Stabilization of Non-Native Folds and Programmable Protein Gelation in Compositionally Designed Deep Eutectic Solvents.

Proteins are adjustable units from which biomaterials with designed properties can be developed. However, non-native folded states with controlled topologies are hardly accessible in aqueous environments, limiting their prospects as building blocks. Here, we demonstrate the ability of a series of anhydrous deep eutectic solvents (DESs) to precisely control the conformational landscape of proteins. We reveal that systematic variations in the chemical composition of binary and ternary DESs dictate the stabilization of a wide range of conformations, that is, compact globular folds, intermediate folding states, or unfolded chains, as well as controlling their collective behavior. Besides, different conformational states can be visited by simply adjusting the composition of ternary DESs, allowing for the refolding of unfolded states and vice versa. Notably, we show that these intermediates can trigger the formation of supramolecular gels, also known as eutectogels, where their mechanical properties correlate to the folding state of the protein. Given the inherent vulnerability of proteins outside the native fold in aqueous environments, our findings highlight DESs as tailorable solvents capable of stabilizing various non-native conformations on demand through solvent design.

Modulating protein unfolding and refolding via the synergistic association of an anionic and a nonionic surfactant.

HYPOTHESIS: Nonionic surfactants can counter the deleterious effect that anionic surfactants have on proteins, where the folded states are retrieved from a previously unfolded state. However, further studies are required to refine our understanding of the underlying mechanism of the refolding process. While interactions between nonionic surfactants and tightly folded proteins are not anticipated, we hypothesized that intermediate stages of surfactant-induced unfolding could define new interaction mechanisms by which nonionic surfactants can further alter protein conformation. EXPERIMENTS: In this work, the behavior of three model proteins (human growth hormone, bovine serum albumin, and ß-lactoglobulin) was investigated in the presence of the anionic surfactant sodium dodecylsulfate, the nonionic surfactant ß-dodecylmaltoside, and mixtures of both surfactants. The transitions occurring to the proteins were determined using intrinsic fluorescence spectroscopy and far-UV circular dichroism. Based on these results, we developed a detailed interaction model for human growth hormone. Using nuclear magnetic resonance and contrast-variation small-angle neutron scattering, we studied the amino acid environment and the conformational state of the protein. FINDINGS: The results demonstrate the key role of surfactant cooperation in defining the conformational state of the proteins, which can shift away or toward the folded state depending on the nonionic-to-ionic surfactant ratio. Dodecylmaltoside, initially a non-interacting surfactant, can unexpectedly associate with sodium dodecylsulfate-unfolded proteins to further impact their conformation at low nonionic-to-ionic surfactant ratio. When this ratio increases, the protein begins to retrieve the folded state. However, the native conformation cannot be fully recovered due to remnant surfactant molecules still adsorbed to the protein. This study demonstrates that the conformational landscape of the protein depends on a delicate interplay between the surfactants, ultimately controlled by the ratio between them, resulting in unpredictable changes in the protein conformation.

Outcomes of Simultaneous Versus Staged Resection for Stage IV Colorectal Cancer with Synchronous Liver Metastases.

INTRODUCTION: Management of stage IV colorectal cancer with synchronous liver metastases remains debated, as colorectal and liver resections can be performed simultaneously or staged apart. OBJECTIVE: This study aims to determine any demographic or outcome differences between simultaneous and staged resection. PARTICIPANTS: Retrospective review was performed on patients diagnosed with synchronous colorectal primary and liver metastases within Southern California Kaiser Permanente (KP) hospitals between 2010 and 2020. Patients with other metastases on diagnosis or those who did not receive both primary and liver resections were excluded. Demographic and outcome data were collected and analyzed. RESULTS: Of the 113 patients who met criteria, 72 (63.7%) received simultaneous and 41 (36.3%) received staged resection. Demographic data were comparable between simultaneous and staged resection, respectively, including median age of diagnosis, sex, and race. Both groups had similar median length of stay, percentage of major colorectal resection, and percentage of major liver resection. Both groups also had similar rates of radiation therapy, chemotherapy, and immunotherapy. There were no statistically significant difference in complications rates, median follow-up time, median overall survival, and median disease-free survival. CONCLUSIONS: Practice patterns within Southern California KP hospitals favor minor colorectal and liver resections. However, there were no significant differences in demographics, treatment rates, or outcomes between simultaneous and staged resection. While not statistically significant, our findings of a 11.9% higher major liver resection rate and 7.5-month longer median disease-free survival in the staged resection group may benefit from further study with higher power datasets.

Towards a global partnership model in interprofessional education for cross-sector problem-solving.

OBJECTIVES: A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. METHODS: This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students' data. RESULTS: We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest-posttest differences in students' readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students' social interaction anxiety after the IPE simulation. CONCLUSIONS: The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education.

Omitting Foley Catheter Use in Mastectomy Patients With or Without Immediate Reconstruction.

BACKGROUND: Foley catheter placement is often advised in surgeries anticipated to exceed 3 hours; however, this time cutoff does not take into account the type of surgery. Complications from Foley catheter placement include urinary tract infections and genitourinary trauma that may be costly to healthcare systems. Our objective was to determine whether mastectomy with or without reconstruction can be done without Foley use, without an increase in urinary retention risk. METHODS: One hundred eighty-seven patients who underwent unilateral or bilateral mastectomies with or without reconstruction in 2020 and 2021 were reviewed. Chart review included intraoperative fluids given, estimated blood loss, lymph node dissection, and duration of procedure. RESULTS: After excluding patients with case duration under 180 minutes, 145 remained. Ninety-four patients did not have a Foley and 51 patients had an intraoperative Foley. None of the patients without a Foley experienced postoperative urinary retention, including 3 patients who also underwent lymphatic microsurgical preventive healing approach. Eighty-six percent of patients were discharged on the day of surgery. Patients with or without a Foley did not differ significantly in terms of race, rate of axillary lymph node dissection, body mass index, rate of same-day discharge, presence of hypertension or diabetes, estimated blood loss, or age. CONCLUSIONS: Patients undergoing unilateral and bilateral mastectomies with or without reconstruction or lymphatic microsurgical preventive healing approach may avoid Foley catheter placement without increased risk of urinary retention, even if the case is anticipated to exceed 3 hours. Advantages include elimination of catheter-associated urinary tract infections and their associated hospital costs, as well as avoiding genitourinary trauma.

Topological Dynamics of Micelles Formed by Geometrically Varied Surfactants.

The molecular architecture of sugar-based surfactants strongly affects their self-assembled structure, i.e., the type of micelles they form, which in turn controls both the dynamics and rheological properties of the system. Here, we report the segmental and mesoscopic structure and dynamics of a series of C16 maltosides with differences in the anomeric configuration and degree of tail unsaturation. Neutron spin-echo measurements showed that the segmental dynamics can be modeled as a one-dimensional array of segments where the dynamics increase with inefficient monomer packing. The network dynamics as characterized by dynamic light scattering show different relaxation modes that can be associated with the micelle structure. Hindered dynamics are observed for arrested networks of worm-like micelles, connected to their shear-thinning rheology, while nonentangled diffusing rods relate to Newtonian rheological behavior. While the design of novel surfactants with controlled properties poses a challenge for synthetic chemistry, we demonstrate how simple variations in the monomer structure can significantly influence the behavior of surfactants.

New Insights into the Interaction of Class II Dihydroorotate Dehydrogenases with Ubiquinone in Lipid Bilayers as a Function of Lipid Composition.

The fourth enzymatic reaction in the de novo pyrimidine biosynthesis, the oxidation of dihydroorotate to orotate, is catalyzed by dihydroorotate dehydrogenase (DHODH). Enzymes belonging to the DHODH Class II are membrane-bound proteins that use ubiquinones as their electron acceptors. We have designed this study to understand the interaction of an N-terminally truncated human DHODH (HsΔ29DHODH) and the DHODH from Escherichia coli (EcDHODH) with ubiquinone (Q10) in supported lipid membranes using neutron reflectometry (NR). NR has allowed us to determine in situ, under solution conditions, how the enzymes bind to lipid membranes and to unambiguously resolve the location of Q10. Q10 is exclusively located at the center of all of the lipid bilayers investigated, and upon binding, both of the DHODHs penetrate into the hydrophobic region of the outer lipid leaflet towards the Q10. We therefore show that the interaction between the soluble enzymes and the membrane-embedded Q10 is mediated by enzyme penetration. We can also show that EcDHODH binds more efficiently to the surface of simple bilayers consisting of 1-palmitoyl, 2-oleoyl phosphatidylcholine, and tetraoleoyl cardiolipin than HsΔ29DHODH, but does not penetrate into the lipids to the same degree. Our results also highlight the importance of Q10, as well as lipid composition, on enzyme binding.

Evolving Escherichia coli Host Strains for Efficient Deuterium Labeling of Recombinant Proteins Using Sodium Pyruvate-d3.

Labeling of proteins with deuterium (2H) is often necessary for structural biology techniques, such as neutron crystallography, NMR spectroscopy, and small-angle neutron scattering. Perdeuteration in which all protium (1H) atoms are replaced by deuterium is a costly process. Typically, expression hosts are grown in a defined medium with heavy water as the solvent, which is supplemented with a deuterated carbon source. Escherichia coli, which is the most widely used host for recombinant protein production, can utilize several compounds as a carbon source. Glycerol-d8 is often used as a carbon source for deuterium labelling due to its lower cost compered to glucose-d7. In order to expand available options for recombinant protein deuteration, we investigated the possibility of producing a deuterated carbon source in-house. E. coli can utilize pyruvate as a carbon source and pyruvate-d3 can be made by a relatively simple procedure. To circumvent the very poor growth of E. coli in minimal media with pyruvate as sole carbon source, adaptive laboratory evolution for strain improvement was applied. E. coli strains with enhanced growth in minimal pyruvate medium was subjected to whole genome sequencing and the genetic changes were revealed. One of the evolved strains was adapted for the widely used T7 RNA polymerase overexpression systems. Using the improved strain E. coli DAP1(DE3) and in-house produced deuterated carbon source (pyruvic acid-d4 and sodium pyruvate-d3), we produce deuterated (>90%) triose-phosphate isomerase, at quantities sufficient enough for large volume crystal production and subsequent analysis by neutron crystallography.

Protecting water birds of wetlands: Using toxicological tests and ecological risk assessment, based on metal/loid (s) of water, sediment and biota samples.

Water, sediment and biota (two fish and one shrimp species) samples were collected from rivers, ponds, mudflat and estuaries within the Mai Po Ramsar site in Hong Kong, China, to determine the concentrations of heavy metals/loid (HMs): cadmium (Cd), copper (Cu), mercury (Hg), lead (Pb), zinc (Zn), and arsenic (As). The mutagenicity and toxicity of water and sediment samples were evaluated using Ames test and Microtox® bioassay, respectively. Ecological risk assessments on water birds were also conducted based on HM concentrations in biota, sediment and water samples. In general, results showed that downstream of Shan Pui River and Ng Tung River had relatively higher HM concentrations (e.g. Cu: 0.992-9.49 µg/L; As: 0.342-5.83 µg/L) when compared with estuaries (Cu: 0.400-3.69 µg/L; As: 0.220-0.931 µg/L) and ponds (Cu: 0.0402-2.41 µg/L; As: 0.0501-2.10 µg/L), except Hg and Cd. On the other hand, sediment samples collected from Ng Tung River showed mutagenicity on Salmonella typhimurium tester strain TA100, while the mudflat samples had mutagenicity on tester strain TA98 used in the Ames tests. Microtox® bioassay indicated that only sediment of Ng Tung River showed acute toxicity with a 15 min half maximal effective concentration (EC50) value of 30.5%. Results of ecological risk assessments showed that grey heron (Ardea cinerea), which feeds on fish and shrimps at Shan Pui River and ponds were not at risk. However, common sandpiper (Actitis hypoleucos), which feeds at ponds were subjected to a potential health risk due to its behavior of seeking food from the sediments, especially this bird species has a small body size. This indicates juvenile birds of other species may also be affected. Remediation should be implemented to relief the potential risk of Cu and Pb, to these water birds in the Mai Po Ramsar site.

Direct localization of detergents and bacteriorhodopsin in the lipidic cubic phase by small-angle neutron scattering.

Lipidic cubic phase (LCP) crystallization methods have been essential in obtaining crystals of certain membrane proteins, particularly G-protein-coupled receptors. LCP crystallization is generally optimized across a large number of potential variables, one of which may be the choice of the solubilizing detergent. A better fundamental understanding of the behavior of detergents in the LCP may guide and simplify the detergent selection process. This work investigates the distribution of protein and detergent in LCP using the membrane protein bacteriorhodopsin (bR), with the LCP prepared from highly deuterated monoolein to allow contrast-matched small-angle neutron scattering. Contrast-matching allows the scattering from the LCP bilayer itself to be suppressed, so that the distribution and behavior of the protein and detergent can be directly studied. The results showed that, for several common detergents, the detergent micelle dissociates and incorporates into the LCP bilayer essentially as free detergent monomers. In addition, the detergent octyl glucoside dissociates from bR, and neither the protein nor detergent forms clusters in the LCP. The lack of detergent assemblies in the LCP implies that, upon incorporation, micelle sizes and protein/detergent interactions become less important than they would be in solution crystallization. Crystallization screening confirmed this idea, with crystals obtained from bR in the presence of most detergents tested. Thus, in LCP crystallization, detergents can be selected primarily on the basis of protein stabilization in solution, with crystallization suitability a lesser consideration.

Molecular structure of maltoside surfactants controls micelle formation and rheological behavior.

HYPOTHESIS: The anomeric configuration (α or ß) of n-hexadecyl-d-maltopyranoside (C16G2) has been shown to affect the morphology of the micelle, from elongated for α-C16G2 to worm-like micelles for ß-C16G2. The entanglement of worm-like micelles often leads to strong modifications of the rheological behavior of the system and, as such, the anomeric configuration of C16G2 could also provide the possibility of controlling this. Furthermore, mixing these surfactants are hypothesized to result in mixed micelles allowing to finely tune the rheology of a system containing these sustainable surfactants. EXPERIMENTS: The rheology of α- and ß-C16G2, and mixtures of those, was determined by rotational and oscillatory rheology at different temperatures and surfactant concentrations. Micelle structure and composition for these systems were characterized using contrast variation small-angle neutron scattering and small-angle X-ray scattering. The results from these were connected in order to elaborate a molecular understanding of the rheological response of the system. FINDINGS: The self-assembly of these surfactants have been found to result in different rheological properties. ß-C16G2 show a high viscosity with a non-Newtonian viscoelastic behavior, which was linked to the formation of worm-like micelles. In contrast, α-C16G2 self-assembled into short cylindrical micelles, resulting in a Newtonian fluid with low viscosity. Furthermore, mixtures of these two surfactants lead to systems with intermediate rheological properties as a result of the formation of micelles with intermediate morphology to those of the pure anomers. These results also show that the rheological properties of the system can be tuned to change the micelle morphology, which in turn depends on the anomeric configuration of the surfactant. Also, surfactant concentration, temperature of the system, and micelle composition for surfactant mixtures provide control over the rheological properties of the system in a wide temperature range. Therefore, these results open new possibilities in the development of sustainable excipients for formulation technology, where the characteristics of the system can be easily tailored through geometric variations in the monomer structure whilst maintaining the chemical composition of the system.

Tail unsaturation tailors the thermodynamics and rheology of a self-assembled sugar-based surfactant.

HYPOTHESIS: The self-assembly of long-tail surfactants results in the formation of nanoscale structures, e.g. worm-like micelles, with the ability to modify the rheology of the system. However, micelle formation, and thus the alteration of the rheology, is subject to the high Krafft temperature of saturated long-tail surfactants. Hexadecylmaltosides are sustainable surfactants that, in solution, form tailorable viscoelastic fluids. The preparation of monounsaturated sugar-based surfactants is hypothesised to reduce the Krafft point compared to the saturated analogues, therefore increasing the temperature range where the surfactant remains in the micellar form. EXPERIMENTS: Here we report the synthesis and characterisation of a novel sugar-based surfactant with an unsaturated C16-tail, namely palmitoleyl-ß-d-maltoside (ß-C16-1G2). Differential scanning calorimetry was used to probe the temperature stability of the system. The rheology of ß-C16-1G2 solutions was investigated by means of rotational and oscillatory rheology, and these results were connected to the mesoscopic structure of the system as shown by small-angle neutron and X-ray scattering, and dynamic light scattering. FINDINGS: The presence of a double bond on the alkyl chain moiety leads to a depression in the Krafft point, allowing the surfactant to form a thermodynamically stable micellar solution over a wide range of temperatures, i.e. 5-95 °C. The surfactant self-assembles into worm-like micelles which, upon entanglement in the semi-dilute regime, result in the formation of a non-Newtonian, viscoelastic fluid. These observations have important implications in the development of new sustainable formulated products, enabling the preparation of surfactant phases with remarkable thermal resilience.

Complex by design: Hydrotrope-induced micellar growth in deep eutectic solvents.

HYPOTHESIS: The self-assembly of ionic surfactants in deep eutectic solvents has recently been demonstrated, opening up new possibilities in terms of the development of formulated products and templating of nanostructured materials. As it occurs in an aqueous environment, the solvophobic effect drives the formation of micelles in these solvents and specific-ion interactions alter the resulting structures. We hypothesized that the presence of hydrotropic salts would greatly affect the micellar structure in deep eutectic solvents, ultimately leading to the formation of worm-like aggregates. EXPERIMENTS: A systematic investigation performed on hydrotrope-surfactant assemblies in neat and hydrated 1:2 choline chloride:glycerol is presented. The effect of choline salicylate on the micellization of hexadecyltrimethylammonium chloride at different hydrotrope-to-surfactant ratios was probed by contrast variation small-angle neutron scattering. FINDINGS: Here the first investigation on salt-induced micellar growth in deep eutectic solvents is presented. The microscopic characterization of the system shows that the micelle-hydrotrope interaction in pure and hydrated deep eutectic solvents results in a significant increase in micelle elongation. The condensation of the hydrotrope on the micelle, which alters the effective monomer packing, leads to the formation of worm-like micelles with tunable morphology and flexibility. The results presented here present new possibilities in terms of self-assembly and co-assembly in neoteric solvents, where micelle morphology can be controlled through surfactant-salt interactions.

Predictors of Progression of Appendiceal Mucinous Neoplasm to Pseudomyxoma Peritonei.

Appendiceal mucinous neoplasm (AMN) can present with a spectrum of disease. Predicting factors in development of pseudomyxoma peritonei (PMP) from AMN could aid in management and treatment. The aim of this study was to determine factors predictive of PMP from AMN. This was a retrospective multicenter study of all patients diagnosed with AMN from 2006-2017. Diagnosis of PMP was compared by (1) patient demographics, (2) tumor characteristics, and (3) surgery. Secondary end points were disease-specific survival (DSS) and overall survival (OS).One-hundred thirty-eight patients with AMN were identified. Thirty-six patients (26.1%) had a ruptured appendix at presentation, and 12 patients (8.7%) were diagnosed with PMP during the study period. Eight patients presented with PMP at the time of surgery. No demographic factors were predictive of PMP. Operative approach and extent of initial resection did not correlate with PMP. Tumor rupture at presentation was the only factor associated with PMP, though only 14% of patients who presented with simple rupture eventually progressed to PMP.OS was not different between those who were diagnosed with PMP and those who were not. DSS was significantly lower for the group diagnosed with PMP (P = .007). Tumor rupture at presentation did not influence OS or DSS. The only factor found to be significantly associated with PMP was tumor rupture at presentation. Diagnosis of PMP did not affect OS but did lead to decreased DSS.In conclusion, though a majority of patients who presented with rupture did not go on to develop PMP, tumor rupture at presentation was the only factor significantly associated with PMP. Diagnosis of PMP did not affect OS at 5 years. In patients with AMN who present with a ruptured appendix on final pathology, we recommended continued surveillance, though overall risk of PMP is relatively low.

Enzyme-Assisted Synthesis of High-Purity, Chain-Deuterated 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine.

1-Palmitoyl-d 31-2-oleoyl-d 32-sn-glycero-3-phosphocholine (POPC-d 63) with the palmitoyl and oleoyl chains deuterium-labeled was produced in three steps from 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine, deuterated palmitic acid, and deuterated oleic anhydride. Esterification at the sn-2 position was achieved under standard chemical conditions, using DMAP to catalyze the reaction between the 2-lysolipid and oleic anhydride-d 64. Complete regioselective sn-1 acyl substitution was achieved in two steps using operationally simple, enzyme-catalyzed regioselective hydrolysis and esterification to substitute the sn-1 chain for a perdeuterated analogue. This method provides chain-deuterated POPC with high chemical purity (>96%) and complete regiopurity, useful for a variety of experimental techniques. This chemoenzymatic semisynthetic approach is a general, modular method of producing highly pure, mixed-acyl phospholipids, where the advantages of both chemical synthesis (efficiency, high yields) and biocatalytic synthesis (specificity, nontoxicity) are realized.

Surgical management of appendiceal mucinous neoplasm: Is appendectomy sufficient?

BACKGROUND AND OBJECTIVES: Due to the rarity of appendiceal mucinous neoplasms (AMNs), there are few established treatment guidelines. The clinical course varies from incidental detection to progressive spread with pseudomyxoma peritonei (PMP). This study investigated the extent of resection on the prognosis and outcomes of AMNs. METHODS: This multicenter retrospective study evaluated patients with AMN who underwent surgery between 4/2006 to 9/2017. Primary endpoints included overall survival (OS) and disease-specific survival (DSS). Secondary endpoints included PMP incidence and treatment with cytoreductive surgery (CRS). RESULTS: Of the 138 patients with AMN, 70 patients (54%) underwent appendectomy, 26 (19%) cecectomy, and 37 (27%) right hemicolectomy. The median age was 59.7 years and 57 patients (41%) were male. Males were less likely to undergo cecectomy (P = .03). Rupture rates, tumor characteristics, and incidence of PMP were similar across surgery groups. Median follow-up was 61.3 months. Five-year OS and DSS for the total cohort were 94.9% and 98.6%, respectively, and remained similar across all surgery groups. CRS patients were more likely to undergo right hemicolectomy with no difference in survival by surgery type (P = .03). CONCLUSIONS: Patients with AMN have a good overall prognosis and there may be minimal benefit to performing extended surgical resection in these patients.

Ecological risks of heavy metals/metalloid discharged from two sewage treatment works to Mai Po Ramsar site, South China.

The concentrations of six heavy metal/metalloids (HMs) cadmium (Cd), copper (Cu), mercury (Hg), lead (Pb), zinc (Zn), and arsenic (As) were determined in the influent, effluent, and dewatered sludge of two sewage treatment works (Yuen Long Sewage Treatment Work (YLSTW) and Shek Wu Hui Sewage Treatment Work (SWHSTW)) and river waters and sediment (Shan Pui River and Ng Tung River) within the Mai Po Ramsar site in Hong Kong SAR, China. In both STWs, Pb had the highest removal efficiencies (YLSTW 86.5 ± 19.0% to 97.3 ± 3.04%; SWHSTW 87.4 ± 12.8% to 100 ± 0.0800%). In the whole effluent toxicity test, both STWs were effective in lowering the toxicity of the effluent to zebrafish and cherry shrimp. The environmental risk assessments of these HMs on three local aquatic organisms, three species of fish, two species of crustaceans, and three species of algae, were calculated based on measured HMs concentrations in river water and sewage samples, and the predicted no-effect concentrations. Results showed that Zn concentrations in all collected samples posed potential risks to all studied aquatic organisms (average risk quotient = 445). The concentrations of Cu in the rivers posed potential risks (average risk quotient = 5.42) to all fish species. It was concluded that Zn and Hg derived from the STWs might pose potential risks to the living organisms inhabiting the Ramsar site, and Cu, Cd, Pb, and As in the rivers were originated from the two rivers and possibly other tributaries.

Perdeuterated Conjugated Polymers for Ultralow-Frequency Magnetic Resonance of OLEDs.

The formation of excitons in OLEDs is spin dependent and can be controlled by electron-paramagnetic resonance, affecting device resistance and electroluminescence yield. We explore electrically detected magnetic resonance in the regime of very low magnetic fields (<1 mT). A pronounced feature emerges at zero field in addition to the conventional spin- 1 / 2 Zeeman resonance for which the Larmor frequency matches that of the incident radiation. By comparing a conventional π-conjugated polymer as the active material to a perdeuterated analogue, we demonstrate the interplay between the zero-field feature and local hyperfine fields. The zero-field peak results from a quasistatic magnetic-field effect of the RF radiation for periods comparable to the carrier-pair lifetime. Zeeman resonances are resolved down to 3.2 MHz, approximately twice the Larmor frequency of an electron in Earth's field. However, since reducing hyperfine fields sharpens the Zeeman peak at the cost of an increased zero-field peak, we suggest that this result may constitute a fundamental low-field limit of magnetic resonance in carrier-pair-based systems. OLEDs offer an alternative solid-state platform to investigate the radical-pair mechanism of magnetic-field effects in photochemical reactions, allowing models of biological magnetoreception to be tested by measuring spin decoherence directly in the time domain by pulsed experiments.

Perinatal Management of Bart's Hemoglobinopathy: Paradoxical Effects of Intrauterine, Transplacental, and Partial Exchange Transfusions.

We describe a fetus at 24 3/7 weeks' gestation that showed ultrasound evidence of anemia, hydrops, and severe growth restriction. Both parents were known to be cis heterozygous carriers for SEA α-thalassemia deletion (αα/-). Cordocentesis confirmed fetal anemia and homozygous α-thalassemia (-/-) in the fetus. Fetal intrauterine transfusions corrected the anemia, treated the hydrops, and improved fetal growth. The postnatal course was complicated by hypoxic respiratory failure and persistent pulmonary hypertension of the newborn, which resolved only after partial volume exchange transfusion. This case report is presented to point out the potential unintended outcomes with transplacental transfusion via delayed cord clamping and cord milking at delivery in the setting of congenital Bart's hemoglobinopathy, and demonstrates that partial exchange transfusion of the newborn may optimize oxygen delivery due to the more favorable oxygen affinity of transfused adult hemoglobin compared with the Bart's hemoglobin.

An integrative toolbox to unlock the structure and dynamics of protein-surfactant complexes.

The interactions between protein and surfactants play an important role in the stability and performance of formulated products. Due to the high complexity of such interactions, multi-technique approaches are required to study these systems. Here, an integrative approach is used to investigate the various interactions in a model system composed of human growth hormone and sodium dodecyl sulfate. Contrast variation small-angle neutron scattering was used to obtain information on the structure of the protein, surfactant aggregates and surfactant-protein complexes. 1H and 1H-13C HSQC nuclear magnetic resonance spectroscopy was employed to probe the local structure and dynamics of specific amino acids upon surfactant addition. Through the combination of these advanced methods with fluorescence spectroscopy, circular dichroism and isothermal titration calorimetry, it was possible to identify the interaction mechanisms between the surfactant and the protein in the pre- and post-micellar regimes, and interconnect the results from different techniques. As such, the protein was revealed to evolve from a partially unfolded conformation at low SDS concentration to a molten globule at intermediate concentrations, where the protein conformation and local dynamics of hydrophobic amino acids are partially affected compared to the native state. At higher surfactant concentrations the local structure of the protein appears disrupted, and a decorated micelle structure is observed, where the protein is wrapped around a surfactant assembly. Importantly, this integrative approach allows for the identification of the characteristic fingerprints of complex transitions as seen by each technique, and establishes a methodology for an in-detail study of surfactant-protein systems.