Formal total synthesis of (±)-conduramine E utilising the Bryce-Smith-Gilbert photoamination reaction

Utilising a Bryce-Smith-Gilbert photoamination of benzene as a key step, a synthesis of ()-conduramine E was carried out. A highly regioselective dihydroxylation of a cyclic diene was effected utilising Sharpless AD-mix-b

A Small-Molecule Inhibitor of Mps1 Blocks the Spindle-Checkpoint Response to a Lack of Tension on Mitotic Chromosomes

SummaryThe spindle checkpoint prevents chromosome loss by preventing chromosome segregation in cells with improperly attached chromosomes [1–3]. The checkpoint senses defects in the attachment of chromosomes to the mitotic spindle [4] and the tension exerted on chromosomes by spindle forces in mitosis [5–7]. Because many cancers have defects in chromosome segregation, this checkpoint may be required for survival of tumor cells and may be a target for chemotherapy. We performed a phenotype-based chemical-genetic screen in budding yeast and identified an inhibitor of the spindle checkpoint, called cincreasin. We used a genome-wide collection of yeast gene-deletion strains and traditional genetic and biochemical analysis to show that the target of cincreasin is Mps1, a protein kinase required for checkpoint function [8]. Despite the requirement for Mps1 for sensing both the lack of microtubule attachment and tension at kinetochores, we find concentrations of cincreasin that selectively inhibit the tension-sensitive branch of the spindle checkpoint. At these concentrations, cincreasin causes lethal chromosome missegregation in mutants that display chromosomal instability. Our results demonstrate that Mps1 can be exploited as a target and that inhibiting the tension-sensitive branch of the spindle checkpoint may be a way of selectively killing cancer cells that display chromosomal instability

The CATH Domain Structure Database and related resources Gene3D and DHS provide comprehensive domain family information for genome analysis

The CATH database of protein domain structures (http://www.biochem.ucl.ac.uk/bsm/cath/) currently contains 43 229 domains classified into 1467 superfamilies and 5107 sequence families. Each structural family is expanded with sequence relatives from GenBank and completed genomes, using a variety of efficient sequence search protocols and reliable thresholds. This extended CATH protein family database contains 616 470 domain sequences classified into 23 876 sequence families. This results in the significant expansion of the CATHHMMmodel library to include models built from the CATH sequence relatives, giving a10%increase in coveragefor detecting remote homologues. An improved Dictionary of Homologous superfamilies (DHS) (http://www.biochem.ucl.ac.uk/bsm/dhs/) containing specific sequence, structural and functional information for each superfamily in CATH considerably assists manual validation of homologues. Information on sequence relatives in CATH superfamilies, GenBank and completed genomes is presented in the CATH associated DHS and Gene3D resources. Domain partnership information can be obtained from Gene3D (http://www.biochem.ucl.ac.uk/bsm/cath/Gene3D/). A new CATH server has been implemented (http://www.biochem.ucl.ac.uk/cgi-bin/cath/CathServer.pl) providing automatic classification of newly determined sequences and structures using a suite of rapid sequence and structure comparison methods. The statistical significance of matches is assessed and links are provided to the putative superfamily or fold group to which the query sequence or structure is assigned

ACE-ASIA - Regional climatic and atmospheric chemical effects of Asian dust and pollution

Although continental-scale plumes of Asian dust and pollution reduce the amount of solar radiation reaching the earth's surface and perturb the chemistry of the atmosphere, our ability to quantify these effects has been limited by a lack of critical observations, particularly of layers above the surface. Comprehensive surface, airborne, shipboard, and satellite measurements of Asian aerosol chemical composition, size, optical properties, and radiative impacts were performed during the Asian Pacific Regional Aerosol Characterization Experiment (ACE-Asia) study. Measurements within a massive Chinese dust storm at numerous widely spaced sampling locations revealed the highly complex structure of the atmosphere, in which layers of dust, urban pollution, and biomass-burning smoke may be transported long distances as distinct entities or mixed together. The data allow a first-time assessment of the regional climatic and atmospheric chemical effects of a continental-scale mixture of dust and pollution. Our results show that radiative flux reductions during such episodes are sufficient to cause regional climate change

Impaired postprandial skeletal muscle vascular responses to a mixed meal challenge in normoglycaemic people with a parent with type 2 diabetes

Aims/hypothesis: Microvascular blood flow (MBF) increases in skeletal muscle postprandially to aid in glucose delivery and uptake in muscle. This vascular action is impaired in individuals who are obese or have type 2 diabetes. Whether MBF is impaired in normoglycaemic people at risk of type 2 diabetes is unknown. We aimed to determine whether apparently healthy people at risk of type 2 diabetes display impaired skeletal muscle microvascular responses to a mixed-nutrient meal. Methods: In this cross-sectional study, participants with no family history of type 2 diabetes (FH-) for two generations (n = 18), participants with a positive family history of type 2 diabetes (FH+; i.e. a parent with type 2 diabetes; n = 16) and those with type 2 diabetes (n = 12) underwent a mixed meal challenge (MMC). Metabolic responses (blood glucose, plasma insulin and indirect calorimetry) were measured before and during the MMC. Skeletal muscle large artery haemodynamics (2D and Doppler ultrasound, and Mobil-O-graph) and microvascular responses (contrast-enhanced ultrasound) were measured at baseline and 1 h post MMC. Results: Despite normal blood glucose concentrations, FH+ individuals displayed impaired metabolic flexibility (reduced ability to switch from fat to carbohydrate oxidation vs FH-; p \u3c 0.05) during the MMC. The MMC increased forearm muscle microvascular blood volume in both the FH- (1.3-fold, p \u3c 0.01) and FH+ (1.3-fold, p \u3c 0.05) groups but not in participants with type 2 diabetes. However, the MMC increased MBF (1.9-fold, p \u3c 0.01), brachial artery diameter (1.1-fold, p \u3c 0.01) and brachial artery blood flow (1.7-fold, p \u3c 0.001) and reduced vascular resistance (0.7-fold, p \u3c 0.001) only in FH- participants, with these changes being absent in FH+ and type 2 diabetes. Participants with type 2 diabetes displayed significantly higher vascular stiffness (p \u3c 0.001) compared with those in the FH- and FH+ groups; however, vascular stiffness did not change during the MMC in any participant group. Conclusions/interpretation: Normoglycaemic FH+ participants display impaired postprandial skeletal muscle macro- and microvascular responses, suggesting that poor vascular responses to a meal may contribute to their increased risk of type 2 diabetes. We conclude that vascular insulin resistance may be an early precursor to type 2 diabetes in humans, which can be revealed using an MMC

Mars Aeronomy Observer: Report of the Science Working Team

The Mars Aeronomy Observer (MAO) is a candidate follow-on mission to Mars Observer (MO) in the Planetary Observer Program. The four Mariner and two Viking spacecraft sent to Mars between 1965 and 1976 have provided a wealth of information concerning Martian planetology. The Mars Observer, to be launched in 1990, will build on their results by further examining the elemental and mineralogical composition of the surface, the strength and multipolar composition of the planetary magnetic field, the gravitational field and topography, and the circulation of the lower atmosphere. The Mars Aeronomy Observer is intended to address the last major aspects of Martian environment which have yet to be investigated: the upper atmosphere, the ionsphere, and the solar wind interaction region

Modelling the perceptual similarity of facial expressions from image statistics and neural responses

The ability to perceive facial expressions of emotion is essential for effective social communication. We investigated how the perception of facial expression emerges from the image properties that convey this important social signal, and how neural responses in face-selective brain regions might track these properties. To do this, we measured the perceptual similarity between expressions of basic emotions, and investigated how this is reflected in image measures and in the neural response of different face-selective regions. We show that the perceptual similarity of different facial expressions (fear, anger, disgust, sadness, happiness) can be predicted by both surface and feature shape information in the image. Using block design fMRI, we found that the perceptual similarity of expressions could also be predicted from the patterns of neural response in the face-selective posterior superior temporal sulcus (STS), but not in the fusiform face area (FFA). These results show that the perception of facial expression is dependent on the shape and surface properties of the image and on the activity of specific face-selective regions

Formation Flying and Change Detection for the UNSW Canberra Space ‘M2’ Low Earth Orbit Formation Flying CubeSat Mission

The University of New South Wales, Canberra (UNSW Canberra) embarked on an ambitious CubeSatellite research, development, and education program in 2017 through funding provided by the Royal Australian Air Force (RAAF). The program consisted of M1 (Mission 1), M2 Pathfinder, and concludes with the formation flying mission M2. M2 is the final mission comprising two 6U CubeSatellites flying in formation using differential aerodynamic drag control. The M2 satellites were launched in a conjoined 12U form factor on RocketLab’s ‘They Go Up So Fast’ launch in March 2021. On 10th September 2021 the spacecraft divided into two 6U CubeSats (M2-A and M2-B) under the action of a small spring force in their near-circular 550km, 45-degree inclination orbit. The formation is controlled by varying the spacecrafts’ attitude, which creates a large variation in the aerodynamic drag force due to the change in the cross-sectional area from the large, double-deployable, solar arrays located on the zenith face of the spacecraft. This paper presents the outcomes of the Formation Flying and Change Detection primary mission objectives for the mission. The results are generated by collecting and analysing optical and RF (Radio Frequency) space domain awareness sensor data from the ground and validating them against GPS (Global Positioning System) and attitude data downlinked from the spacecraft. The outcomes of the broader mission objectives, which include increasing the Technology Readiness Level for a suite of intelligent on-board optical and RF sensor technologies, will be presented in subsequent publications. The results presented here comprise two major campaigns: 1.) The spacecraft separation campaign when the original 12U form factor deployed following launch split in half to form the M2-A and M2-B satellites, and 2) the demonstration of active formation control of the spacecraft via differential aerodynamic drag. M2-A and M2-B underwent several major configuration changes during the spacecraft separation campaign. The results from ground-based sensors detecting the 12U spacecraft separating into two distinct (6U) objects are presented. The effect of the double-deployable solar arrays deployment on the relative orbital motion of the M2-A and M2-B spacecraft is illustrated and compared to data from optical and RF ground-based measurements taken during this window. The formation control campaign involved actively controlling the spacecraft via differential aerodynamic drag in order to significantly alter the separation distance. The mission demonstrated the capability to switch the leading spacecraft’s position between M2-A and M2-B and to actively control separation distance ranging from 130km down to 1km. Formation control is achieved via open-loop, pre-scheduled, commands issued from the UNSW Canberra Space ground station. A two-stage modelling and simulation process is used to derive the scheduled attitude states. Firstly, a batch least squares orbit determination algorithm is applied to GPS data from a steady-state differential drag actuation period (where one spacecraft is in maximum drag and the other in its minimum drag attitude configuration). The batch least squares orbit determination is conducted out using the NASA General Mission Analysis Tool (GMAT), resulting in precise state estimates for each spacecraft and drag coefficient (Cd) estimates for both the maximum and minimum drag configurations. Predictions of trajectory for various attitude profiles can be produced by tailoring the spacecraft’s drag coefficients between the maximum and minimum values generated by the batch least squares state estimation process. Ground-based optical and RF space domain awareness (SDA) sensor measurements collected during the manoeuvre campaign are compared to the spacecraft’s GPS and attitude telemetry data. The SDA sensors are actively seeking to detect changes in the separation distance between the spacecraft. Initial results from an investigation into whether changes observed in photometric light curve signatures can signal the commencement of a differential drag manoeuvre are presented