Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways

Anosmin-1, encoded by the KAL1 gene, is an extracellular matrix (ECM)-associated protein which plays essential roles in the establishment of olfactory and GNRH neurons during early brain development. Loss-of-function mutations of KAL1 results in Kallmann syndrome with delayed puberty and anosmia. There is, however, little comprehension of its role in the developed brain. As reactivation of developmental signal pathways often takes part in tumorigenesis, we investigated if anosmin-1-mediated cellular mechanisms associated with brain tumors. Our meta-analysis of gene expression profiles of patients' samples and public microarray datasets indicated that KAL1 mRNA was significantly upregulated in high-grade primary brain tumors compared with the normal brain and low-grade tumors. The tumor-promoting capacity of anosmin-1 was demonstrated in the glioblastoma cell lines, where anosmin-1 enhanced cell motility and proliferation. Notably, anosmin-1 formed a part of active β1 integrin complex, inducing downstream signaling pathways. ShRNA-mediated knockdown of anosmin-1 attenuated motility and growth of tumor cells and induced apoptosis. Anosmin-1 may also enhance the invasion of tumor cells within the ECM by modulating cell adhesion and activating extracellular proteases. In a mouse xenograft model, anosmin-1-expressing tumors grew faster, indicating the role of anosmin-1 in tumor microenvironment in vivo. Combined, these data suggest that anosmin-1 can facilitate tumor cell proliferation, migration, invasion, and survival. Therefore, although the normal function of anosmin-1 is required in the proper development of GNRH neurons, overexpression of anosmin-1 in the developed brain may be an underlying mechanism for some brain tumors

Gliese 12 b, a temperate Earth-sized planet at 12 parsecs discovered with TESS and CHEOPS

We report on the discovery of Gliese 12 b, the nearest transiting temperate, Earth-sized planet found to date. Gliese 12 is a bright (V = 12.6 mag, K = 7.8 mag) metal-poor M4V star only 12.162 ± 0.005 pc away from the Solar system with one of the lowest stellar activity levels known for M-dwarfs. A planet candidate was detected by TESS based on only 3 transits in sectors 42, 43, and 57, with an ambiguity in the orbital period due to observational gaps. We performed follow-up transit observations with CHEOPS and ground-based photometry with MINERVA-Australis, SPECULOOS, and Purple Mountain Observatory, as well as further TESS observations in sector 70. We statistically validate Gliese 12 b as a planet with an orbital period of 12.76144 ± 0.00006 d and a radius of 1.0 ± 0.1 R⊕, resulting in an equilibrium temperature of ∼315 K. Gliese 12 b has excellent future prospects for precise mass measurement, which may inform how planetary internal structure is affected by the stellar compositional environment. Gliese 12 b also represents one of the best targets to study whether Earth-like planets orbiting cool stars can retain their atmospheres, a crucial step to advance our understanding of habitability on Earth and across the galaxy

Gliese 12 b, A Temperate Earth-sized Planet at 12 Parsecs Discovered with TESS and CHEOPS

We report on the discovery of Gliese 12 b, the nearest transiting temperate, Earth-sized planet found to date. Gliese 12 is a bright ($V=12.6$ mag, $K=7.8$ mag) metal-poor M4V star only $12.162\pm0.005$ pc away from the Solar System with one of the lowest stellar activity levels known for an M-dwarf. A planet candidate was detected by TESS based on only 3 transits in sectors 42, 43, and 57, with an ambiguity in the orbital period due to observational gaps. We performed follow-up transit observations with CHEOPS and ground-based photometry with MINERVA-Australis, SPECULOOS, and Purple Mountain Observatory, as well as further TESS observations in sector 70. We statistically validate Gliese 12 b as a planet with an orbital period of $12.76144\pm0.00006$ days and a radius of $1.0\pm{0.1}$ R$_\oplus$, resulting in an equilibrium temperature of $\sim$315K. Gliese 12 b has excellent future prospects for precise mass measurement, which may inform how planetary internal structure is affected by the stellar compositional environment. Gliese 12 b also represents one of the best targets to study whether Earth-like planets orbiting cool stars can retain their atmospheres, a crucial step to advance our understanding of habitability on Earth and across the Galaxy.Comment: 19 pages, 7 figures, Accepted for publication in MNRAS, Authors Shishir Dholakia and Larissa Palethorpe contributed equall

Gliese 12 b, a temperate Earth-sized planet at 12 parsecs discovered with TESS and CHEOPS

We report on the discovery of Gliese 12 b, the nearest transiting temperate, Earth-sized planet found to date. Gliese 12 is a bright (V = 12.6 mag, K = 7.8 mag) metal-poor M4V star only 12.162 ± 0.005 pc away from the Solar system with one of the lowest stellar activity levels known for M-dwarfs. A planet candidate was detected by TESS based on only 3 transits in sectors 42, 43, and 57, with an ambiguity in the orbital period due to observational gaps. We performed follow-up transit observations with CHEOPS and ground-based photometry with MINERVA-Australis, SPECULOOS, and Purple Mountain Observatory, as well as further TESS observations in sector 70. We statistically validate Gliese 12 b as a planet with an orbital period of 12.76144 ± 0.00006 d and a radius of 1.0 ± 0.1 R⊕, resulting in an equilibrium temperature of ∼315 K. Gliese 12 b has excellent future prospects for precise mass measurement, which may inform how planetary internal structure is affected by the stellar compositional environment. Gliese 12 b also represents one of the best targets to study whether Earth-like planets orbiting cool stars can retain their atmospheres, a crucial step to advance our understanding of habitability on Earth and across the galaxy

The mass of the exo-Venus Gliese 12 b, as revealed by HARPS-N, ESPRESSO, and CARMENES

Small temperate planets are prime targets for exoplanet studies due to their possible similarities with the rocky planets in the Solar System. M dwarfs are promising hosts since the planetary signals are within our current detection capabilities. Gliese 12 b is a Venus-sized temperate planet orbiting a quiet M dwarf. We present here the first precise mass measurement of this small exoplanet. We performed a detailed analysis using HARPS-N, ESPRESSO, and CARMENES radial velocities, along with new and archival TESS, CHEOPS, and MuSCAT2/3 photometry data. From fitting the available data, we find that the planet has a radius of Rp = 0.93 ± 0.06 R⊕ and a mass of Mp = +0.29-0.30 M⊕ (a 3.2σ measurement of the semi-amplitude K=0.67 ± 21 ms-1, and is on an orbit with a period of 12.761418+0.000060-0.000055 d. A variety of techniques were utilised to attenuate stellar activity signals. Gliese 12 b has an equilibrium temperature of Teq=317 ± 8 K, assuming an albedo of zero, and a density consistent with that of Earth and Venus (ρp=6.4 ± 2.4g cm-3. We find that Gliese 12 b has a predominantly rocky interior and simulations indicate that it is unlikely to have retained any of its primordial gaseous envelope. The bulk properties of Gliese 12 b place it in an extremely sparsely populated region of both mass--radius and density-Teq parameter space, making it a prime target for follow-up observations, including Lyman-α studies

FLUNARIZINE IN PRIMARY HEADACHE DISORDERS

BackgroundFlunarizine is a widely used migraine preventive not licensed in the UK. In September 2014, the National Institute for Clinical Excellence (NICE) published supportive guidelines for flunarizine use in migraine based on available randomised controlled evidence.AimTo collect data for an audit of flunarizine use from our tertiary headache practice in the UK over twenty years, to try to establish indications for its use, typical doses, short and long term side effects, and treatment outcomes, including changes in acute treatment use and change in frequency and intensity of headache on treatment.ResultsFor the first 30 patients audited the most common indication for flunarizine was chronic migraine, followed by migraine with aura, sporadic hemiplegic migraine and familial hemiplegic migraine and then new persistent daily headache of a migrainous type. Doses up to 15mg were generally well tolerated, with only five patients stopping treatment due to adverse effects. Flunarizine is generally effective; with only three patients reporting no clinical effect: two had hemiplegic migraine and one chronic migraine. The commonest dose used was 10mg and a significant proportion of patients continued treatment for more than one year.ConclusionFlunarizine is an effective, well tolerated migraine preventive that can be used for extended periods in a range of migraine sub-types.</jats:sec

Effects of sex and age on the susceptibility of C57BL/6J mice to infection with Brachylaima cribbi and the course of infection in NOD SCID mice

Abstract The C57BL/6J strain of Mus musculus is susceptible to the terrestrial trematode Brachylaima cribbi. The duration of infection in these mice is generally 9-12 weeks with a peak excretion of eggs at 4 weeks postinfection (wpi). The effects of age and sex on the course of infection were investigated by comparing infections in male and female mice aged 8 or 28 weeks at the time of infection. There were no significant differences in the susceptibility of the adolescent mice of either sex or older male mice. However, older, mature female mice were significantly more resistant to B. cribbi infection than older mature males and adolescent females with reduced worm burden, fecundity and egg fertility. In comparison with young males, all three parameters were again reduced but this was only significant statistically for reduced egg fertility. It is likely that mature female sex hormones influence resistance to B. cribbi infection. The susceptibility of immunodeficient NOD SCID mice was evaluated and compared with C57BL/6J mice. NOD SCID mice were susceptible to B. cribbi infection with the infection persisting with a relatively unchanged worm burden for the life of the mouse with the longest surviving mice being 31 wpi. The life-span of B. cribbi is therefore at least 31 weeks. There were no significant differences in egg excretion, worm burden or fecundity among NOD SCID mice at 4, 8 or 18 wpi. As the infection progressed in NOD SCID mice, the location of worms in the small intestine moved from the anterior third in the early stages of the infection to the mid-to posterior intestine in the later stages. Comparison of the infection in NOD SCID mice with C57BL/6J mice indicates that the expulsion of worms in the latter is mediated by an immune response

Assessment in the early years: A symposium about measurement, applications and going to scale

Assessment in the early years is seen as contentious. Yet there is significant and growing interest in knowing more about what children can do and how we can best support learning and development. This is true in global monitoring of progress towards Sustainable Development Goal 4.2 with UNICEF promoting parent-report of children’s learning, health, and psychosocial wellbeing development at ages 2-5 years. It is also true in Australia’s ECEC system, with the Commonwealth Department of Education advancing a reform agenda that includes a preschool outcome measure for children in the year before school (typically 4 years old) and state jurisdictions pursuing the development of assessments (e.g. Victoria) and the use of learning progressions (e.g. Queensland). Within ECEC providers, too, significant effort has been placed on developing and deploying tools to monitor learning and to inform practice in the pursuit of better learning, development and well-being outcomes for children. There are, therefore, multiple agendas driving increased development of use of assessment in the early years: international comparative reporting, systems monitoring and improvement, assessment for learning, and research among them. Within a system that is not traditionally well-prepared or experienced in conducting assessment, it is unlikely that there is room for all these agendas to operate separately and introduce separate approaches to assessment. In this symposium, cutting-edge perspectives on early childhood assessment are provided from research, intervention, and practice perspectives. Together the symposium focuses on new perspectives on assessment and how a new approach can prioritise and focus on assessment\u27s primary purpose – teaching and learning – while delivering on other priorities, including monitoring and research without imposing additional burden on educators and providers. The sessions take the perspective that the primary purpose of assessment in early childhood is to improve outcomes for children by supporting educators to: collect evidence about children’s learning and development; use that evidence to inform planning and practice; act in evidence-informed ways, and to reflect on and adapt their impact over time. The first paper in the session focuses on the development of a high-quality measure of early learning and development focusing on oral language and literacy. The aim is to develop a measure that is authentic – focused on adult–child interactions – but that also uses contemporary measurement theory and approaches used in large scale assessment programs like OECD’s International Early Learning and Wellbeing Study to construct measures that can reliably measure the growth of individual children and also support system monitoring and reporting (without the need for additional assessment). The second paper in the session focuses on the deployment of a new assessment of oral language and literacy in early childhood contexts in the Northern Territory, which is supporting educators working in a vulnerable community to improve outcomes. A focus is given on how educators can be trained to use assessment and learning progressions to target their practice to have impacts on learning and development – including across the transition to school and progression through the year levels. The third paper in the session focuses on taking assessment to scale in a large ECEC provider in Australia. This includes the groundwork needed to ensure consistent assessment practice as well as to get buy-in from educators at large. The paper will report on the how evidence from assessment can be used at the individual child level, but also the provider and system level, alongside other evidence-based approaches to measurement to inform the deployment of resources and support better outcomes in underserved communities