A SUMO Ligase AtMMS21 Regulates the Stability of the Chromatin Remodeler BRAHMA in Root Development.

Chromatin remodeling is essential for gene expression regulation in plant development and response to stresses. Brahma (BRM) is a conserved ATPase in the SWI/SNF chromatin remodeling complex and is involved in various biological processes in plant cells, but the regulation mechanism on BRM protein remains unclear. Here, we report that BRM interacts with AtMMS21, a SUMO ligase in Arabidopsis ().

Ablation of Interferon Regulatory Factor 3 Protects Against Atherosclerosis in Apolipoprotein E-Deficient Mice.

The secretion of adhesion molecules by endothelial cells, as well as the subsequent infiltration of macrophages, determines the initiation and progression of atherosclerosis. Accumulating evidence suggests that IRF3 (interferon regulatory factor 3) is required for the induction of proinflammatory cytokines and for endothelial cell proliferation. However, the effect and underlying mechanism of IRF3 on atherogenesis remain unknown.

TATA Box Insertion Provides a Selection Mechanism Underpinning Adaptations to Fe Deficiency.

Intraspecific genetic variation is essential for the responses and adaption of plants to evolutionary challenges, such as changing environmental conditions. The development of the Earth's aerobic atmosphere has increased the demand for iron (Fe) in organisms, and Fe deficiency has become a limiting environmental factor for plant growth. Here, we demonstrate that genus Malus adapt to Fe deficiency through modification of the Iron-Regulated Transporter1 (IRT1) promoter.

SHADE AVOIDANCE 4 Is Required for Proper Auxin Distribution in the Hypocotyl.

The phytohormone auxin is involved in virtually every aspect of plant growth and development. Through polar auxin transport, auxin gradients can be established, which then direct plant differentiation and growth. Shade avoidance responses are well-known processes that require polar auxin transport.

Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer Patients by Targeted Sequencing.

Circulating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non-small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA. We identified frequent driver mutations in plasma ctDNA and tDNA in EGFR, KRAS, PIK3CA, and TP53, and less frequent mutations in other genes, with an overall study concordance of 50.

US-guided Microwave Ablation of Hyperplastic Parathyroid Glands: Safety and Efficacy in Patients with End-Stage Renal Disease-A Pilot Study.

Purpose To evaluate the safety and efficacy of microwave ablation (MWA) in patients with end-stage renal disease and secondary hyperparathyroidism. Materials and Methods The study protocol was approved by the human ethics review committee. Between March 1, 2014, and June 30, 2015, 51 patients (25 men, 26 women; mean age ± standard deviation, 53.

Integrative Analyses of Nontargeted Volatile Profiling and Transcriptome Data Provide Molecular Insight into VOC Diversity in Cucumber Plants (Cucumis sativus).

Plant volatile organic compounds, which are generated in a tissue-specific manner, play important ecological roles in the interactions between plants and their environments, including the well-known functions of attracting pollinators and protecting plants from herbivores/fungi attacks. However, to date, there have not been reports of holistic volatile profiling of the various tissues of a single plant species, even for the model plant species. In this study, we qualitatively and quantitatively analyzed 85 volatile chemicals, including 36 volatile terpenes, in 23 different tissues of cucumber (Cucumis sativus) plants using solid-phase microextraction combined with gas chromatography-mass spectrometry.

Disrupted Brain Connectivity Patterns in Patients with Type 2 Diabetes.

Background And Purpose: Type 2 diabetes is associated with an increased risk of dementia. This study investigated the global connectivity patterns in the brains of patients with type 2 diabetes by using a functional MR imaging technique.

Materials And Methods: Forty patients and 43 age-, sex-, and education-matched healthy controls underwent resting-state functional imaging in a 3T MR imaging unit.

Geometric Parameter Analysis of Ruptured and Unruptured Aneurysms in Patients with Symmetric Bilateral Intracranial Aneurysms: A Multicenter CT Angiography Study.

Background And Purpose: Previous studies of geometric and morphologic parameters of intracranial aneurysms have been conducted to determine rupture risk, which remains incompletely defined due to patient-specific risk factors, such as sex, hypertension, and age. To this end, we compared characteristics of ruptured and unruptured aneurysms in the same patients with symmetric bilateral intracranial aneurysms.

Materials And Methods: Between January 2008 and March 2014, 2361 patients with 2674 aneurysms were diagnosed by CT angiography or surgical findings at 4 medical centers.

Genomic Alterations Observed in Colitis-Associated Cancers Are Distinct From Those Found in Sporadic Colorectal Cancers and Vary by Type of Inflammatory Bowel Disease.

Background & Aims: Patients with inflammatory bowel diseases, such as Crohn's disease (CD) and ulcerative colitis (UC), are at increased risk for small bowel or colorectal cancers (colitis-associated cancers [CACs]). We compared the spectrum of genomic alterations in CACs with those of sporadic colorectal cancers (CRCs) and investigated differences between CACs from patients with CD vs UC.

Methods: We studied tumor tissues from patients with CACs treated at Memorial Sloan Kettering Cancer Center or Weill Cornell Medical College from 2003 through 2015.

CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice.

Circadian misalignment induces insulin resistance in both human and animal models, and skeletal muscle is the largest organ response to insulin. However, how circadian clock regulates muscle insulin sensitivity and the underlying molecular mechanisms are still largely unknown. Here we show circadian locomotor output cycles kaput (CLOCK) and brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (BMAL)-1, two core circadian transcription factors, are down-regulated in insulin-resistant C2C12 myotubes and mouse skeletal muscle.

Predictors of Outcome After Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: An Echocardiography and Cardiovascular Magnetic Resonance Imaging Study.

Background: Alcohol septal ablation (ASA) is used for treatment of medically refractory hypertrophic obstructive cardiomyopathy patients with severe left ventricular outflow tract (LVOT) obstruction. The current recommendations restrict the procedure to adults with favorable anatomy and no other coexisting surgically amenable disease. Some patients remain symptomatic with residual LVOT obstruction, thus better patient selection is required.

Discovery, Optimization, and Characterization of Novel Chlorcyclizine Derivatives for the Treatment of Hepatitis C Virus Infection.

Recently, we reported that chlorcyclizine (CCZ, Rac-2), an over-the-counter antihistamine piperazine drug, possesses in vitro and in vivo activity against hepatitis C virus. Here, we describe structure-activity relationship (SAR) efforts that resulted in the optimization of novel chlorcyclizine derivatives as anti-HCV agents. Several compounds exhibited EC50 values below 10 nM against HCV infection, cytotoxicity selectivity indices above 2000, and showed improved in vivo pharmacokinetic properties.

Association of Left Ventricular Hypertrophy With a Faster Rate of Renal Function Decline in Elderly Patients With Non-End-Stage Renal Disease.

Background: Several studies have indicated that chronic kidney disease is independently associated with the presence of left ventricular hypertrophy (LVH). However, little clinical data are currently available regarding the detailed correlation between LVH and renal function in elderly patients with non-end-stage renal disease.

Methods And Results: A total of 300 in- and outpatients (more than 60 years of age, non-end-stage renal disease), 251 with LVH and 49 without LVH, seen at Beijing Friendship Hospital from January 2000 to December 2010 were included in this retrospective study.

Feasibility, Safety, and Efficacy of Accurate Uterine Fibroid Ablation Using Magnetic Resonance Imaging-Guided High-Intensity Focused Ultrasound With Shot Sonication.

The aim of this study was to investigate the feasibility, safety, and efficacy of uterine fibroid treatment using magnetic resonance imaging (MRI)-guided high-intensity focused ultrasound (US) with shot sonication for accurate ablation. Forty-three patients with 51 symptomatic uterine fibroids were treated with MRI-guided high-intensity focused US with shot sonication, which was a small acoustic focus of higher intensity with a shorter time (2 seconds) of US exposure and a shorter cooling time (2-3 seconds). The treatment efficacy and adverse events were analyzed, and the changes in the severity of symptoms and the reduction in fibroid volume were assessed 3 and 6 months after the procedure.

HMGB1-Driven Inflammation and Intimal Hyperplasia After Arterial Injury Involves Cell-Specific Actions Mediated by TLR4.

Objective: Endoluminal vascular interventions such as angioplasty initiate a sterile inflammatory response resulting from local tissue damage. This response drives the development of intimal hyperplasia (IH) that, in turn, can lead to arterial occlusion. We hypothesized that the ubiquitous nuclear protein and damage-associated molecular pattern molecule, high-mobility group box 1 (HMGB1), is one of the endogenous mediators that activates processes leading to IH after endoluminal injury to the arterial wall.

Genomic Foundation of Starch-to-Lipid Switch in Oleaginous Chlorella spp.

The ability to rapidly switch the intracellular energy storage form from starch to lipids is an advantageous trait for microalgae feedstock. To probe this mechanism, we sequenced the 56.8-Mbp genome of Chlorella pyrenoidosa FACHB-9, an industrial production strain for protein, starch, and lipids.

Organocatalytic multicomponent synthesis of polysubstituted pyrroles from 1,2-diones, aldehydes and arylamines.

We have developed an organocatalyzed three-component reaction of 1,2-diones, aldehydes and arylamines, which provides an efficient approach to access polysubstituted pyrroles. In the catalysis of 4-methylbenzenesulfonic acid monohydrate, the reactions of a wide range of 1,2-diones, arylamines and aldehydes took place smoothly to generate the corresponding polysubstituted pyrroles in acceptable to good yields under mild reaction conditions.

Ajuba Preferentially Binds LXRα/RXRγ Heterodimer to Enhance LXR Target Gene Expression in Liver Cells.

The liver X receptors (LXRs) are important regulators of lipid, cholesterol, and glucose homeostasis by transcriptional regulation of many key genes in these processes, and the transcriptional activities of LXRs are finely controlled by cooperating with retinoid X receptors and many other coregulators. Here, we report that the LIM protein Ajuba binds to the hinge and the ligand binding domains of LXRα via its C-terminal tandem LIM motifs and enhances LXR target gene expression in liver cells. Depletion of Ajuba in HepG2 cells and in mouse primary hepatocytes decreases LXR target gene expression, whereas stable expression of Ajuba in HepG2 cells results in increased expression of these genes.

Periventricular Location as a Risk Factor for Hemorrhage and Severe Clinical Presentation in Pediatric Patients with Untreated Brain Arteriovenous Malformations.

Background And Purpose: The morphologic features of brain arteriovenous malformations differ between children and adults; therefore, our aim was to analyze various features of brain arteriovenous malformations to assess the risk of hemorrhage in children.

Materials And Methods: We identified all consecutive children admitted to Beijing Tiantan Hospital for brain arteriovenous malformations between July 2009 and April 2014. The effects of demographic characteristics and brain arteriovenous malformation morphology on hemorrhage presentation, annual bleeding rates, postnatal hemorrhage, and immediate posthemorrhagic neurologic outcomes were studied by using univariate and multivariable regression analyses.

A SIGMAR1 splice-site mutation causes distal hereditary motor neuropathy.

Objective: To identify the underlying genetic cause in a consanguineous Chinese family segregating distal hereditary motor neuropathy (dHMN) in an autosomal recessive pattern.

Methods: We used whole-exome sequencing and homozygosity mapping to detect the genetic variant in 2 affected individuals of the consanguineous Chinese family with dHMN. RNA analysis of peripheral blood leukocytes and immunofluorescence and immunoblotting of stable cell lines were performed to support the pathogenicity of the identified mutation.

GENERAL CONTROL NONREPRESSED PROTEIN5-Mediated Histone Acetylation of FERRIC REDUCTASE DEFECTIVE3 Contributes to Iron Homeostasis in Arabidopsis.

Iron homeostasis is essential for plant growth and development. Here, we report that a mutation in GENERAL CONTROL NONREPRESSED PROTEIN5 (GCN5) impaired iron translocation from the root to the shoot in Arabidopsis (Arabidopsis thaliana). Illumina high-throughput sequencing revealed 879 GCN5-regulated candidate genes potentially involved in iron homeostasis.

Acupuncture efficacy on ischemic stroke recovery: multicenter randomized controlled trial in China.

Background And Purpose: Acupuncture is a frequently used complementary treatment for ischemic stroke in China but the evidence available from previous randomized trials is inconclusive. The objective of this study was to assess the efficacy and safety of acupuncture in a more robustly designed larger scale trial.

Methods: This is a multicenter, single-blinded, randomized controlled trial.

Repurposing of the antihistamine chlorcyclizine and related compounds for treatment of hepatitis C virus infection.

Hepatitis C virus (HCV) infection affects an estimated 185 million people worldwide, with chronic infection often leading to liver cirrhosis and hepatocellular carcinoma. Although HCV is curable, there is an unmet need for the development of effective and affordable treatment options. Through a cell-based high-throughput screen, we identified chlorcyclizine HCl (CCZ), an over-the-counter drug for allergy symptoms, as a potent inhibitor of HCV infection.

Lotus japonicus clathrin heavy Chain1 is associated with Rho-Like GTPase ROP6 and involved in nodule formation.

Mechanisms underlying nodulation factor signaling downstream of the nodulation factor receptors (NFRs) have not been fully characterized. In this study, clathrin heavy chain1 (CHC1) was shown to interact with the Rho-Like GTPase ROP6, an interaction partner of NFR5 in Lotus japonicus. The CHC1 gene was found to be expressed constitutively in all plant tissues and induced in Mesorhizobium loti-infected root hairs and nodule primordia.