208 research outputs found
The RNA Binding Protein Quaking Regulates Formation of circRNAs
SummaryCircular RNAs (circRNAs), formed by non-sequential back-splicing of pre-mRNA transcripts, are a widespread form of non-coding RNA in animal cells. However, it is unclear whether the majority of circRNAs represent splicing by-products without function or are produced in a regulated manner to carry out specific cellular functions. We show that hundreds of circRNAs are regulated during human epithelial-mesenchymal transition (EMT) and find that the production of over one-third of abundant circRNAs is dynamically regulated by the alternative splicing factor, Quaking (QKI), which itself is regulated during EMT. Furthermore, by modulating QKI levels, we show the effect on circRNA abundance is dependent on intronic QKI binding motifs. Critically, the addition of QKI motifs is sufficient to induce de novo circRNA formation from transcripts that are normally linearly spliced. These findings demonstrate circRNAs are both purposefully synthesized and regulated by cell-type specific mechanisms, suggesting they play specific biological roles in EMT
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Heterodimerization of Arabidopsis calcium/proton exchangers contributes to regulation of guard cell dynamics and plant defense responses.
Arabidopsis thaliana cation exchangers (CAX1 and CAX3) are closely related tonoplast-localized calcium/proton (Ca2+/H+) antiporters that contribute to cellular Ca2+ homeostasis. CAX1 and CAX3 were previously shown to interact in yeast; however, the function of this complex in plants has remained elusive. Here, we demonstrate that expression of CAX1 and CAX3 occurs in guard cells. Additionally, CAX1 and CAX3 are co-expressed in mesophyll tissue in response to wounding or flg22 treatment, due to the induction of CAX3 expression. Having shown that the transporters can be co-expressed in the same cells, we demonstrate that CAX1 and CAX3 can form homomeric and heteromeric complexes in plants. Consistent with the formation of a functional CAX1-CAX3 complex, CAX1 and CAX3 integrated into the yeast genome suppressed a Ca2+-hypersensitive phenotype of mutants defective in vacuolar Ca2+ transport, and demonstrated enzyme kinetics different from those of either CAX protein expressed by itself. We demonstrate that the interactions between CAX proteins contribute to the functioning of stomata, because stomata were more closed in cax1-1, cax3-1, and cax1-1/cax3-1 loss-of-function mutants due to an inability to buffer Ca2+ effectively. We hypothesize that the formation of CAX1-CAX3 complexes may occur in the mesophyll to affect intracellular Ca2+ signaling during defense responses
Anion-polarisation--directed short-range-order in antiperovskite LiFeSO
Short-range ordering in cation-disordered cathodes can have a significant
effect on their electrochemical properties. Here, we characterise the cation
short-range order in the antiperovskite cathode material LiFeSO, using
density functional theory, Monte Carlo simulations, and synchrotron X-ray
pair-distribution-function data. We predict partial short-range
cation-ordering, characterised by favourable OLiFe oxygen coordination
with a preference for polar cis-OLiFe over non-polar
trans-OLiFe configurations. This preference for polar cation
configurations produces long-range disorder, in agreement with experimental
data. The predicted short-range-order preference contrasts with that for a
simple point-charge model, which instead predicts preferential
trans-OLiFe oxygen coordination and corresponding long-range
crystallographic order. The absence of long-range order in LiFeSO can
therefore be attributed to the relative stability of cis-OLiFe and
other non-OLiFe oxygen-coordination motifs. We show that this effect is
associated with the polarisation of oxide and sulfide anions in polar
coordination environments, which stabilises these polar short-range cation
orderings. We propose similar anion-polarisation-directed short-range-ordering
may be present in other heterocationic materials that contain cations with
different formal charges. Our analysis also illustrates the limitations of
using simple point-charge models to predict the structure of cation-disordered
materials, where other factors, such as anion polarisation, may play a critical
role in directing both short- and long-range structural correlations
Dynamics in the satellite system of Triangulum: Is AndXXII a dwarf satellite of M33?
We present results from a spectroscopic survey of the dwarf spheroidal And
XXII and the two extended clusters EC1 and EC2. These three objects are
candidate satellites of the Triangulum galaxy, M33, which itself is likely a
satellite of M31. We use the DEep Imaging Multi-Object Spectrograph mounted on
the Keck-II telescope to derive radial velocities for candidate member stars of
these objects and thereby identify the stars that are most likely actual
members. Eleven most probable stellar members (of 13 candidates) are found for
AndXXII. We obtain an upper limit of sigma_v < 6.0 km s-1 for the velocity
dispersion of AndXXII, [Fe/H] ~ -1.6 for its metallicity, and 255pc for the
Plummer radius of its projected density profile. We construct a colour
magnitude diagram for AndXXII and identify both the red giant branch and the
horizontal branch. The position of the latter is used to derive a heliocentric
distance to And XXII of 853 pm 26 kpc. The combination of the radial velocity,
distance, and angular position of AndXXII indicates that it is a strong
candidate for being the first known satellite of M33 and one of the very few
examples of a galactic satellite of a satellite. N-body simulations imply that
this conclusion is unchanged even if M31 and M33 had a strong encounter in the
past few Gyr. We test the hypothesis that the extended clusters highlight
tidally stripped galaxies by searching for an excess cloud of halo-like stars
in their vicinity. We find such a cloud for the case of EC1 but not EC2. The
three objects imply a dynamical mass for M33 that is consistent with previous
estimates.Comment: 14 pages, 14 figures, revised for MNRAS publicatio
Adherence to treatment in children and adolescents with cystic fibrosis:a cross-sectional, multi-method study investigating the influence of beliefs about treatment and parental depressive symptoms
Background: Adherence to treatment is often reported to be low in children with cystic fibrosis. Adherence in cystic fibrosis is an important research area and more research is needed to better understand family barriers to adherence in order for clinicians to provide appropriate intervention. The aim of this study was to evaluate adherence to enzyme supplements, vitamins and chest physiotherapy in children with cystic fibrosis and to determine if any modifiable risk factors are associated with adherence. Methods: A sample of 100 children (≤18 years) with cystic fibrosis (44 male; median [range] 10.1 [0.2-18.6] years) and their parents were recruited to the study from the Northern Ireland Paediatric Cystic Fibrosis Centre. Adherence to enzyme supplements, vitamins and chest physiotherapy was assessed using a multi-method approach including; Medication Adherence Report Scale, pharmacy prescription refill data and general practitioner prescription issue data. Beliefs about treatments were assessed using refined versions of the Beliefs about Medicines Questionnaire-specific. Parental depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Results: Using the multi-method approach 72% of children were classified as low-adherers to enzyme supplements, 59% low-adherers to vitamins and 49% low-adherers to chest physiotherapy. Variations in adherence were observed between measurement methods, treatments and respondents. Parental necessity beliefs and child age were significant independent predictors of child adherence to enzyme supplements and chest physiotherapy, but parental depressive symptoms were not found to be predictive of adherence. Conclusions: Child age and parental beliefs about treatments should be taken into account by clinicians when addressing adherence at routine clinic appointments. Low adherence is more likely to occur in older children, whereas, better adherence to cystic fibrosis therapies is more likely in children whose parents strongly believe the treatments are necessary. The necessity of treatments should be reinforced regularly to both parents and children
A Rogues’ Gallery of Andromeda's Dwarf Galaxies. I. A Predominance of Red Horizontal Branches
We present homogeneous, sub-horizontal branch photometry of twenty dwarf
spheroidal satellite galaxies of M31 observed with the Hubble Space Telescope.
Combining our new data for sixteen systems with archival data in the same
filters for another four, we show that Andromeda dwarf spheroidal galaxies
favor strikingly red horizontal branches or red clumps down to ~10^{4.2} Lsun
(M_V ~ -5.8). The age-sensitivity of horizontal branch stars implies that a
large fraction of the M31 dwarf galaxies have extended star formation histories
(SFHs), and appear inconsistent with early star formation episodes that were
rapidly shutdown. Systems fainter than ~10^{5.5} Lsun show the widest range in
the ratios and morphologies of red and blue horizontal branches, indicative of
both complex SFHs and a diversity in quenching timescales and/or mechanisms,
which is qualitatively different from what is currently known for faint Milky
Way (MW) satellites of comparable luminosities. Our findings bolster similar
conclusions from recent deeper data for a handful of M31 dwarf galaxies. We
discuss several sources for diversity of our data such as varying halo masses,
patchy reionization, mergers/accretion, and the environmental influence of M31
and the Milky Way on the early evolution of their satellite populations. A
detailed comparison between the histories of M31 and MW satellites would shed
signifiant insight into the processes that drive the evolution of low-mass
galaxies. Such a study will require imaging that reaches the oldest main
sequence turnoffs for a significant number of M31 companions.Comment: 11 pages, 5 figures, 2 tables. ApJ in press. v2: small tweaks to the
results and discussion sectio
Long-acting injectable Cabotegravir + Rilpivirine for HIV maintenance therapy: Week 48 pooled analysis of phase 3 ATLAS and FLAIR trials
BACKGROUND: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1. SETTING: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies. METHODS: Adult participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints. RESULTS: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA <50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm. CONCLUSION: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression
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