‘Evidence of an auxin signal pathway, microRNA167-ARF8-GH3, and its response to exogenous auxin in cultured rice cells’

MicroRNA167 (miR167) was shown to cleave auxin responsive factor 8 (ARF8) mRNA in cultured rice cells. MiR167 level was found to be controlled by the presence of auxin in the growth medium. When cells grew in auxin-free medium, miR167 level decreased, resulting in an increase in the level of ARF8 mRNA. Cells growing in the normal growth medium containing auxin showed a reversed trend. It was also shown that expression of OsGH3-2, an rice IAA-conjugating enzyme, was positively regulated by ARF8. Delivery of synthesized miR167 into cells led to decrease of both ARF8 mRNA and OsGH3-2 mRNA. This study provides an evidence in which the exogeneous auxin signal is transduced to OsGH3-2 through miR167 and ARF8 in sequence. This proposed auxin signal transduction pathway, auxin-miR167-ARF8-OsGH3-2, could be, in conjunction with the other microRNA-mediated auxin signals, an important one for responding to exogeneous auxin and for determining the cellular free auxin level which guides appropriate auxin responses

Methicillin-Resistant Staphylococcus aureus Blood Isolates Harboring a Novel Pseudo-staphylococcal Cassette Chromosome mec Element

The aim of this work was to assess a novel pseudo-staphylococcal cassette chromosome mec (ΨSCCmec) element in methicillin-resistant Staphylococcus aureus (MRSA) blood isolates. Community-associated MRSA E16SA093 and healthcare-associated MRSA F17SA003 isolates were recovered from the blood specimens of patients with S. aureus bacteremia in 2016 and in 2017, respectively. Antimicrobial susceptibility was determined via the disk diffusion method, and SCCmec typing was conducted by multiplex polymerase chain reaction. Whole genome sequencing was carried out by single molecule real-time long-read sequencing. Both isolates belonged to sequence type 72 and agr-type I, and they were negative for Panton-Valentine leukocidin and toxic shock syndrome toxin. The spa-types of E16SA093 and F17SA003 were t324 and t2460, respectively. They had a SCCmec IV-like element devoid of the cassette chromosome recombinase (ccr) gene complex, designated as ΨSCCmecE16SA093. The element was manufactured from SCCmec type IV and the deletion of the ccr gene complex and a 7.0- and 31.9-kb portion of each chromosome. The deficiency of the ccr gene complex in the SCCmec unit is likely resulting in mobility loss, which would be an adaptive evolutionary mechanism. The dissemination of this clone should be monitored closely

Contribution of Resistance-Nodulation-Cell Division Efflux Systems to Antibiotic Resistance and Biofilm Formation in Acinetobacter baumannii

International audienceABSTRACT : Acinetobacter baumannii is a nosocomial pathogen of increasing importance due to its multiple resistance to antibiotics and ability to survive in the hospital environment linked to its capacity to form biofilms. To fully characterize the contribution of AdeABC, AdeFGH, and AdeIJK resistance-nodulation-cell division (RND)-type efflux systems to acquired and intrinsic resistance, we constructed, from an entirely sequenced susceptible A. baumannii strain, a set of isogenic mutants overexpressing each system following introduction of a point mutation in their cognate regulator or a deletion for the pump by allelic replacement. Pairwise comparison of every derivative with the parental strain indicated that AdeABC and AdeFGH are tightly regulated and contribute to acquisition of antibiotic resistance when overproduced. AdeABC had a broad substrate range, including β-lactams, fluoroquinolones, tetracyclines-tigecycline, macrolides-lincosamides, and chloramphenicol, and conferred clinical resistance to aminoglycosides. Importantly, when combined with enzymatic resistance to carbapenems and aminoglycosides, this pump contributed in a synergistic fashion to the level of resistance of the host. In contrast, AdeIJK was expressed constitutively and was responsible for intrinsic resistance to the same major drug classes as AdeABC as well as antifolates and fusidic acid. Surprisingly, overproduction of AdeABC and AdeIJK altered bacterial membrane composition, resulting in decreased biofilm formation but not motility. Natural transformation and plasmid transfer were diminished in recipients overproducing AdeABC. It thus appears that alteration in the expression of efflux systems leads to multiple changes in the relationship between the host and its environment, in addition to antibiotic resistance.IMPORTANCE: Increased expression of chromosomal genes for RND-type efflux systems plays a major role in bacterial multidrug resistance. Acinetobacter baumannii has recently emerged as an important human pathogen responsible for epidemics of hospital-acquired infections. Besides its remarkable ability to horizontally acquire resistance determinants, it has a broad intrinsic resistance due to low membrane permeability, endogenous resistance genes, and antibiotic efflux. The study of isogenic mutants from a susceptible A. baumannii clinical isolate overproducing or deleted for each of the three major RND-type pumps demonstrated their major contribution to intrinsic resistance and to the synergism between overproduction of an efflux system and acquisition of a resistance gene. We have also shown that modulation of expression of the structural genes for the efflux systems results in numerous alterations in membrane-associated cellular functions, in particular, in a decrease in biofilm formation and resistance gene acquisition

Clinical Efficacy of Primary Tumor Volume Measurements: Comparison of Different Primary Sites

ObjectivesThe purpose of study was to determine the clinical efficacy of primary tumor volume measurements of different primary sites in the oropharynx compared to the oral cavity.MethodsA retrospective analysis of 85 patients with oral cavity or oropharynx cancer. The tumor area was manually outlined from axial magnetic resonance (MR) series. The software calculated the tumor volumes, automatically. The values of the primary tumor volumes were then subdivided into separate groups (≤3,500 mm3, >3,500 mm3).ResultsThe prognostic indicators were the cT and cN (oral cavity); age, primary site, cT, cN, and primary tumor volume (oropharynx) on the univariate analysis. There was no significant prognostic factor for oral cavity cancer on the multivariate analysis. Primary site, cN, and primary tumor volume were independent prognostic indicators for oropharynx cancer by multivariate analysis.ConclusionPrimary tumor volume measurement is a reliable way to stratify outcome, and make up for the weak points in the American Joint Committee on Cancer staging system with oropharynx cancer

Structural abnormalities in benign childhood epilepsy with centrotemporal spikes (BCECTS)

AbstractPurposeThe aim of this study was to investigate cortical thickness and gray matter volume abnormalities in benign childhood epilepsy with centrotemporal spikes (BCECTS). We additionally assessed the effects of comorbid attention-deficit/hyperactivity (ADHD) on these abnormalities.MethodsSurface and volumetric MR imaging data of children with newly diagnosed BCECTS (n=20, 14 males) and age-matched healthy controls (n=20) were analyzed using FreeSurfer (version 5.3.0, https://surfer.nmr.mgh.harvard.edu). An additional comparison was performed between BCECTS children with and without ADHD (each, n=8). A group comparison was carried out using an analysis of covariance with a value of significance set as p<0.01 or p<0.05.ResultsChildren with BCECTS had significantly thicker right superior frontal, superior temporal, middle temporal, and left pars triangularis cortices. Voxel-based morphometric analysis revealed significantly larger cortical gray matter volumes of the right precuneus, left orbitofrontal, pars orbitalis, precentral gyri, and bilateral putamen and the amygdala of children with BCECTS compared to healthy controls. BCECTS patients with ADHD had significantly thicker left caudal anterior and posterior cingulate gyri and a significantly larger left pars opercularis gyral volume compared to BCECTS patients without ADHD.ConclusionChildren with BCECTS have thicker or larger gray matters in the corticostriatal circuitry at the onset of epilepsy. Comorbid ADHD is also associated with structural aberrations. These findings suggest structural disruptions of the brain network are associated with specific developmental electro-clinical syndromes

YAF2 promotes TP53-mediated genotoxic stress response via stabilization of PDCD5

AbstractProgrammed cell death 5 (PDCD5) plays a crucial role in TP53-mediated apoptosis, but the regulatory mechanism of PDCD5 itself during apoptosis remains obscure. We identified YY1-associated factor 2 (YAF2) as a novel PDCD5-interacting protein in a yeast two-hybrid screen for PDCD5-interacting proteins. We found that YY1-associated factor 2 (YAF2) binds to and increases PDCD5 stability by inhibiting the ubiquitin-dependent proteosomal degradation pathway. However, knocking-down of YAF2 diminishes the levels of PDCD5 protein but not the levels of PDCD5 mRNA. Upon genotoxic stress response, YAF2 promotes TP53 activation via association with PDCD5. Strikingly, YAF2 failed to promote TP53 activation in the deletion of PDCD5, whereas restoration of wild-type PDCD5WT efficiently reversed the ineffectiveness of YAF2 on TP53 activation. Conversely, PDCD5 efficiently overcame the knockdown effect of YAF2 on ET-induced TP53 activation. Finally, impaired apoptosis upon PDCD5 ablation was substantially rescued by restoration of PDCD5WT but not YAF2-interacting defective PDCD5E4D nor TP53-interacting defective PDCD5E16D mutant. Our findings uncovered an apoptotic signaling cascade linking YAF2, PDCD5, and TP53 during genotoxic stress responses

A Gaia view on the star formation in the Monoceros OB1 and R1 associations

Stellar kinematics provides the key to understanding star formation process. In this respect, we present a kinematic study of the Monoceros OB1 (Mon OB1) and R1 (Mon R1) associations using the recent Gaia data and radial velocities of stars derived from high-resolution spectroscopy and the literature. A total of 728 members are selected using the criteria based on the intrinsic properties of young stars, parallaxes, and proper motions. The spatial distribution and kinematic properties of members show that these associations have distinct substructures. In Mon OB1, we find one northern group and two southern groups. Mon R1 is composed of three small stellar groups that are spatially and kinematically distinct. Some stars are found in a halo around these two associations. We detect patterns of expansion for most stellar groups in the associations. In addition, two stellar groups in Mon OB1 show the signature of rotation, which provides an important constraint on cluster formation. The star formation history of Mon OB1 is slightly revised. Star formation first occurred in the southern region and subsequently in the northern region. Recent star-forming events ignited deeper into the southern region, while some stars are escaping from Mon OB1, forming a halo. Mon R1 might have formed at the same epoch as the formation of the northern group in Mon OB1. Given that star formation is taking place on different scales along a large arc-like structure, Mon OB1 and Mon R1 may be the results of hierarchical star formation.Comment: 18 pages, 16 figures, accepted for publication in A

The association of fatty liver index and BARD score with all-cause and cause-specific mortality in patients with type 2 diabetes mellitus: a nationwide population-based study

Background Type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) commonly coexist. However, NAFLD’s effect on mortality in Asian patients with type 2 diabetes awaits full elucidation. Therefore, we examined NAFLD-related all-cause and cause-specific mortality in a nationwide Asian population with type 2 diabetes. Methods We included patients who had undergone general health checkups between 2009 and 2012 using the National Health Insurance Service database linked to death-certificate data. Hepatic steatosis was defined as a fatty liver index (FLI) ≥ 60, and advanced hepatic fibrosis was determined using the BARD score. Findings During the follow-up period of 8.1 years, 222,242 deaths occurred, with a mortality rate of 14.3/1000 person-years. An FLI ≥ 60 was significantly associated with increased risks of all-cause and cause-specific mortality including cardiovascular disease (CVD)-, cancer-, and liver disease (FLI ≥ 60: hazard ratio [HR] = 1.02, 95% confidence interval [CI] 1.01–1.03 for all-cause; 1.07, 1.04–1.10 for CVD; 1.12, 1.09–1.14 for cancer; and 2.63, 2.50–2.77 for liver disease). Those with an FLI ≥ 60 and fibrosis (BARD ≥ 2) exhibited increased risks of all-cause (HR, 95% CI 1.11, 1.10–1.12), CVD- (HR, 95% CI 1.11, 1.09–1.14), cancer- (HR, 95% CI 1.17, 1.15–1.19), and liver disease-related (HR, 95% CI 2.38, 2.29–2.49) mortality. Conclusion Hepatic steatosis and advanced fibrosis were significantly associated with risks of overall and cause-specific mortality in patients with type 2 diabetes. Our results provide evidence that determining the presence of hepatic steatosis and/or fibrosis potentially plays a role in risk stratification of mortality outcomes in patients with type 2 diabetes mellitus.This work was supported by grants from the Seoul National University Hospital Research Fund (06‑2020‑4150) and from Liver Research Foundation of Korea as part of the Bio Future Strategies Research Project

Effectiveness of mechanical thrombectomy in cancer-related stroke and associated factors with unfavorable outcome

Background The effectiveness of mechanical thrombectomy (MT) in cancer-related stroke (CRS) is largely unknown. This study aims to investigate the clinical and radiological outcomes of MT in CRS patients. We also explored the factors that independently affect functional outcomes of patients with CRS after MT. Methods We retrospectively reviewed 341 patients who underwent MT after acute ischemic stroke onset between May 2014 and May 2020. We classified the patients into CRS (n = 34) and control (n = 307) groups and compared their clinical details. Among CRS patients, we analyzed the groups with and without good outcomes (3-months modified Rankin scale [mRS] score 0, 1, 2). Multivariate analysis was performed to investigate the independent predictors of unfavorable outcomes in patients with CRS after MT. Results A total of 341 acute ischemic stroke patients received MT, of whom 34 (9.9%) had CRS. Although the baseline National institute of health stroke scale (NIHSS) score and the rate of successful recanalization was not significantly different between CRS patients and control group, CRS patients showed more any cerebral hemorrhage after MT (41.2% vs. controls 23.8%, p = 0.037) and unfavorable functional outcome at 3 months (CRS patients median 3-month mRS score 4, interquartile range [IQR] 2 to 5.25 vs. controls median 3-month mRS score 3, IQR 1 to 4, [p = 0.026]). In the patients with CRS, elevated serum D-dimer level and higher baseline NIHSS score were independently associated with unfavorable functional outcome at 3 months (adjusted odds ratio [aOR]: 1.524, 95% confidence interval [CI]: 1.043–2.226; aOR: 1.264, 95% CI: 1.010–1.582, respectively). Conclusions MT is an appropriate therapeutic treatment for revascularization in CRS patients. However, elevated serum D-dimer levels and higher baseline NIHSS scores were independent predictors of unfavorable outcome. Further research is warranted to evaluate the significance of these predictors.This research was supported by a fund (#2020ER620200) by the Korea Centers for Disease Control & Prevention and Clinical Research Society for Stroke, Republic of Korea