Rheumatoid arthritis associated vasculitis: a rare entity; case and review.

We present a case of a 60-year-old male with known seropositive rheumatoid arthritis and cerebral vasculitis who presented to the emergency room with abrupt onset lower back and abdominal pain. The patient developed peritonitis which led to an abdominal laparotomy where jejunal ischemia, necrosis, and perforation were found, requiring bowel resection. On pathology examination, the patient had mesenteric vessel intramural inflammation indicative of vasculitis. He developed an anastomotic leak on postoperative Day 4 and elected hospice care. A high index of suspicion for mesenteric vasculitis should be considered in patients presenting with abdominal pain in the setting of known rheumatoid arthritis associated vasculitis, especially patients with long-standing rheumatoid arthritis. The high mortality represented by gastrointestinal involvement in rheumatoid arthritis associated vasculitis warrants investigation in high-risk patients, despite its low prevalence. Treatment may consist of high-dose corticosteroids, immunosuppressive agents, biologic therapies that target the underlying autoimmune process, and in severe cases, bowel resection.

Myeloperoxidase-ANCA IgG induces different forms of small vessel vasculitis based on type of synergistic immune stimuli.

Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis has diverse patterns of injury including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Necrotizing and crescentic glomerulonephritis (NCGN) occurs in all syndromes and as renal limited vasculitis (RLV). Single dose intravenous ANCA IgG-specific for mouse myeloperoxidase (MPO) causes RLV in mice. Although multiple mouse models have elucidated ANCA-IgG induced necrotizing and crescentic glomerulonephritis (NCGN), pathogenesis of ANCA-induced granulomatosis and vasculitis outside the kidney has not been clarified. To investigate this, we used intravenous MPO-ANCA IgG in the same strain of mice to induce different patterns of lung disease mirroring patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Repeated intravenous MPO-ANCA IgG induced GPA with NCGN, lung capillaritis, arteritis and granulomatosis. Lung leukocyte phenotypes were evaluated by immunohistochemical image analysis and by flow cytometry. ANCA lung capillaritis and microabscesses began within one day and evolved into granulomas in under seven days. Influenza plus single dose MPO-ANCA IgG induced MPA with NCGN, lung capillaritis and arteritis, but no granulomatosis. Allergic airway disease caused by house dust mites or ovalbumin plus single dose intravenous MPO-ANCA IgG induced EGPA with eosinophilic bronchiolitis, NCGN, capillaritis, arteritis, and granulomatosis. Thus, our study shows that the occurrence and pattern of lung lesions are determined by the same ANCA IgG accompanied by different synergistic immune factors.

Moderately thermostable GH1 ß-glucosidases from hyperacidophilic archaeon Cuniculiplasma divulgatum S5.

Family GH1 glycosyl hydrolases are ubiquitous in prokaryotes and eukaryotes and are utilised in numerous industrial applications, including bioconversion of lignocelluloses. In this study, hyperacidophilic archaeon Cuniculiplasma divulgatum (S5T=JCM 30642T) was explored as a source of novel carbohydrate-active enzymes. The genome of C. divulgatum encodes three GH1 enzyme candidates, from which CIB12 and CIB13 were heterologously expressed and characterised. Phylogenetic analysis of CIB12 and CIB13 clustered them with ß-glucosidases from genuinely thermophilic archaea including Thermoplasma acidophilum, Picrophilus torridus, Sulfolobus solfataricus, Pyrococcus furiosus and Thermococcus kodakarensis. Purified enzymes showed maximal activities at pH 4.5-6.0 (CIB12) and 4.5-5.5 (CIB13) with optimal temperatures at 50 °C, suggesting a high-temperature origin of Cuniculiplasma spp. ancestors. Crystal structures of both enzymes revealed a classical (α/ß)8 TIM barrel fold with the active site located inside the barrel close to the C-termini of ß-strands including the catalytic residues Glu204 and Glu388 (CIB12), and Glu204 and Glu385 (CIB13). Both enzymes preferred cellobiose over lactose as substrates and were classified as cellobiohydrolases. Cellobiose addition increased the biomass yield of Cuniculiplasma cultures growing on peptides by 50%, suggesting that the cellobiohydrolases expand the carbon substrate range and hence environmental fitness of Cuniculiplasma.

Claisen Self-Condensation of Lactones in the Synthesis of Ionizable Lipids.

The Claisen self-condensation of lactones can be carried out safely and efficiently under Mukaiyama conditions, in the presence of TiCl4 and triethylamine. The primary Claisen products can be elaborated to various derivatives or converted directly into dihydroxyketones. Such compounds are valuable educts for the synthesis of ionizable lipids for the delivery of nucleic acid therapeutics and can now be accessed through a concise, economical, scalable route that avoids more technically challenging reaction sequences.

Performance of a pilot-scale microbial electrolysis cell coupled with biofilm-based reactor for household wastewater treatment: simultaneous pollutant removal and hydrogen production.

The septic tank is the most commonly used decentralized wastewater treatment systems for household wastewater treatment in on-site applications. The removal rate of various pollutants is lower in different septic tank configurations. The integration of a microbial electrolysis cells (MEC) into septic tank or biofilm-based reactors can be a green and sustainable technology for household wastewater treatment and energy production. In this study, a 50-L septic tank was converted into a 50-L MEC coupled with biofilm-based reactor for simultaneous household wastewater treatment and hydrogen production. The biofilm-based reactor was integrated by an anaerobic packed-bed biofilm reactor (APBBR) and an aerobic moving bed biofilm reactor (aeMBBR). The MEC/APBBR/aeMBBR was evaluated at different organic loading rates (OLRs) by applying voltage of 0.7 and 1.0 V. Result showed that the increase of OLRs from 0.2 to 0.44 kg COD/m3 d did not affect organic matter removals. Nutrient and solids removal decreased with increasing OLR up to 0.44 kg COD/m3 d. Global removal of chemical oxygen demand (COD), biochemical oxygen demand (BOD), total nitrogen (TN), ammoniacal nitrogen (NH4+), total phosphorus (TP) and total suspended solids (TSS) removal ranged from 81 to 84%, 84 to 85%, 53 to 68%, 88 to 98%, 11 to 30% and 76 to 88% respectively, was obtained in this study. The current density generated in the MEC from 0 to 0.41 A/m2 contributed to an increase in hydrogen production and pollutants removal. The maximum volumetric hydrogen production rate obtained in the MEC was 0.007 L/L.d (0.072 L/d). The integration of the MEC into biofilm-based reactors applying a voltage of 1.0 V generated different bioelectrochemical nitrogen and phosphorus transformations within the MEC, allowing a simultaneous denitrification-nitrification process with phosphorus removal.

Chemical optimization and derivatization of micrococcin p2 to target multiple bacterial infections: new antibiotics from thiopeptides.

Antimicrobial resistance poses a significant threat to humanity, and the development of new antibiotics is urgently needed. Our research has focused on thiopeptide antibiotics such as micrococcin P2 (MP2) and derivatives thereof as new anti-infective agents. Thiopeptides are sulfur-rich, structurally complex substances that exhibit potent activity against Gram-positive pathogens and Mycobacteria species, including clinically resistant strains. The clinical development of thiopeptides has been hampered by the lack of efficient synthetic platforms to conduct detailed structure-activity relationship studies of these natural products. The present contribution touches upon efficient synthetic routes to MP2 that laid the groundwork for clinical translation. The medicinal chemistry campaign on MP2 has been guided by computational molecular dynamic simulations and parallel investigations to improve drug-like properties, such as enhancing the aqueous solubility and optimizing antibacterial activity. Such endeavors have enabled identification of promising lead compounds, AJ-037 and AJ-206, against Mycobacterium avium complex (MAC). Extensive in vitro studies revealed that these compounds exert potent activity against MAC species, a subspecies of non-tuberculous mycobacteria (NTM) that proliferate inside macrophages. Two additional pre-clinical candidates have been identified: AJ-024, for the treatment of Clostridioides difficile infections, and AJ-147, for methicillin-resistant Staphylococcus aureus impetigo. Both compounds compare quite favorably with current first-line treatments. In particular, the ability of AJ-147 to downregulate pro-inflammatory cytokines adds a valuable dimension to its clinical use. In light of above, these new thiopeptide derivatives are well-poised for further clinical development.

Exploring the relationship between ulcerative colitis, colorectal cancer, and prostate cancer.

Chronic systemic inflammation caused by diseases such as ulcerative colitis (UC) and Crohn's disease (CD) increases the risk of developing colorectal cancer (CRC). Recent evidence indicates that patients with UC are more susceptible to prostate cancer (PCa), and individuals with PCa may also be at a higher risk of developing CRC. However, these relationships are not well defined. A better understanding of this phenomenon could improve the identification of high-risk populations. In this study, we characterized these relationships with experiments using preclinical mouse models of dextran sulfate sodium (DSS)-induced colitis (DSS-UC) and DSS/azoxymethane (AOM)-induced CRC (DSS/AOM-CRC) in wild-type and conditional transgenic mice of PCa. We showed that DSS-induced UC was more severe in mice with PCa and resulted in the development of CRC in the absence of AOM. We further showed that PCa-free mice that developed DSS-induced UC also showed histological changes in the normal prostate that resembled proliferative inflammatory atrophy. Finally, we used immunohistochemical immune profiling to show that mice with PCa-induced chronic systemic inflammation accumulated Gr1+ myeloid cells in the normal colon and exposure to DSS further enriched these cells in active colitis regions and colon tumors. Our study provides evidence to support a link between systemic chronic inflammation and cancer.

Compression-dependent microtubule reinforcement enables cells to navigate confined environments.

Cells migrating through complex three-dimensional environments experience considerable physical challenges, including tensile stress and compression. To move, cells need to resist these forces while also squeezing the large nucleus through confined spaces. This requires highly coordinated cortical contractility. Microtubules can both resist compressive forces and sequester key actomyosin regulators to ensure appropriate activation of contractile forces. Yet, how these two roles are integrated to achieve nuclear transmigration in three dimensions is largely unknown. Here, we demonstrate that compression triggers reinforcement of a dedicated microtubule structure at the rear of the nucleus by the mechanoresponsive recruitment of cytoplasmic linker-associated proteins, which dynamically strengthens and repairs the lattice. These reinforced microtubules form the mechanostat: an adaptive feedback mechanism that allows the cell to both withstand compressive force and spatiotemporally organize contractility signalling pathways. The microtubule mechanostat facilitates nuclear positioning and coordinates force production to enable the cell to pass through constrictions. Disruption of the mechanostat imbalances cortical contractility, stalling migration and ultimately resulting in catastrophic cell rupture. Our findings reveal a role for microtubules as cellular sensors that detect and respond to compressive forces, enabling movement and ensuring survival in mechanically demanding environments.

Multimethod Analysis of a Novel Multi-coloured Heat-treated Nickel-Titanium Rotary System: Design, Metallurgy, Mechanical Properties, and Shaping Ability.

INTRODUCTION: This study aimed to compare a new multicolored rotary system with four heat-treated rotary instruments using the multimethod approach. METHODS: Three-hundred instruments of RCS Rainbow, Rotate, RaCe EVO, OneCurve, and ProTaper Ultimate systems were evaluated regarding their design (stereomicroscopy, scanning electron microscopy, and 3D surface scanning), metallurgy, and mechanical performance (cyclic fatigue, torsional resistance, bending and buckling resistance, and cutting ability). Unprepared surfaces after canal preparation of maxillary molars were evaluated using micro-computed tomography. Kruskal-Wallis and one-way analysis of variance post hoc Tukey tests were used for statistical comparisons (α = 5%). RESULTS: Instruments exhibited variations in active blade length, number of spirals, and cross-sectional designs. RCS Rainbow showed specific phase transformation temperatures, highest bending (400.5gf) and buckling (286gf) resistance values, and lowest mean angle of rotation (529°) (P < .05). OneCurve exhibited superior cutting ability (8.4 mm) and longer time to fracture (112s). RaCe EVO displayed the lowest time to fracture (51s), maximum torque (1.2 N.cm), buckling (174gf), and bending resistance (261gf) values (P < .05). ProTaper Ultimate showed the highest torque (1.6 N.cm) and angle of rotation (611°) (P < .05), while its bending load (262gf) was comparable to RaCe EVO (P > .05). Rotate instrument showed intermediate values in the mechanical tests. No difference was observed regarding the unprepared canal surfaces (P > .05) CONCLUSIONS: RCS Rainbow demonstrates a trade-off between flexibility and other mechanical properties. Its dimensions exceeded those of other instruments, affording it higher torque resistance, yet concurrently reducing its flexibility, angle of rotation, and cutting ability. OneCurve stands out as a well-balanced choice by integrating geometric design and mechanical performance.

Confronting the challenge: a regional perspective by the Latin American pediatric infectious diseases society (SLIPE) expert group on respiratory syncytial virus-tackling the burden of disease and implementing preventive solutions.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children around the world. The post-pandemic era has resulted in a notable increase in reported cases of RSV infections, co-circulation of other respiratory viruses, shifts in epidemiology, altered respiratory season timing, and increased healthcare demand. Low- and middle-income countries are responsible for the highest burden of RSV disease, contributing significantly to health expenses during respiratory seasons and RSV-associated mortality in children. Until recently, supportive measures were the only intervention to treat or prevent RSV-infection, since preventive strategies like palivizumab are limited for high-risk populations. Advances in new available strategies, such as long-acting monoclonal antibodies during the neonatal period and vaccination of pregnant women, are now a reality. As the Regional Expert Group of the Latin American Pediatric Infectious Diseases Society (SLIPE), we sought to evaluate the burden of RSV infection in Latin America and the Caribbean (LAC) region, analyze current strategies to prevent RSV infection in children, and provide recommendations for implementing new strategies for preventing RSV infection in children in LAC region.

Cupuaçu (Theobroma grandiflorum): A Multifunctional Amazonian Fruit with Extensive Benefits.

The Amazon region is known for its continental dimension, water abundance, and especially for the rich biodiversity that this biome hosts. Among the thousands of plant species in the Amazon, many represent food sources. Among these, cupuaçu (Theobroma grandiflorum (Willd. ex Spreng.) K.Schum.) stands out as an iconic fruit with an exotic flavor, appreciated for its remarkable organoleptic properties. The present review aims to provide a comprehensive description of its biology, agronomical uses, nutritional values, chemical compositions, medicinal properties, and industrial applications. The search based on scientific articles demonstrates T. grandiflorum as a valuable ingredient for the food, cosmetic and pharmaceutical sectors. Data analysis demonstrates that cupuaçu cultivation and processing contribute to the strengthening of local production chains and promotes the development of small communities, and thus the bioeconomy in the Amazon region. In this sense, since the last decade, cultivar improvement has required multidisciplinary efforts, resulting in disease-resistant plants with better productivity. Regarding its chemical composition, T. grandiflorum is a notable source of methylxanthine alkaloids, polyphenols, aroma compounds, and lipids. The presence of these compounds supports the use of cupuaçu in various products and help us to understand the potential health benefits of its consumption. Through the integration of all collected information, key gaps in basic and applied sciences were observed, highlighting the need for more research to uncover novel applications and products of T. grandiflorum. The development of new products based on biodiversity is fundamental to promoting environmental and economic sustainability, which are key steps to the survival of the Amazon rainforest. Therefore, this work summarizes the knowledge on this source and sheds light on a food source that is little known outside of the Amazon borders.

CO2 Hydrogenation to Methanol over Mesoporous SiO2-Coated Cu-Based Catalysts.

Although chemical promotion led to essential improvements in Cu-based catalysts for CO2 hydrogenation to methanol, surpassing structural limitations such as active phase aggregation under reaction conditions remains challenging. In this report, we improved the textural properties of Cu/In2O3/CeO2 and Cu/In2O3/ZrO2 catalysts by coating the nanoparticles with a mesoporous SiO2 shell. This strategy limited particle size up to 3.5 nm, increasing metal dispersion and widening the metal-metal oxide interface region. Chemometric analysis revealed that these structures could maintain high activity and selectivity in a wide range of reaction conditions, with methanol space-time yields up to 4 times higher than those of the uncoated catalysts.

Genetic Engineering of Transfusable Platelets with mRNA-Lipid Nanoparticles is Compatible with Blood Banking Practices.

Platelets contribute to a variety of physiological processes including inflammation, sepsis and cancer. However, due to their primary role in hemostasis, platelet transfusions are largely restricted to managing thrombocytopenia and bleeding. One way to expand the utility of platelet transfusions would be to genetically engineer donor platelets with new or enhanced functions. We have previously shown that lipid nanoparticles containing mRNA (mRNA-LNP) can be used to genetically modify authentic platelets in a non-clinical crystalloid solution. Currently, platelets collected for transfusion are stored in plasma or in plasma supplemented with platelet additive solution (PAS) at supraphysiological concentrations at room temperature, or at 4 ºC if intended for use in acute hemorrhage. Here we describe a new plasma-optimized mRNA-LNP for transfecting platelets directly in plasma and plasma supplemented with PAS that is scalable to physiological and supraphysiological platelet concentrations. Transfecting platelets in clinical solutions with mRNA-LNP does not affect aspects of in vitro physiology, and transfected platelets are storable. The compatibility of this transfection system with current clinical practices could enable future mRNA-LNP based platelet products and cell therapies.

Chronic Total Occlusions and Coronary Artery Bypass Grafting Outcomes.

OBJECTIVE: Investigate the association between the presence and grafting of chronic total occlusions (CTO) and coronary artery bypass grafting (CABG) outcomes. METHODS: This was a post hoc analysis of the REGROUP trial, which randomized veterans undergoing isolated on-pump CABG to endoscopic versus open vein harvest (2014-2017). Patients were stratified based on the presence of at least one CTO vessel (a 100% occluded coronary lesion for greater than or equal to 3 months), and according to whether all CTO vessels were bypassed. Rates of major cardiac adverse events (MACE) were compared. RESULTS: At least 1 CTO was present in 453/1,149 patients (39.4%). Over a median follow up of 4.7 years (interquartile range 3.84-5.45), MACE rates were 23.4% vs. 22.2% for the CTO vs. no CTO group, respectively (adjusted hazard ratio [AHR] 0.92, 95% CI 0.70-1.20). MACE rates for patients with complete CTO grafting vs. not were 23.1% vs. 25.0%, respectively (AHR 0.95, 95% CI 0.57-1.57) . In patients with right coronary dominance undergoing LAD grafting, bypassing a RCA CTO was associated with significantly lower rates of all-cause mortality (AHR 0.38, 95% CI 0.17-0.83). CONCLUSIONS: In this REGROUP trial subanalysis, neither CTO presence or complete grafting of CTO vessels were associated with significantly different rates of MACE. However, the finding of possible survival benefit among a subgroup of patients undergoing grafting of a dominant RCA CTO vessel alongside LAD grafting warrants additional study.

An evidence-informed pedagogical approach to support professional identity formation in medical students: AMEE Guide No. 171.

There is a long and impressive scholarly history evidencing why it is important to address professional identity formation (PIF) in medical curricula. In this AMEE Guide, the authors present an evidence-informed pedagogical approach to assist educators in developing educational practices to foster a healthy PIF in medical students. The authors first describe the theoretical framework that underpin this approach. At the core of this framework is the recognition that, for a healthy PIF, students need to become aware that they have the autonomy, but also responsibility, to form their professional identity in a way that fits both their personality and their (future) professional role. In other words, students need to learn to navigate the interplay between socialization and subjectification. Next, the authors outline the six-step structure of their pedagogical approach, designed to help students: (1) undergo a PIF-related experience, (2) observe their responses to the experience, (3) externalize their reflections, (4) share their reflections, (5) broaden their perspective, and (6) explore their freedom of choice through experimentation. The authors also describe six conducive conditions to facilitate the implementation of the pedagogical approach. These conditions include (1) creating a setting that enables students to slow down, (2) adopting a longitudinal approach, (3) making it part of the formal curriculum, (4) refraining from grading, (5) establishing an interdisciplinary expert team, and (6) providing teacher training. The authors conclude that the theoretical framework leads to a coherent and consistent pedagogical approach that, when implemented according to the conducive conditions, enables students to gradually internalize the reflective process and help them to cultivate a reflective attitude towards their PIF.

Influence of ß2-adrenergic selective agonist formoterol on the motor unit of a mouse model of a congenital myasthenic syndrome with complete VAChT deletion.

Congenital Myasthenic Syndromes (CMS) are a set of genetic diseases that affect the neuromuscular transmission causing muscular weakness. The standard pharmacological treatment aims at ameliorating the myasthenic symptom by acetylcholinesterase inhibitors. Most patients respond well in the short and medium term, however, over time the beneficial effects rapidly fade, and the efficacy of the treatment diminishes. Increasing evidence shows that ß2-adrenergic agonists can be a suitable choice for the treatment of neuromuscular disorders, including CMS, as they promote beneficial effects in the neuromuscular system. The exact mechanism on which they rely is not completely understood, although patients and animal models respond well to the treatment, especially over extended periods. Here, we report the use of the long-lasting specific ß2-adrenergic agonist formoterol in a myasthenic mouse model (mnVAChT-KD), featuring deletion of VAChT (Vesicular Acetylcholine Transporter) specifically in the α-motoneurons. Our findings demonstrate that formoterol treatment (300 µg/kg/day; sc) for 30 days increased the neuromuscular junction area, induced skeletal muscle hypertrophy and altered fibre type composition in myasthenic mice. Interestingly, ß2-adrenergic agonists have shown efficacy even in the absence of ACh (acetylcholine). Our data provide important evidence supporting the potential of ß2-adrenergic agonists in treating neuromuscular disorders of pre-synaptic origin and characterized by disruptions in nerve-muscle communication, through a direct and beneficial action within the motor unit.

Oxyplasma meridianum gen. nov., sp. nov., an extremely acidophilic organotrophic member of the order Thermoplasmatales.

A mesophilic, hyperacidophilic archaeon, strain M1T, was isolated from a rock sample from Vulcano Island, Italy. Cells of this organism were cocci with an average diameter of 1 µm. Some cells possessed filaments. The strain grew in the range of temperatures between 15 and 52 °C and pH 0.5-4.0 with growth optima at 40 °C and pH 1.0. Strain M1T was aerobic and chemoorganotrophic, growing on complex substrates, such as casamino acids, trypticase, tryptone, yeast and beef extracts. No growth at expenses of oxidation of elemental sulphur or reduced sulphur compounds, pyrite, or ferrous sulphate was observed. The core lipids were glycerol dibiphytanyl glycerol tetraether lipids (membrane spanning) with 0 to 4 cyclopentane moieties and archaeol, with trace amounts of hydroxy archaeol. The dominant quinone was MK-7 : 7. The genome size of M1T was 1.67 Mbp with a G+C content of 39.76 mol%, and both characteristics were well within the common range for Thermoplasmatales. The phylogenetic analysis based on 16S rRNA gene sequence placed the strain M1T within the order Thermoplasmatales with sequence identities of 90.9, 90.3 and 90.5% to the closest SSU rRNA gene sequences from organisms with validly published names, Thermoplasma acidophilum, Thermoplasma volcanium and Thermogymnomonas acidicola, respectively. Based on the results of our genomic, phylogenetic, physiological and chemotaxonomic studies, we propose that strain M1T (=DSM 116605T=JCM 36570T) represents a new genus and species, Oxyplasma meridianum gen. nov., sp. nov., within the order Thermoplasmatales.

Flow Activation Energy of High-Concentration Monoclonal Antibody Solutions and Protein-Protein Interactions Influenced by NaCl and Sucrose.

The solution viscosity and protein-protein interactions (PPIs) as a function of temperature (4-40 °C) were measured at a series of protein concentrations for a monoclonal antibody (mAb) with different formulation conditions, which include NaCl and sucrose. The flow activation energy (Eη) was extracted from the temperature dependence of solution viscosity using the Arrhenius equation. PPIs were quantified via the protein diffusion interaction parameter (kD) measured by dynamic light scattering, together with the osmotic second virial coefficient and the structure factor obtained through small-angle X-ray scattering. Both viscosity and PPIs were found to vary with the formulation conditions. Adding NaCl introduces an attractive interaction but leads to a significant reduction in the viscosity. However, adding sucrose enhances an overall repulsive effect and leads to a slight decrease in viscosity. Thus, the averaged (attractive or repulsive) PPI information is not a good indicator of viscosity at high protein concentrations for the mAb studied here. Instead, a correlation based on the temperature dependence of viscosity (i.e., Eη) and the temperature sensitivity in PPIs was observed for this specific mAb. When kD is more sensitive to the temperature variation, it corresponds to a larger value of Eη and thus a higher viscosity in concentrated protein solutions. When kD is less sensitive to temperature change, it corresponds to a smaller value of Eη and thus a lower viscosity at high protein concentrations. Rather than the absolute value of PPIs at a given temperature, our results show that the temperature sensitivity of PPIs may be a more useful metric for predicting issues with high viscosity of concentrated solutions. In addition, we also demonstrate that caution is required in choosing a proper protein concentration range to extract kD. In some excipient conditions studied here, the appropriate protein concentration range needs to be less than 4 mg/mL, remarkably lower than the typical concentration range used in the literature.

Persistence and pathway of glyphosate degradation in the coastal wetland soil of central Delaware.

Glyphosate is a globally dominant herbicide. Here, we studied the degradation and microbial response to glyphosate application in a wetland soil in central Delaware for controlling invasive species (Phragmites australis). We applied a two-step solid-phase extraction method using molecularly imprinted polymers designed for the separation and enrichment of glyphosate and aminomethylphosphonic acid (AMPA) from soils before their analysis by ultra-high-performance liquid chromatography (UHPLC) and Q Exactive Orbitrap mass spectrometry methods. Our results showed that approximately 90 % of glyphosate degraded over 100 d after application, with AMPA being a minor (<10 %) product. Analysis of glyphosate-specific microbial genes to identify microbial response and function revealed that the expression of the phnJ gene, which codes C-P lyase enzyme, was consistently dominant over the gox gene, which codes glyphosate oxidoreductase enzyme, after glyphosate application. Both gene and concentration data independently suggested that C-P bond cleavage-which forms sarcosine or glycine-was the dominant degradation pathway. This is significant because AMPA, a more toxic product, is reported to be the preferred pathway of glyphosate degradation in other soil and natural environments. The degradation through a safer pathway is encouraging for minimizing the detrimental impacts of glyphosate on the environment.

Learning from regulatory failure: How Ostrom's restorative justice design principle helps naïve groups create wiser enforcement systems to overcome the tragedy of the commons.

Rule enforcement is critical in democratic, self-governing societies. Many political disputes occur when citizens do not understand the fundamental rationales for enforcement (e.g., COVID-19 pandemic). We examined how naïve groups learn and develop wise enforcement systems. Based on theories from behavioral economics, political science, psychology, and education, we predicted that groups need to experience failure of an enforcement system, but be guided on restorative justice principles to collectively learn from this failure. Undergraduate students (N = 288) from a Midwestern U.S. metropolitan university self-governed a simulated common-pool resource with real financial payoffs. Groups began with one of three conditions designed to create different experiences with enforcement and regulatory failure: (a) no enforcement (no communication or peer sanctioning), (b) lax enforcement (communication with peer-sanctioning), or (c) regulatory abuse (peer sanctioning without communication). Half then received facilitated guidance on restorative justice principles (e.g., discuss whether/why to use sanctions). To examine cooperation, we measured how well participants maintained the resource. To examine group learning, we created a novel coding system, which tracked groups' constitutional decisions about conservation agreements and enforcement, conceptual understanding, and the enforcement systems they created. The no-enforcement and lax-enforcement conditions quickly yielded moderate cooperation via voluntary agreements. However, such agreements prevented groups from discovering how and why to use enforcement (peer sanctioning) to improve performance. Initial exposure to regulatory failure had different effects depending on facilitation. Unfacilitated groups fixated on initial misconceptions, causing them to abandon or create less sophisticated enforcement systems, hindering cooperation. Facilitated groups learned from prior failure-discovering principles of wise enforcement (e.g., collective efficiency, self-restraint)-and created more sophisticated enforcement systems (e.g., coordinated sanctions) that improved cooperation. Guidance on restorative justice principles and experience with regulatory abuse may be necessary preconditions for naïve individuals to understand and develop wiser collective enforcement systems.