Searching for new young stars in the northern hemisphere: The Pisces Moving Group

Using the kinematically unbiased technique described in Binks, Jeffries & Maxted (2015), we present optical spectra for a further 122 rapidly-rotating (rotation periods <6 days), X-ray active FGK stars, selected from the SuperWASP survey. We identify 17 new examples of young, probably single stars with ages of <200 Myr and provide additional evidence for a new northern hemisphere kinematic association: the Pisces Moving Group (MG). The group consists of 14 lithium-rich G- and K-type stars, that have a dispersion of only ∼3 km s−1 in each Galactic space velocity coordinate. The group members are approximately co-eval in the colour-magnitude diagram, with an age of 30–50 Myr, and have similar, though not identical, kinematics to the Octans-Near MG. stars: low-mass, stars: pre-main-sequenc

The hand of Homo naledi

A nearly complete right hand of an adult hominin was recovered from the Rising Star cave system, South Africa. Based on associated hominin material, the bones of this hand are attributed to Homo naledi. This hand reveals a long, robust thumb and derived wrist morphology that is shared with Neandertals and modern humans, and considered adaptive for intensified manual manipulation. However, the finger bones are longer and more curved than in most australopiths, indicating frequent use of the hand during life for strong grasping during locomotor climbing and suspension. These markedly curved digits in combination with an otherwise human-like wrist and palm indicate a significant degree of climbing, despite the derived nature of many aspects of the hand and other regions of the postcranial skeleton in H. naledi

Balancing charge-transfer strength and triplet states for deep-blue thermally activated delayed fluorescence with an unconventional electron rich dibenzothiophene acceptor

Manipulation of the emission properties of deep-blue emitters exhibiting thermally activated delayed fluorescence (TADF) through molecular design is challenging. We present an effective strategy to probe deeper into the role of localized (LE) and charge transfer (CT) states in the reverse intersystem crossing (RISC) mechanism. In a series of donor–acceptor–donor (D–A–D) blue emitters the dibenzothiophene functionality is used as an unconventional acceptor, while derivatives of 9,10-dihydro-9,9-dimethylacridine are used as electron-donors. tert-Butyl and methoxy substituents in the para-positions of the donor greatly enhance the donor strength, which allows exploration of different energy alignments among CT and LE triplet states. In the tert-butyl substituted compound the low energy triplet is localized on the acceptor unit, with the RISC mechanism (kRISC = 0.17 × 105 s−1) likely involving the mixture of CT and LE triplet states that are separated by less than 0.09 eV. An optimized organic light-emitting diode (OLED) based on the tBu-compound presents a maximum external quantum efficiency of 10.5% and deep-blue emission with Commission Internationale de l'Eclairage coordinates of (0.133, 0.129). However, when methoxy substituents are used, the low-energy triplet state moves away from the emissive 1CT singlet increasing the energy gap to 0.24 eV. Despite a larger ΔEST, a faster RISC rate (kRISC = 2.28 × 105 s−1) is observed due to the upper-state RISC occurring from the high-energy triplet state localized on the D (or A) units. This work shows the importance of fine-tuning the electronic interactions of the donor and acceptor units to control the TADF mechanism and achieve a deep-blue TADF OLED

Antimalarial 4(1H)-pyridones bind to the Qisite of cytochromebc1

Cytochrome bc1 is a proven drug target in the prevention and treatment of malaria. The rise in drug-resistant strains of Plasmodium falciparum, the organism responsible for malaria, has generated a global effort in designing new classes of drugs. Much of the design/redesign work on overcoming this resistance has been focused on compounds that are presumed to bind the Qo site (one of two potential binding sites within cytochrome bc1) using the known crystal structure of this large membrane-bound macromolecular complex via in silico modeling. Cocrystallization of the cytochrome bc1 complex with the 4(1H)-pyridone class of inhibitors, GSK932121 and GW844520, that have been shown to be potent antimalarial agents in vivo, revealed that these inhibitors do not bind at the Qo site but bind at the Qi site. The discovery that these compounds bind at the Qi site may provide a molecular explanation for the cardiotoxicity and eventual failure of GSK932121 in phase-1 clinical trial and highlight the need for direct experimental observation of a compound bound to a target site before chemical optimization and development for clinical trials. The binding of the 4(1H)-pyridone class of inhibitors to Qi also explains the ability of this class to overcome parasite Qo-based atovaquone resistance and provides critical structural information for future design of new selective compounds with improved safety profiles

Photodissociation dynamics of methyl iodide probed using femtosecond extreme ultraviolet photoelectron spectroscopy

Femtosecond pump-probe photoelectron spectroscopy measurements using an extreme ultraviolet probe have been made on the photodissociation dynamics of UV (269 nm) excited CH3I. The UV excitation leads to population of the 3Q0 state which rapidly dissociates. The dissociation is manifested as shifts in the measured photoelectron kinetic energy that map the extending C-I bond. The increased energy available in the XUV probe relative to a UV probe means the dynamics are followed over the chemically important region as far as C-I bond lengths of approximately 4 Å

Mitochondrial function remains impaired in the hypertrophied right ventricle of pulmonary hypertensive rats following short duration metoprolol treatment

Pulmonary hypertension (PH) increases the work of the right ventricle (RV) and causes right-sided heart failure. This study examined RV mitochondrial function and ADP transfer in PH animals advancing to right heart failure, and investigated a potential therapy with the specific β1-adrenergic-blocker metoprolol. Adult Wistar rats (317 ± 4 g) were injected either with monocrotaline (MCT, 60 mg kg-1) to induce PH, or with an equivalent volume of saline for controls (CON). At three weeks post-injection the MCT rats began oral metoprolol (10 mg kg-1 day-1-) or placebo treatment until heart failure was observed in the MCT group. Mitochondrial function was then measured using high-resolution respirometry from permeabilised RV fibres. Relative to controls, MCT animals had impaired mitochondrial function but maintained coupling between myofibrillar ATPases and mitochondria, despite an increase in ADP diffusion distances. Cardiomyocytes from the RV of MCT rats were enlarged, primarily due to an increase in myofibrillar protein. The ratio of mitochondria per myofilament area was decreased in both MCT groups (p ≤ 0.05) in comparison to control (CON: 1.03 ± 0.04; MCT: 0.74 ± 0.04; MCT + BB: 0.74 ± 0.03). This not only implicates impaired energy production in PH, but also increases the diffusion distance for metabolites within the MCT cardiomyocytes, adding an additional hindrance to energy supply. Together, these changes may limit energy supply in MCT rat hearts, particularly at high cardiac workloads. Metoprolol treatment did not delay the onset of heart failure symptoms, improve mitochondrial function, or regress RV hypertrophy

Contact Manifolds, Contact Instantons, and Twistor Geometry

Recently, Kallen and Zabzine computed the partition function of a twisted supersymmetric Yang-Mills theory on the five-dimensional sphere using localisation techniques. Key to their construction is a five-dimensional generalisation of the instanton equation to which they refer as the contact instanton equation. Subject of this article is the twistor construction of this equation when formulated on K-contact manifolds and the discussion of its integrability properties. We also present certain extensions to higher dimensions and supersymmetric generalisations.Comment: v3: 28 pages, clarifications and references added, version to appear in JHE

<i>Schizosaccharomyces pombe</i> Pol II transcription elongation factor ELL functions as part of a rudimentary super elongation complex

ELL family transcription factors activate the overall rate of RNA polymerase II (Pol II) transcription elongation by binding directly to Pol II and suppressing its tendency to pause. In metazoa, ELL regulates Pol II transcription elongation as part of a large multisubunit complex referred to as the Super Elongation Complex (SEC), which includes P-TEFb and EAF, AF9 or ENL, and an AFF family protein. Although orthologs of ELL and EAF have been identified in lower eukaryotes including Schizosaccharomyces pombe, it has been unclear whether SEClike complexes function in lower eukaryotes. In this report, we describe isolation from S. pombe of an ELL-containing complex with features of a rudimentary SEC. This complex includes S. pombe Ell1, Eaf1, and a previously uncharacterized protein we designate Ell1 binding protein 1 (Ebp1), which is distantly related to metazoan AFF family members. Like the metazoan SEC, this S. pombe ELL complex appears to function broadly in Pol II transcription. Interestingly, it appears to have a particularly important role in regulating genes involved in cell separation

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease