Estimation of Early Graft Function Using the BETA-2 Score Following Clinical Islet Transplantation.

Little is known about how early islet graft function evolves in the clinical setting. The BETA-2 score is a validated index of islet function that can be calculated from a single blood sample and lends itself to frequent monitoring of graft function. In this study, we characterized early graft function by calculating weekly BETA-2 score in recipients who achieved insulin independence after single transplant (group 1, = 8) compared to recipients who required a second transplant before achieving insulin independence (group 2, = 7).

Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction.

Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested.

Oxygenated Cyclopentenones via the Pauson-Khand Reaction of Silyl Enol Ether Substrates.

We report here the application of silyl enol ether moieties as efficient alkene coupling partners within cobalt-mediated intramolecular Pauson-Khand reactions. This cyclization strategy delivers synthetically valuable oxygenated cyclopentenone products in yields of ≤93% from both ketone- and aldehyde-derived silyl enol ethers, incorporates both terminal and internal alkyne partners, and delivers a variety of decorated systems, including more complex tricyclic structures. Facile removal of the silyl protecting group reveals oxygenated sites for potential further elaboration.

Genome-wide screening identifies Polycomb repressive complex 1.3 as an essential regulator of human naïve pluripotent cell reprogramming.

Uncovering the mechanisms that establish naïve pluripotency in humans is crucial for the future applications of pluripotent stem cells including the production of human blastoids. However, the regulatory pathways that control the establishment of naïve pluripotency by reprogramming are largely unknown. Here, we use genome-wide screening to identify essential regulators as well as major impediments of human primed to naïve pluripotent stem cell reprogramming.

Estimating the Product of the X-ray Spectrum and Quantum Detection Efficiency of a CT System and Its Application to Beam Hardening Correction.

Lab-based X-ray computed tomography (XCT) systems use X-ray sources that emit a polychromatic X-ray spectrum and detectors that do not detect all X-ray photons with the same efficiency. A consequence of using a polychromatic X-ray source is that beam hardening artefacts may be present in the reconstructed data, and the presence of such artefacts can degrade XCT image quality and affect quantitative analysis. If the product of the X-ray spectrum and the quantum detection efficiency (QDE) of the detector are known, alongside the material of the scanned object, then beam hardening artefacts can be corrected algorithmically.

C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones: Studies towards the identification of potent, cell penetrant Jumonji C domain containing histone lysine demethylase 4 subfamily (KDM4) inhibitors, compound profiling in cell-based target engagement assays.

Residues in the histone substrate binding sites that differ between the KDM4 and KDM5 subfamilies were identified. Subsequently, a C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-one series was designed to rationally exploit these residue differences between the histone substrate binding sites in order to improve affinity for the KDM4-subfamily over KDM5-subfamily enzymes. In particular, residues E169 and V313 (KDM4A numbering) were targeted.

Comparison of metabolic responses to the mixed meal tolerance test vs the oral glucose tolerance test after successful clinical islet transplantation.

Following islet transplantation, mixed meal tolerance tests (MMTs) are routinely utilized to assess graft function, but how the 90-minute MMTT glucose value relates to a 120-minute glucose concentration of ≥11.1 mmol/L used to diagnose diabetes following a standardized 75 g-OGTT, is not known. We examined this relationship further.

BMX-001, a novel redox-active metalloporphyrin, improves islet function and engraftment in a murine transplant model.

Islet transplantation has become a well-established therapy for select patients with type 1 diabetes. Viability and engraftment can be compromised by the generation of oxidative stress encountered during isolation and culture. We evaluated whether the administration of BMX-001 (MnTnBuOE-2-PyP [Mn(III) meso-tetrakis-(N-b-butoxyethylpyridinium-2-yl)porphyrin]) and its earlier derivative, BMX-010 (MnTE-2-PyP [Mn(III) meso-tetrakis-(N-methylpyridinium-2-yl)porphyrin]) could improve islet function and engraftment outcomes.

Beta Cell Death by Cell-free DNA and Outcome After Clinical Islet Transplantation.

Background: Optimizing engraftment and early survival after clinical islet transplantation is critical to long-term function, but there are no reliable, quantifiable measures to assess beta cell death. Circulating cell-free DNA (cfDNA) derived from beta cells has been identified as a novel biomarker to detect cell loss and was recently validated in new-onset type 1 diabetes and in islet transplant patients.

Methods: Herein we report beta cell cfDNA measurements after allotransplantation in 37 subjects and the correlation with clinical outcomes.

Primary care follow-up of radical prostatectomy patients: A regional New Zealand experience.

Background: Contemporary recommendations regarding the duration of follow-up after radical prostatectomy (RP) are highly heterogeneous. Protocol-based follow-up schemes have been implemented to facilitate the expeditious identification of patients with recurrence. The aim of this study is to assess the reliability and comfort of general practitioners (GPs) in follow-up of RP.

Photoacoustic imaging of angiogenesis in a subcutaneous islet transplant site in a murine model.

Islet transplantation (IT) is an established clinical therapy for select patients with type-1 diabetes. Clinically, the hepatic portal vein serves as the site for IT. Despite numerous advances in clinical IT, limitations remain, including early islet cell loss posttransplant, procedural complications, and the inability to effectively monitor islet grafts.

A microelectromechanical systems-enabled, miniature triple quadrupole mass spectrometer.

Miniaturized mass spectrometers are becoming increasingly capable, enabling the development of many novel field and laboratory applications. However, to date, triple quadrupole tandem mass spectrometers, the workhorses of quantitative analysis, have not been significantly reduced in size. Here, the basis of a field-deployable triple quadrupole is described.

A simulation-based study on the influence of beam hardening in X-ray computed tomography for dimensional metrology.

X-ray computed tomography (CT) is a radiographic scanning technique for visualising cross-sectional images of an object non-destructively. From these cross-sectional images it is possible to evaluate internal dimensional features of a workpiece which may otherwise be inaccessible to tactile and optical instruments. Beam hardening is a physical process that degrades the quality of CT images and has previously been suggested to influence dimensional measurements.

A miniature mass spectrometer for liquid chromatography applications.

A miniature mass spectrometer capable of detecting analytes eluting from a high-performance liquid chromatography (HPLC) system is described and demonstrated for the first time. The entire instrument, including all pumps and the computer, is contained within a single enclosure that may be conveniently accommodated at the base of the HPLC stack. The microspray ion source, vacuum interface, ion guide, and quadrupole ion filter are all microengineered.

Comparison of positional surfactant isomers for displacement of rubisco protein from the air-water interface.

Protein-surfactant interaction, which is a function of the protein and surfactant characteristics, is a common phenomenon in a wide range of industrial applications. In this work, we used rubisco, the most abundant protein in nature, as a model protein and sodium dodecylbenzenesulfonate (SDOBS), one of the most widely used commercial surfactants, with two positional isomers (SDOBS-2 and SDOBS-6), as a model surfactant. We first examined the surface tension and the mechanical properties of interfacial mixed rubisco-SDOBS films adsorbed at the air-water interface.

Insulin-heparin infusions peritransplant substantially improve single-donor clinical islet transplant success.

Background: Successful islet transplantation can result in insulin independence in many patients with type 1 diabetes mellitus, but it often requires more than one islet infusion. The ability to achieve insulin independence with a single donor is an important goal in clinical islet transplantation due to the limited organ supply.

Methods: We examined factors that may be associated with insulin independence after islet transplantation with islets from a single donor, using univariate and multivariate analysis.

Supplemental islet infusions restore insulin independence after graft dysfunction in islet transplant recipients.

Background: The ability of supplemental islet infusions (SII) to restore insulin independence in islet transplant recipients with graft dysfunction has been attributed to the coadministration of exenatide. However, improving islet transplant outcomes could explain the success of SII. We aimed to determine the effect on islet graft function and insulin independence of SII using these new protocols, without the use of exenatide.

Miniature mass spectrometer systems based on a microengineered quadrupole filter.

Two miniature mass spectrometer systems based on a microengineered quadrupole mass filter have been developed. One of the instruments has a footprint of 27 cm x 20 cm and is intended for laboratory use when space is at a premium. The other is portable and intended for use in the field.

Cooperative tuneable interactions between a designed peptide biosurfactant and positional isomers of SDOBS at the air-water interface.

Rationally designed peptide biosurfactant AM1 was mixed with sodium dodecyl benzene sulfonate (SDOBS) to self-assemble a mixed surfactant-biosurfactant layer at the air-water interface. Under optimal conditions in the presence of Zn2+, the interfacial elasticity of the mixed layer was approximately 5-fold higher than for biosurfactant alone. Two head positional isomers, SDOBS-2 and SDOBS-6, were compared for their ability to enhance interfacial film strength.

Tuneable control of interfacial rheology and emulsion coalescence.

Breaking point: Switchable peptide surfactants are used to demonstrate that the extent of cross-linking in an interfacial surfactant layer can control the rate of emulsion coalescence. Pictured is the rupture of an aqueous thin film where the peptide layer lacks sufficient strength to prevent hole formation, but nonetheless dramatically slows the rate of hole expansion.

Mixed system of Eudragit s-100 with a designed amphipathic peptide: control of interfacial elasticity by solution composition.

We report an interfacially active system based on an informational peptide surfactant mixed with an oppositely charged polyelectrolyte. The 21-residue cationic peptide, AM1, has previously been shown to respond reversibly to pH and metal ions at fluid interfaces, forming elastic films that can be rapidly switched to collapse foams or emulsions on demand. Here we report the reversible association of AM1 with the methacrylate-based anionic polymer Eudragit S-100.

Directed disassembly of an interfacial rubisco protein network.

We present the first study of the directed disassembly of a protein network at the air-water interface by the synergistic action of a surfactant and an enzyme. We seek to understand the fundamentals of protein network disassembly by using rubisco adsorbed at the air-water interface as a model. We propose that rubisco adsorption at the air-water interface results in the formation of a fishnet-like network of interconnected protein molecules, capable of transmitting lateral force.

Foaming properties of a peptide designed to form stimuli-responsive interfacial films.

We have designed an amphipathic peptide, AM1, that can self-assemble at the air-water interface to form an interfacial ensemble capable of switching between a mechanically strong cohesive film state and a mobile detergent state in response to changes in the solution conditions. The mechanical properties of the AM1 ensemble in the cohesive film state are qualitatively equivalent to the protein β-LG, while in the mobile detergent state they are equivalent to the low molecular weight surfactant, SDS. In this work the foaming properties of AM1 are compared to those of β-LG and SDS at the same weight concentration and it is found that AM1 adsorbs rapidly to the interface, initially forming a dense foam like that formed by SDS and superior to β-LG.