Perinatal dysfunction of innate immunity in cystic fibrosis.

In patients with cystic fibrosis (CF), repeated cycles of infection and inflammation eventually lead to fatal lung damage. Although diminished mucus clearance can be restored by highly effective CFTR modulator therapy, inflammation and infection often persist. To elucidate the role of the innate immune system in CF etiology, we investigated a CF pig model and compared these results with those for preschool children with CF.

Gene network-based and ensemble modeling-based selection of tumor-associated antigens with a predicted low risk of tissue damage for targeted immunotherapy.

Background: Tumor-associated antigens and their derived peptides constitute an opportunity to design off-the-shelf mainline or adjuvant anti-cancer immunotherapies for a broad array of patients. A performant and rational antigen selection pipeline would lay the foundation for immunotherapy trials with the potential to enhance treatment, tremendously benefiting patients suffering from rare, understudied cancers.

Methods: We present an experimentally validated, data-driven computational pipeline that selects and ranks antigens in a multipronged approach.

Unconventional Charge-Density-Wave Gap in Monolayer NbS.

Using scanning tunneling microscopy and spectroscopy, for a monolayer of transition metal dichalcogenide H-NbS grown by molecular beam epitaxy on graphene, we provide unambiguous evidence for a charge density wave (CDW) with a 3 × 3 superstructure, which is not present in bulk NbS. Local spectroscopy displays a pronounced gap on the order of 20 meV at the Fermi level. Within the gap, low-energy features are present.

Effects of lumacaftor-ivacaftor therapy on cystic fibrosis transmembrane conductance regulator function in F508del homozygous patients with cystic fibrosis aged 2-11 years.

Lumacaftor/ivacaftor was approved for the treatment of patients with cystic fibrosis who are homozygous for F508del aged 2 years and older following positive results from phase three trials. However, the improvement in CFTR function associated with lumacaftor/ivacaftor has only been studied in patients over 12 years of age, while the rescue potential in younger children is unknown. In a prospective study, we aimed to evaluate the effect of lumacaftor/ivacaftor on the CFTR biomarkers sweat chloride concentration and intestinal current measurement as well as clinical outcome parameters in F508del homozygous CF patients 2-11 years before and 8-16 weeks after treatment initiation.

The histone H4K20 methyltransferase SUV4-20H1/KMT5B is required for multiciliated cell differentiation in Xenopus.

H4 lysine 20 dimethylation (H4K20me2) is the most abundant histone modification in vertebrate chromatin. It arises from sequential methylation of unmodified histone H4 proteins by the mono-methylating enzyme PR-SET7/KMT5A, followed by conversion to the dimethylated state by SUV4-20H (KMT5B/C) enzymes. We have blocked the deposition of this mark by depleting Xenopus embryos of SUV4-20H1/H2 methyltransferases.

Stable and Unstable Perturbations in Universal Scaling Phenomena Far from Equilibrium.

We study the dynamics of perturbations around nonthermal fixed points associated with universal scaling phenomena in quantum many-body systems far from equilibrium. For an N-component scalar quantum field theory in 3+1 space-time dimensions, we determine the stability scaling exponents using a self-consistent large-N expansion to next-to-leading order. Our analysis reveals the presence of both stable and unstable perturbations, the latter leading to quasiexponential deviations from the fixed point in the infrared.

The ongoing need for rates: can physiology and omics come together to co-design the measurements needed to understand complex ocean biogeochemistry?

The necessity to understand the influence of global ocean change on biota has exposed wide-ranging gaps in our knowledge of the fundamental principles that underpin marine life. Concurrently, physiological research has stagnated, in part driven by the advent and rapid evolution of molecular biological techniques, such that they now influence all lines of enquiry in biological oceanography. This dominance has led to an implicit assumption that physiology is outmoded, and advocacy that ecological and biogeochemical models can be directly informed by omics.

Growth parameters and responses of green algae across a gradient of phototrophic, mixotrophic and heterotrophic conditions.

Many studies have shown that algal growth is enhanced by organic carbon and algal mixotrophy is relevant for physiology and commercial cultivation. Most studies have tested only a single organic carbon concentration and report different growth parameters which hampers comparisons and improvements to algal cultivation methodology. This study compared growth of green algae and across a gradient of photoautotrophic-mixotrophic-heterotrophic culture conditions, with five acetate concentrations.

Thermalization dynamics of a gauge theory on a quantum simulator.

Gauge theories form the foundation of modern physics, with applications ranging from elementary particle physics and early-universe cosmology to condensed matter systems. We perform quantum simulations of the unitary dynamics of a U(1) symmetric gauge field theory and demonstrate emergent irreversible behavior. The highly constrained gauge theory dynamics are encoded in a one-dimensional Bose-Hubbard simulator, which couples fermionic matter fields through dynamical gauge fields.

Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Patients with Cystic Fibrosis and One or Two Alleles.

We recently demonstrated that triple-combination CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves CFTR function in airway and intestinal epithelia to 40-50% of normal in patients with cystic fibrosis (CF) with one or two alleles. In previous studies, this improvement of CFTR function was shown to improve clinical outcomes; however, effects on the lung clearance index (LCI) determined by multiple-breath washout and abnormalities in lung morphology and perfusion detected by magnetic resonance imaging (MRI) have not been studied. To examine the effect of ELX/TEZ/IVA on LCI and lung MRI scores in patients with CF and one or two alleles aged ⩾12 years.

Transient accumulation and bidirectional movement of KIF13B in primary cilia.

Primary cilia are microtubule-based sensory organelles whose assembly and function rely on the conserved bidirectional intraflagellar transport (IFT) system, which is powered by anterograde kinesin-2 and retrograde cytoplasmic dynein-2 motors. Nematodes additionally employ a cell-type-specific kinesin-3 motor, KLP-6, which moves within cilia independently of IFT and regulates ciliary content and function. Here, we provide evidence that a KLP-6 homolog, KIF13B, undergoes bursts of bidirectional movement within primary cilia of cultured immortalized human retinal pigment epithelial (hTERT-RPE1) cells.

Krüppel-like factor 2 controls IgA plasma cell compartmentalization and IgA responses.

Krüppel-like factor 2 (KLF2) is a potent regulator of lymphocyte differentiation, activation and migration. However, its functional role in adaptive and humoral immunity remains elusive. Therefore, by using mice with a B cell-specific deletion of KLF2, we investigated plasma cell differentiation and antibody responses.

Transcriptomes of MPO-Deficient Patients with Generalized Pustular Psoriasis Reveals Expansion of CD4 Cytotoxic T Cells and an Involvement of the Complement System.

Generalized pustular psoriasis is a severe psoriatic subtype characterized by epidermal neutrophil infiltration. Although variants in IL36RN and MPO have been shown to affect immune cells, a systematic analysis of neutrophils and PBMC subsets and their differential gene expression dependent on MPO genotypes was not performed yet. We assessed the transcriptomes of MPO-deficient patients using single-cell RNA sequencing of PBMCs and RNA sequencing of neutrophils in a stable disease state.

Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on CFTR Function in Patients with Cystic Fibrosis and One or Two Alleles.

The CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to improve clinical outcomes and sweat chloride concentration in patients with cystic fibrosis (CF) and one or two alleles. However, the effect of ELX/TEZ/IVA on CFTR function in the airways and intestine has not been studied. To assess the effect of ELX/TEZ/IVA on CFTR function in airway and intestinal epithelia in patients with CF and one or two alleles aged 12 years and older.

A full gap above the Fermi level: the charge density wave of monolayer VS.

In the standard model of charge density wave (CDW) transitions, the displacement along a single phonon mode lowers the total electronic energy by creating a gap at the Fermi level, making the CDW a metal-insulator transition. Here, using scanning tunneling microscopy and spectroscopy and ab initio calculations, we show that VS realizes a CDW which stands out of this standard model. There is a full CDW gap residing in the unoccupied states of monolayer VS.

Scalable Cold-Atom Quantum Simulator for Two-Dimensional QED.

We propose a scalable analog quantum simulator for quantum electrodynamics in two spatial dimensions. The setup for the U(1) lattice gauge field theory employs interspecies spin-changing collisions in an ultracold atomic mixture trapped in an optical lattice. We engineer spatial plaquette terms for magnetic fields, thus solving a major obstacle toward experimental realizations of realistic gauge theories in higher dimensions.

Model-Based Estimation of the Strength of Laser-Based Plastic-Metal Joints Using Finite Element Microstructure Models and Regression Models.

Plastic-metal joints with a laser-structured metal surface have a high potential to reduce cost and weight compared to conventional joining technologies. However, their application is currently inhibited due to the absence of simulation methods and models for mechanical design. Thus, this paper presents a model-based approach for the strength estimation of laser-based plastic-metal joints.

Role of nearshore benthic algae in the Lake Michigan silica cycle.

Si cycling is linked with processes from global carbon sequestration to community composition and is especially important in aquatic ecosystems. Lake Michigan has seen dramatic fluctuations in dissolved silica (dSi) over several decades, which have been examined in the context of planktonic processes (diatom blooms), but the role of benthic organisms (macroalgae and their epiphytes) in Si cycling have not been explored. To assess significance of nearshore benthic algae in Si dynamics, we assembled dSi data from an offshore site sampled since the late 1980's, and sampled off three Milwaukee beaches during 2005-19.

Photoactivation and photoregeneration of TiO2/PAC mixture applied in suspension in water treatments: approach to a real application.

The process TiO/PAC/UV-vis has been under study and compared with the isolated treatments of adsorption and photocatalysis determining possible synergies between adsorption and photocatalysis of target antibiotics: amoxicillin, enrofloxacin, sulfadiazine, and trimethoprim. The characterization of the TiO2/PAC mixture was carried out via FESEM and FTIR. Moreover, a kinetic study has been performed.

Antibiotics removal from aquatic environments: adsorption of enrofloxacin, trimethoprim, sulfadiazine, and amoxicillin on vegetal powdered activated carbon.

This study addresses the growing concern about the high levels of antibiotics in water, outlining an alternative for their removal. The adsorption of four representative antibiotics from commonly used families (fluoroquinolones, β-lactams, trimethoprim, and sulfonamides) was performed over vegetal powdered activated carbon. The evolution of the adsorption was studied during 60 min for different initial antibiotic concentrations, not only individually but also simultaneously to determine competitive adsorption.

Classification and Nomenclature of Metacaspases and Paracaspases: No More Confusion with Caspases.

Metacaspases and paracaspases are proteases that were first identified as containing a caspase-like structural fold (Uren et al., 2000). Like caspases, meta- and paracaspases are multifunctional proteins regulating diverse biological phenomena, such as aging, immunity, proteostasis and programmed cell death.