An unusual dual sugar-binding lectin domain controls the substrate specificity of a mucin-type O-glycosyltransferase.

N-acetylgalactosaminyl-transferases (GalNAc-Ts) initiate mucin-type O-glycosylation, an abundant and complex posttranslational modification that regulates host-microbe interactions, tissue development, and metabolism. GalNAc-Ts contain a lectin domain consisting of three homologous repeats (α, β, and γ), where α and β can potentially interact with O-GalNAc on substrates to enhance activity toward a nearby acceptor Thr/Ser. The ubiquitous isoenzyme GalNAc-T1 modulates heart development, immunity, and SARS-CoV-2 infectivity, but its substrates are largely unknown.

Association between air pollution levels and drug sales for asthma and allergy in 63 million people in metropolitan France.

Introduction: Air pollution is known to have an impact on respiratory health. However, the assessment of this relationship is far from complete and is rarely extended to the country level. We used drug sales data, both Over-The-Counter (OTC) and prescription drugs, to assess exhaustively the impact of air pollution on asthma and allergy at the national level in France.

Monitoring TRPC7 Conformational Changes by BRET Following GPCR Activation.

Transient receptor potential canonical (TRPC) channels are membrane proteins involved in regulating Ca homeostasis, and whose functions are modulated by G protein-coupled receptors (GPCR). In this study, we developed bioluminescent resonance energy transfer (BRET) biosensors to better study channel conformational changes following receptor activation. For this study, two intramolecular biosensors, GFP10-TRPC7-RLucII and RLucII-TRPC7-GFP10, were constructed and were assessed following the activation of various GPCRs.

Bispecific repurposed medicines targeting the viral and immunological arms of COVID-19.

Effective agents to treat coronavirus infection are urgently required, not only to treat COVID-19, but to prepare for future outbreaks. Repurposed anti-virals such as remdesivir and human anti-inflammatories such as barcitinib have received emergency approval but their overall benefits remain unclear. Vaccines are the most promising prospect for COVID-19, but will need to be redeveloped for any future coronavirus outbreak.

Patient Empowerment Reduces Pain in Geriatric Patients After Gynecologic Onco-Surgery: Subgroup Analysis of a Prospective Randomized Controlled Clinical Trial.

Purpose: This study aimed to determine the effect of patient empowerment on acute postoperative pain. This research was part of the Patient Empowerment and Risk-Assessed Treatment to Improve Outcome in the Elderly After Onco-Surgery Trial.

Design: This research was a prospective randomized controlled interventional study.

An exploration of nurse-physician perceptions of collaborative behaviour.

Interprofessional collaboration is a key element in providing safe, holistic patient care in the acute care setting. Trended data at a community hospital indicated opportunities for improvement in collaboration on micro, meso, and macro levels. The aim of this survey study was to assess the current state of collaboration between frontline nurses and physicians at a non-academic acute care hospital.

Dust observations at orbital altitudes surrounding Mars.

Dust is common close to the martian surface, but no known process can lift appreciable concentrations of particles to altitudes above ~150 kilometers. We present observations of dust at altitudes ranging from 150 to above 1000 kilometers by the Langmuir Probe and Wave instrument on the Mars Atmosphere and Volatile Evolution spacecraft. Based on its distribution, we interpret this dust to be interplanetary in origin.

3 MV hypervelocity dust accelerator at the Colorado Center for Lunar Dust and Atmospheric Studies.

A hypervelocity dust accelerator for studying micrometeorite impacts has been constructed at the Colorado Center for Lunar Dust and Atmospheric Studies (CCLDAS) at the University of Colorado. Based on the Max-Planck-Institüt für Kernphysik (MPI-K) accelerator, this accelerator is capable of emitting single particles of a specific mass and velocity selected by the user. The accelerator consists of a 3 MV Pelletron generator with a dust source, four image charge pickup detectors, and two interchangeable target chambers: a large high-vacuum test bed and an ultra-high vacuum impact study chamber.

1,1-Diarylalkenes as anticancer agents: dual inhibitors of tubulin polymerization and phosphodiesterase 4.

A series of 1,1-diarylalkene derivatives were prepared to optimize the properties of CC-5079 (1), a dual inhibitor of tubulin polymerization and phosphodiesterase 4 (PDE4). By using the 3-ethoxy-4-methoxyphenyl PDE4 pharmacophore as one of the aromatic rings, a significant improvement in PDE4 inhibition was achieved. Compound 28 was identified as a dual inhibitor with potent PDE4 (IC(50)=54 nM) and antitubulin activity (HCT-116 IC(50)=34 nM and tubulin polymerization IC(50) ∼1 μM).

Structure of an exploding laser-produced plasma.

We describe the first-ever volumetric, time-resolved measurements performed with a moving probe within an expanding dense plasma, embedded in a background magnetized plasma. High-resolution probe measurements of the magnetic field and floating potential in multiple 2D cut planes combined with a 1 Hz laser system reveal complex three-dimensional current systems within the expanding plasma. Static (ωreal=0) flutelike density striations are observed at the leading edge of the plasma, which are correlated to variations in the current layer at the edge of the expanding plasma.

Two-dimensional micron-step probe drive for laboratory plasma measurement.

Laboratory measurement of small-scale ( approximately 1 mm) magnetic phenomena over an extended area is a challenge requiring precise diagnostics. We present a novel two dimensional magnetic probe platform capable of directly measuring the magnetic field over a 36 cm(2) region at spatial resolutions better than 1 mm. The platform is discussed in the context of an experiment at the Large Plasma Device facility at UCLA, designed to measure the magnetic interaction between two counterpropagating laser-produced plasmas.

Monitoring mesenchymal stromal cell developmental stage to apply on-time mechanical stimulation for ligament tissue engineering.

To evaluate the appropriate time frame for applying mechanical stimuli to induce mesenchymal stromal cell (MSC) differentiation for ligament tissue engineering, developmental cell phenotypes were monitored during a period of in vitro culture. MSCs were seeded onto surface-modified silk fibroin fiber matrices and cultured in Petri dishes for 15 days. Cell metabolic activity, morphology, and gene expression of extracellular matrix (ECM) proteins (collagen type I and III and fibronectin), ECM receptors (integrins alpha-2, alpha-5, and beta-1), and heat-shock protein 70 (HSP-70) were monitored during the culture of MSC.

Mechanisms of silk fibroin sol-gel transitions.

Silk fibroin sol-gel transitions were studied by monitoring the process under various physicochemical conditions with optical spectroscopy at 550 nm. The secondary structural change of the fibroin from a disordered state in solution to a beta-sheet-rich conformation in the gel state was assessed by FTIR and CD over a range of fibroin concentrations, temperatures, and pH values. The structural changes were correlated to the degree of gelation based on changes in optical density at 550 nm.

Mechanisms of the natural reactivity of lymphocytes from noninfected individuals to membrane-associated Leishmania infantum antigens.

Membrane-associated Leishmania Ags (MLA) or soluble Leishmania Ags were used in vitro to stimulate cord blood or PBMC from healthy donors noninfected by Leishmania parasites. MLA, but not soluble Leishmania Ags, constantly induce strong proliferation of cord blood mononuclear cells and PBMC from noninfected individuals. Responding cells are CD3+, CD4+, TCRalphabeta+, CD45RO+, and CD45RA+ and secrete IFN-gamma and IL-10, but not IL-4.

In vitro degradation of silk fibroin.

A significant need exists for long-term degradable biomaterials which can slowly and predictably transfer a load-bearing burden to developing biological tissue. In this study Bombyx mori silk fibroin yarns were incubated in 1mg/ml Protease XIV at 37 degrees C to create an in vitro model system of proteolytic degradation. Samples were harvested at designated time points up to 12 weeks and (1) prepared for scanning electron microscopy (SEM), (2) lyophilized and weighed, (3) mechanical properties determined using a servohydraulic Instron 8511, (4) dissolved and run on a SDS-PAGE gel, and (5) characterized with Fourier transform infrared spectroscopy.

A profound alteration of blood TCRB repertoire allows prediction of cerebral malaria.

Cerebral malaria (CM) is one of the severe complications of Plasmodium infection. In murine models of CM, Talphabeta cells have been implicated in the neuropathogenesis. To obtain insights into the TCRB repertoire during CM, we used high throughput CDR3 spectratyping and set up new methods and software tools to analyze data.

Comparative study of brain CD8+ T cells induced by sporozoites and those induced by blood-stage Plasmodium berghei ANKA involved in the development of cerebral malaria.

To obtain insight into the mechanisms that contribute to the pathogenesis of Plasmodium infections, we developed an improved rodent model that mimics human malaria closely by inducing cerebral malaria (CM) through sporozoite infection. We used this model to carry out a detailed study on isolated T cells recruited from the brains of mice during the development of CM. We compared several aspects of the immune response related to the experimental model of Plasmodium berghei ANKA infection induced by sporozoites in C57BL/6 mice and those related to a blood-stage infection.

New methods and software tools for high throughput CDR3 spectratyping. Application to T lymphocyte repertoire modifications during experimental malaria.

Immune repertoires of T or B cells are very often studied by Complementary Determining Region 3 (CDR3) spectratyping. However, data obtained with this method is usually subject to a biased eye analysis. We developed recently the ISEApeaks software package to retrieve and handle peak data from automated sequencers, from which CDR3 spectratype data is obtained.

Collaborative partnership for optimizing heart failure outcomes in the long-term care environment: a clinical experience.

Rationale: Heart failure (HF) is a devastating cardiovascular syndrome affecting more than 4.6 million Americans and resulting in a substantial economic burden. It is the number one cause of hospitalization in the older population.

A new statistical method for quantitative analyses: application to the precise quantification of T cell receptor repertoires.

In experimental immunology, a situation quite commonly arises in which there are a large number of potential events but the probability of any individual event is small and one wishes to measure the number of events which actually occur. We present a new general statistical method, denoted Continuous Poisson Method (COPOM), for estimating the number of events underlying a quantitative measurement. This situation is well illustrated in the case of quantitative analyses of the immune receptor repertoire in a diverse population of cells.