Lessons on the force-form-function connection in cell biology from modeling a syncytial germline.

Germline architecture plays a critical role in the production of functional gametes. Across species, oogenesis involves not only the preparation of the genome for sexual reproduction, but also the dramatic enlargement of a cell compartment to reach a volume sufficient to support embryogenesis. Creating exceptionally large cells is accomplished by a syncytial structure, in which many nucleus-containing compartments are interconnected by cytoplasmic bridges.

Subcellular context-specific tuning of actomyosin ring contractility within a common cytoplasm.

The non-muscle actomyosin cytoskeleton generates contractile force through the dynamic rearrangement of its constituent parts. Actomyosin rings are a specialization of the non-muscle actomyosin cytoskeleton that drive cell shape changes during division, wound healing, and other events. Contractile rings throughout phylogeny and in a range of cellular contexts are built from conserved components including non-muscle myosin II (NMMII), actin filaments (F-actin), and crosslinking proteins.

Understanding the role of negative charge in the scaffold of an artificial enzyme for CO hydrogenation on catalysis.

We have approached the construction of an artificial enzyme by employing a robust protein scaffold, lactococcal multidrug resistance regulator, LmrR, providing a structured secondary and outer coordination spheres around a molecular rhodium complex, [Rh(PNP)]. Previously, we demonstrated a 2-3 fold increase in activity for one Rh-LmrR construct by introducing positive charge in the secondary coordination sphere. In this study, a series of variants was made through site-directed mutagenesis where the negative charge is located in the secondary sphere or outer coordination sphere, with additional variants made with increasingly negative charge in the outer coordination sphere while keeping a positive charge in the secondary sphere.

Thermodynamic and Kinetic Activity Descriptors for the Catalytic Hydrogenation of Ketones.

Activity descriptors are a powerful tool for the design of catalysts that can efficiently utilize H with minimal energy losses. In this study, we develop the use of hydricity and H self-exchange rates as thermodynamic and kinetic descriptors for the hydrogenation of ketones by molecular catalysts. Two complexes with known hydricity, HRh(dmpe) and HCo(dmpe), were investigated for the catalytic hydrogenation of ketones under mild conditions (1.

Model-based trajectory classification of anchored molecular motor-biopolymer interactions.

During zygotic mitosis in many species, forces generated at the cell cortex are required for the separation and migration of paternally provided centrosomes, pronuclear migration, segregation of genetic material, and cell division. Furthermore, in some species, force-generating interactions between spindle microtubules and the cortex position the mitotic spindle asymmetrically within the zygote, an essential step in asymmetric cell division. Understanding the mechanical and molecular mechanisms of microtubule-dependent force generation and therefore asymmetric cell division requires identification of individual cortical force-generating units .

Follow that cell: Leukocyte migration in L-plastin mutant zebrafish.

Actin assemblies are important in motile cells such as leukocytes, which form dynamic plasma membrane extensions or podia. L-plastin (LCP1) is a leukocyte-specific calcium-dependent actin-bundling protein that, in mammals, is known to affect immune cell migration. Previously, we generated CRISPR/Cas9 engineered zebrafish lacking L-plastin (lcp1-/-) and reported that they had reduced survival to adulthood, suggesting that lack of this actin-bundler might negatively affect the immune system.

Designing Catalytic Systems Using Binary Solvent Mixtures: Impact of Mole Fraction of Water on Hydride Transfer.

The free energy for hydride transfer reactions of transition metal hydrides is known to be influenced by solvent effects. The first-row transition metal hydride [HNi(dmpe)][BF] (dmpe = 1,2-bis(dimethylphosphino)ethane) has starkly different hydride transfer reactivities with CO in different solvents. A binary mixture of water and acetonitrile was used to tune the hydride transfer reactivity of HNi(dmpe) with CO so that the free energy for this reaction approached zero.

High-pressure apparatus for monitoring solid-liquid phase transitions.

This work presents a new technique for evaluating the solid-liquid phase transformations in complex diesel fuel blends and diesel surrogates under high-pressure conditions intended to simulate those occurring in vehicle fuel injectors. A high-pressure apparatus based on a visual identification of freezing and thawing has been designed and built to monitor phase behavior and determine the crystallization temperature of complex fuels to predict wax precipitation. The proposed methodology was validated using pure substances-n-hexadecane (CH), cyclohexane (CH), and a mixture of 0.

Core Competencies for Undergraduates in Bioengineering and Biomedical Engineering: Findings, Consequences, and Recommendations.

This paper provides a synopsis of discussions related to biomedical engineering core curricula that occurred at the Fourth BME Education Summit held at Case Western Reserve University in Cleveland, Ohio in May 2019. This summit was organized by the Council of Chairs of Bioengineering and Biomedical Engineering, and participants included over 300 faculty members from 100+ accredited undergraduate programs. This discussion focused on six key questions: QI: Is there a core curriculum, and if so, what are its components? QII: How does our purported core curriculum prepare students for careers, particularly in industry? QIII: How does design distinguish BME/BIOE graduates from other engineers? QIV: What is the state of engineering analysis and systems-level modeling in BME/BIOE curricula? QV: What is the role of data science in BME/BIOE undergraduate education? QVI: What core experimental skills are required for BME/BIOE undergrads? s.

Thermodynamic and kinetic studies of H and N binding to bimetallic nickel-group 13 complexes and neutron structure of a Ni(η-H) adduct.

Understanding H binding and activation is important in the context of designing transition metal catalysts for many processes, including hydrogenation and the interconversion of H with protons and electrons. This work reports the first thermodynamic and kinetic H binding studies for an isostructural series of first-row metal complexes: NiML, where M = Al (), Ga (), and In (), and L = [N(-(NCHPPr)CH)]. Thermodynamic free energies (Δ°) and free energies of activation (Δ ) for binding equilibria were obtained variable-temperature P NMR studies and lineshape analysis.

Evaluating the impacts of amino acids in the second and outer coordination spheres of Rh-bis(diphosphine) complexes for CO hydrogenation.

To explore the influence of a biologically inspired second and outer coordination sphere on Rh-bis(diphosphine) CO2 hydrogenation catalysts, a series of five complexes were prepared by varying the substituents on the pendant amine in the P(Et)2CH2NRCH2P(Et)2 ligands (PEtNRPEt), where R consists of methyl ester modified amino acids, including three neutral (glycine methyl ester (GlyOMe), leucine methyl ester (LeuOMe), and phenylalanine methyl ester (PheOMe)), one acidic (aspartic acid dimethyl ester (AspOMe)) and one basic (histidine methyl ester (MeHisOMe)) amino acid esters. The turnover frequencies (TOFs) for CO2 hydrogenation for each of these complexes were compared to those of the non-amino acid containing [Rh(depp)2]+ (depp) and [Rh(PEtNMePEt)2]+ (NMe) complexes. Each complex is catalytically active for CO2 hydrogenation to formate under mild conditions in THF.

Assessing the Legal and Practical Implications of Copay Accumulator and Maximizer Programs.

Drug manufacturers have relied on coupons to promote access to branded drugs by reducing patients' out-of-pocket costs. Insurers and PBMs, on the other hand, have opposed coupons because they undermine the effectiveness of cost-sharing requirements and benefit designs that incentivize cost-effective drug prescribing and purchasing choices.

Making a Splash in Homogeneous CO Hydrogenation: Elucidating the Impact of Solvent on Catalytic Mechanisms.

Molecular catalysts for hydrogenation of CO are widely studied as a means of chemical hydrogen storage. Catalysts are traditionally designed from the perspective of controlling the ligands bound to the metal. In recent years, studies have shown that the solvent can also play a key role in the mechanism of CO hydrogenation.

Does rectal diclofenac reduce post-ERCP pancreatitis? A district general hospital experience.

Introduction: There is controversy in the literature recently regarding the efficacy of rectal non-steroidal anti-inflammatory drugs (NSAID) to prevent post-ERCP pancreatitis (PEP). The aim of this study was to compare the incidence of PEP in three distinct groups of patients at the Royal United Hospital, Bath: no use of rectal diclofenac, selective use and blanket use without contraindication.

Method: Readmission data, blood results, radiology reports and discharge summaries were used to identify patients with PEP from August 2010 to December 2015.

Changing the Mechanism for CO Hydrogenation Using Solvent-Dependent Thermodynamics.

A critical scientific challenge for utilization of CO is the development of catalyst systems that function in water and use inexpensive and environmentally friendly reagents. We have used thermodynamic insights to predict and demonstrate that the HCo (dmpe) catalyst system, previously described for use in organic solvents, can hydrogenate CO to formate in water with bicarbonate as the only added reagent. Replacing tetrahydrofuran as the solvent with water changes the mechanism for catalysis by altering the thermodynamics for hydride transfer to CO from a key dihydride intermediate.

A Bimetallic Nickel-Gallium Complex Catalyzes CO Hydrogenation via the Intermediacy of an Anionic d Nickel Hydride.

Large-scale CO hydrogenation could offer a renewable stream of industrially important C chemicals while reducing CO emissions. Critical to this opportunity is the requirement for inexpensive catalysts based on earth-abundant metals instead of precious metals. We report a nickel-gallium complex featuring a Ni(0)→Ga(III) bond that shows remarkable catalytic activity for hydrogenating CO to formate at ambient temperature (3150 turnovers, turnover frequency = 9700 h), compared with prior homogeneous Ni-centered catalysts.

Detection of an Iridium-Dihydrogen Complex: A Proposed Intermediate in Ionic Hydrogenation.

Addition of high pressures of H to five-coordinate [(POCOP)Ir(CO)(H)]OTf [(POCOP) = κ-CH-2,6-(OP(Bu))] complexes results in observation of two new iridium-dihydrogen complexes. If the aryl moiety of the POCOP ligand is substituted with an electron withdrawing protonated dimethylamino group at the para position, hydrogen coordination is enhanced. Five-coordinate Ir-H complexes generated by addition of triflic acid to (POCOP)Ir(CO) species show an Ir-H H NMR chemical shift dependence on the number of equivalents of acid present.

Triphosphine-Ligated Copper Hydrides for CO2 Hydrogenation: Structure, Reactivity, and Thermodynamic Studies.

The copper(I) triphosphine complex LCu(MeCN)PF6 (L = 1,1,1-tris(diphenylphosphinomethyl)ethane), which we recently demonstrated is an active catalyst precursor for hydrogenation of CO2 to formate, reacts with H2 in the presence of a base to form a cationic dicopper hydride, [(LCu)2H]PF6. [(LCu)2H](+) is also an active precursor for catalytic CO2 hydrogenation, with equivalent activity to that of LCu(MeCN)(+), and therefore may be a relevant catalytic intermediate. The thermodynamic hydricity of [(LCu)2H](+) was determined to be 41.

Solvent influence on the thermodynamics for hydride transfer from bis(diphosphine) complexes of nickel.

The thermodynamic hydricity of a metal hydride can vary considerably between solvents. This parameter can be used to determine the favourability of a hydride-transfer reaction, such as the reaction between a metal hydride and CO2 to produce formate. Because the hydricities of these species do not vary consistently between solvents, reactions that are thermodynamically unfavourable in one solvent can be favourable in others.

Dementia in older people admitted to hospital: a regional multi-hospital observational study of prevalence, associations and case recognition.

Background: Previous studies have indicated a prevalence of dementia in older admissions of ∼42% in a single London teaching hospital, and 21% in four Queensland hospitals. However, there is a lack of published data from any European country on the prevalence of dementia across hospitals and between patient groups.

Objective: To determine the prevalence and associations of dementia in older patients admitted to acute hospitals in Ireland.

Photoswitching a molecular catalyst to regulate CO2 hydrogenation.

Inspired by nature's ability to regulate catalysis using physiological stimuli, azobenzene was incorporated into Rh(bis)diphosphine CO2 hydrogenation catalysts to photoinitiate structural changes to modulate the resulting catalytic activity. The rhodium bound diphosphine ligands (P(Ph2)-CH2-N(R)-CH2-P(Ph2)) contain the terminal amine of a non-natural amino acid, with the R-group being either β-alanine (β-Ala) or γ-aminobutyric acid (GABA). For both β-Ala and GABA containing complexes, the carboxylic acids of the amino acids were coupled to the amines of diaminoazobenzene, creating a complex consisting of a rhodium bound to a photo-responsive tetradentate ligand.

Homogeneous hydrogenation of CO₂ to methyl formate utilizing switchable ionic liquids.

Combined capture of CO2 and subsequent hydrogenation allows for base/methanol-promoted homogeneous hydrogenation of CO2 to methyl formate. The CO2, captured as an amidinium methyl carbonate, reacts with H2 with no applied pressure of CO2 in the presence of a catalyst to produce sequentially amidinium formate, then methyl formate. The production of methyl formate releases the base back into the system, thereby reducing one of the flaws of catalytic hydrogenations of CO2: the notable consumption of one mole of base per mole of formate produced.

Beyond the active site: the impact of the outer coordination sphere on electrocatalysts for hydrogen production and oxidation.

Redox active metalloenzymes play a major role in energy transformation reactions in biological systems. Examples include formate dehydrogenases, nitrogenases, CO dehydrogenase, and hydrogenases. Many of these reactions are also of interest to humans as potential energy storage or utilization reactions for photoelectrochemical, electrolytic, and fuel cell applications.

Molecular dynamics study of the proposed proton transport pathways in [FeFe]-hydrogenase.

Possible proton transport pathways in Clostridium pasteurianum (CpI) [FeFe]-hydrogenase were investigated with molecular dynamics simulations. This study was undertaken to evaluate the functional pathway and provide insight into the hydrogen bonding features defining an active proton transport pathway. Three pathways were evaluated, two of which consist of water wires and one of predominantly amino acid residues.