Effect of Aggregation and Molecular Size on the Ice Nucleation Efficiency of Proteins.

Aerosol acts as ice-nucleating particles (INPs) by catalyzing the formation of ice crystals in clouds at temperatures above the homogeneous nucleation threshold (-38 °C). In this study, we show that the immersion mode ice nucleation efficiency of the environmentally relevant protein, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), occurs at temperatures between -6.8 and -31.6 °C. Further, we suggest that this range is controlled by the RuBisCO concentration and protein aggregation. The warmest median nucleation temperature (-7.9 ± 0.8 °C) was associated with the highest concentration of RuBisCO (2 × 10-1 mg mL-1) and large aggregates with a hydrodynamic diameter of ∼103 nm. We investigated four additional chemically and structurally diverse proteins, plus the tripeptide glutathione, and found that each of them was a less effective INP than RuBisCO. Ice nucleation efficiency of the proteins was independent of the size (molecular weight) for the five proteins investigated in this study. In contrast to previous work, increasing the concentration and degree of aggregation did not universally increase ice nucleation efficiency. RuBisCO was the exception to this generalization, although the underlying molecular mechanism determining why aggregated RuBisCO is such an effective INP remains elusive.

Glass Transition Temperatures of Organic Mixtures from Isoprene Epoxydiol-Derived Secondary Organic Aerosol.

The phase states and glass transition temperatures (Tg) of secondary organic aerosol (SOA) particles are important to resolve for understanding the formation, growth, and fate of SOA as well as their cloud formation properties. Currently, there is a limited understanding of how Tg changes with the composition of organic and inorganic components of atmospheric aerosol. Using broadband dielectric spectroscopy, we measured the Tg of organic mixtures containing isoprene epoxydiol (IEPOX)-derived SOA components, including 2-methyltetrols (2-MT), 2-methyltetrol-sulfate (2-MTS), and 3-methyltetrol-sulfate (3-MTS). The results demonstrate that the Tg of mixtures depends on their composition. The Kwei equation, a modified Gordon-Taylor equation with an added quadratic term and a fitting parameter representing strong intermolecular interactions, provides a good fit for the Tg-composition relationship of complex mixtures. By combining Raman spectroscopy with geometry optimization simulations obtained using density functional theory, we demonstrate that the non-linear deviation of Tg as a function of composition may be caused by changes in the extent of hydrogen bonding in the mixture.

JNK Signaling as a Key Modulator of Soft Connective Tissue Physiology, Pathology, and Healing.

In healthy individuals, the healing of soft tissues such as skin after pathological insult or post injury follows a relatively predictable and defined series of cell and molecular processes to restore tissue architecture and function(s). Healing progresses through the phases of hemostasis, inflammation, proliferation, remodeling, and concomitant with re-epithelialization restores barrier function. Soft tissue healing is achieved through the spatiotemporal interplay of multiple different cell types including neutrophils, monocytes/macrophages, fibroblasts, endothelial cells/pericytes, and keratinocytes. Expressed in most cell types, c-Jun N-terminal kinases (JNK) are signaling molecules associated with the regulation of several cellular processes involved in soft tissue wound healing and in response to cellular stress. A member of the mitogen-activated protein kinase family (MAPK), JNKs have been implicated in the regulation of inflammatory cell phenotype, as well as fibroblast, stem/progenitor cell, and epithelial cell biology. In this review, we discuss our understanding of JNKs in the regulation of cell behaviors related to tissue injury, pathology, and wound healing of soft tissues. Using models as diverse as Drosophila, mice, rats, as well as human tissues, research is now defining important, but sometimes conflicting roles for JNKs in the regulation of multiple molecular processes in multiple different cell types central to wound healing processes. In this review, we focus specifically on the role of JNKs in the regulation of cell behavior in the healing of skin, cornea, tendon, gingiva, and dental pulp tissues. We conclude that while parallels can be drawn between some JNK activities and the control of cell behavior in healing, the roles of JNK can also be very specific modes of action depending on the tissue and the phase of healing.

Modeling the single and multiple scattering properties of soot-laden mineral dust aerosols.

Fractal particle morphologies are employed to study the light scattering properties of soot-laden mineral dust aerosols. The applicability of these models is assessed in comparison with measurements and other numerical studies. To quantify the dust-soot mixing effects on the single and multiple scattering properties, a parameterization of the effective bulk properties is developed. Based on the parameterized bulk properties, polarized one-dimensional radiative transfer simulations are performed. The results indicate that small uncertainties in conjunction with soot contamination parameters may lead to large uncertainties in both forward and inverse modeling involving mineral dust contaminated with soot.

Anti-hIgE gene therapy of peanut-induced anaphylaxis in a humanized murine model of peanut allergy.

BACKGROUND: Peanuts are the most common food to provoke fatal or near-fatal anaphylactic reactions. Treatment with an anti-hIgE mAb is efficacious but requires frequent parenteral administration. OBJECTIVE: Based on the knowledge that peanut allergy is mediated by peanut-specific IgE, we hypothesized that a single administration of an adeno-associated virus (AAV) gene transfer vector encoding for anti-hIgE would protect against repeated peanut exposure in the host with peanut allergy. METHODS: We developed a novel humanized murine model of peanut allergy that recapitulates the human anaphylactic response to peanuts in NOD-scid IL2Rgammanull mice transferred with blood mononuclear cells from donors with peanut allergy and then sensitized with peanut extract. As therapy, we constructed an adeno-associated rh.10 serotype vector coding for a full-length, high-affinity, anti-hIgE antibody derived from the Fab fragment of the anti-hIgE mAb omalizumab (AAVrh.10anti-hIgE). In the reconstituted mice peanut-specific IgE was induced by peanut sensitization and hypersensitivity, and reactions were provoked by feeding peanuts to mice with symptoms similar to those of human subjects with peanut allergy. RESULTS: A single administration of AAVrh.10anti-hIgE vector expressed persistent levels of anti-hIgE. The anti-hIgE vector, administered either before sensitization or after peanut sensitization and manifestation of the peanut-induced phenotype, blocked IgE-mediated alterations in peanut-induced histamine release, anaphylaxis scores, locomotor activity, and free IgE levels and protected animals from death caused by anaphylaxis. CONCLUSION: If this degree of persistent efficacy translates to human subjects, AAVrh.10anti-hIgE could be an effective 1-time preventative therapy for peanut allergy and possibly other severe, IgE-mediated allergies.

Role of Organic Hydrocarbons in Atmospheric Ice Formation via Contact Freezing.

An optical ice microscope apparatus equipped with a sealed cooling stage and a CCD camera was used to examine contact freezing events between a water droplet and ice nucleating particles (INP) containing organic hydrocarbons including octacosane, squalane, and squalene. Sample viscosities were measured with a capillary viscometer and compositions were characterized using Fourier transfer infrared spectroscopy with horizontal attenuated total reflectance and Raman microspectroscopy. All of the samples proved to be moderately efficient ice nuclei that induced freezing between -23 and -26 °C, regardless of whether the INP was solid or liquid. At their ice nucleating temperatures, the viscosity of the liquid samples (squalane and squalene) was 0.6 P or greater. Oxidation increased the viscosity of squalene to over 1330 P, but decreased the viscosity of squalane to 0.07 P at room temperature. Most importantly, our results demonstrate that even moderately viscous liquids in contact with water droplets can act to catalyze freezing, plausibly by providing a flexible template which decreases the energy barrier to ice nucleation. The simple soccer ball model of nucleation theory was used to derive the probability of freezing and nucleation rate coefficients as a function of temperature for each type of INP.

Hemolytic disease of the fetus and newborn caused by anti-Lan.

BACKGROUND: Antibodies to the high-incidence red blood cell (RBC) antigen Lan (Langereis) are typically immunoglobulin G and have been shown to fix complement and cause hemolysis of Lan antigen-positive RBCs. Only three cases of hemolytic disease of the fetus and newborn (HDFN) have been reported involving anti-Lan and all have been characterized as "mild." CASE REPORT: A 26-year-old Hispanic female presented in her fifth pregnancy for routine obstetric care. Due to progressively rising anti-Lan titers, middle cerebral artery (MCA) Dopplers were performed. At 32 weeks of gestation, the antibody titer had reached 128; the MCA Doppler indicated that fetal anemia was severe. An intrauterine transfusion with Lan antigen-negative RBCs was performed and a viable infant was delivered 25 days later. DISCUSSION: Three cases of HDFN associated with anti-Lan have been previously reported. While these cases have been associated with somewhat variable serologic findings, none have resulted in fetal demise or severe symptomatology requiring pre- or postnatal intervention other than routine phototherapy. The current report, however, suggests that in some instances anti-Lan can result in a more severe form of HDFN requiring more aggressive prenatal therapy. CONCLUSION: In spite of previous case reports suggesting that anti-Lan is associated with relatively mild HDFN, this case suggests that in some instances, this antibody can cause severe HDFN requiring prenatal intervention.

Effects of chemical aging on the ice nucleation activity of soot and polycyclic aromatic hydrocarbon aerosols.

The role of soot particles as ice nuclei (IN) in heterogeneous freezing processes in the atmosphere remains uncertain. Determination of the freezing efficiency of soot is complicated by the changing properties of soot particles undergoing atmospheric aging processes. In this study, the heterogeneous freezing temperatures of droplets in contact with fresh and oxidized soot particles were determined using an optical microscope apparatus equipped with a sealed cooling stage and a CCD video camera. Experiments were also conducted using fresh and oxidized polycyclic aromatic hydrocarbons (PAHs), including anthracene, pyrene, and phenanthrene, as potential ice nuclei. Chemical changes at the surface of the aerosols caused by exposure to ozone were characterized using Fourier transform infrared spectroscopy with horizontal attenuated total reflectance (FTIR-HATR). In addition, Brunauer-Emmett-Teller (BET) measurements were used to determine the specific surface areas of the soot particles. Mean freezing temperatures on fresh particles ranged from -19 to -24 °C, depending on the IN composition and size. In all cases, exposure to ozone facilitated ice nucleation at warmer temperatures, by 2-3 °C, on average. In addition, nucleation rate coefficients for a single temperature and IN type increased by as much as 4 orders of magnitude because of oxidation. Furthermore, a fraction of the oxidized soot particles froze at temperatures above -10 °C. A modified version of classical nucleation theory that accounts for a range of contact angles on nucleation sites within an IN population was used to derive the probability of freezing as a function of temperature for each type of IN. In summary, our results suggest that atmospheric oxidation processes may both extend the range over which particles can act as ice nuclei to warmer temperatures and increase heterogeneous nucleation rates on soot and pollutant aerosols.

A critical evaluation of nemolizumab for prurigo nodularis.

INTRODUCTION: Prurigo nodularis (PN) is a chronic inflammatory skin condition that presents with intensely pruritic, hyperkeratotic nodules. The pathophysiology underlying PN is not entirely clear, making treatment challenging. Patients often require a multimodal approach, although many of the available therapies have low efficacy or adverse effects. AREAS COVERED: In this review, we discuss the use of nemolizumab for the treatment of PN in adults. Nemolizumab is a biological therapy that reduces type 2 cytokines and the neuroimmune response implicated in the pathophysiology of PN. It also helps maintain skin barrier integrity, which may be damaged during the vicious itch-scratch cycle. Nemolizumab has demonstrated great efficacy in improving itch and clearing lesions in recent clinical trials with respectable tolerance. EXPERT OPINION: Nemolizumab is a promising drug for PN that seems comparable to the recently approved dupilumab in terms of its therapeutic effect and excellent safety profile, although nemolizumab may work more rapidly on itch. JAK inhibitors are also emerging as competitors of biologics for PN, however, their safety profile in this population may differ. Trials evaluating these drugs are needed to assess which is preferable. Additional data on the durability and longevity of nemolizumab for PN treatment is highly anticipated.

Unmet needs in treating itch: reaching beyond eczema.

PURPOSE: Pruritus is an unpleasant sensation that creates the urge to scratch. In many chronic conditions, relentless pruritus and scratching perpetuates a vicious itch-scratch cycle. Uncontrolled itch can detrimentally affect quality of life and may lead to sleep disturbance, impaired concentration, financial burden, and psychological suffering. Recent strides have been made to develop guidelines and investigate new therapies to treat some of the most common severely pruritic conditions, however, a large group of diseases remains underrecognized and undertreated. The purpose of this article is to provide a comprehensive review of the challenges hindering the treatment of pruritus. METHODS: An online search was performed using PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov from 1994 to 2024. Included studies were summarized and assessed for quality and relevance in treating pruritus. RESULTS: Several barriers to treating pruritus emerged, including variable presentation, objective measurement of itch, and identifying therapeutic targets. Itch associated with autoimmune conditions, connective tissue diseases, genodermatoses, cutaneous T-cell lymphoma, and pruritus of unknown origin were among the etiologies with the greatest unmet needs. CONCLUSION: Treating pruritus poses many challenges and there are many itchy conditions that have no yet been addressed. There is an urgent need for large-scale controlled studies to investigate potential targets for these conditions and novel therapies.

Current and emerging drugs for the treatment of pruritus: an update of the literature.

INTRODUCTION: Pruritus, particularly in its chronic form, often imposes significant suffering and reductions in patients' quality of life. The pathophysiology of itch is varied depending on disease context, creating opportunities for unique drug development and multimodal therapy. AREAS COVERED: The purpose of this article is to provide an update of the literature regarding current and emerging therapeutics in itch. We review the multitudes of drug targets available and corresponding drugs that have shown efficacy in clinical trials, with a particular emphasis on phase 2 and 3 trials and beyond. Broadly, these targets include therapies directed against type 2 inflammation (i.e. Th2 cytokines, JAK/STAT, lipid mediators, T-cell mediators, and other enzymes and receptors) and neural receptors and targets (i.e. PARs, TRP channels, opioid receptors, MRGPRs, GABA receptors, and cannabinoid receptors). EXPERT OPINION: Therapeutics for itch are emerging at a remarkable pace, and we are entering an era with more and more specialized therapies. Increasingly, these treatments are able to relieve itch beyond their effect on inflammation by directly targeting the neurosensory system.

Spatially distributed atmospheric boundary layer properties in Houston - A value-added observational dataset.

In 2022, Houston, TX became a nexus for field campaigns aiming to further our understanding of the feedbacks between convective clouds, aerosols and atmospheric boundary layer (ABL) properties. Houston's proximity to the Gulf of Mexico and Galveston Bay motivated the collection of spatially distributed observations to disentangle coastal and urban processes. This paper presents a value-added ABL dataset derived from observations collected by eight research teams over 46 days between 2 June - 18 September 2022. The dataset spans 14 sites distributed within a ~80-km radius around Houston. Measurements from three types of instruments are analyzed to objectively provide estimates of nine ABL parameters, both thermodynamic (potential temperature, and relative humidity profiles and thermodynamic ABL depth) and dynamic (horizontal wind speed and direction, mean vertical velocity, updraft and downdraft speed profiles, and dynamical ABL depth). Contextual information about cloud occurrence is also provided. The dataset is prepared on a uniform time-height grid of 1 h and 30 m resolution to facilitate its use as a benchmark for forthcoming numerical simulations and the fundamental study of atmospheric processes.

Production of a chiral alcohol, 1-(3,4-dihydroxyphenyl) ethanol, by mushroom tyrosinase.

1-(3,4-Dihydroxyphenyl) ethanol was produced biocatalytically for the first time using mushroom tyrosinase. 4-Ethylphenol at 1 mM was consumed over 12 min giving 0.23 mM 4-ethylcatechol and 0.36 mM (R/S)-1-(3,4-dihydroxyphenyl) ethanol (ee 0.5 %). Mushroom tyrosinase consumed 4-ethylphenol at 6.7 µmol min(-1) mg protein(-1) while the rates of formation of 4-ethylcatechol and 1-(3,4-dihydroxyphenyl) ethanol were 1.1 and 1.9 µmol min(-1) mg protein(-1). Addition of the ascorbic acid, as a reducing agent to biotransformation reactions, increased 4-ethylcatechol formation by 340 %. However, accumulation of 1-(3,4-dihydroxyphenyl) ethanol was not observed in the presence of ascorbic acid. While the 1-(3,4-dihydroxyphenyl) ethanol was racemic, it is the first chiral product produced by tyrosinase starting from a non-chiral substrate.

Contact Guidance of Connective Tissue Fibroblasts on Submicrometer Anisotropic Topographical Cues Is Dependent on Tissue of Origin, ß1 Integrins, and Tensin-1 Recruitment.

The substratum topography of both natural and synthetic materials is a prominent regulator of cell behaviors including adhesion, migration, matrix fibrillogenesis, and cell phenotype. Connective tissue fibroblasts are known to respond to repeating groove topographical modifications by aligning and exhibiting directed migration, a phenomenon termed contact guidance. Although both reside in collagen rich connective tissues, dermal and gingival fibroblasts are known to exhibit differences in phenotype during wound healing, with gingival tissue showing a fetal-like scarless response. Differences in adhesion formation and maturation are known to underlie both a scarring phenotype and cell response to topographical features. Utilizing repeating groove substrates with periodicities of 600, 900, and 1200 nm (depth, 100 nm), we investigated the roles of integrins αvß3 and ß1 associated adhesions on contact guidance of human gingival (HGFs) and dermal fibroblasts (HDFs). HGFs showed a higher degree of orientation with the groove long axis than HDFs, with alignment of both vinculin and tensin-1 evident on 600 and 900 nm periodicities in both cell types. Orientation with grooves of any periodicity in HGFs and HDFs did not alter the adhesion number or area compared to smooth control surfaces. Growth of both cell types on all periodicities reduced fibronectin fibrillogenesis compared to control surfaces. Independent inhibition of integrin αvß3 and ß1 in both cell types induced changes in spreading up to 6 h and reduced alignment with the groove long axis. At 24 h post-seeding with blocking antibodies, HGFs recovered orientation, but in HDFs, blocking of ß1, but not αvß3 integrins, inhibited alignment. Blocking of ß1 and αvß3 in HDFs, but not HGFs, inhibited tensin-1-associated fibrillar adhesion formation. Furthermore, inhibition of ß1 integrins in HDFs, but not HGFs, resulted in recruitment of tensin-1 to αvß3 focal adhesions, preventing HDFs from aligning with the groove long axis. Our work demonstrates that tensin-1 localization with specific integrins in adhesion sites is an important determinant of contact guidance. This work emphasizes further the need for tissue-specific biomaterials, when integration into host tissues is required.

Pollen Emissions of Subpollen Particles and Ice Nucleating Particles.

Pollen grains significantly contribute to the aerosol population, and levels are predicted to increase in the future. Under humid atmospheric conditions, pollen grains can rupture creating pollen grain fragments referred to as subpollen particles (SPPs) which are dispersed into the atmosphere with wind. In this laboratory study, SPP emission factors were determined for ryegrass, Lolium sp., and giant ragweed,Ambrosia trifida, in terms of the number of SPPs produced per pollen grain and the number of SPPs produced per m2, which were compared to previously measured live oak,Quercus virginiana, emission factors. The SPP emission factors were 4.9 × 1013 ± 4.3 × 1013 SPPs per m2 for ryegrass, 1.3 × 1015 ± 1.1 × 1015 SPPs per m2 for giant ragweed, and 1.1 × 1015 ± 1.6 × 1015 SPPs per m2 for live oak. SPPs and whole pollen grains from these species were evaluated for their ice nucleation efficiency in immersion and contact mode freezing. Measurements of the ice nucleation efficiency indicate that SPPs are weakly effective INPs in immersion mode, but that pollen grains represent a source of moderately efficient INPs in immersion and contact modes.

Effect of Acidity on Ice Nucleation by Inorganic-Organic Mixed Droplets.

Aerosol acidity significantly influences heterogeneous chemical reactions and human health. Additionally, acidity may play a role in cloud formation by modifying the ice nucleation properties of inorganic and organic aerosols. In this work, we combined our well-established ice nucleation technique with Raman microspectroscopy to study ice nucleation in representative inorganic and organic aerosols across a range of pH conditions (pH -0.1 to 5.5). Homogeneous nucleation was observed in systems containing ammonium sulfate, sulfuric acid, and sucrose. In contrast, droplets containing ammonium sulfate mixed with diethyl sebacate, poly(ethylene glycol) 400, and 1,2,6-hexanetriol were found to undergo liquid-liquid phase separation, exhibiting core-shell morphologies with observed initiation of heterogeneous freezing in the cores. Our experimental findings demonstrate that an increased acidity reduces the ice nucleation ability of droplets. Changes in the ratio of bisulfate to sulfate coincided with shifts in ice nucleation temperatures, suggesting that the presence of bisulfate may decrease the ice nucleation efficiency. We also report on how the morphology and viscosity impact ice nucleation properties. This study aims to enhance our fundamental understanding of acidity's effect on ice nucleation ability, providing context for the role of acidity in atmospheric ice cloud formation.

Multi-campaign ship and aircraft observations of marine cloud condensation nuclei and droplet concentrations.

In-situ marine cloud droplet number concentrations (CDNCs), cloud condensation nuclei (CCN), and CCN proxies, based on particle sizes and optical properties, are accumulated from seven field campaigns: ACTIVATE; NAAMES; CAMP2EX; ORACLES; SOCRATES; MARCUS; and CAPRICORN2. Each campaign involves aircraft measurements, ship-based measurements, or both. Measurements collected over the North and Central Atlantic, Indo-Pacific, and Southern Oceans, represent a range of clean to polluted conditions in various climate regimes. With the extensive range of environmental conditions sampled, this data collection is ideal for testing satellite remote detection methods of CDNC and CCN in marine environments. Remote measurement methods are vital to expanding the available data in these difficult-to-reach regions of the Earth and improving our understanding of aerosol-cloud interactions. The data collection includes particle composition and continental tracers to identify potential contributing CCN sources. Several of these campaigns include High Spectral Resolution Lidar (HSRL) and polarimetric imaging measurements and retrievals that will be the basis for the next generation of space-based remote sensors and, thus, can be utilized as satellite surrogates.