Darwin at the Drugstore? Testing the Biological Fitness of Antibiotic Resistant Bacteria

The issue of antibiotic resistance in bacteria is growing. For example, methicillin-resistant Staphylococcus aureus (MRSA) is a leading human pathogen. New strains of MRSA are resistant to methicillin and numerous other antibiotics, placing the patient in significant danger. Indeed, the Centers for Disease Control revealed in 2007 that the number of deaths due to MRSA exceeded that of AIDS in the United States. It is no wonder that antibiotic resistance is one of the most significant and important health care issues. The ability of bacterial pathogens to evade traditional antibiotics is faster than the drug makers’ ability to make new types of clinical drugs (Gillen, 2007)

Implementation Challenges and Training Needs for Comprehensive School Counseling Programs in Wisconsin High Schools

The data from this study details the challenges to implementing comprehensive school counseling programs in Wisconsin high schools. Results suggest that current professional development training practices may be ineffective in assisting high school counselors to implement key components of the ASCA National Model in their schools. This article discusses obstacles to conducting more rigorous, statewide evaluations, and describes connections to markers of student success

Codon optimality in cancer.

A key characteristic of cancer cells is their increased proliferative capacity, which requires elevated levels of protein synthesis. The process of protein synthesis involves the translation of codons within the mRNA coding sequence into a string of amino acids to form a polypeptide chain. As most amino acids are encoded by multiple codons, the nucleotide sequence of a coding region can vary dramatically without altering the polypeptide sequence of the encoded protein. Although mutations that do not alter the final amino acid sequence are often thought of as silent/synonymous, these can still have dramatic effects on protein output. Because each codon has a distinct translation elongation rate and can differentially impact mRNA stability, each codon has a different degree of 'optimality' for protein synthesis. Recent data demonstrates that the codon preference of a transcriptome matches the abundance of tRNAs within the cell and that this supply and demand between tRNAs and mRNAs varies between different cell types. The largest observed distinction is between mRNAs encoding proteins associated with proliferation or differentiation. Nevertheless, precisely how codon optimality and tRNA expression levels regulate cell fate decisions and their role in malignancy is not fully understood. This review describes the current mechanistic understanding on codon optimality, its role in malignancy and discusses the potential to target codon optimality therapeutically in the context of cancer

Optimisation of sample preparation from primary mouse tissue to maintain RNA integrity for methods examining translational control

The protein output of different mRNAs can vary by two orders of magnitude; therefore, it is critical to understand the processes that control gene expression operating at the level of translation. Translatome-wide techniques, such as polysome profiling and ribosome profiling, are key methods for determining the translation rates occurring on specific mRNAs. These techniques are now widely used in cell lines; however, they are underutilised in tissues and cancer models. Ribonuclease (RNase) expression is often found to be higher in complex primary tissues in comparison to cell lines. Methods used to preserve RNA during lysis often use denaturing conditions, which need to be avoided when maintaining the interaction and position of the ribosome with the mRNA is required. Here, we detail the cell lysis conditions that produce high-quality RNA from several different tissues covering a range of endogenous RNase expression levels. We highlight the importance of RNA integrity for accurate determination of the global translation status of the cell as determined by polysome gradients and discuss key aspects to optimise for accurate assessment of the translatome from primary mouse tissue

NGTS clusters survey -- II. White-light flares from the youngest stars in Orion

We present the detection of high energy white-light flares from pre-main sequence stars associated with the Orion complex, observed as part of the Next Generation Transit Survey (NGTS). With energies up to $5.2\times10^{35}$ erg these flares are some of the most energetic white-light flare events seen to date. We have used the NGTS observations of flaring and non-flaring stars to measure the average flare occurrence rate for 4 Myr M0-M3 stars. We have also combined our results with those from previous studies to predict average rates for flares above $1\times10^{35}$ ergs for early M stars in nearby young associations.STFC ST/M001962/1; ST/P000495/

eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5′UTR

BackgroundRegulation of the mRNA life cycle is central to gene expression control and determination of cell fate. miRNAs represent a critical mRNA regulatory mechanism, but despite decades of research, their mode of action is still not fully understood.ResultsHere, we show that eIF4A2 is a major effector of the repressive miRNA pathway functioning via the Ccr4-Not complex. We demonstrate that while DDX6 interacts with Ccr4-Not, its effects in the mechanism are not as pronounced. Through its interaction with the Ccr4-Not complex, eIF4A2 represses mRNAs at translation initiation. We show evidence that native eIF4A2 has similar RNA selectivity to chemically inhibited eIF4A1. eIF4A2 exerts its repressive effect by binding purine-rich motifs which are enriched in the 5′UTR of target mRNAs directly upstream of the AUG start codon.ConclusionsOur data support a model whereby purine motifs towards the 3′ end of the 5′UTR are associated with increased ribosome occupancy and possible uORF activation upon eIF4A2 binding.</p

NGTS-21b: An Inflated Super-Jupiter Orbiting a Metal-poor K dwarf

We report the discovery of NGTS-21b, a massive hot Jupiter orbiting a low-mass star as part of the Next Generation Transit Survey (NGTS). The planet has a mass and radius of $2.36 \pm 0.21$ M$_{\rm J}$, and $1.33 \pm 0.03$ R$_{\rm J}$, and an orbital period of 1.543 days. The host is a K3V ($T_{\rm eff}=4660 \pm 41$, K) metal-poor (${\rm [Fe/H]}=-0.26 \pm 0.07$, dex) dwarf star with a mass and radius of $0.72 \pm 0.04$, M$_{\odot}$,and $0.86 \pm 0.04$, R$_{\odot}$. Its age and rotation period of $10.02^{+3.29}_{-7.30}$, Gyr and $17.88 \pm 0.08$, d respectively, are in accordance with the observed moderately low stellar activity level. When comparing NGTS-21b with currently known transiting hot Jupiters with similar equilibrium temperatures, it is found to have one of the largest measured radii despite its large mass. Inflation-free planetary structure models suggest the planet's atmosphere is inflated by $\sim21\%$, while inflationary models predict a radius consistent with observations, thus pointing to stellar irradiation as the probable origin of NGTS-21b's radius inflation. Additionally, NGTS-21b's bulk density ($1.25 \pm 0.15$, g/cm$^3$) is also amongst the largest within the population of metal-poor giant hosts ([Fe/H] < 0.0), helping to reveal a falling upper boundary in metallicity-planet density parameter space that is in concordance with core accretion formation models. The discovery of rare planetary systems such as NGTS-21 greatly contributes towards better constraints being placed on the formation and evolution mechanisms of massive planets orbiting low-mass stars.Comment: 12 pages, 13 figures, accepted for publication in MNRA

NGTS clusters survey – V. Rotation in the Orion star-forming complex

We present a study of rotation across 30 square degrees of the Orion Star-forming Complex, following a ∼200 d photometric monitoring campaign by the Next Generation Transit Survey (NGTS). From 5749 light curves of Orion members, we report periodic signatures for 2268 objects and analyse rotation period distributions as a function of colour for 1789 stars with spectral types F0–M5. We select candidate members of Orion using Gaia data and assign our targets to kinematic sub-groups. We correct for interstellar extinction on a star-by-star basis and determine stellar and cluster ages using magnetic and non-magnetic stellar evolutionary models. Rotation periods generally lie in the range 1–10 d, with only 1.5 per cent of classical T Tauri stars or Class I/II young stellar objects rotating with periods shorter than 1.8 d, compared with 14 per cent of weak-line T Tauri stars or Class III objects. In period–colour space, the rotation period distribution moves towards shorter periods among low-mass (&amp;gt;M2) stars of age 3–6 Myr, compared with those at 1–3 Myr, with no periods longer than 10 d for stars later than M3.5. This could reflect a mass-dependence for the dispersal of circumstellar discs. Finally, we suggest that the turnover (from increasing to decreasing periods) in the period–colour distributions may occur at lower mass for the older-aged population: ∼K5 spectral type at 1–3 Myr shifting to ∼M1 at 3–6 Myr

NGTS-28Ab:a short period transiting brown dwarf

We report the discovery of a brown dwarf orbiting a M1 host star. We first identified the brown dwarf within the Next Generation Transit Survey data, with supporting observations found in TESS sectors 11 and 38. We confirmed the discovery with follow-up photometry from the South African Astronomical Observatory, SPECULOOS-S, and TRAPPIST-S, and radial velocity measurements from HARPS, which allowed us to characterize the system. We find an orbital period of ∼1.25 d, a mass of 69.0+5.3-4.8 MJ, close to the hydrogen burning limit, and a radius of 0.95 ± 0.05 RJ. We determine the age to be &gt;0.5 Gyr, using model isochrones, which is found to be in agreement with spectral energy distribution fitting within errors. NGTS-28Ab is one of the shortest period systems found within the brown dwarf desert, as well as one of the highest mass brown dwarfs that transits an M dwarf. This makes NGTS-28Ab another important discovery within this scarcely populated region.</div