Expression of innate immune complement regulators on brain epithelial cells during human bacterial meningitis

BACKGROUND: In meningitis, the cerebrospinal fluid contains high levels of innate immune molecules (e.g. complement) which are essential to ward off the infectious challenge and to promote the infiltration of phagocytes (neutrophils, monocytes). However, epithelial cells of either the ependymal layer, one of the established niche for adult neural stem cells, or of the choroid plexus may be extremely vulnerable to bystander attack by cytotoxic and cytolytic complement components. METHODS: In this study, we assessed the capacity of brain epithelial cells to express membrane-bound complement regulators (ie, CD35, CD46, CD55 and CD59) in vitro and in situ by immunostaining of control and meningitis human brain tissue sections. RESULTS: Double immunofluorescence experiments for ependymal cell markers (GFAP, S100, ZO-1, E-cadherin) and complement regulators indicated that the human ependymal cell line model was strongly positive for CD55, CD59 compared to weak stainings for CD46 and CD35. In tissues, we found that CD55 was weakly expressed in control choroid plexus and ependyma but was abundantly expressed in meningitis. Anti-CD59 stained both epithelia in apical location while increased CD59 staining was solely demonstrated in inflamed choroid plexus. CD46 and CD35 were not detected in control tissue sections. Conversely, in meningitis, the ependyma, subependyma and choroid plexus epithelia were strongly stained for CD46 and CD35. CONCLUSION: This study delineates for the first time the capacity of brain ependymal and epithelial cells to respond to and possibly sustain the innate complement-mediated inflammatory insult

Photovoltaic Water Pumping: Comparison Between Direct and Lithium Battery Solutions

[EN] This work presents the conversion of a photovoltaic water pumping system (PVWPS) to its corresponding battery-based solution, while maintaining the components of the PVWPS facility and adding the power converter needed to manage the operation of a lithium-ion battery. A complete analysis of the direct PVWPS is performed based on the values obtained by the monitoring system developed for the installation. The efficiencies and performance ratios of the various elements of the facility are calculated, as well as other relevant factors (such as irradiance thresholds). The dependence of some variables on the solar resource is analyzed to model the system. A similar study is carried out in the battery-based solution and a comparative analysis of the two modes of operation is then performed to find which aspects could be improved in the battery-based solution to increase the pumping time and total daily pumped volume. The results presented demonstrate the benefits of including a battery (reduction in start/stop cycles and improved performance on cloudy days). Aspects that can be improved to make the battery-based solution more efficient and achieve better results are suggested.This work was supported in part by the Universitat Politecnica de Valencia (UPV-Program ADSIDEO-cooperation 2017-Project Characterization of sustainable systems for the pumping of water for human consumption in developing regions or refugee camps in Kenya through the implementation of isolated photovoltaic systems with new generation lithium-ion batteries), and in part by the International Organization for Migration under Contract entitled "Design, Assembly, Testing and Documenting Parameters of Solar and Ion-Lithium Energy Storage Equipment for Powering of Water Pumps under Laboratory Conditions'' from the Bureau for Humanitarian Assistance-USAID.Orts-Grau, S.; González Altozano, P.; Gimeno Sales, FJ.; Balbastre Peralta, I.; Martínez Márquez, CI.; Gasque Albalate, M.; Segui-Chilet, S. (2021). Photovoltaic Water Pumping: Comparison Between Direct and Lithium Battery Solutions. IEEE Access. 9:101147-101163. https://doi.org/10.1109/ACCESS.2021.3097246101147101163

Shocklets and Short Large Amplitude Magnetic Structures (SLAMS) in the high Mach foreshock of Venus

Shocklets and short large-amplitude magnetic structures (SLAMS) are steepened magnetic fluctuations commonly found in Earth's upstream foreshock. Here we present Venus Express observations from the 26th of February 2009 establishing their existence in the steady-state foreshock of Venus, building on a past study which found SLAMS during a substantial disturbance of the induced magnetosphere. The Venusian structures were comparable to those reported near Earth. The 2 Shocklets had magnetic compression ratios of 1.23 and 1.34 with linear polarization in the spacecraft frame. The 3 SLAMS had ratios between 3.22 and 4.03, two of which with elliptical polarization in the spacecraft frame. Statistical analysis suggests SLAMS coincide with unusually high solar wind Alfvén mach-number at Venus (12.5, this event). Thus, while we establish Shocklets and SLAMS can form in the stable Venusian foreshock, they may be rarer than at Earth. We estimate a lower limit of their occurrence rate of ≳14%

Complement activation in multiple sclerosis plaques: an immunohistochemical analysis

INTRODUCTION: Inflammation and complement activation are firmly implicated in the pathology of multiple sclerosis; however, the extent and nature of their involvement in specific pathological processes such as axonal damage, myelin loss and disease progression remains uncertain. This study aims to bring clarity to these questions. RESULTS: We describe a detailed immunohistochemical study to localise a strategically selected set of complement proteins, activation products and regulators in brain and spinal cord tissue of 17 patients with progressive multiple sclerosis and 16 control donors, including 9 with central nervous system disease. Active, chronic active and chronic inactive multiple sclerosis plaques (35 in total) and non-plaque areas were examined.Multiple sclerosis plaques were consistently positive for complement proteins (C3, factor B, C1q), activation products (C3b, iC3b, C4d, terminal complement complex) and regulators (factor H, C1-inhibitor, clusterin), suggesting continuing local complement synthesis, activation and regulation despite the absence of other evidence of ongoing inflammation. Complement staining was most apparent in plaque and peri-plaque but also present in normal appearing white matter and cortical areas to a greater extent than in control tissue. C1q staining was present in all plaques suggesting a dominant role for the classical pathway. Cellular staining for complement components was largely restricted to reactive astrocytes, often adjacent to clusters of microglia in close apposition to complement opsonised myelin and damaged axons. CONCLUSIONS: The findings demonstrate the ubiquity of complement involvement in multiple sclerosis, suggest a pathogenic role for complement contributing to cell, axon and myelin damage and make the case for targeting complement for multiple sclerosis monitoring and therapy

670-nm light treatment reduces complement propagation following retinal degeneration

AIM: Complement activation is associated with the pathogenesis of age-related macular degeneration (AMD). We aimed to investigate whether 670-nm light treatment reduces the propagation of complement in a light-induced model of atrophic AMD. METHODS: Sprague–Dawley (SD) rats were pretreated with 9 J/cm(2) 670-nm light for 3 minutes daily over 5 days; other animals were sham treated. Animals were exposed to white light (1,000 lux) for 24 h, after which animals were kept in dim light (5 lux) for 7 days. Expression of complement genes was assessed by quantitative polymerase chain reaction (qPCR), and immunohistochemistry. Counts were made of C3-expressing monocytes/microglia using in situ hybridization. Photoreceptor death was also assessed using outer nuclear layer (ONL) thickness measurements, and oxidative stress using immunohistochemistry for 4-hydroxynonenal (4-HNE). RESULTS: Following light damage, retinas pretreated with 670-nm light had reduced immunoreactivity for the oxidative damage maker 4-HNE in the ONL and outer segments, compared to controls. In conjunction, there was significant reduction in retinal expression of complement genes C1s, C2, C3, C4b, C3aR1, and C5r1 following 670 nm treatment. In situ hybridization, coupled with immunoreactivity for the marker ionized calcium binding adaptor molecule 1 (IBA1), revealed that C3 is expressed by infiltrating microglia/monocytes in subretinal space following light damage, which were significantly reduced in number after 670 nm treatment. Additionally, immunohistochemistry for C3 revealed a decrease in C3 deposition in the ONL following 670 nm treatment. CONCLUSIONS: Our data indicate that 670-nm light pretreatment reduces lipid peroxidation and complement propagation in the degenerating retina. These findings have relevance to the cellular events of complement activation underling the pathogenesis of AMD, and highlight the potential of 670-nm light as a non-invasive anti-inflammatory therapy

Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes.

There are currently limited Food and Drug Administration (FDA)-approved drugs and vaccines for the treatment or prevention of Coronavirus Disease 2019 (COVID-19). Enhanced understanding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and pathogenesis is critical for the development of therapeutics. To provide insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2, we performed single-cell (sc) RNA sequencing (RNA-seq) of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures over a time course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target at the onset of infection, which we confirmed by electron and immunofluorescence microscopy. Over the course of infection, the cell tropism of SARS-CoV-2 expands to other epithelial cell types including basal and club cells. Infection induces cell-intrinsic expression of type I and type III interferons (IFNs) and interleukin (IL)-6 but not IL-1. This results in expression of interferon-stimulated genes (ISGs) in both infected and bystander cells. This provides a detailed characterization of genes, cell types, and cell state changes associated with SARS-CoV-2 infection in the human airway

Adrenal adenomatoid tumor in a patient with human immunodeficiency virus

We present the clinical course of a patient with human immunodeficiency virus and an adrenal adenomatoid tumor (AAT). We describe the clinical course and laboratory, radiographic, and microscopic findings of a patient with human immunodeficiency virus (HIV) and an adenomatoid tumor of the right adrenal gland. A review of the literature was also done via electronic searches through PubMed for articles from 1965 to 2008 that contained the following search terms, adenomatoid tumor limited to the English language only. A 22 year-old African-American male with HIV was incidentally found to have a hypermetabolic right adrenal mass. The patient underwent laparoscopic adrenalectomy and the mass had morphological and immunohistochemical features that were consistent with an AAT. A review of the medical literature reveals that almost all cases of AAT were in male patients (96%) with a mean age of 41±11 years (range=22–64) with no significant difference in laterality (right side=46%, left side=50%, unknown=4%). AAT have an average size of 4.2±3.5 cm (range=0.5–14.3 cm). Pre-operative imaging studies do not appear to be able to reliably distinguish AAT from other types of adrenocortical tumors. For reasons that require further research, AAT typically occur in male patients and may be associated with immunosuppression. AAT can be safely removed laparoscopically with no evidence of long-term recurrence even with tumor extension beyond the adrenal capsule