ABCD of IA: A multi-scale agent-based model of T cell activation in inflammatory arthritis.

Biomaterial-based agents have been demonstrated to regulate the function of immune cells in models of autoimmunity. However, the complexity of the kinetics of immune cell activation can present a challenge in optimizing the dose and frequency of administration. Here, we report a model of autoreactive T cell activation, which are key drivers in autoimmune inflammatory joint disease.

Biodegradable scaffolds for enhancing vaccine delivery.

Sustained release of vaccine components is a potential method to boost efficacy compared with traditional bolus injection. Here, we show that a biodegradable hyaluronic acid (HA)-scaffold, termed HA cryogel, mediates sustained antigen and adjuvant release in vivo leading to a durable immune response. Delivery from subcutaneously injected HA cryogels was assessed and a formulation which enhanced the immune response while minimizing the inflammation associated with the foreign body response was identified, termed CpG-OVA-HAC2.

Immunomodulatory Nanoparticles for Modulating Arthritis Flares.

Disease-modifying drugs have improved the treatment for autoimmune joint disorders, such as rheumatoid arthritis, but inflammatory flares are a common experience. This work reports the development and application of flare-modulating poly(lactic--glycolic acid)-poly(ethylene glycol)-maleimide (PLGA-PEG-MAL)-based nanoparticles conjugated with joint-relevant peptide antigens, aggrecan and type 2 bovine collagen. Peptide-conjugated PLGA-PEG-MAL nanoparticles encapsulated calcitriol, which acted as an immunoregulatory agent, and were termed calcitriol-loaded nanoparticles (CLNP).

Implementation of a pediatric bed prioritization process in a rural Minnesota community-based hospital.

Inpatient capacity constraints have been a pervasive challenge for hospitals throughout the COVID-19 pandemic. The Mayo Clinic Health System - Southwest Minnesota region primarily serves patients in rural southwestern Minnesota and part of Iowa and consists of 1 postacute care hospital, 1 tertiary care medical center, and 3 critical access hospitals. The main hub, Mayo Clinic Health System in Mankato, Minnesota, has a pediatric unit with dedicated pediatric hospitalists.

Inverted region in the reaction of the quinone reduction in the A-site of photosystem I from cyanobacteria.

Photosystem I from the menB strain of Synechocystis sp. PCC 6803 containing foreign quinones in the A sites was used for studying the primary steps of electron transfer by pump-probe femtosecond laser spectroscopy. The free energy gap (- ΔG) of electron transfer between the reduced primary acceptor A and the quinones bound in the A site varied from 0.

Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis.

Disease modifying antirheumatic drugs (DMARDs) have improved the prognosis of autoimmune inflammatory arthritides but a large fraction of patients display partial or nonresponsiveness to front-line DMARDs. Here, an immunoregulatory approach based on sustained joint-localized release of all-trans retinoic acid (ATRA), which modulates local immune activation and enhances disease-protective T cells and leads to systemic disease control is reported. ATRA imprints a unique chromatin landscape in T cells, which is associated with an enhancement in the differentiation of naïve T cells into anti-inflammatory regulatory T cells (T ) and suppression of T destabilization.

Immune-responsive biodegradable scaffolds for enhancing neutrophil regeneration.

Neutrophils are essential effector cells for mediating rapid host defense and their insufficiency arising from therapy-induced side-effects, termed neutropenia, can lead to immunodeficiency-associated complications. In autologous hematopoietic stem cell transplantation (HSCT), neutropenia is a complication that limits therapeutic efficacy. Here, we report the development and in vivo evaluation of an injectable, biodegradable hyaluronic acid (HA)-based scaffold, termed HA cryogel, with myeloid responsive degradation behavior.

Short-chain fatty acid-mediated epigenetic modulation of inflammatory T cells in vitro.

Short-chain fatty acids (SCFAs) are major metabolic products of indigestible polysaccharides in the gut and mediate the function of immune cells to facilitate homeostasis. The immunomodulatory effect of SCFAs has been attributed, at least in part, to the epigenetic modulation of immune cells through the inhibition the nucleus-resident enzyme histone deacetylase (HDAC). Among the downstream effects, SCFAs enhance regulatory T cells (T) over inflammatory T helper (Th) cells, including Th17 cells, which can be pathogenic.

Intensive care unit adaptations in the COVID-19 pandemic: Lessons learned.

The coronavirus disease 2019 pandemic had deleterious effects on the healthcare systems around the world. To increase intensive care units (ICUs) bed capacities, multiple adaptations had to be made to increase surge capacity. In this editorial, we demonstrate the changes made by an ICU of a midwest community hospital in the United States.

3D-Bioprinted Phantom with Human Skin Phototypes for Biomedical Optics.

3D-bioprinted skin-mimicking phantoms with skin colors ranging across the Fitzpatrick scale are reported. These tools can help understand the impact of skin phototypes on biomedical optics. Synthetic melanin nanoparticles of different sizes (70-500 nm) and clusters are fabricated to mimic the optical behavior of melanosome.

Lipid-based regulators of immunity.

Lipids constitute a diverse class of molecular regulators with ubiquitous physiological roles in sustaining life. These carbon-rich compounds are primarily sourced from exogenous sources and may be used directly as structural cellular building blocks or as a substrate for generating signaling mediators to regulate cell behavior. In both of these roles, lipids play a key role in both immune activation and suppression, leading to inflammation and resolution, respectively.

A Case of Medial Tibial Crest Friction Syndrome: A Rare Cause of Medial Knee Pain.

Knee pain is among the most common problems in active patients, with common causes of medial knee pain including meniscal injury, osteoarthritis, medial collateral ligament (MCL) injury, and pes anserine bursopathy/distal hamstring tendinopathy. Some cases of medial knee pain are refractory to standard treatment options and may be caused by rare pathology. We present a case of medial knee pain secondary to medial tibial crest friction syndrome (MTCFS) in a 22-year-old male training for a sprint triathlon after rapidly increasing his training program.

Ultrasound-Guided Fasciotomy for Chronic Exertional Compartment Syndrome: A Case Report.

Chronic exertional compartment syndrome (CECS) is characterized by an excessive increase in intracompartmental muscle pressures after exercise. Athletes with CECS report pain, pressure, and occasionally neurologic symptoms in the affected compartment during exercise that abates with rest. Although many treatment options have been proposed, athletes often require a fasciotomy to return to unrestricted sports participation.

Winter Adaptive Sports Participation, Injuries, and Equipment.

As the participation rate and popularity of winter adaptive sports increases, understanding injury patterns and equipment is crucial for athletes, coaches, athletic trainers, sports physicians, prosthetists/orthotists, and all the staff involved. While the inaugural Winter Paralympics in 1976 had 17 participating countries, the most recent paralympic games in Pyeongchang, South Korea had >500 athletes from 49 different countries competing in 6 disciplines: alpine skiing, nordic skiing, sledge hockey, wheelchair curling, biathlon, and snowboarding. In this paper, we review participation rates, injury trends and equipment, with a focus on the 3 most popular events: alpine skiing, nordic skiing, and sledge hockey.

Critical evaluation of electron transfer kinetics in P-F/F, P-F, and P-A Photosystem I core complexes in liquid and in trehalose glass.

This work aims to fully elucidate the effects of a trehalose glassy matrix on electron transfer reactions in cyanobacterial Photosystem I (PS I). Forward and backward electron transfer rates from A and A to F and charge recombination rates from A, A, A, F, and [F/F] to P were measured in P-F/F complexes, P-F cores, and P-A cores, both in liquid and in a trehalose glassy matrix at 11% humidity. By comparing CONTIN-resolved kinetic events over 6 orders of time in increasingly simplified versions of PS I at 480 nm, a wavelength that reports primarily A/A oxidation, and over 9 orders of time at 830 nm, a wavelength that reports P reduction and A oxidation, assignments could be made for nearly all of the resolved kinetic phases.

Spectral Hole Burning in Cyanobacterial Photosystem I with P700 in Oxidized and Neutral States.

We explored the rich satellite hole structures emerging as a result of spectral hole burning in cyanobacterial photosystem I (PSI) and demonstrated that hole burning properties of PSI, particularly at high resolution, are strongly affected by the oxidation state of the primary donor P700, as P700 effectively quenches the excitations of the lowest-energy antenna states responsible for fluorescence. Obtaining better control of this variable will be crucial for high-resolution ensemble experiments on protein energy landscapes in PSI. The separate nonphotochemical spectral hole burning (NPHB) signatures of various red antenna states were obtained, allowing for additional constraints on excitonic structure-based calculations.

Induction and analysis of epithelial to mesenchymal transition.

Epithelial to mesenchymal transition (EMT) is essential for proper morphogenesis during development. Misregulation of this process has been implicated as a key event in fibrosis and the progression of carcinomas to a metastatic state. Understanding the processes that underlie EMT is imperative for the early diagnosis and clinical control of these disease states.

[2Fe-2S] proteins in Chlorosomes: redox properties of CsmI, CsmJ, and CsmX of the Chlorosome envelope of Chlorobaculum tepidum.

The chlorosome envelope of Chlorobaculum tepidum contains 10 polypeptides, three of which, CsmI, CsmJ, and CsmX, have an adrenodoxin-like domain harboring a single [2Fe-2S] cluster. Mutants that produced chlorosomes containing two, one, or none of these Fe-S proteins were constructed [Li, H., et al.

Spectral resolution of the primary electron acceptor A0 in Photosystem I.

The reduced state of the primary electron acceptor of Photosystem I, A(0), was resolved spectroscopically in its lowest energy Q(y) region for the first time without the addition of chemical reducing agents and without extensive data manipulation. To carry this out, we used the menB mutant of Synechocystis sp. PCC 6803 in which phylloquinone is replaced by plastoquinone-9 in the A(1) sites of Photosystem I.

Synthesis and evaluation of substrate analogue inhibitors of trypanothione reductase.

Trypanothione reductase (TR) is found in the trypanosomatid parasites, where it catalyses the NADPH-dependent reduction of the glutathione analogue, trypanothione, and is a key player in the parasite's defenses against oxidative stress. TR is a promising target for the development of antitrypanosomal drugs; here, we report our synthesis and evaluation of compounds 3-5 as low micromolar Trypanosoma cruzi TR inhibitors. Although 4 and 5 were designed as potential irreversible inhibitors, these compounds, as well as 3, displayed reversible competitive inhibition.

Overview of the generation, validation, and application of phosphosite-specific antibodies.

Protein phosphorylation is a universal key posttranslational modification that affects the activity and other properties of intracellular proteins. Phosphosite-specific antibodies can be produced as polyclonals or monoclonals in different animal species, and each approach offers its own benefits and disadvantages. The validation of phosphosite-specific antibodies requires multiple techniques and tactics to demonstrate their specificity.

Allele-specific suppressors of lin-1(R175Opal) identify functions of MOC-3 and DPH-3 in tRNA modification complexes in Caenorhabditis elegans.

The elongator (ELP) complex consisting of Elp1-6p has been indicated to play roles in multiple cellular processes. In yeast, the ELP complex has been shown to genetically interact with Uba4p/Urm1p and Kti11-13p for a function in tRNA modification. Through a Caenorhabditis elegans genetic suppressor screen and positional cloning, we discovered that loss-of-function mutations of moc-3 and dph-3, orthologs of the yeast UBA4 and KTI11, respectively, effectively suppress the Multivulva (Muv) phenotype of the lin-1(e1275, R175Opal) mutation.