Biogenesis of the inner membrane complex is dependent on vesicular transport by the alveolate specific GTPase Rab11B

Apicomplexan parasites belong to a recently recognised group of protozoa referred to as Alveolata. These protists contain membranous sacs (alveoli) beneath the plasma membrane, termed the Inner Membrane Complex (IMC) in the case of Apicomplexa. During parasite replication the IMC is formed de novo within the mother cell in a process described as internal budding. We hypothesized that an alveolate specific factor is involved in the specific transport of vesicles from the Golgi to the IMC and identified the small GTPase Rab11B as an alveolate specific Rab-GTPase that localises to the growing end of the IMC during replication of Toxoplasma gondii. Conditional interference with Rab11B function leads to a profound defect in IMC biogenesis, indicating that Rab11B is required for the transport of Golgi derived vesicles to the nascent IMC of the daughter cell. Curiously, a block in IMC biogenesis did not affect formation of sub-pellicular microtubules, indicating that IMC biogenesis and formation of sub-pellicular microtubules is not mechanistically linked. We propose a model where Rab11B specifically transports vesicles derived from the Golgi to the immature IMC of the growing daughter parasites

A non-repeating fast radio burst in a dwarf host galaxy

We present the discovery of as-of-yet non-repeating Fast Radio Burst (FRB), FRB 20210117A, with the Australian Square Kilometer Array Pathfinder (ASKAP) as a part of the Commensal Real-time ASKAP Fast Transients (CRAFT) Survey. The sub-arcsecond localization of the burst led to the identification of its host galaxy at a $z=0.214(1)$. This redshift is much lower than what would be expected for a source dispersion measure (DM) of 729 pc cm$^{-3}$, given typical contributions from the intergalactic medium and the host galaxy. Optical observations reveal the host to be a dwarf galaxy with little on-going star formation, very different to the dwarf host galaxies of known repeating FRBs 20121102A, and 20190520B. We find an excess DM contribution from the host and attribute it to the FRB's local environment. We do not find any radio emission from the FRB site or host galaxy. The low magnetized environment and lack of a persistent radio source (PRS) indicate that the FRB source is older than those found in other dwarf host galaxies, and establish the diversity of FRB sources in dwarf galaxy environments. We find our observations to be fully consistent with the hypernebula model, where the FRB is powered by accretion-jet from a hyper-accreting black hole. Finally, our high-time resolution analysis reveals burst characteristics similar to those seen in repeating FRBs. We encourage follow-up observations of FRB 20210117A to establish any repeating nature.Comment: 15 pages, 9 figures, 2 Table

Probing the distant universe with a very luminous fast radio burst at redshift 1

Fast radio bursts are millisecond-duration pulses of radio emission that have been found to originate at extragalactic distances. The bursts show dispersion imparted by intervening plasma, with the bulk attributed to the intergalactic medium. Here we report the discovery of a burst, FRB20220610A, in a complex host galaxy system at a redshift of $z=1.016 \pm 0.002$. The relationship between its redshift and dispersion confirm that the bulk of the baryonic matter was ionized and in the intergalactic medium when the universe was almost half its present age. The burst shows evidence for passage through a significant additional column of turbulent and magnetized high-redshift plasma. It extends the maximum observed burst energy by a factor of four, confirming the presence of an energetic burst population at high redshift.Comment: 40 page

Subcellular Location, Phosphorylation and Assembly into the Motor Complex of GAP45 during Plasmodium falciparum Schizont Development

An actomyosin motor complex assembled below the parasite's plasma membrane drives erythrocyte invasion by Plasmodium falciparum merozoites. The complex is comprised of several proteins including myosin (MyoA), myosin tail domain interacting protein (MTIP) and glideosome associated proteins (GAP) 45 and 50, and is anchored on the inner membrane complex (IMC), which underlies the plasmalemma. A ternary complex of MyoA, MTIP and GAP45 is formed that then associates with GAP50. We show that full length GAP45 labelled internally with GFP is assembled into the motor complex and transported to the developing IMC in early schizogony, where it accumulates during intracellular development until merozoite release. We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. Replacing these serine residues with alanine or aspartate has no apparent effect on GAP45 assembly into the motor protein complex or its subcellular location in the parasite. The early assembly of the motor complex suggests that it has functions in addition to its role in erythrocyte invasion

Impaction bone grafting of the acetabulum at hip revision using a mix of bone chips and a biphasic porous ceramic bone graft substitute: Good outcome in 43 patients followed for a mean of 2 years

Background and purpose One of the greatest problems of revision hip arthroplasty is dealing with lost bone stock. Good results have been obtained with impaction grafting of allograft bone. However, there have been problems of infection, reproducibility, antigenicity, stability, availability of bone, and cost. Thus, alternatives to allograft have been sought. BoneSave is a biphasic porous ceramic specifically designed for use in impaction grafting. BoneSave is 80% tricalcium phosphate and 20% hydroxyapatite. Previous in vitro and in vivo studies have yielded good results using mixtures of allograft and BoneSave, when compared with allograft alone. This study is the first reported human clinical trial of BoneSave in impaction grafting

Bricoleurs Extraordinaire: Sports Coaches in Inter War Britain

In Inter War Britain, individuals exploited their athletic skills by pursuing professional careers, or adopting amateur roles, as instructors, trainers and coaches, invariably drawing from, and elaborating on, existing practices. The coach was the master of a body of specialist craft knowledge, the tacit nature of which was transmitted through ‘stealing with the eyes’ as the apprentice watched the master in action (Gamble, 2001). Professional coaches saw themselves as practical men whose experiential knowledge concerning diet, physiological and psychological preparation, stimulants, massaging, medical treatments, talent identification, and so on provided critical components in their coaching ‘toolbox’ (Nelson, 1924, 25-26). Craft knowledge was never static. Coaching expertise is a fluid, cyclical process with practitioners continuously redeveloping their competencies (Turner, Nelson and Potrac, 2012, 323), and part of traditional craft expertise was the ability to react positively to shifting circumstances. Coaches were constantly stimulated to experiment by competitors, commercialisation, and emerging technologies (Clegg, 1977, 244), and they exemplified the notion of the ‘Bricoleur’ in constantly trialling emerging knowledge, intuitively accepting or rejecting appropriate material. This paper explores the ways in which practitioners developed their coaching ‘toolbox’ in Inter War Britain by drawing on examples from newspaper reports, personal and public archives, and instructional texts (eg. Tilden, 1920; Gent, 1922; Nelson, 1924; Mussabini, 1926; Lowe and Porritt, 1929; Abrahams and Abrahams, 1936). The author highlights the range of knowledge that coaches had at their command, well before the emergence of sports science and coaching certification programmes, and questions assumptions that coaches can no longer rely solely on ‘learning the trade’ through experience (Evans and Light, 2007). As Winchester et al. (2013) have emphasised, knowledge, skills, attitudes, and insights are developed from daily experiences in sport, work and at home, as well as through exposure to the coaching environment, and contemporary coaches still employ a largely implicit form of knowledge, closely connected to past experiences, which shares similarities with Inter War craft knowledge (Smith and Cushion, 2006, 363; Jones, Armour and Potrac, 2003), while identifying experimentation and experience as key reference points (Irwin, Hanton and Kerwin, 2004, 436, 439; Potrac, Jones and Cushion, 2007)

Minor Body Science with the Nancy Grace Roman Space Telescope

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The discovery of I-BRD9, a selective cell active chemical probe for bromodomain containing protein 9 inhibition

Acetylation of histone lysine residues is one of the most well-studied post-translational modifications of chromatin, selectively recognized by bromodomain “reader” modules. Inhibitors of the bromodomain and extra terminal domain (BET) family of bromodomains have shown profound anticancer and anti-inflammatory properties, generating much interest in targeting other bromodomain-containing proteins for disease treatment. Herein, we report the discovery of I-BRD9, the first selective cellular chemical probe for bromodomain-containing protein 9 (BRD9). I-BRD9 was identified through structure-based design, leading to greater than 700-fold selectivity over the BET family and 200-fold over the highly homologous bromodomain-containing protein 7 (BRD7). I-BRD9 was used to identify genes regulated by BRD9 in Kasumi-1 cells involved in oncology and immune response pathways and to the best of our knowledge, represents the first selective tool compound available to elucidate the cellular phenotype of BRD9 bromodomain inhibition