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Virus-associated chronic inflammation may contribute to autoimmunity in a number of diseases. In the brain, autoimmune encephalitis appears related to fluctuating reactivation states of neurotropic viruses. In addition, viral miRNAs and proteins can be transmitted via exosomes, which constitute novel but highly relevant mediators of cellular communication. The current study questioned the role of HSV-1-encoded and host-derived miRNAs in cerebrospinal fluid (CSF)-derived exosomes, enriched from stress-induced neuroinflammatory diseases, mainly subarachnoid hemorrhage (SAH), psychiatric disorders (AF and SZ), and various other neuroinflammatory diseases. The results were compared with CSF exosomes from control donors devoid of any neuroinflammatory pathology. Serology proved positive, but variable immunity against herpesviruses in the majority of patients, except controls. Selective ultrastructural examinations identified distinct, herpesvirus-like particles in CSF-derived lymphocytes and monocytes. The likely release of extracellular vesicles and exosomes was most frequently observed from CSF monocytes. The exosomes released were structurally similar to highly purified stem-cell-derived exosomes. Exosomal RNA was quantified for HSV-1-derived miR-H2-3p, miR-H3-3p, miR-H4-3p, miR-H4-5p, miR-H6-3p, miR-H27 and host-derived miR-21-5p, miR-146a-5p, miR-155-5p, and miR-138-5p and correlated with the oxidative stress chemokine IL-8 and the axonal damage marker neurofilament light chain (NfL). Replication-associated miR-H27 correlated with neuronal damage marker NfL, and cell-derived miR-155-5p correlated with oxidative stress marker IL-8. Elevated miR-138-5p targeting HSV-1 latency-associated ICP0 inversely correlated with lower HSV-1 antibodies in CSF. In summary, miR-H27 and miR-155-5p may constitute neuroinflammatory markers for delineating frequent and fluctuating HSV-1 replication and NfL-related axonal damage in addition to the oxidative stress cytokine IL-8 in the brain. Tentatively, HSV-1 remains a relevant pathogen conditioning autoimmune processes and a psychiatric clinical phenotype. [ABSTRACT FROM AUTHOR]

Introduction: Extracellular ATP (eATP) released from damaged cells activates the P2X7 receptor (P2X7R) ion channel on the surface of surrounding cells, resulting in calcium influx, potassium efflux and inflammasome activation. Inherited changes in the P2X7R gene (P2RX7) influence eATP induced responses. Single nucleotide polymorphisms (SNPs) of P2RX7 influence both function and signaling of the receptor, that in addition to ion flux includes pathogen control and immunity. Methods: Subjects (n = 105) were admitted to the ICU at the University Hospital Ulm, Germany between June 2018 and August 2019. Of these, subjects with a diagnosis of sepsis (n = 75), were also diagnosed with septic shock (n = 24), and/ or pneumonia (n = 42). Subjects with pneumonia (n = 43) included those without sepsis (n = 1), sepsis without shock (n = 29) and pneumonia with septic shock (n = 13). Out of the 75 sepsis/septic shock patients, 33 patients were not diagnosed with pneumonia. Controls (n = 30) were recruited to the study from trauma patients and surgical patients without sepsis, septic shock, or pneumonia. SNP frequencies were determined for 16 P2RX7 SNPs known to affect P2X7R function, and association studies were performed between frequencies of these SNPs in sepsis, septic shock, and pneumonia compared to controls. Results: The loss-of-function (LOF) SNP rs17525809 (T253C) was found more frequently in patients with septic shock, and non-septic trauma patients when compared to sepsis. The LOF SNP rs2230911 (C1096G) was found to be more frequent in patients with sepsis and septic shock than in non-septic trauma patients. The frequencies of these SNPs were even higher in sepsis and septic patients with pneumonia. The current study also confirmed a previous study by our group that showed a five SNP combination that included the GOF SNPs rs208294 (C489T) and rs2230912 (Q460R) that was designated #21211 was associated with increased odds of survival in severe sepsis. Discussion: The results found an association between expression of LOF P2RX7 SNPs and presentation to the ICU with sepsis, and septic shock compared to control ICU patients. Furthermore, frequencies of LOF SNPs were found to be higher in sepsis patients with pneumonia compared to those without pneumonia. In addition, a five SNP GOF combinationwas associated with increased odds of survival in severe sepsis. These results suggest that P2RX7 is required to control infection in pneumonia and that inheritance of LOF variants increases the risk of sepsis when associated with pneumonia. This study confirms that P2RX7 genotyping in pneumonia may identify patients at risk of developing sepsis. The study also identifies P2X7R as a target in sepsis associated with an excessive immune response in subjects with GOF SNP combinations. [ABSTRACT FROM AUTHOR]

During the last decade, there has been a rapidly growing trend toward the use of cellphone-based devices (CBDs) in bioanalytical sciences. For example, they have been used for digital microscopy, cytometry, read-out of immunoassays and lateral flow tests, electrochemical and surface plasmon resonance based bio-sensing, colorimetric detection and healthcare monitoring, among others. Cellphone can be considered as one of the most prospective devices for the development of next-generation point-of-care (POC) diagnostics platforms, enabling mobile healthcare delivery and personalized medicine. With more than 6.5 billion cellphone subscribers worldwide and approximately 1.6 billion new devices being sold each year, cellphone technology is also creating new business and research opportunities. Many cellphone-based devices, such as those targeted for diabetic management, weight management, monitoring of blood pressure and pulse rate, have already become commercially-available in recent years. In addition to such monitoring platforms, several other CBDs are also being introduced, targeting e.g., microscopic imaging and sensing applications for medical diagnostics using novel computational algorithms and components already embedded on cellphones. This report aims to review these recent developments in CBDs for bioanalytical sciences along with some of the challenges involved and the future opportunities.

Introduction: In septic patients the damage of the endothelial barrier is decisive leading to circulatory septic shock with disseminated vascular coagulation, edema and multiorgan failure. Hemadsorption therapy leads to rapid resolution of clinical symptoms. We propose that the isolation of proteins adsorbed to hemadsorption devices contributes to the identification of mediators responsible for endothelial barrier dysfunction. Material and methods: Plasma materials enriched to hemadsorption filters (CytoSorb®) after therapy of patients in septic shock were fractionated and functionally characterized for their effect on cell integrity, viability, proliferation and ROS formation by human endothelial cells. Fractions were further studied for their contents of oxidized nucleic acids as well as peptides and proteins by mass spectrometry. Results: Individual fractions exhibited a strong effect on endothelial cell viability, the endothelial layer morphology, and ROS formation. Fractions with high amounts of DNA and oxidized DNA correlated with ROS formation in the target endothelium. In addition, defined proteins such as defensins (HNP-1), SAA1, CXCL7, and the peptide bikunin were linked to the strongest additive effects in endothelial damage. Conclusion: Our results indicate that hemadsorption is efficient to transiently remove strong endothelial damage mediators from the blood of patients with septic shock, which explains a rapid clinical improvement of inflammation and endothelial function. The current work indicates that a combination of stressors leads to the most detrimental effects. Oxidized ssDNA, likely derived from mitochondria, SAA1, the chemokine CXCL7 and the human neutrophil peptide alpha-defensin 1 (HNP-1) were unique for their significant negative effect on endothelial cell viability. However, the strongest damage effect occurred, when, bikunin -- cleaved off from alpha-1-microglobulin was present in high relative amounts (>65%) of protein contents in the most active fraction. Thus, a relevant combination of stressors appears to be removed by hemadsorption therapy which results in fulminant and rapid, though only transient, clinical restitution. [ABSTRACT FROM AUTHOR]

We analyze the redshift- and luminosity-dependent sizes of dropout galaxy candidates in the redshift range z ∼ 7-12 using deep images from the 2012 Hubble Ultra Deep Field (UDF12) campaign, which offers two advantages over that used in earlier work. First, we utilize the increased signal-to-noise ratio offered by the UDF12 imaging to provide improved measurements for known galaxies at z ≃ 6.5-8 in the HUDF. Second, because the UDF12 data have allowed the construction of the first robust galaxy sample in the HUDF at z > 8, we have been able to extend the measurement of average galaxy size out to higher redshifts. Restricting our measurements to sources detected at >15σ, we confirm earlier indications that the average half-light radii of z ∼ 7-12 galaxies are extremely small, 0.3-0.4 kpc, comparable to the sizes of giant molecular associations in local star-forming galaxies. We also confirm that there is a clear trend of decreasing half-light radius with increasing redshift, and provide the first evidence that this trend continues beyond z ≃ 8. Modeling the evolution of the average half-light radius as a power law, (1 + z)s, we obtain a best-fit index of over z ∼ 4-12. A clear size-luminosity relation is evident in our dropout samples. This relation can be interpreted in terms of a constant surface density of star formation over a range in luminosity of . The average star formation surface density in dropout galaxies is 2-3 orders of magnitude lower than that found in extreme starburst galaxies, but is comparable to that seen today in the centers of normal disk galaxies. © 2013. The American Astronomical Society. All rights reserved.

We present the 2012 Hubble Ultra Deep Field campaign (UDF12), a large 128 orbit Cycle 19 Hubble Space Telescope program aimed at extending previous Wide Field Camera 3 (WFC3)/IR observations of the UDF by quadrupling the exposure time in the F105W filter, imaging in an additional F140W filter, and extending the F160W exposure time by 50%, as well as adding an extremely deep parallel field with the Advanced Camera for Surveys (ACS) in the F814W filter with a total exposure time of 128 orbits. The principal scientific goal of this project is to determine whether galaxies reionized the universe; our observations are designed to provide a robust determination of the star formation density at z ≳ 8, improve measurements of the ultraviolet continuum slope at z ∼ 7-8, facilitate the construction of new samples of z ∼ 9-10 candidates, and enable the detection of sources up to z ∼ 12. For this project we committed to combining these and other WFC3/IR imaging observations of the UDF area into a single homogeneous dataset to provide the deepest near-infrared observations of the sky. In this paper we present the observational overview of the project and describe the procedures used in reducing the data as well as the final products that were produced. We present the details of several special procedures that we implemented to correct calibration issues in the data for both the WFC3/IR observations of the main UDF field and our deep 128 orbit ACS/WFC F814W parallel field image, including treatment for persistence, correction for time-variable sky backgrounds, and astrometric alignment to an accuracy of a few milliarcseconds. We release the full, combined mosaics comprising a single, unified set of mosaics of the UDF, providing the deepest near-infrared blank-field view of the universe currently achievable, reaching magnitudes as deep as AB ∼ 30 mag in the near-infrared, and yielding a legacy dataset on this field. © 2013. The American Astronomical Society. All rights reserved.

The quantity and activation state of adipose tissue macrophages (ATMs) impact the development of obesity-induced metabolic diseases. Appetite-controlling hormones play key roles in obesity; however, our understanding of their effects on ATMs is limited. Here, we have shown that human and mouse ATMs express NPFFR2, a receptor forthe appetite-reducing neuropeptide FF (NPFF), and that NPFFR2 expression is upregulated by IL-4, an M2-polarizing cytokine. Plasma levels of NPFF decreased in obese patients and high-fat diet-fed mice and increased following caloric restriction. NPFF promoted M2 activation and increased the proliferation of murine and human ATMs. Both M2 activation and increased ATM proliferation were abolished in NPFFR2-deficient ATMs. Mechanistically, the effects of NPFF involved the suppression of E3 ubiquitin ligase RNF128 expression, resulting in enhanced stability of phosphorylated STAT6 and increased transcription of the M2 macrophage-associated genes IL-4 receptor [alpha](lI/4ra), arginase 1 {Arg1), IL-10 (lI10), and alkylglycerol monooxygenase (Agmo). NPFF induced ATM proliferation concomitantly with the increase in N-Myc downstream-regulated gene 2 (Ndrg2) expression and suppressed the transcription of Ifi200 cell-cycle inhibitor family members and MAF bZIP transcription factor B (Mafb), a negative regulator of macrophage proliferation. NPFF thus plays an important role in supporting healthy adipose tissue via the maintenance of metabolically beneficial ATMs., Introduction Adipose tissue macrophages (ATMs) are immune cells of adipose tissue (AT) stroma with key roles in AT development and metabolism (1). ATMs accumulate in AT in obesity and undergo [...]

The authors find that the deficiency of the model precipitation simulation may be attributed to the use of an enhanced orography in the integrations. Replacement of this orography with a mean orography results in a much more realistic simulation of Indian monsoon circulation and rainfall. Experiments with a linear primitive equation model on the sphere suggest that this striking improvement is due to modulations of the orographically forced waves in the lower troposphere. This improvement in the monsoon simulation is due to the kinematic and dynamical effects of changing the topography, rather than the thermal effects, which were minimal. The magnitude of the impact on the Indian monsoon of the other sensitivity experiments varied considerably but was consistently less than the impact of using the mean orography. However, results from the soil moisture sensitivity experiments suggest a possibly important role for soil moisture in simulating tropical precipitation. -from Authors