Adding Depth to Microplastics

The effects and risks of microplastics correlate with three-dimensional (3D) properties, such as the volume and surface area of the biologically accessible fraction of the diverse particle mixtures as they occur in nature. However, these 3D parameters are difficult to estimate because measurement methods for spectroscopic and visible light image analysis yield data in only two dimensions (2D). The best-existing 2D to 3D conversion models require calibration for each new set of particles, which is labor-intensive. Here we introduce a new model that does not require calibration and compare its performance with existing models, including calibration-based ones. For the evaluation, we developed a new method in which the volumes of environmentally relevant microplastic mixtures are estimated in one go instead of on a cumbersome particle-by-particle basis. With this, the new Barchiesi model can be seen as the most universal. The new model can be implemented in software used for the analysis of infrared spectroscopy and visual light image analysis data and is expected to increase the accuracy of risk assessments based on particle volumes and surface areas as toxicologically relevant metrics

Identification of a geometrically nonlinear micromorphic continuum via granular micromechanics

Describing the emerging macro-scale behavior by accounting for the micro-scale phenomena calls for microstructure-informed continuum models accounting properly for the deformation mechanisms identifiable at the micro-scale. Classical continuum theory, in contrast to the micromorphic continuum theory, is unable to take into account the effects of complex kinematics and distribution of elastic energy in internal deformation modes within the continuum material point. In this paper, we derive a geometrically nonlinear micromorphic continuum theory on the basis of granular mechanics, utilizing grain-scale deformation as the fundamental building block. The definition of objective kinematic descriptors for relative motion is followed by Piola’s ansatz for micro–macro-kinematic bridging and, finally, by a limit process leading to the identification of the continuum stiffness parameters in terms of few micro-scale constitutive quantities. A key aspect of the presented approach is the identification of relevant kinematic measures that describe the deformation of the continuum body and link it to the micro-scale deformation. The methodology, therefore, has the ability to reveal the connections between the micro-scale mechanisms that store elastic energy and lead to particular emergent behavior at the macro-scale

Equilibria determination of elastic articulated duoskelion beams in 2D via a Riks-type algorithm

The overall behavior of an articulated beam structure constituted by elements arranged according to a specific chirality is studied. The structure as a whole, due to its slenderness and geometry, is called duoskelion beam. The name duoskelion is a neologism which is inspired by the Greek word δύοσκέλιον (two-legged). A discrete model for shearable beams, formulated recently, is exploited to investigate its mechanics. A purposely designed numerical scheme, adapting the Riks rationale, is used to calculate large displacement and deformation equilibria of duoskelion beams. Aimed at computing the current step correction, the Riks arc-length method is modified and made more efficient by applying a specific orthogonality condition, defined via the stiffness matrix, to an adapted extrapolation step. The robustness of the resulting scheme and its capability to follow equilibrium branches allows, in principle, for the exploration of the whole set of local energy minima in the introduced space of configurations, by using suitably modulated perturbative external loads. The developed numerical tool can be used to understand the mechanics of duoskelion beams. It is proved that there exists a stable principal equilibrium branch in which only compression is observed for any compression load. Additional stable equilibrium branches are found in compression such that the clamped–clamped compressed beam assumes a characteristic S shape which, upon reaching a critical load, is significantly amplified. A mechanically relevant stable equilibrium is also found in extension, being observed the S-shaped configuration experimentally found in Misra et al. (2020)

Mitochondrial translocation of APE1 relies on the MIA pathway

APE1 is a multifunctional protein with a fundamental role in repairing nuclear and mitochondrial DNA lesions caused by oxidative and alkylating agents. Unfortunately, comprehensions of the mechanisms regulating APE1 intracellular trafficking are still fragmentary and contrasting. Recent data demonstrate that APE1 interacts with the mitochondrial import and assembly protein Mia40 suggesting the involvement of a redox-assisted mechanism, dependent on the disulfide transfer system, to be responsible of APE1 trafficking into the mitochondria. The MIA pathway is an import machinery that uses a redox system for cysteine enriched proteins to drive them in this compartment. It is composed by two main proteins: Mia40 is the oxidoreductase that catalyzes the formation of the disulfide bonds in the substrate, while ALR reoxidizes Mia40 after the import. In this study, we demonstrated that: (i) APE1 and Mia40 interact through disulfide bond formation; and (ii) Mia40 expression levels directly affect APE1's mitochondrial translocation and, consequently, play a role in the maintenance of mitochondrial DNA integrity. In summary, our data strongly support the hypothesis of a redox-assisted mechanism, dependent on Mia40, in controlling APE1 translocation into the mitochondrial inner membrane space and thus highlight the role of this protein transport pathway in the maintenance of mitochondrial DNA stability and cell survival

Presence and fate of microplastics in the water sources: focus on the role of wastewater and drinking water treatment plants

Microplastics are nowadays considered as ubiquitous pollutants since have been found widespread in all environmental compartments, particularly in the water sources. In the urban water cycle, the drinking water treatment plants and the wastewater treatment plants are the first and last barriers to microplastics pollution, respectively. The present work aims at presenting the information available on microplastic presence in the urban water cycle, reporting and linking what is known at the different stages. Focus is on the water sources and on the role of the water treatment plants as source and control of microplastics pollution. Aspects evaluated are microplastics abundance, characterization in terms of morphology, size and polymer composition, spatial and temporal variations, factors influencing their distribution and abundance, effects of treatments on their removal. Up to now there is no common framework for microplastics collection, sample pre-treatment, identification, quantification and classification. Data comparison is hindered due to the various analytical protocols implemented; hence the conclusions driven are mostly indicative or of very local significance. The available information is not evenly distributed among the urban water cycle components. For the establishment of proper microplastics pollution control strategies, the relative role of wastewater and drinking water treatment plants needs to be better deepened in terms of both quantity and quality effects. All these aspects are afforded in the present review which is based on the more recent data published by the specialized literature

Mitochondrial apurinic/apyrimidinic endonuclease 1 enhances mtDNA repair contributing to cell proliferation and mitochondrial integrity in early stages of hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the leading cause of primary liver cancers. Surveillance of individuals at specific risk of developing HCC, early diagnostic markers, and new therapeutic approaches are essential to obtain a reduction in disease-related mortality. Apurinic/apyrimidinic endonuclease 1 (APE1) expression levels and its cytoplasmic localization have been reported to correlate with a lower degree of differentiation and shorter survival rate. The aim of this study is to fully investigate, for the first time, the role of the mitochondrial form of APE1 in HCC. Methods: As a study model, we analyzed samples from a cohort of patients diagnosed with HCC who underwent surgical resection. Mitochondrial APE1 content, expression levels of the mitochondrial import protein Mia40, and mtDNA damage of tumor tissue and distal non-tumor liver of each patient were analyzed. In parallel, we generated a stable HeLa clone for inducible silencing of endogenous APE1 and re-expression of the recombinant shRNA resistant mitochondrially targeted APE1 form (MTS-APE1). We evaluated mtDNA damage, cell growth, and mitochondrial respiration. Results: APE1's cytoplasmic positivity in Grades 1 and 2 HCC patients showed a significantly higher expression of mitochondrial APE1, which accounted for lower levels of mtDNA damage observed in the tumor tissue with respect to the distal area. In the contrast, the cytoplasmic positivity in Grade 3 was not associated with APE1's mitochondrial accumulation even when accounting for the higher number of mtDNA lesions measured. Loss of APE1 expression negatively affected mitochondrial respiration, cell viability, and proliferation as well as levels of mtDNA damage. Remarkably, the phenotype was efficiently rescued in MTS-APE1 clone, where APE1 is present only within the mitochondrial matrix. Conclusions: Our study confirms the prominent role of the mitochondrial form of APE1 in the early stages of HCC development and the relevance of the non-nuclear fraction of APE1 in the disease progression. We have also confirmed overexpression of Mia40 and the role of the MIA pathway in the APE1 import process. Based on our data, inhibition of the APE1 transport by blocking the MIA pathway could represent a new therapeutic approach for reducing mitochondrial metabolism by preventing the efficient repair of mtDNA

Microplastics Determination with μ-Raman: Potential and Practical Aspects

Drinking water is the result of a chain of treatments aimed at purifying the water source from normed pollutants. However, thanks to the increasing analytical power of the available techniques, more pollutants of concern are being discovered both in the water source and in drinking water. In order to keep the drinking water as safe as possible, such pollutants need to be identified in terms of associated risk and fate in the drinking water treatment plants (DWTPs). Among such pollutants, Micoplastics (MPs) raise concern due to their unknown associated risk and their widspread presence and persistance. The European Union has addressed such concern imposing the definition of a method for MPs analysis by 2024 and their monitoring up to 2029. This work aims therefore at shedding light on the potential and practical aspects linked to the use of μ-Raman for the routine analysis of MPs in drinking water

Effects of caspofungin against Candida guilliermondii and Candida parapsilosis.

The in vitro activity of caspofungin (CAS) was investigated against 28 yeast isolates belonging to Candida albicans (n = 5), Candida guilliermondii (n = 10), and Candida parapsilosis (n = 13). CAS MICs obtained by broth dilution and Etest methods clearly showed a rank order of susceptibility to the echinocandin compound with C. albicans > C. parapsilosis > C. guilliermondii. Similarly, time-kill assays performed on selected isolates showed that CAS was fungistatic against C. albicans and C. parapsilosis, while it did not exert any activity against C. guilliermondii. In a murine model of systemic candidiasis, CAS given at doses as low as 1 mg/kg of body weight/day was effective at reducing the kidney burden of mice infected with either C. albicans or C. guilliermondii isolates. Depending on the isolate tested, mice infected with C. parapsilosis responded to CAS given at 1 and/or 5 mg/kg/day. However, the overall CFU reduction for C. guilliermondii and C. parapsilosis was approximately 100-fold less than that for C. albicans. Our study shows that CAS was active in experimental systemic candidiasis due to C. guilliermondii and C. parapsilosis, but this activity required relatively high drug dosages

Capecitabine and Temozolomide (CAPTEM) in advanced neuroendocrine neoplasms (NENs): a systematic review and pooled analysis

Background Retrospective studies and single center experiences suggest a role of capecitabine combined with temozolomide (CAPTEM) in neuroendocrine tumors (NENs). Methods We performed a systematic review to assess the efficacy and safety of CAPTEM in patients affected with NENs, with the aim to better clarify the role of this regimen in the therapeutic algorithm of NENs. Results A total of 42 articles and 1818 patients were included in our review. The overall disease control rate was 77% (range 43.5%-100%). The median progression free survival ranged from 4 to 38.5 months, while the median overall survival ranged from 8 to 103 months. Safety analysis showed an occurrence of G3-G4 toxicities in 16.4% of the entire population. The most common toxicities were hematological (27.2%), gastrointestinal (8.3%,) and cutaneous (3.2%). Conclusion This systematic review demonstrated that CAPTEM was an effective and relatively safe treatment for patients with advanced well-moderate differentiated NENs of gastroenteropancreatic, lung and unknown origin

Starch Synthesis in Ostreococcus tauri: The Starch-Binding Domains of Starch Synthase III-B Are Essential for Catalytic Activity

Starch is the major energy storage carbohydrate in photosynthetic eukaryotes. Several enzymes are involved in building highly organized semi-crystalline starch granules, including starch-synthase III (SSIII), which is widely conserved in photosynthetic organisms. This enzyme catalyzes the extension of the α-1,4 glucan chain and plays a regulatory role in the synthesis of starch. Interestingly, unlike most plants, the unicellular green alga Ostreococcus tauri has three SSIII isoforms. In the present study, we describe the structure and function of OsttaSSIII-B, which has a similar modular organization to SSIII in higher plants, comprising three putative starch-binding domains (SBDs) at the N-terminal region and a C-terminal catalytic domain (CD). Purified recombinant OsttaSSIII-B displayed a high affinity toward branched polysaccharides such as glycogen and amylopectin, and to ADP-glucose. Lower catalytic activity was detected for the CD lacking the associated SBDs, suggesting that they are necessary for enzyme function. Moreover, analysis of enzyme kinetic and polysaccharide-binding parameters of site-directed mutants with modified conserved aromatic amino acid residues W122, Y124, F138, Y147, W279, and W304, belonging to the SBDs, revealed their importance for polysaccharide binding and SS activity. Our results suggest that OT_ostta13g01200 encodes a functional SSIII comprising three SBD domains that are critical for enzyme function