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An Xq22.2 region upstream of PLP1 has been proposed to underly a neurological disease trait when deleted in 46,XX females. Deletion mapping revealed that heterozygous deletions encompassing the smallest region of overlap (SRO) spanning six Xq22.2 genes (BEX3, RAB40A, TCEAL4, TCEAL3, TCEAL1, and MORF4L2) associate with an early-onset neurological disease trait (EONDT) consisting of hypotonia, intellectual disability, neurobehavioral abnormalities, and dysmorphic facial features. None of the genes within the SRO have been associated with monogenic disease in OMIM. Through local and international collaborations facilitated by GeneMatcher and Matchmaker Exchange, we have identified and herein report seven de novo variants involving TCEAL1 in seven unrelated families: three hemizygous truncating alleles; one hemizygous missense allele; one heterozygous TCEAL1 full gene deletion; one heterozygous contiguous deletion of TCEAL1, TCEAL3, and TCEAL4; and one heterozygous frameshift variant allele. Variants were identified through exome or genome sequencing with trio analysis or through chromosomal microarray. Comparison with previously reported Xq22 deletions encompassing TCEAL1 identified a more-defined syndrome consisting of hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features include strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies. An additional maternally inherited hemizygous missense allele of uncertain significance was identified in a male with hypertonia and spasticity without syndromic features. These data provide evidence that TCEAL1 loss of function causes a neurological rare disease trait involving significant neurological impairment with features overlapping the EONDT phenotype in females with the Xq22 deletion.

The spikelet is a unique inflorescence structure in grasses. However, the molecular mechanism that regulates its development remains unclear, and we therefore characterize a spikelet mutant of rice (Oryza sativa L.), aberrant-floral spikelet 1 (afs1), which was derived from treatment of Xinong 1B with ethyl methanesulfonate. In the afs1 mutant, the spikelet developed an additional lemma-like organ alongside the other normally developed floral organs, and the paleae were degenerated to differing degrees with or without normally developed inner floral organs. Genetic analysis revealed that the afs1 phenotype was controlled by a single recessive gene. The AFS1 gene was mapped between the insertion/deletion (InDel) marker Indel19 and the simple sequence repeat marker RM16893, with a physical distance of 128.5 kb on chromosome 4. Using sequence analysis, we identified the deletion of a 5-bp fragment and a transversion from G to A within LOC_Os04g32510/LAX2, which caused early termination of translation in the afs1 mutant. These findings suggest that AFS1 may be a new allele of LAX2, and is involved in the development of floral organs by regulating the expression of genes related to their development. The above results provide a new view on the function of LAX2, which may also regulate the development of spikelets.

Background The role of right atrial (RA) dysfunction in patients with pulmonary hypertension (PH), as evaluated by two-dimensional speckle-tracking echocardiography (2D-STE) remains to be determined. Methods Sixty consecutive PH patients and 30 healthy volunteers were included. RA function was evaluated by 2D-STE, and the following parameters were recorded: an average longitudinal strain (LS) curve that included LSpos during RA filling and LSneg representing RA active contraction (their summation is LStot), the phasic RA volumes, total RA emptying fraction, and the ratio of RA passive and active emptying to total emptying. The associations between these indices and the results of invasive pulmonary hemodynamics, cardiac structure and function, and NT-terminal pro brain natriuretic peptide (NT-proBNP) level were evaluated. Results LStot, total RA emptying fraction, LSpos, passive RA emptying fraction were significantly lower, while the contribution of active RA empting fraction/total RA emptying fraction was higher in PH patients than in controls. Among PH patients, LStot was negatively correlated with greater RA size, RA pressure, and pulmonary vascular resistance, but not pulmonary artery pressure, while LStot was also negatively associated with right ventricular enlargement and higher NT-proBNP. In receiver–operator characteristic analysis, RA LStot was of optimal accuracy for prediction of WHO-function class ≥III in PH patients. Conclusions PH was associated with impaired reservoir and conduit function, but enhanced active contract function of RA, while RA LStot confers an optimal predictive effect of poor WHO-function class in PH patients.

The formation of crystalline structures and defects in GaN at three different cooling rates were investigated based on molecular dynamics simulations by using the Stillinger–Weber potential. The structural properties of GaN during the solidification processes were analyzed by several structural analysis methods. The system formed crystals at 200 K when cooled at rates of 10 11 K/s and 10 12 K/s, whereas the amorphous state that formed at the cooling rate of 10 13 K/s included some crystal clusters. The 〈4 0 0 0〉 and 〈2 3 0 0〉 Voronoi polyhedrons were dominant in GaN during the rapid quenching processes. The 〈4 0 0 0〉 polyhedrons can aggregate to form cubic and hexagonal phases in GaN at lower temperatures. After solidification, cubic and hexagonal structures were coexistent in the system with a hybrid disordered region and crystal defects. When the temperature was decreased at a rate of 10 11 K/s, coherent twin boundaries, having excellent structural stability and configural continuity, were easily formed between the cubic and hexagonal crystal structures.

The growth of GaN crystals at different pressures was studied by molecular dynamics simulation employing the Stillinger–Weber potential, and their structural properties and defects were characterized using the radial distribution function, the Voronoi polyhedron index method, and a suitable visualization technology. Crystal structures formed at 0, 1, 5, 10, and 20 GPa featured an overwhelming number of Voronoi polyhedra, whereas amorphous structures comprising numerous disordered polyhedra were produced at 50 GPa. During quenching, coherent twin boundaries were easily formed between zinc-blende and wurtzite crystal structures in GaN. Notably, point defects usually appeared at low pressure, whereas dislocations were observed at high pressure, since the simultaneous growth of two crystal grains with different crystal orientations and their boundary expansion was hindered in the latter case, resulting in the formation of a dislocation between these grains.

The solidification process of liquid gallium nitride has been studied by molecular dynamics simulation using the Stillinger-Weber potential at cooling rate of 10 K/ps. The structural properties of gallium nitride during the rapid cooling process were investigated in detail by the radial distribution functions, Voronoi polyhedron index and the visualization technology. The amorphous structures were formed with many medium range order structures at 200 K. The polyhedron as the main polyhedron was more stable than other polyhedron in GaN during the quenching process. The cubic and hexahedral medium range order structures were formed by the close link between polyhedron. The cubic crystal structures grew up through the crystalline surface by a layer-by-layer method to become more stable structures during the quenching process.

The nuclear factor κB (NF-κB) transcription factor family regulates genes involved in cell proliferation and inflammation. The promoters of these genes often contain NF-κB-binding sites (κB sites) arranged in tandem. How NF-κB activates transcription through these multiple sites is incompletely understood. We report here an X-ray crystal structure of homodimers comprising the RelA DNA-binding domain containing the Rel homology region (RHR) in NF-κB bound to an E-selectin promoter fragment with tandem κB sites. This structure revealed that two dimers bind asymmetrically to the symmetrically arranged κB sites at which multiple cognate contacts between one dimer to the corresponding DNA are broken. Because simultaneous RelA-RHR dimer binding to tandem sites in solution was anti-cooperative, we inferred that asymmetric RelA-RHR binding with fewer contacts likely indicates a dissociative binding mode. We found that both κB sites are essential for reporter gene activation by full-length RelA homodimer, suggesting that dimers facilitate DNA binding to each other even though their stable co-occupation is not promoted. Promoter variants with altered spacing and orientation of tandem κB sites displayed unexpected reporter activities that were not explained by the solution-binding pattern of RelA-RHR. Remarkably, full-length RelA bound all DNAs with a weaker affinity and specificity. Moreover, the transactivation domain played a negative role in DNA binding. These observations suggest that other nuclear factors influence full-length RelA binding to DNA by neutralizing the transactivation domain negative effect. We propose that DNA binding by NF-κB dimers is highly complex and modulated by facilitated association-dissociation processes.

Background Pulmonary hypertension (PH) can be caused by a fistula between the systemic and pulmonary arteries. Here, we report a case of PH due to multiple fistulas between systemic arteries and the right pulmonary artery where the ventilation/perfusion scan showed no perfusion in the right lung. Methods A 32-year-old male patient was hospitalised for community-acquired pneumonia. After treatment with antibiotics, the pneumonia was alleviated but dyspnoea persisted. Pulmonary hypertension was diagnosed using right heart catheterisation, which detected the mean pulmonary artery pressure as 37mmHg. The anomalies were confirmed by contrast-enhanced CT scan (CT pulmonary angiography), systemic arterial angiography and pulmonary angiography. Results Following embolisation of the largest fistula, the haemodynamics and oxygen dynamics did not improve, and even worsened to some extent. After supportive therapy including diuretics and oxygen, the patient's dyspnoea, WHO function class and right heart function by transthoracic echocardiography all improved during follow-up. Conclusions Pulmonary hypertension can be present even when the right lung perfusion is lost. Closure of fistulas by embolisation, when those fistulas act as the proliferating vessels, may be harmful.

The aims of this study were to apply integrative cardiopulmonary ultrasound (thoracic ultrasound) to the evaluation of patients with interstitial lung disease (ILD) and to determine the relationship between lung ultrasound signs and echocardiographic parameters such as systolic pulmonary artery pressure (SPAP) and various right ventricular parameters. ILD patients and healthy controls underwent lung ultrasound (LUS) and echocardiographic tests. In addition to traditional echocardiographic parameters, right ventricular free wall longitudinal strain (RVLS_FW) was measured using 2-D speckle-tracking echocardiography. The degree of pulmonary fibrosis or the disease severity of each ILD patient was scored with a semiquantitative scoring method, taking into account multiple LUS signs. Statistical analyses were performed to compare various parameters between ILD patients with and those without pulmonary hypertension. Correlations between the different parameters were then evaluated, and the LUS scores were used to predict pulmonary hypertension using a receiver operating characteristic curve analysis. Among the 90 patients who qualified for entry into this study, 30% (n = 27) had pulmonary hypertension. The patients with pulmonary hypertension had larger right ventricular dimensions, lower RVLS_FW and higher LUS scores. An effective correlation was found between ILD LUS scores and echocardiographic parameters, especially SPAP (r = 0.735, p 0.001). The groups were comparable with respect to most echocardiographic parameters, with mild, moderate and severe pulmonary fibrosis, whereas SPAP was significantly higher in the moderate and severe groups. RVLS_FW was obviously reduced in the group with severe pulmonary fibrosis. Although RVLS_FW in the mild pulmonary fibrosis group was in the normal range, it was slightly reduced compared with that of the controls. A cutoff of more than 16 LUS points had 85.2% sensitivity and 80.3% specificity in predicting elevated SPAP (36 mm Hg). Thoracic ultrasound is useful in the assessment of ILD. As ILD progresses, the structure or function of the right ventricle gradually deteriorates. LUS not only detects lung conditions in ILD, but also indirectly reflects SPAP and right ventricular function. Integrated use of LUS and echocardiography will provide an invaluable point-of-care imaging modality to facilitate the diagnosis, management and treatment of patients with ILD.

The Central China represented by Henan Province is one of the most haze-polluted regions in China with high levels of black carbon (BC) and organic carbon (OC) emissions. In this study, a 2016-based BC and OC emission inventory of Henan Province was developed based on detailed activity data and latest emission factors from different sources involving particulate matter. The total annual emissions of BC and OC were estimated to be 117.6 kt and 162.8 kt, respectively. Industrial process (44.2%) and industrial combustion (17.0%) were the top two contributors for BC emission, whereas OC emission was mainly from biomass burning (36.8%). Typical industrial cities were the major contributors to BC emission, by contrast, relatively higher OC emission was concentrated on agricultural cities in the southeast of Henan Province. The OC/BC ratios of industrial cities were generally lower than those of southeastern agricultural cities. The monthly variations presented that the highest BC and OC emissions were concentrated in January and June, respectively. Overall, in this study, the quantitative uncertainty ranges on the 95% confidence interval were approximately −30%–47% for BC and −38%–65% for OC. The emission inventory was also verified by qualitative comparison with other studies and indirect evaluation of OCpri/EC ratios, and the result was within a reasonable range. The ways of discussion and evaluation in this study can provide reference for other regions.

Pulmonary endarterectomy (PEA) is an effective treatment for chronic thromboembolic pulmonary hypertension (CTEPH) by dissecting the residual thrombus from the native vessel wall. The goal of PEA is to improve pulmonary hemodynamics and right ventricular dysfunction, and thus increase exercise capacity, alleviate symptoms and decrease mortality. The aim of this study, accordingly, was to assess the ability of echocardiography to provide a mechanism to monitor the time course of RV functional improvement after PEA.Twenty-six consecutive adult patients who underwent PEA for CTEPH were included in the study. All the patients underwent transthoracic echocardiography and right heart catheterization before surgery. Follow-up echocardiography was performed within 3, 12, and 24 months of surgery. The parameters of right ventricle were compared with baseline data.In all cases, the RV was enlarged and systolic function was impaired before surgery. RV systolic pressure fell from 92±16 mm Hg before surgery to 41±9 mm Hg by the 3 month post-PEA follow-up (P0.001). RV end-diastolic area and end-systolic area likewise decreased from 35.8±4.4 cm(2) to 26.6±4.8 cm(2) (P0.001) and from 27.1±3.8 cm(2) to 17.9±3.8 cm(2) (P0.001), respectively. The RV myocardial performance index also decreased from a ratio of 0.8±0.1 to 0.5±0.1 (P0.001). The tricuspid annular plane systolic excursion increased from 8.8±0.6mm to 10.1±0.9 mm (P0.001). Tricuspid regurgitation (TR) improved from a mean grade of 3.1±0.5 to 2.2±0.7 (P0.001). At the 12 and 24 month follow-up examinations, RV systolic pressure and function remained improved, respectively. The RV systolic pressure remained above 50 mmHg in only two cases.In patients with CTEPH who undergo PEA, echocardiography is a useful tool for the evaluation of RV function. Echocardiographic measurements of RV size, systolic pressure, systolic function, and TR show significant improvement, and this effect is sustained for up to 24 months after surgery.