Mutations in PINK1 and Parkin are two of the main causes of recessive early-onset Parkinson’s disease (PD). We generated human induced pluripotent stem cells (hiPSCs) from fibroblasts of a ...64-year-old male patient with a homozygous ILE368ASN mutation in PINK1, who experienced disease onset at 33 years, and from fibroblasts of a 61-year-old female patient heterozygous for the R275W mutation in Parkin, who experienced disease onset at 44 years. Array comparative genomic hybridization (aCGH) determined genotypic variation in each line. The cell lines were successfully used to generate midbrain dopaminergic neurons, the neuron type primarily affected in PD.
Parkinson's disease (PD) is the second-most prevalent neurodegenerative disorder, characterized by the loss of dopaminergic neurons (mDA) in the midbrain. The underlying mechanisms are only partly ...understood and there is no treatment to reverse PD progression. Here, we investigated the disease mechanism using mDA neurons differentiated from human induced pluripotent stem cells (hiPSCs) carrying the ILE368ASN mutation within the PINK1 gene, which is strongly associated with PD. Single-cell RNA sequencing (RNAseq) and gene expression analysis of a PINK1-ILE368ASN and a control cell line identified genes differentially expressed during mDA neuron differentiation. Network analysis revealed that these genes form a core network, members of which interact with all known 19 protein-coding Parkinson's disease-associated genes. This core network encompasses key PD-associated pathways, including ubiquitination, mitochondrial function, protein processing, RNA metabolism, and vesicular transport. Proteomics analysis showed a consistent alteration in proteins of dopamine metabolism, indicating a defect of dopaminergic metabolism in PINK1-ILE368ASN neurons. Our findings suggest the existence of a network onto which pathways associated with PD pathology converge, and offers an inclusive interpretation of the phenotypic heterogeneity of PD.
The benefits of inspiratory muscle training (IMT) have been demonstrated in patients with cardiovascular diseases (CVD); however, the optimal training intensity is not yet fully clarified. The ...purpose of this study was to review the impact of IMT intensity on respiratory muscle strength, functional and exercise capacity, pulmonary function, and quality of life in patients with CVD. This systematic review was carried out according to PRISMA statement and registered in the PROSPERO database (review protocol: CRD42023442378). Randomized controlled trials were retrieved on 3 July 2023 in the following electronic databases: Web of Science, PubMed, EMBASE, and SCOPUS. Studies were included if they assessed the impact of isolated IMT on CVD patients in comparison with sham, different intensities and/or intervention groups. Eight studies were included for final analysis; IMT consistently led to significantly greater improvements in inspiratory muscle strength compared to control (CON) groups. The intensity of IMT varied in the studies based on different percentages of maximal inspiratory pressure (MIP), ranging from 25% to 60% of MIP. The time of intervention ranged from 4 to 12 weeks. Despite this variability, the studies collectively suggested that IMT is beneficial for enhancing CVD patients’ conditions. However, the optimal intensity range for benefits appeared to vary, and no single intensity emerged as universally superior across all studies.
Abstract
Microglia, the immune cells of the brain, are a focus of studies in neurodegenerative diseases. Similarly, research about induced pluripotent stem cell (iPSC)-derived whole brain and ...region-specific organoids is increasing. In organoids, the complexity of the culture systems increases, mimicking better the actual scenario in the human brain. Furthermore, animal models do not always recapitulate human neurodegeneration, and they imply more ethical concerns compared to organoid systems. Recently the integration of iPSC-derived microglia into brain organoids has been achieved, and on-chip technologies have been focusing on microglia interaction with neural cells. In this review, we discuss the achievements on integrating microglia into brain organoids. We study the cell organization, ultrastructure and cell signalling of microglia with respect to other cell types in organoids as well as their functionality in the system. A particular focus here is on the interaction with the midbrain and dopaminergic systems. Finally, we discuss the achievements until now concerning neuroinflammation and disease modelling, and the possible therapeutic approaches targeting microglia and neuroinflammation in 3D systems.
This is a short and accessible introduction to the complex and evolving debates around queer theories, advocating for their critical role in academia and society. The book traces the roots of queer ...theories and argues that Foucault owed an important debt to other European authors including the feminist and homosexual liberation movements of the 1960s–1970s and the anticolonial movements of the 1950s.
Going beyond a simple introduction to queer theories, this book situates them firmly in a European and Italian context to offer a crucial set of arguments in defence of LGBTQI+ rights, in defence of the freedom of teaching and research, and in defence of a radical idea of democracy. The narrative of the book is divided into three short chapters which can be read independently or in sequence. The first chapter argues that queer theories are rooted in the critical philosophical tradition, the second presents a critique of heterosexism and the binary inherent to the gender-sex-sexual orientation system, and the third chapter sketches a history of the queer debate. The book offers a useful typology of queer theories by sorting them into three basic paradigms: Freudo-Marxism, radical constructivism, and antisocial and affective theories, clarifying the complexities of the nature of the debates for undergraduates.
The book is both accessible and original, and is suitable for both specialist researchers and undergraduate students new to queer studies. It will be essential reading for those studying philosophy, sexuality studies and gender studies.
Alkaptonuria (AKU) is an ultra-rare metabolic disease caused by the accumulation of homogentisic acid (HGA), an intermediate product of phenylalanine and tyrosine degradation. AKU patients carry ...variants within the gene coding for homogentisate-1,2-dioxygenase (HGD), which are responsible for reducing the enzyme catalytic activity and the consequent accumulation of HGA and formation of a dark pigment called the ochronotic pigment. In individuals with alkaptonuria, ochronotic pigmentation of connective tissues occurs, leading to inflammation, degeneration, and eventually osteoarthritis. The molecular mechanisms underlying the multisystemic development of the disease severity are still not fully understood and are mostly limited to the metabolic pathway segment involving HGA. In this view, untargeted metabolomics of biofluids in metabolic diseases allows the direct investigation of molecular species involved in pathways alterations and their interplay. Here, we present the untargeted metabolomics study of AKU through the nuclear magnetic resonance of urine from a cohort of Italian patients; the study aims to unravel molecular species and mechanisms underlying the AKU metabolic disorder. Dysregulation of metabolic pathways other than the HGD route and new potential biomarkers beyond homogentisate are suggested, contributing to a more comprehensive molecular signature definition for AKU and the development of future adjuvant treatment.
Utilizing plant-based resources, particularly their by-products, aligns with sustainability principles and circular bioeconomy, contributing to environmental preservation. The therapeutic potential ...of plant extracts is garnering increasing interest, and this study aimed to demonstrate promising outcomes from an extract obtained from an underutilized plant waste.
, an invasive macroalga found in the Orbetello Lagoon, thrives in eutrophic conditions, forming persistent mats covering approximately 400 hectares since 2005. The biomass of
undergoes mechanical harvesting and is treated as waste, requiring significant human efforts and economic resources-A critical concern for municipalities. Despite posing challenges to local ecosystems, the study identified
as a natural source of bioactive metabolites. Phytochemical characterization revealed lipids, amino acids, and other compounds with potential anti-inflammatory activity in
extract. In vitro assays with LPS-stimulated RAW 264.7 and TNF-α/IFN-γ-stimulated HaCaT cells showed the extract inhibited reactive oxygen species (ROS), nitric oxide (NO), and prostaglandin E2 (PGE2) productions, and reduced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions via NF-κB nuclear translocation, in RAW 264.7 cells. It also reduced chemokines (TARC/CCL17, RANTES/CCL5, MCP-1/CCL2, and IL-8) and the cytokine IL-1β production in HaCaT cells, suggesting potential as a therapeutic candidate for chronic diseases like atopic dermatitis. Finally, in silico studies indicated palmitic acid as a significant contributor to the observed effect. This research not only uncovered the untapped potential of
but also laid the foundation for its integration into the circular bioeconomy, promoting sustainable practices, and innovative applications across various industries.
Iron-based superconductors are under study for their potential for high-field applications due to their excellent superconducting properties such as low structural anisotropy, large upper critical ...fields and low field dependence of the critical current density. Between them, Fe(Se,Te) is simple to be synthesized and can be fabricated as a coated conductor through laser ablation on simple metallic templates. In order to make all the steps simple and fast, we have applied the spark plasma sintering technique to synthesize bulk Fe(Se,Te) to obtain quite dense polycrystals in a very short time. The resulting polycrystals are very well connected and show excellent superconducting properties, with a critical temperature onset of about 16 K. In addition, when used as targets for pulsed laser ablation, good thin films are obtained with a critical current density above 105 A cm−2 up to 16 T.
Queer Theories Bernini, Lorenzo; Baldo, Michela; Basile, Elena
2020
eBook
Going beyond a simple introduction to queer theories, this book situates them firmly in a European and Italian context to offers a crucial set of arguments in defence of LGBTQI+ rights, in defence of ...the freedom of teaching and research, and in defence of a radical idea of democracy.
Utilizing plant-based resources, particularly their by-products, aligns with sustainability principles and circular bioeconomy, contributing to environmental preservation. The therapeutic potential ...of plant extracts is garnering increasing interest, and this study aimed to demonstrate promising outcomes from an extract obtained from an underutilized plant waste. Chaetomorpha linum , an invasive macroalga found in the Orbetello Lagoon, thrives in eutrophic conditions, forming persistent mats covering approximately 400 hectares since 2005. The biomass of C. linum undergoes mechanical harvesting and is treated as waste, requiring significant human efforts and economic resources—A critical concern for municipalities. Despite posing challenges to local ecosystems, the study identified C. linum as a natural source of bioactive metabolites. Phytochemical characterization revealed lipids, amino acids, and other compounds with potential anti-inflammatory activity in C. linum extract. In vitro assays with LPS-stimulated RAW 264.7 and TNF-α/IFN-γ-stimulated HaCaT cells showed the extract inhibited reactive oxygen species (ROS), nitric oxide (NO), and prostaglandin E2 (PGE2) productions, and reduced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions via NF-κB nuclear translocation, in RAW 264.7 cells. It also reduced chemokines (TARC/CCL17, RANTES/CCL5, MCP-1/CCL2, and IL-8) and the cytokine IL-1β production in HaCaT cells, suggesting potential as a therapeutic candidate for chronic diseases like atopic dermatitis. Finally, in silico studies indicated palmitic acid as a significant contributor to the observed effect. This research not only uncovered the untapped potential of C. linum but also laid the foundation for its integration into the circular bioeconomy, promoting sustainable practices, and innovative applications across various industries.
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