Heme Peroxidases at Unperturbed and Inflamed Mucous Surfaces

In our organism, mucous surfaces are important boundaries against the environmental milieu with defined fluxes of metabolites through these surfaces and specific rules for defense reactions. Major mucous surfaces are formed by epithelia of the respiratory system and the digestive tract. The heme peroxidases lactoperoxidase (LPO), myeloperoxidase (MPO), and eosinophil peroxidase (EPO) contribute to immune protection at epithelial surfaces and in secretions. Whereas LPO is secreted from epithelial cells and maintains microbes in surface linings on low level, MPO and EPO are released from recruited neutrophils and eosinophils, respectively, at inflamed mucous surfaces. Activated heme peroxidases are able to oxidize (pseudo)halides to hypohalous acids and hypothiocyanite. These products are involved in the defense against pathogens, but can also contribute to cell and tissue damage under pathological conditions. This review highlights the beneficial and harmful functions of LPO, MPO, and EPO at unperturbed and inflamed mucous surfaces. Among the disorders, special attention is directed to cystic fibrosis and allergic reactions.

Galantamine prevents and reverses neuroimmune induction and loss of adult hippocampal neurogenesis following adolescent alcohol exposure

Background Binge ethanol exposure during adolescence reduces hippocampal neurogenesis, a reduction which persists throughout adulthood despite abstinence. This loss of neurogenesis, indicated by reduced doublecortin+ immunoreactivity (DCX+IR), is paralleled by an increase in hippocampal proinflammatory signaling cascades. As galantamine, a cholinesterase inhibitor, has anti-inflammatory actions, we tested the hypothesis that galantamine would prevent (study 1) or restore (study 2) AIE induction of proinflammatory signals within the hippocampus as well as AIE-induced loss of hippocampal neurogenesis. Methods Galantamine (4 mg/kg) or vehicle (saline) was administered to Wistar rats during adolescent intermittent ethanol (AIE; 5.0 g/kg ethanol, 2 days on/2 days off, postnatal day [P] 25-54) (study 1, prevention) or after AIE during abstinent maturation to adulthood (study 2, restoration). Results Results indicate AIE reduced DCX+IR and induced cleaved caspase3 (Casp3) in DCX-expressing immature neurons. Excitingly, AIE induction of activated Casp3 in DCX-expressing neurons is both prevented and reversed by galantamine treatment, which also resulted in prevention and restoration of neurogenesis (DCX+IR). Similarly, galantamine prevented and/or reversed AIE induction of proinflammatory markers, including the chemokine (C-C motif) ligand 2 (CCL2), cyclooxygenase-2 (COX-2), and high mobility group box 1 (HMGB1) protein, suggesting that AIE induction of proinflammatory signaling mediates both cell death cascades and hippocampal neurogenesis. Interestingly, galantamine treatment increased Ki67+IR generally as well as increased pan-Trk expression specifically in AIE-treated rats but failed to reverse AIE induction of NADPH-oxidase (gp91phox). Conclusions Collectively, our studies suggest that (1) loss of neurogenesis after AIE is mediated by persistent induction of proinflammatory cascades which drive activation of cell death machinery in immature neurons, and (2) galantamine can prevent and restore AIE disruptions in the hippocampal environmental milieu to then prevent and restore AIE-mediated loss of neurogenesis.

Does Covera-19 know ‘when to hold ‘em or ‘when to fold ‘em? A translational thought experiment

The function of proteins depends on their structure. The structural integrity of proteins is dynamic and depends on interacting nearby neighboring moieties that influence their properties and induce folding and structural changes. The conformational changes induced by these nearby neighbors in the micro-environmental milieu at that moment are guided by chemical or electrical bonding attractions.There are few literature references that describe the potential for environmental milieu changes to disfavor SARS-CoV-2 attachment to a receptor for survival outside of a host. There are many studies on the effects of pH (acid and base balance) supporting its importance for protein structure and function, but few focus on pH role in extracellular or intracellular protein or actionable requirements of Covera-19.‘Fold ‘em or Hold ‘em’ is seen by the various functions and effects of furin as it seeks an acidic milieu for action or compatible amino acid sequences which is currently aided by its histidine component and the structural changes of proteins as they enter or exit the host. Questions throughout the text are posed to focus on current thoughts as reviewing applicable COVID-19 translational research science in order to understand the complexities of Covid-19.The pH needs of COVID-19 players and its journey through the human host and environment as well as some efficacious readily available repurposed drugs and out-of-the box and easily available treatments are reviewed.

After traumatic brain injury oligodendrocytes regain a plastic phenotype and can become astrocytes

After acute brain injuries various response cascades are evoked that direct the formation of the glial scar. Here, we report that acute lesions associated with a disruption of the blood-brain barrier trigger a re-programming within the oligodendrocyte lineage. In PLP-DsRed1/GFAP-EGFP and PLP-EGFPmem/GFAP-mRFP1 transgenic mice with cortical injuries, we transiently found PLP transgene-labelled cells with activated GFAP promoter activity adjacent to the lesion site. We termed them AO cells, based on their concomitant activity of astro- and oligodendroglial genes. By fate mapping using PLP- and GFAP-split Cre complementation and NG2-CreERT2 mice we observed that major portions of AO cells surprisingly differentiated into astrocytes. Using repeated long-term in vivo two-photon laser-scanning microscopy (2P-LSM) we followed oligodendrocytes after injury. We observed their conversion into astrocytes via the AO cell stage with silencing of the PLP promoter and simultaneous activation of the GFAP promoter. In addition, we provide evidence that this oligodendrocyte-to-astrocyte conversion depends on local cues. At the lesion site higher expression levels of various glial differentiation factors were detected. And indeed, local injection of IL-6 promoted the formation of AO cells. In summary, our findings highlight the plastic potential of oligodendrocytes in acute brain trauma. An altered environmental milieu affects gene expression programs of mature oligodendrocytes and induces a plastic differentiation stage with astrogliogenic potential via transitional AO cells.

Dichotomy in Growth and Invasion From Low to High Grade Glioma Cellular Variants

Glial dysfunction outraging CNS plasticity and integrity results into one of the most dangerous cancer, namely glioma, featuring little median survival period and high recurrence. The hallmark properties of proliferation, invasion and angiogenesis with the infiltrated macrophages in glioma are expected to be tightly coupled or cross-linked, but not definitely related so far. Present study is aimed to find a relationship between this featured quadrangle from lower to higher grades of post-operative glioma tissues and their invading subsets. Elevated Ki67 associated proliferation in lower grades was supported with VEGF dependent angiogenic maintenance which found decrease unlikely in higher grades. In contrast, MMP-2 and 9 associated invasions augmented high in higher grades with dominant presence of CD204+ M2 polarized macrophages and a general increase in global DNMT1 associated methylation. Marked differences found in ECM invading cellular subsets of higher grades showing high proliferative capacity indicating rationally for recurrence, contrasting the nature of gross tumor tissue of same grade. Thus in lower grades the neoplastic lesion is more inclined for its growth while in higher grade more disposed towards tissue wreckage in support with cellular environmental milieu whereas the cellular variants and subsets of invaded cells showed different trends. Therefore, some operational dichotomy or coupling among cellular variants in glioma is active in determining its low to high grade transition and aggressive progression.

Oligodendrocyte lineage cells and depression

Depression is a common mental illness, affecting more than 300 million people worldwide. Decades of investigation have yielded symptomatic therapies for this disabling condition but have not led to a consensus about its pathogenesis. There are data to support several different theories of causation, including the monoamine hypothesis, hypothalamic–pituitary–adrenal axis changes, inflammation and immune system alterations, abnormalities of neurogenesis and a conducive environmental milieu. Research in these areas and others has greatly advanced the current understanding of depression; however, there are other, less widely known theories of pathogenesis. Oligodendrocyte lineage cells, including oligodendrocyte progenitor cells and mature oligodendrocytes, have numerous important functions, which include forming myelin sheaths that enwrap central nervous system axons, supporting axons metabolically, and mediating certain forms of neuroplasticity. These specialized glial cells have been implicated in psychiatric disorders such as depression. In this review, we summarize recent findings that shed light on how oligodendrocyte lineage cells might participate in the pathogenesis of depression, and we discuss new approaches for targeting these cells as a novel strategy to treat depression.

Psychiatric presentations among older people living in low- and middle-income countries

Psychiatric presentations among older people living in low- and middle-income countries (LMICs) and their management pose many challenges. However, population ageing, which is being seen across nearly all countries and cultures and is the most significant social transformation of the twenty-first century, continues to receive limited attention and resources in LMICs. While the syndrome approach (with its inherent clinical heterogeneity) currently employed by international psychiatry is used in LMICs, the differences in environmental milieu mandate a contextual understanding. This chapter reviews common psychiatric presentations among older people with a focus on similarities and differences between LMICs and high-income countries (HICs), in order to achieve a contextual understanding of diagnosis and management across settings. It discusses dementia, mild cognitive impairment (MCI), delirium, late-onset psychosis, depression, anxiety, suicide, and substance use, and highlights issues related to burden of care, culture, and health systems. It emphasizes social, economic, political, and cultural contextual understanding.

Direct Actions in the Czech Environmental Movement

Direct actions constitute an important repertoire of action for environmental movements in Western countries. This article differentiates two ideal types of this repertoire of action: the anarchist concept, which understands direct action in terms of values and as a preferred way of doing things; and the liberal concept, which uses direct action in an instrumental way. Based on my empirical research in post-socialist Czech Republic, the article focuses on debates over environmentalism and, to be more precise, on uses of direct actions by environmental organizations. It explains why the liberal concept was very limited and why direct action as a preferred way of doing things has not become a part of the repertoire of collective action. The article argues that the movement was politically moderate due to a combination of reasons: the very specific historical experience of the Czech environmental movement, which inclines it to use dialogue rather than confrontations with power; the fear of political hostility and marginalization by the state; and the internal dynamics of the environmental milieu.

Embodiment: Spirit, Material– Maternal Dependence, and the Problem of the in utero

Chapter six, in turn, begins to critically read Hegel against Hegel. It reads his notion of spirit (beginning with finite subjectivity) in terms of the concept of nature established in Part I. The chapter argues that the problem nature poses for subjective spirit presents itself in two ‘symptomatic’ moments of Hegel’s anthropology. First, in his analysis of subjectivity’s embodiment, its “primordial grasp on the world.” Second, in his analysis of the fetus-mother dynamic. Reconstructing both analyses, the chapter argues that they reveal spirit as over-immersed in exterior determinations and unable to assert itself as an autarkic center, as subject. Over-immersion in its environmental milieu, the chapter argues, is the problem of spirit’s origins, i.e. the problem of nature. It must move beyond this displacement in externality. However, there are no facile guarantees that this will transpire in the concrete actuality of life. Therefore, the origin of spirit is a developmental confrontation with nature and a protracted attempt to break with it.

Overview of Trends in the Application of Metagenomic Techniques in the Analysis of Human Enteric Viral Diversity in Africa’s Environmental Regimes

There has been an increase in the quest for metagenomics as an approach for the identification and study of the diversity of human viruses found in aquatic systems, both for their role as waterborne pathogens and as water quality indicators. In the last few years, environmental viral metagenomics has grown significantly and has enabled the identification, diversity and entire genome sequencing of viruses in environmental and clinical samples extensively. Prior to the arrival of metagenomics, traditional molecular procedures such as the polymerase chain reaction (PCR) and sequencing, were mostly used to identify and classify enteric viral species in different environmental milieu. After the advent of metagenomics, more detailed reports have emerged about the important waterborne viruses identified in wastewater treatment plant effluents and surface water. This paper provides a review of methods that have been used for the concentration, detection and identification of viral species from different environmental matrices. The review also takes into consideration where metagenomics has been explored in different African countries, as well as the limitations and challenges facing the approach. Procedures including sample processing, experimental design, sequencing technology, and bioinformatics analysis are discussed. The review concludes by summarising the current thinking and practices in the field and lays bare key issues that those venturing into this field need to consider and address.