Pulsed Electromagnetic Field Stimulation in Osteogenesis and Chondrogenesis: Signaling Pathways and Therapeutic Implications

Mesenchymal stem cells (MSCs) are the main cell players in tissue repair and thanks to their self-renewal and multi-lineage differentiation capabilities, they gained significant attention as cell source for tissue engineering (TE) approaches aimed at restoring bone and cartilage defects. Despite significant progress, their therapeutic application remains debated: the TE construct often fails to completely restore the biomechanical properties of the native tissue, leading to poor clinical outcomes in the long term. Pulsed electromagnetic fields (PEMFs) are currently used as a safe and non-invasive treatment to enhance bone healing and to provide joint protection. PEMFs enhance both osteogenic and chondrogenic differentiation of MSCs. Here, we provide extensive review of the signaling pathways modulated by PEMFs during MSCs osteogenic and chondrogenic differentiation. Particular attention has been given to the PEMF-mediated activation of the adenosine signaling and their regulation of the inflammatory response as key player in TE approaches. Overall, the application of PEMFs in tissue repair is foreseen: (1) in vitro: to improve the functional and mechanical properties of the engineered construct; (2) in vivo: (i) to favor graft integration, (ii) to control the local inflammatory response, and (iii) to foster tissue repair from both implanted and resident MSCs cells.     

In Silico Analysis of the Molecular-Level Impact of SMPD1 Variants on Niemann-Pick Disease Severity

Sphingomyelin phosphodiesterase (SMPD1) is a key enzyme in the sphingolipid metabolism. Genetic SMPD1 variants have been related to the Niemann-Pick lysosomal storage disorder, which has different degrees of phenotypic severity ranging from severe symptomatology involving the central nervous system (type A) to milder ones (type B). They have also been linked to neurodegenerative disorders such as Parkinson and Alzheimer. In this paper, we leveraged structural, evolutionary and stability information on SMPD1 to predict and analyze the impact of variants at the molecular level. We developed the SMPD1-ZooM algorithm, which is able to predict with good accuracy whether variants cause Niemann-Pick disease and its phenotypic severity; the predictor is freely available for download. We performed a large-scale analysis of all possible SMPD1 variants, which led us to identify protein regions that are either robust or fragile with respect to amino acid variations, and show the importance of aromatic-involving interactions in SMPD1 function and stability. Our study also revealed a good correlation between SMPD1-ZooM scores and in vitro loss of SMPD1 activity. The understanding of the molecular effects of SMPD1 variants is of crucial importance to improve genetic screening of SMPD1-related disorders and to develop personalized treatments that restore SMPD1 functionality.     

Unsupervised Segmentation of Stereoscopic Video Objects: Constrained Segmentation Fusion Versus Greedy Active Contours

In this paper, we present a novel memory access reduction scheme (MARS) for two-dimension fast cosine transform (2-D FCT). It targets programmable DSPs with high memory-access latency. It reduces the number of memory accesses by: 1) reducing the number of weighting factors and 2) combining butterflies in vector-radix 2-D FCT pruning diagram from two stages to one stage with an efficient structure. Hardware platform based on general purpose processor is used to verify the effectiveness of the proposed method for vector-radix 2-D FCT pruning implementation. Experimental results validate the benefits of the proposed method with reduced memory access, less clock cycle and fewer memory space compared with the conventional implementation.     

Expression of RCAS1 Correlates with Urothelial Bladder Cancer Malignancy

RCAS1 is a protein that participates in regulation of the tumor microenvironment and its immune responses, all in order to evade the immune system. The aim of this study was to analyze RCAS1 expression in urothelial bladder cancer cells (and in fibroblasts and macrophages of the tumor stroma) and its relationship with the histological pattern of malignancy. Eighty-three postcystectomy patients were enrolled. We analyzed the histological maturity (grade), progress (pT stage), tissue invasion type (TIT), nonclassic differentiation number (NDN), and the ability to metastasize (pN). The expression of RCAS1 protein was analyzed by immunohistochemistry. Indicators of histological malignancy were observed solely in association with the RCAS1 expression in cells in the border parts (BPs) of the tumor. Histological malignancy of the tumor, indicated by the pT and pN, and metastasis-free survival time, correlated significantly with RCAS1 expression in tumor neoplastic cells, whereas malignancy determined by grade, TIT, and NDN correlated with RCAS1 expression in fibroblasts and macrophages in the tumor microenvironment. These findings suggest that the increased RCAS1 expression depends on its cellular source and that RCAS1 expression itself is a component of various signaling pathways. The immune escape occurs within the tumor BPs, where the increase in the RCAS1 expression occurs within tumor cells and stromal cells in its microenvironment. We conclude that the histological pattern of tumor malignancy, indicated by grade, TIT, NDN, pT, and pN is a morphological indicator of immune escape.     

Sperm metabolism is altered during storage by female insects: evidence from two-photon autofluorescence lifetime measurements in bedbugs

We explore the possibility of characterizing sperm cells without the need to stain them using spectral and fluorescence lifetime analyses after multi-photon excitation in an insect model. The autofluorescence emission spectrum of sperm of the common bedbug, Cimex lectularius, was consistent with the presence of flavins and NAD(P)H. The mean fluorescence lifetimes showed smaller variation in sperm extracted from the male (tau m, τ_m = 1.54–1.84 ns) than in that extracted from the female sperm storage organ (tau m, τ_m = 1.26–2.00 ns). The fluorescence lifetime histograms revealed four peaks. These peaks (0.18, 0.92, 2.50 and 3.80 ns) suggest the presence of NAD(P)H and flavins and show that sperm metabolism can be characterized using fluorescence lifetime imaging. The difference in fluorescence lifetime variation between the sexes is consistent with the notion that female animals alter the metabolism of sperm cells during storage. It is not consistent, however, with the idea that sperm metabolism represents a sexually selected character that provides females with information about the male genotype.     

Histone Methylation Marks on Circulating Nucleosomes as Novel Blood-Based Biomarker in Colorectal Cancer

Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer as potential non-invasive biomarkers, as stable structure in circulation nucleosomes could be valuable sources for detection of cancer-specific alterations in histone modifications. Our interest is in histone methylation marks with a focus on colorectal cancer, one of the leading cancers respective the incidence and mortality. Our previous work included the analysis of trimethylations of lysine 9 on histone 3 (H3K9me3) and of lysine 20 on histone 4 (H4K20me3) by chromatin immuno- precipitation-related PCR in circulating nucleosomes. Here we asked whether global immunologic measurement of histone marks in circulation could be a suitable approach to show their potential as biomarkers. In addition to H3K9me3 and H4K20me3 we also measured H3K27me3 in plasma samples from CRC patients (n = 63) and cancer free individuals (n = 40) by ELISA-based methylation assays. Our results show that of three marks, the amounts of H3K27me3 (p = 0.04) and H4K20me3 (p < 0.001) were significantly lower in CRC patients than in healthy controls. For H3K9me3 similar amounts were measured in both groups. Areas under the curve (AUC) in receiver operating characteristic (ROC) curves indicating the power of CRC detection were 0.620 for H3K27me3, 0.715 for H4K20me3 and 0.769 for the combination of both markers. In conclusion, findings of this preliminary study reveal the potential of blood-based detection of CRC by quantification of histone methylation marks and the additive effect of the marker combination.     

The Reciprocal Influences among Motivation,Personality Traits,and Game Habits for Playing Pokémon GO

This article reports a study exploring motivations of Pokémon Game use, individual differences related to personality traits, and game habits. First, it analyzed Pokémon GO motivations through exploratory factor analysis (EFA) by administering online the Pokémon GO Motivational Scale to a group of Italian gamers (N = 560). Successively, a Confirmatory Factor Analysis (CFA) was conducted testing three factorial models of Pokémon Game motivations on a selected random sample (N = 310). Results showed a three-factor model of Pokémon GO Game motivations (i.e. Personal Needs, Social Needs and Recreation), accounting for 68.9% of total variance plus a general higher order factor that best fits the data. Individual differences in Pokémon GO motivations and personality traits have been explored showing that high involved Pokémon GO players are introverted, low agreeableness, and conscientiousness people, driven by personal social and recreational needs. Reciprocal influences on motivational involvement, personality, and game habits were discussed.     

Tracking influent inorganic suspended solids through wastewater treatment plants.

From an experimental and theoretical investigation of the continuity of influent inorganic suspended solids (ISS) along the links connecting the primary settling tank (PST), fully aerobic or N removal activated sludge (AS) and anaerobic and aerobic sludge digestion unit operations, it was found that the influent wastewater (fixed) ISS concentration is conserved through primary sludge anaerobic digestion, activated sludge and aerobic digestion unit operations. However, the measured ISS flux at different stages through a series of wastewater treatment plant (WWTP) unit operations is not equal to the influent ISS flux, because the ordinary heterotrophic organisms (OHO) biomass contributes to the ISS flux by differing amounts depending on the active fraction of the VSS solids at that stage.     

Prominent consequences of role stress: A meta-analytic review.

Role stress has received a lot of research attention in psychological, sociological, and organizational studies over the last several decades. Based on a literature review of about 300 journal articles, this article examines prominent consequences of role stress. Specific focus is on researching differences in relationships between facets of role stress (i.e., role ambiguity, role conflict, and role overload) and frequently cited consequences using techniques of meta-analysis. Findings indicate that each role stress facet has a different relationship with the eight consequences studied. Role stress research can benefit from looking at each facet individually in addition to role stress generally. (PsycINFO Database Record (c) 2010 APA, all rights reserved)