The orphan receptor GPR35 contributes to angiotensin II–induced hypertension and cardiac dysfunction in mice

BACKGROUND: The orphan receptor G protein–coupled receptor 35 (GPR35) has been associated with a range of diseases, including cancer, inflammatory bowel disease, diabetes, hypertension, and heart failure. To assess the potential for GPR35 as a therapeutic target in cardiovascular disease, this study investigated the cardiovascular phenotype of a GPR35 knockout mouse under both basal conditions and following pathophysiological stimulation. METHODS: Blood pressure was monitored in male wild-type and GPR35 knockout mice over 7–14 days using implantable telemetry. Cardiac function and dimensions were assessed using echocardiography, and cardiomyocyte morphology evaluated histologically. Two weeks of angiotensin II (Ang II) infusion was used to investigate the effects of GPR35 deficiency under pathophysiological conditions. Gpr35 messenger RNA expression in cardiovascular tissues was assessed using quantitative polymerase chain reaction. RESULTS: There were no significant differences in blood pressure, cardiac function, or cardiomyocyte morphology in GPR35 knockout mice compared with wild-type mice. Following Ang II infusion, GPR35 knockout mice were protected from significant increases in systolic, diastolic, and mean arterial blood pressure or impaired left ventricular systolic function, in contrast to wild-type mice. There were no significant differences in Gpr35 messenger RNA expression in heart, kidney, and aorta following Ang II infusion in wild-type mice. CONCLUSIONS: Although GPR35 does not appear to influence basal cardiovascular regulation, these findings demonstrate that it plays an important pathological role in the development of Ang II–induced hypertension and impaired cardiac function. This suggests that GPR35 is a potential novel drug target for therapeutic intervention in hypertension

Hearing the Past

Recent developments in computer technology are providing historians with new ways to see—and seek to hear, touch, or smell—traces of the past. Place-based augmented reality applications are an increasingly common feature at heritage sites and museums, allowing historians to create immersive, multifaceted learning experiences. Now that computer vision can be directed at the past, research involving thousands of images can recreate lost or destroyed objects or environments, and discern patterns in vast datasets that could not be perceived by the naked eye. Seeing the Past with Computers is a collection of twelve thought-pieces on the current and potential uses of augmented reality and computer vision in historical research, teaching, and presentation. The experts gathered here reflect upon their experiences working with new technologies, share their ideas for best practices, and assess the implications of—and imagine future possibilities for—new methods of historical study. Among the experimental topics they explore are the use of augmented reality that empowers students to challenge the presentation of historical material in their textbooks; the application of seeing computers to unlock unusual cultural knowledge, such as the secrets of vaudevillian stage magic; hacking facial recognition technology to reveal victims of racism in a century-old Australian archive; and rebuilding the soundscape of an Iron Age village with aural augmented reality. This volume is a valuable resource for scholars and students of history and the digital humanities more broadly. It will inspire them to apply innovative methods to open new paths for conducting and sharing their own research

Utilising proteomics to understand and define hypertension: where are we and where do we go?

Introduction: Hypertension is a complex and multifactorial cardiovascular disorder. With different mechanisms contributing to a different extent to an individual’s blood pressure the discovery of novel pathogenetic principles of hypertension is challenging. However, there is an urgent and unmet clinical need to improve prevention, detection and therapy of hypertension in order to reduce the global burden associated with hypertension-related cardiovascular diseases. Areas covered: Proteomic techniques have been applied in reductionist experimental models including angiotensin II infusion models in rodents and the spontaneously hypertensive rat in order to unravel mechanisms involved in blood pressure control and end organ damage. In humans proteomic studies mainly focus on prediction and detection of organ damage, particularly of heart failure and renal disease. Whilst there are only few proteomic studies specifically addressing human primary hypertension there are more data available in hypertensive disorders in pregnancy such as preeclampsia. We will review these studies and discuss implications of proteomics on precision medicine approaches. Expert commentary: Despite the potential of proteomic studies in hypertension there has been moderate progress in this area of research. Standardised large-scale studies are required in order to make best use of the potential that proteomics offers in hypertension and other cardiovascular diseases

Assessing the CO2 concentration at the surface of photosynthetic mesophyll cells

We present a robust estimation of the CO2 concentration at the surface of photosynthetic mesophyll cells (cw), applicable under reasonable assumptions of assimilation distribution within the leaf. We used Capsicum annuum, Helianthus annuus and Gossypium hirsutumas model plants for our experiments. We introduce calculations to estimate cw using independent adaxial and abaxial gas exchange measurements, and accounting for the mesophyll airspace resistances. The cw was lower than adaxial and abaxial estimated intercellular CO2 concentrations (ci). Differences between cw and the ci of each surface were usually larger than 10 μmol mol−1. Differences between adaxial and abaxial ci ranged from a few μmol mol−1 to almost 50 μmol mol−1, where the largest differences were found at high air saturation deficits (ASD). Differences between adaxial and abaxial ci and the ci estimated by mixing both fluxes ranged from −30 to +20 μmol mol−1, where the largest differences were found under high ASD or high ambient CO2 concentrations. Accounting for cw improves the information that can be extracted from gas exchange experiments, allowing a more detailed description of the CO2 and water vapor gradients within the leaf

Preparation of Biomass-Derived Furfuryl Acetals by Transacetalization Reactions Catalyzed by Nanoporous Aluminosilicates

Nanoporous aluminosilicate materials efficiently catalyze the formation of furaldehyde dimethyl acetal directly from methanol in high yields and in short reaction times. The facile nature of this reaction has led to the development of a telescoped protocol in which the acyclic acetal is produced in situ and subsequently functions as a substrate for a transacetalization reaction with glycerol to produce the corresponding dioxane and dioxolane products, which are potentially useful biofuel additives. These products are generated in high yield without the requirement for high reaction temperatures of prolonged reaction times, and the aluminosilicate catalysts are operationally simple to produce, are effective with either purified furaldehyde or crude furaldehyde, and are fully recyclable

Dehydrative etherification reactions of glycerol with alcohols catalyzed by recyclable nanoporous aluminosilicates: telescoped routes to glyceryl ethers

Catalytic strategies for the efficient transformation of abundant sustainable bioderived molecules, such as glycerol, into higher value more useful products is an important research goal. In this study, we demonstrate that atom efficient dehydrative etherification reactions of glycerol with activated alcohols are effectively catalyzed by nanoporous aluminosilicate materials in dimethylcarbonate (DMC) to produce the corresponding 1-substituted glyceryl ethers in high yield. By carrying out the reaction in acetone, it is possible to capitalize on the ability of these materials to catalyze the corresponding acetalization reaction, allowing for the development of novel, telescoped acetalization-dehydrative etherification reaction sequences to selectively produce protected solketal derivatives. These materials also catalyze the telescoped reaction of glycerol with <i>tert</i>-butanol (TBA) in acetone to produce the corresponding solketal mono <i>tert</i>-butyl ether product in high yield, providing a potential route to convert glycerol directly into a useful and sustainable fuel additive

Folding-competent and folding-defective forms of Ricin A chain have different fates following retrotranslocation from the endoplasmic reticulum

We report that a toxic polypeptide retaining the potential to refold upon dislocation from the endoplasmic reticulum (ER) to the cytosol (ricin A chain; RTA) and a misfolded version that cannot (termed RTAΔ), follow ER-associated degradation (ERAD) pathways in Saccharomyces cerevisiae that substantially diverge in the cytosol. Both polypeptides are dislocated in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex and subsequently degraded. Canonical polyubiquitylation is not a prerequisite for this interaction because a catalytically inactive Hrd1p E3 ubiquitin ligase retains the ability to retrotranslocate RTA, and variants lacking one or both endogenous lysyl residues also require the Hrd1p complex. In the case of native RTA, we established that dislocation also depends on other components of the classical ERAD-L pathway as well as an ongoing ER–Golgi transport. However, the dislocation pathways deviate strikingly upon entry into the cytosol. Here, the CDC48 complex is required only for RTAΔ, although the involvement of individual ATPases (Rpt proteins) in the 19S regulatory particle (RP) of the proteasome, and the 20S catalytic chamber itself, is very different for the two RTA variants. We conclude that cytosolic ERAD components, particularly the proteasome RP, can discriminate between structural features of the same substrate

Synthesis of hydroxylated group IV metal oxides inside hollow graphitised carbon nanofibers: nano-sponges and nanoreactors for enhanced decontamination of organophosphates

The confinement and enhanced catalytic properties of hydroxylated group IV metal oxide nanostructures inside hollow graphitised carbon nanofibers (GNF) has been demonstrated. GNF – a structural analogue of carbon nanotubes – were effectively filled with suitable precursor molecules of metal chlorides from the gas and liquid phases. Subsequent basecatalysed hydrolysis afforded amorphous, nanostructured hydroxylated metal oxide (MOx(OH)y where M = Zr, Ti, and Hf) thin films, which coat the internal surfaces of GNF. This versatile and general strategy allows the chemical composition and morphology of the encapsulated material to be modified by varying the conditions used for hydrolysis and post-synthesis thermal treatment. The increased Lewis acidic properties and high surface area of the zirconium composite promote the catalysed hydrolysis of dimethyl nitrophenyl phosphate (DMNP) – a toxic organophosphorus chemical. A four-fold enhancement in the rate of DMNP hydrolysis relative to its separate constituent components was observed, highlighting the surprising synergistic abilities of this composite material to perform both as a ‘nano-sponge’, absorbing the harmful compounds inside the GNF, and a nanoreactor, enhancing the local concentration of organophosphate around the hydroxylated metal oxide species, leading to improved catalytic performance