X-ray structure of Galdieria Rubisco complexed with one sulfate ion per active site

AbstractRibulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the reactions of carboxylation and oxygenation of ribulose-1,5-bisphosphate. These reactions require that the active site should be closed by a flexible loop (loop 6) of the large subunit. Rubisco from a red alga, Galdieria partita, has the highest specificity for carboxylation reaction among the Rubiscos hitherto reported. The crystal structure of unactivated Galdieria Rubisco has been determined at 2.6 Å resolution. The electron density map reveals that a sulfate binds only to the P1 anion-binding site of the active site and the loop 6 is closed. Galdieria Rubisco has a unique hydrogen bond between the main chain oxygen of Val332 on the loop 6 and the ϵ-amino group of Gln386 of the same large subunit. This interaction is likely to be crucial to understanding for stabilizing the loop 6 in the closed state and to making a higher affinity for anionic ligands

Quantitative characterization of myocardial infarction by cardiovascular magnetic resonance predicts future cardiovascular events in patients with ischemic cardiomyopathy

<p>Abstract</p> <p>Background</p> <p>Cardiovascular magnetic resonance (CMR) can provide quantitative data of the myocardial tissue utilizing high spatial and temporal resolution along with exquisite tissue contrast. Previous studies have correlated myocardial scar tissue with the occurrence of ventricular arrhythmia. This study was conducted to evaluate whether characterization of myocardial infarction by CMR can predict cardiovascular events in patients with ischemic cardiomyopathy (ICM).</p> <p>Results</p> <p>We consecutively studied 86 patients with ICM (LVEF < 50%, mean LVEF: 26 ± 12%) with CMR before revascularization or medication therapy ± implantable cardiac defibrillator, determined the amount of myocardial scar, and followed for development of cardiovascular events. Thirty-three patients (38%) had cardiovascular events (mean follow-up: 20 ± 16 months). Patients who developed cardiovascular events had larger scar volume and scar percentage of the myocardium than those who did not develop cardiovascular events (16.8 ± 12.4 cm3 vs. 11.7 ± 12.6 cm3, p = 0.023 and 10.2 ± 6.9% vs. 7.2 ± 6.7%, p = 0.037, respectively). There were no significant differences in LVEDV, LVESV and LVEF between the patients with and without cardiovascular events (231 ± 76 ml vs. 230 ± 88 ml; 180 ± 73 ml vs. 175 ± 90 ml; and 25 ± 10% vs. 27 ± 13%, respectively).</p> <p>Conclusion</p> <p>Quantification of the scar volume and scar percentage by CMR is superior to LVEDV, LVESV, and LVEF in prognosticating the future likelihood of the development of cardiovascular events in patients with ICM.</p

Brain structure alterations in girls with central precocious puberty

PurposeCentral precocious puberty (CPP) is puberty that occurs at an unusually early age with several negative psychological outcomes. There is a paucity of data on the morphological characteristics of the brain in CPP. This study aimed to determine the structural differences in the brain of patients with CPP.MethodsWe performed voxel- and surface-based morphometric analyses of 1.5 T T1-weighted brain images scanned from 15 girls with CPP and 13 age-matched non-CPP controls (NC). All patients with CPP were diagnosed by gonadotropin-releasing hormone (GnRH) stimulation test. The magnetic resonance imaging (MRI) data were evaluated using Levene’s test for equality of variances and a two-tailed unpaired t-test for equality of means. False discovery rate correction for multiple comparisons was applied using the Benjamini–Hochberg procedure.ResultsMorphometric analyses of the brain scans identified 33 candidate measurements. Subsequently, increased thickness of the right precuneus was identified in the patients with CPP using general linear models and visualizations of cortical thickness with a t-statistical map and a random field theory map.ConclusionThe brain scans of the patients with CPP showed specific morphological differences to those of the control. The features of brain morphology in CPP identified in this study could contribute to further understanding the association between CPP and detrimental psychological outcomes

Prediction of common hepatic artery catheter insertion based on celiac trunk morphology

PURPOSEThis study aimed to predict the ability to insert a 4–5 French (Fr) catheter insertion with a guidewire into the common hepatic artery (CHA) based on celiac trunk morphology.METHODSThis retrospective study included 64 patients who underwent balloon-occluded transcatheter arterial chemoembolization (n = 56), transcatheter arterial chemotherapy (n = 2), or were fitted with an implantable port system (n = 6) between June 2019 and December 2019 in our institution. The morphology of the celiac trunk was classified into three types (upward, horizontal, and downward) based on celiac angiography. The aortic–celiac trunk angle was measured on sagittal images of preprocedural contrast-enhanced computed tomography (CT). We reviewed whether a 4–5-Fr shepherd’s hook catheter could advance beyond the CHA using a 0.035-inch guidewire (Radifocus® Guidewire M; Terumo). Three patients were diagnosed with median arcuate ligament syndrome (MALS) based on the characteristic hook shape of the celiac artery on sagittal images of contrast-enhanced CT. The predictive ability of celiac angiography and preprocedural CT for CHA insertion success was evaluated. In unsuccessful cases, the balloon anchor technique (BAT) was attempted as follows: (1) a 2.7/2.8-Fr microballoon catheter (Attendant Delta; Terumo) was placed beyond the proper hepatic artery, and (2) the balloon was inflated as an anchor for parent catheter advancement.RESULTSUpward, horizontal, and downward celiac trunk types were noted in 42, 9, and 13 patients, respectively. The median CT angle was 122.83° (first quartile–third quartile, 102.88°–136.55°). Insertion in the CHA using the guidewire was successful in 56 of 64 patients (87.50%), and the success rate in the downward type was significantly lower than that in the upward type [42/42 (100%) vs. 7/13 (53.85%), P < 0.001]. The CT angle was significantly larger downward in the unsuccessful group than in the successful group (121.03° vs. 140.70°, P = 0.043). Celiac angiography had a significantly higher area under the curve (AUC) than preprocedural CT (AUC = 0.91 vs. AUC = 0.72, P = 0.040). All three cases of MALS showed unsuccessful CHA insertion. In all eight patients with unsuccessful insertion, the catheter could be advanced using the BAT [8/8 (100%)].CONCLUSIONCeliac angiography and preprocedural CT could predict CHA catheter insertion using a guidewire, and celiac angiography had high predictability. CT could detect MALS, a risk factor for unsuccessful CHA insertion

A simplified PCR assay for fast and easy mycoplasma mastitis screening in dairy cattle

A simplified polymerase chain reaction (PCR) assay was developed for fast and easy screening of mycoplasma mastitis in dairy cattle. Species of major mycoplasma strains [Mycoplasma (M.) bovis, M. arginini, M. bovigenitalium, M. californicum, M. bovirhinis, M. alkalescens and M. canadense] in cultured milk samples were detected by this simplified PCR-based method as well as a standard PCR technique. The minimum concentration limit for detecting mycoplasma by the simplified PCR was estimated to be about 2.5 × 103 cfu/mL and was similar to that of the standard PCR. We compared the specificity and sensitivity of the simplified PCR to those of a culture method. Out of 1,685 milk samples cultured in mycoplasma broth, the simplified PCR detected Mycoplasma DNA in 152 that were also positive according to the culture assay. The sensitivity and specificity of the simplified PCR were 98.7% and 99.7%, respectively, for detecting mycoplasma in those cultures. The results obtained by the simplified PCR were consistent with ones from standard PCR. This newly developed simplified PCR, which does not require DNA purification, can analyze about 300 cultured samples within 3 h. The results from our study suggest that the simplified PCR can be used for mycoplasma mastitis screening in large-scale dairy farms

Event-free survival at 36 months is a suitable endpoint for diffuse large B-cell lymphoma patients treated with immunochemotherapy: real-world evidence from the North Japan Hematology Study Group

Information regarding follow-up duration after treatment for newly diagnosed diffuse large B-cell lymphoma (DLBCL) is important. However, a clear endpoint has yet to be established. We totally enrolled 2182 patients newly diagnosed with DLBCL between 2008 and 2018. The median age of the patients was 71 years. All patients were treated with rituximab- and anthracycline-based chemotherapies. Each overall survival (OS) was compared with the age- and sex-matched Japanese general population (GP) data. At a median follow-up of 3.4 years, 985 patients experienced an event and 657 patients died. Patients who achieved an event-free survival (EFS) at 36 months (EFS36) had an OS equivalent to that of the matched GP (standard mortality ratio [SMR], 1.17; P=0.1324), whereas those who achieved an EFS24 did not have an OS comparable to that of the matched GP (SMR, 1.26; P=0.0095). Subgroup analysis revealed that relatively old patients (>60 years), male patients, those with limited-stage disease, those with a good performance status, and those with low levels of soluble interleukin 2 receptor already had a comparable life expectancy to the matched GP at an EFS24. In contrast, relatively young patients had a shorter life expectancy than matched GP, even with an EFS36. In conclusion, an EFS36 was shown to be a more suitable endpoint for newly diagnosed DLBCL patients than an EFS24. Of note, younger patients require a longer EFS period than older patients in order to obtain an equivalent life expectancy to the matched GP

Cyp26b1 Regulates Retinoic Acid-Dependent Signals in T Cells and Its Expression Is Inhibited by Transforming Growth Factor-β

The vitamin A metabolite, retinoic acid (RA), plays important roles in the regulation of lymphocyte properties. Dendritic cells in gut-related lymphoid organs can produce RA, thereby imprinting gut-homing specificity on T cells and enhancing transforming growth factor (TGF)-β-dependent induction of Foxp3+ regulatory T cells upon antigen presentation. In general, RA concentrations in cells and tissues are regulated by its degradation as well. However, it remained unclear if T cells could actively catabolize RA.We assessed the expression of known RA-catabolizing enzymes in T cells from mouse lymphoid tissues. Antigen-experienced CD44+ T cells in gut-related lymphoid organs selectively expressed Cyp26b1, a member of the cytochrome P450 family 26. However, T cells in the spleen or skin-draining lymph nodes did not significantly express Cyp26b1. Accordingly, physiological levels of RA (1-10 nM) could induce Cyp26b1 expression in naïve T cells upon activation in vitro, but could not do so in the presence of TGF-β. Overexpression of Cyp26b1 significantly suppressed the RA effect to induce expression of the gut-homing receptor CCR9 on T cells. On the other hand, knocking down Cyp26b1 gene expression with small interfering RNA or inhibiting CYP26 enzymatic activity led to enhancement of the RA-induced CCR9 expression.Our data demonstrate a role for CYP26B1 in regulating RA-dependent signals in activated T cells but not during TGF-β-dependent differentiation to Foxp3+ regulatory T cells. Aberrant expression of CYP26B1 may disturb T cell trafficking and differentiation in the gut and its related lymphoid organs