Background
Under saline conditions,
Suaeda salsa
, as a typical halophyte, accumulates large amounts of Na
+
in its leaves during optimal growth. Key transporters involved in Na
+
accumulation in ...plants are HKT-type protein, the plasma membrane Na
+
/H
+
transporter SOS1, and the tonoplast Na
+
/H
+
antiporter NHX1. In this study, the function of SsHKT1;1 and its coordinate expression with SsSOS1 and SsNHX1 to regulate Na
+
homeostasis in
S. salsa
was investigated.
Results
We showed, by yeast complementation assays, that
SsHKT1;1
encoded a Na
+
-selective transporter, which located to the plasma membrane and was preferentially expressed within the stele, and was particularly abundant in xylem parenchyma and pericycle cells. When compared with a treatment of 25 mM NaCl, 150 mM NaCl greatly decreased the transcripts of
SsHKT1;1
, but maintained a relatively constant level of the expression of
SsSOS1
in roots. Consequently, the synergistic effect of SsHKT1;1 and SsSOS1 would result in greater Na
+
loading into the xylem under 150 mM NaCl than 25 mM NaCl. In leaves, 150 mM NaCl up-regulated the abundance of
SsNHX1
compared with levels in 25 mM NaCl. This enabled the permanent sequestering of Na
+
into leaf vacuoles.
Conclusions
Overall, SsHKT1;1 functioned in reducing Na
+
retrieval from the root xylem, and played an important role in coordinating with SsSOS1 and SsNHX1 to maintain Na
+
accumulation in
S. salsa
under saline conditions.
Peripheral T-cell lymphomas (PTCLs) are heterogenous T-cell neoplasms often associated with epigenetic dysregulation. We investigated de novo DNA methyltransferase 3A (DNMT3A) mutations in common ...PTCL entities, including angioimmunoblastic T-cell lymphoma and novel molecular subtypes identified within PTCL-not otherwise specified (PTCL-NOS) designated as PTCL-GATA3 and PTCL-TBX21. DNMT3A-mutated PTCL-TBX21 cases showed inferior overall survival (OS), with DNMT3A-mutated residues skewed toward the methyltransferase domain and dimerization motif (S881-R887). Transcriptional profiling demonstrated significant enrichment of activated CD8+ T-cell cytotoxic gene signatures in the DNMT3A-mutant PTCL-TBX21 cases, which was further validated using immunohistochemistry. Genomewide methylation analysis of DNMT3A-mutant vs wild-type (WT) PTCL-TBX21 cases demonstrated hypomethylation in target genes regulating interferon-γ (IFN-γ), T-cell receptor signaling, and EOMES (eomesodermin), a master transcriptional regulator of cytotoxic effector cells. Similar findings were observed in a murine model of PTCL with Dnmt3a loss (in vivo) and further validated in vitro by ectopic expression of DNMT3A mutants (DNMT3A-R882, -Q886, and -V716, vs WT) in CD8+ T-cell line, resulting in T-cell activation and EOMES upregulation. Furthermore, stable, ectopic expression of the DNMT3A mutants in primary CD3+ T-cell cultures resulted in the preferential outgrowth of CD8+ T cells with DNMT3AR882H mutation. Single-cell RNA sequencing(RNA-seq) analysis of CD3+ T cells revealed differential CD8+ T-cell subset polarization, mirroring findings in DNMT3A-mutated PTCL-TBX21 and validating the cytotoxic and T-cell memory transcriptional programs associated with the DNMT3AR882H mutation. Our findings indicate that DNMT3A mutations define a cytotoxic subset in PTCL-TBX21 with prognostic significance and thus may further refine pathological heterogeneity in PTCL-NOS and suggest alternative treatment strategies for this subset.
Paediatric neurovascular anomalies associated with the vein of Galen (VG) comprise of a spectrum of rare, complex, and life-threatening conditions. In this group, the "vein of Galen aneurysmal ...dilatation" (VGAD) is a distinct entity that often presents with progressive neurological symptoms in older children. Acute haemorrhage in VGAD is uncommon. We present an unusual presentation of VGAD in a neonate and discuss the challenges faced in the management.
Analysis of human sketches in deep learning has advanced immensely through the use of waypoint-sequences rather than raster-graphic representations. We further aim to model sketches as a sequence of ...low-dimensional parametric curves. To this end, we propose an inverse graphics framework capable of approximating a raster or waypoint based stroke encoded as a point-cloud with a variable-degree Bézier curve. Building on this module, we present Cloud2Curve, a generative model for scalable high-resolution vector sketches that can be trained end-to-end using point-cloud data alone. As a consequence, our model is also capable of deterministic vectorization which can map novel raster or waypoint based sketches to their corresponding high-resolution scalable Bézier equivalent. We evaluate the generation and vectorization capabilities of our model on Quick, Draw! and K-MNIST datasets.
The aim of this study was to compare 1-year outcomes after transcatheter aortic valve replacement (TAVR) in low surgical risk patients with bicuspid aortic stenosis to patients with tricuspid aortic ...stenosis.
The pivotal TAVR trials excluded patients with bicuspid aortic valves. The Low Risk Bicuspid Study 30-day primary endpoint of death or disabling stroke was 1.3%.
The Low Risk Bicuspid Study is a prospective, single-arm, TAVR trial that enrolled patients from 25 U.S. sites. A screening committee confirmed bicuspid anatomy and valve classification on computed tomography using the Sievers classification. Valve sizing was by annular measurements. An independent clinical events committee adjudicated all serious adverse events, and an independent core laboratory assessed all echocardiograms. The 150 patients from the Low Risk Bicuspid Study were propensity matched to the TAVR patients in the randomized Evolut Low Risk Trial using the 1:1 5- to-1-digit greedy method, resulting in 145 pairs.
All-cause mortality or disabling stroke at 1 year was 1.4% in the bicuspid and 2.8% in the tricuspid group (P = 0.413). A pacemaker was implanted in 16.6% of bicuspid and 17.9% of tricuspid patients (P = 0.741). The effective orifice area was similar between groups at 1 year (2.2 ± 0.7 cm
vs 2.3 ± 0.6 cm
, P = 0.677) as was the mean gradient (8.7 ± 3.9 mm Hg vs 8.5 ± 3.1 mm Hg, P = 0.754). Fewer patients in the bicuspid group had mild or worse paravalvular leak (21.3% vs 42.6%, P < 0.001).
There were no significant differences in clinical or forward flow hemodynamic outcomes between the propensity-matched groups at 1 year.
A precise understanding of neural circuits controlling lipid mobilization and thermogenesis remains to be determined. We have been studying the sympathetic nervous system (SNS) contributions to white ...adipose tissue (WAT) lipolysis largely in Siberian hamsters. Central melanocortins are implicated in the control of the sympathetic outflow to WAT, and, moreover, the melanocortin 4 receptors (MC4-R) appear to be principally involved. We previously found that acute third ventricular melanotan II (MTII; an MC3/4-R agonist) injections increase sympathetic drive (norepinephrine turnover) to interscapular brown adipose tissue (IBAT) and IBAT temperature. Here we tested whether MC4-R mRNA is expressed in IBAT SNS outflow neurons using in situ hybridization for the former and injections of the transneuronal viral retrograde tract tracer, pseudorabies virus (PRV) into IBAT, for the latter. Significant numbers of double-labeled cells for PRV and MC4-R mRNA were found across the neuroaxis (mean of all brain sites approximately 60%), including the hypothalamic paraventricular nucleus (PVH; approximately 80%). Acute parenchymal MTII microinjections into the PVH of awake, freely-moving hamsters, using doses below those able to increase IBAT temperature when injected into the third ventricle, increased IBAT temperature for as long as 4 h, as measured by temperature transponders implanted below the tissue. Collectively, these data add significant support to the view that central melanocortins are important in controlling IBAT thermogenesis via the SNS innervation of this tissue, likely through the MC4-Rs.
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