To test this hypothesis and access whether iHDACs would modulate tumor cell behavior and plasticity to properly respond to environmental cues in vivo , we xenografted GBM oncospheres in the chick developing the neural tube. Remarkably, upon 5 days in the developing neural tube, iHDAC-treated GBM cells ectopically expressed HNK-1, a tumor-suppressor marker tightly correlated to increased survivor of patients. These results describe, for the first time in the literature, the relevance of iHDACs for in vivo tumor cell morphology and competence to properly respond to environmental cues. Ultimately, our results highlight the relevance of chromatin remodeling for tumor cell plasticity and shed light on clinical perspectives aiming the epigenome as a relevant therapeutic target for GBM therapy., Competing Interests: The authors declare that there are no conflicts of interest.

Microbes can modify their surface structure as an adaptive mechanism for survival and dissemination in the environment or inside the host. Altering their ability to respond to mechanical stimuli is part of this adaptive process. Since the 1990s, powerful micromanipulation tools have been developed that allow mechanical studies of microbial cell surfaces, exploring little known aspects of their dynamic behavior. This review concentrates on the study of mechanical and rheological properties of bacteria and fungi, focusing on their cell surface dynamics and biofilm formation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2019 The Authors.)

Aim: Cryptococcus neoformans is the major agent of cryptococcosis. The main virulence factor is the polysaccharide (PS) capsule. Changes in cryptococcal PS properties have been poorly elucidated. Materials & methods: We analyzed the mechanical properties of secreted PS and intact capsules, using dynamic light scattering and optical tweezers. Results: Storage and loss moduli showed that secreted PS behaves as a viscoelastic liquid, while capsular PS behaves as a viscoelastic solid. The secreted PS remains as a viscoelastic fluid at different temperatures with thermal hysteresis after 85°C. Antibody binding altered the viscoelastic behavior of both secreted and capsular PS. Conclusion: Deciphering the mechanical aspects of these structures could reveal features that may have consequences in novel therapies against cryptococcosis.

Recognition and internalisation of intracellular pathogens by host cells is a multifactorial process, involving both stable and transient interactions. The plasticity of the host cell plasma membrane is fundamental in this infectious process. Here, the participation of macrophage lipid microdomains during adhesion and internalisation of the fungal pathogen Histoplasma capsulatum (Hc) was investigated. An increase in membrane lateral organisation, which is a characteristic of lipid microdomains, was observed during the first steps of Hc-macrophage interaction. Cholesterol enrichment in macrophage membranes around Hc contact regions and reduced levels of Hc-macrophage association after cholesterol removal also suggested the participation of lipid microdomains during Hc-macrophage interaction. Using optical tweezers to study cell-to-cell interactions, we showed that cholesterol depletion increased the time required for Hc adhesion. Additionally, fungal internalisation was significantly reduced under these conditions. Moreover, macrophages treated with the ceramide-glucosyltransferase inhibitor (P4r) and macrophages with altered ganglioside synthesis (from B4galnt1 -/- mice) showed a deficient ability to interact with Hc. Coincubation of oligo-GM1 and treatment with Cholera toxin Subunit B, which recognises the ganglioside GM1, also reduced Hc association. Although purified GM1 did not alter Hc binding, treatment with P4 significantly increased the time required for Hc binding to macrophages. The content of CD18 was displaced from lipid microdomains in B4galnt1 -/- macrophages. In addition, macrophages with reduced CD18 expression (CD18 low ) were associated with Hc at levels similar to wild-type cells. Finally, CD11b and CD18 colocalised with GM1 during Hc-macrophage interaction. Our results indicate that lipid rafts and particularly complex gangliosides that reside in lipid rafts stabilise Hc-macrophage adhesion and mediate efficient internalisation during histoplasmosis., (© 2018 John Wiley & Sons Ltd.)

Glioblastoma is an extremely aggressive and deadly brain tumor known for its striking cellular heterogeneity and capability to communicate with microenvironment components, such as microglia. Microglia-glioblastoma interaction contributes to an increase in tumor invasiveness, and Wnt signaling pathway is one of the main cascades related to tumor progression through changes in cell migration and invasion. However, very little is known about the role of canonical Wnt signaling during microglia-glioblastoma crosstalk. Here, we show for the first time that Wnt3a is one of the factors that regulate interactions between microglia and glioblastoma cells. Wnt3a activates the Wnt/β-catenin signaling of both glioblastoma and microglial cells. Glioblastoma-conditioned medium not only induces nuclear translocation of microglial β-catenin but also increases microglia viability and proliferation as well as Wnt3a, cyclin-D1, and c-myc expression. Moreover, glioblastoma-derived Wnt3a increases microglial ARG-1 and STI1 expression, followed by an upregulation of IL-10 mRNA levels, and a decrease in IL1β gene expression. The presence of Wnt3a in microglia-glioblastoma co-cultures increases the formation of membrane nanotubes accompanied by changes in migration capability. In vivo, tumors formed from Wnt3a-stimulated glioblastoma cells presented greater microglial infiltration and more aggressive characteristics such as growth rate than untreated tumors. Thus, we propose that Wnt3a belongs to the arsenal of factors capable of stimulating the induction of M2-like phenotype on microglial cells, which contributes to the poor prognostic of glioblastoma, reinforcing that Wnt/β-catenin pathway can be a potential therapeutic target to attenuate glioblastoma progression.

Interaction Information (II) generalizes the univariate Shannon entropy to triplets of variables, allowing the detection of redundant (R) or synergetic (S) interactions in dynamical networks. Here, we calculated II from functional magnetic resonance imaging data and asked whether R or S vary across brain regions and along lifespan. Preserved along lifespan, we found high overlapping between the pattern of high R and the default mode network, whereas high values of S were overlapping with different cognitive domains, such as spatial and temporal memory, emotion processing and motor skills. Moreover, we have found a robust balance between R and S among different age intervals, indicating informational compensatory mechanisms in brain networks.

The plasma membrane separates the interior of cells from the outside environment. The membrane tension, defined as the force per unit length acting on a cross-section of membrane, regulates many vital biological processes. In this review, we summarize the first historical findings and the latest advances, showing membrane tension as an important physical parameter in cell biology. We also discuss how this parameter must be better integrated and we propose experimental approaches for key unanswered questions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)