α2,6-Sialylation Is Upregulated in Severe COVID-19, Implicating the Complement Cascade.

Better understanding of the molecular mechanisms underlying COVID-19 severity is desperately needed in current times. Although hyper-inflammation drives severe COVID-19, precise mechanisms triggering this cascade and what role glycosylation might play therein are unknown. Here we report the first high-throughput glycomic analysis of COVID-19 plasma samples and autopsy tissues.

Human hepatocyte PNPLA3-148M exacerbates rapid non-alcoholic fatty liver disease development in chimeric mice.

Advanced non-alcoholic fatty liver disease (NAFLD) is a rapidly emerging global health problem associated with pre-disposing genetic polymorphisms, most strikingly an isoleucine to methionine substitution in patatin-like phospholipase domain-containing protein 3 (PNPLA3-I148M). Here, we study how human hepatocytes with PNPLA3 148I and 148M variants engrafted in the livers of broadly immunodeficient chimeric mice respond to hypercaloric diets. As early as four weeks, mice developed dyslipidemia, impaired glucose tolerance, and steatosis with ballooning degeneration selectively in the human graft, followed by pericellular fibrosis after eight weeks of hypercaloric feeding.

α2,6-Sialylation is Upregulated in Severe COVID-19 Implicating the Complement Cascade.

Better understanding of the mechanisms of COVID-19 severity is desperately needed in current times. Although hyper-inflammation drives severe COVID-19, precise mechanisms triggering this cascade and what role glycosylation might play therein is unknown. Here we report the first high-throughput glycomic analysis of COVID-19 plasma samples and autopsy tissues.

Pulmonary Pathology of End-Stage COVID-19 Disease in Explanted Lungs and Outcomes After Lung Transplantation.

Objectives: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may develop end-stage lung disease requiring lung transplantation. We report the clinical course, pulmonary pathology with radiographic correlation, and outcomes after lung transplantation in three patients who developed chronic respiratory failure due to postacute sequelae of SARS-CoV-2 infection.

Methods: A retrospective histologic evaluation of explanted lungs due to coronavirus disease 2019 was performed.

Membrane attack complex (MAC) deposition in renal tubules is associated with interstitial fibrosis and tubular atrophy: a pilot study.

Introduction: Treatment failures for lupus nephritis (LN) are high with 10%-30% of patients progressing to end-stage renal disease (ESRD) within 10 years. Interstitial fibrosis/tubular atrophy (IFTA) is a predictor of progression to ESRD. Prior studies suggest that tubulointerstitial injury secondary to proteinuria in LN is mediated by complement activation in the tubules, specifically through the membrane attack complex (MAC).

Targeting the Atf7ip-Setdb1 Complex Augments Antitumor Immunity by Boosting Tumor Immunogenicity.

Substantial progress has been made in understanding how tumors escape immune surveillance. However, few measures to counteract tumor immune evasion have been developed. Suppression of tumor antigen expression is a common adaptive mechanism that cancers use to evade detection and destruction by the immune system.

Evidence for continuity of interstitial spaces across tissue and organ boundaries in humans.

Bodies have continuous reticular networks, comprising collagens, elastin, glycosaminoglycans, and other extracellular matrix components, through all tissues and organs. Fibrous coverings of nerves and blood vessels create structural continuity beyond organ boundaries. We recently validated fluid flow through human fibrous tissues, though whether these interstitial spaces are continuous through the body or discontinuous, confined within individual organs, remains unclear.

Ultracold neutron properties of the Eljen-299-02D deuterated scintillator.

In this paper, we report studies of the Fermi potential and loss per bounce of ultracold neutrons (UCNs) on a deuterated scintillator (Eljen-299-02D). These UCN properties of the scintillator enable its use in a wide variety of applications in fundamental neutron research.

Somatic Focal Copy Number Gains of Noncoding Regions of Receptor Tyrosine Kinase Genes in Treatment-Resistant Epilepsy.

Epilepsy is a heterogenous group of disorders defined by recurrent seizure activity due to abnormal synchronized activity of neurons. A growing number of epilepsy cases are believed to be caused by genetic factors and copy number variants (CNV) contribute to up to 5% of epilepsy cases. However, CNVs in epilepsy are usually large deletions or duplications involving multiple neurodevelopmental genes.

Keratin 19 and mesenchymal markers for evaluation of epithelial-mesenchymal transition and stem cell niche components in primary biliary cholangitis by sequential elution-stripping multiplex immunohistochemistry.

Multiplexed immunohistochemical techniques give insight into contextual cellular relationships by offering the ability to collect cell-specific data with spatial information from formalin-fixed, paraffin-embedded tissue sections. We established an automated sequential elution-stripping multiplex immunohistochemical assay to address two controversial scientific questions in the field of hepatopathology: 1) whether epithelial-to-mesenchymal transition or mesenchymal-to-epithelial transition occurs during liver injury and repair of a chronic liver disease and 2) if there is a stromal:epithelial relationship along the canals of Hering that would support the concept of this biliary structure being a stem/progenitor cell niche. Our 4-plex assay includes both epithelial and mesenchymal clinical immunohistochemical markers and was performed on clinical human liver specimens in patients with primary biliary cholangitis.

Cell Surface Notch Ligand DLL3 is a Therapeutic Target in Isocitrate Dehydrogenase-mutant Glioma.

Purpose: Isocitrate dehydrogenase ()-mutant glioma is a distinct glioma molecular subtype for which no effective molecularly directed therapy exists. Low-grade gliomas, which are 80%-90% -mutant, have high RNA levels of the cell surface Notch ligand DLL3. We sought to determine DLL3 expression by IHC in glioma molecular subtypes and the potential efficacy of an anti-DLL3 antibody-drug conjugate (ADC), rovalpituzumab tesirine (Rova-T), in -mutant glioma.

Search for the Neutron Decay n→X+γ, Where X is a Dark Matter Particle.

Fornal and Grinstein recently proposed that the discrepancy between two different methods of neutron lifetime measurements, the beam and bottle methods, can be explained by a previously unobserved dark matter decay mode, n→X+γ. We perform a search for this decay mode over the allowed range of energies of the monoenergetic γ ray for X to be dark matter. A Compton-suppressed high-purity germanium detector is used to identify γ rays from neutron decay in a nickel-phosphorous-coated stainless-steel bottle.

Measurement of the neutron lifetime using a magneto-gravitational trap and in situ detection.

The precise value of the mean neutron lifetime, τ, plays an important role in nuclear and particle physics and cosmology. It is used to predict the ratio of protons to helium atoms in the primordial universe and to search for physics beyond the Standard Model of particle physics. We eliminated loss mechanisms present in previous trap experiments by levitating polarized ultracold neutrons above the surface of an asymmetric storage trap using a repulsive magnetic field gradient so that the stored neutrons do not interact with material trap walls.

Membrane attack complex (mac) deposition in lupus nephritis is associated with hypertension and poor clinical response to treatment.

Objective: To study membrane attack complex in lupus nephritis as a potential biomarker for disease intensity and prognostic indicator for response to treatment.

Methods: Immunohistochemistry was performed using unconjugated, murine anti-human complement C9 on kidney biopsies from 30 SLE patients who fulfilled 4 ACR or SLICC criteria. Clinical parameters were assessed at time of biopsy, 6 and 12 months.

A new method for measuring the neutron lifetime using an in situ neutron detector.

In this paper, we describe a new method for measuring surviving neutrons in neutron lifetime measurements using bottled ultracold neutrons (UCN), which provides better characterization of systematic uncertainties and enables higher precision than previous measurement techniques. An active detector that can be lowered into the trap has been used to measure the neutron distribution as a function of height and measure the influence of marginally trapped UCN on the neutron lifetime measurement. In addition, measurements have demonstrated phase-space evolution and its effect on the lifetime measurement.

Radial distribution of charged particles in a magnetic field.

The radial spread of charged particles emitted from a point source in a magnetic field is a potential source of systematic error for any experiment where magnetic fields guide charged particles to detectors with finite size. Assuming uniform probability as a function of the phase along the particle's helical trajectory, an analytic solution for the radial probability distribution function follows which applies to experiments in which particles are generated throughout a volume that spans a sufficient length along the axis of a homogeneous magnetic field. This approach leads to the same result as a different derivation given by Dubbers et al.

Microheterogeneous monoclonal antibody subspecies with differential hepatitis C virus core antigen binding properties identified by SEC-HPLC.

A monoclonal antibody directed against the core protein of hepatitis C virus was characterized for its utility in a sandwich antigen immunoassay wherein the mAb was used as the conjugate. Analysis of unconjugated and acridinium-conjugated monoclonal IgG using a silica-based HPLC size exclusion column revealed the existence of a single, symmetrical peak. Subsequent analysis of unconjugated IgG using a methacrylate-based HPLC size exclusion column revealed the presence of two species of IgG, but only by using a low ionic strength mobile phase buffer.