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Plasmodium ookinetes use an invasive apparatus to invade mosquito midguts, and tubulins are the major structural proteins of this apical complex. We examined the role of tubulins in malaria transmission to mosquitoes. Our results demonstrate that the rabbit polyclonal antibodies (pAb) against human α-tubulin significantly reduced the number of P. falciparum oocysts in Anopheles gambiae midguts, while rabbit pAb against human β-tubulin did not. Further studies showed that pAb, specifically against P. falciparum α-tubulin-1, also significantly limited P. falciparum transmission to mosquitoes. We also generated mouse monoclonal antibodies (mAb) using recombinant P. falciparum α-tubulin-1. Out of 16 mAb, two mAb, A3 and A16, blocked P. falciparum transmission with EC50 of 12 μg/ml and 2.8 μg/ml. The epitopes of A3 and A16 were determined to be a conformational and linear sequence of EAREDLAALEKDYEE, respectively. To understand the mechanism of the antibody-blocking activity, we studied the accessibility of live ookinete α-tubulin-1 to antibodies and its interaction with mosquito midgut proteins. Immunofluorescent assays showed that pAb could bind to the apical complex of live ookinetes. Moreover, both ELISA and pull-down assays demonstrated that insect cell-expressed mosquito midgut protein, fibrinogen-related protein 1 (FREP1), interacts with P. falciparum α-tubulin-1. Since ookinete invasion is directional, we conclude that the interaction between Anopheles FREP1 protein and Plasmodium α-tubulin-1 anchors and orients the ookinete invasive apparatus towards the midgut PM and promotes the efficient parasite infection in the mosquito.

The extracellular matrix of cartilage primarily constitutes of collagen and aggrecan. Cartilage degradation starts with aggrecan loss in osteoarthritis (OA). Vitamin D (VD) plays an essential role in several inflammation-related diseases and can protect the collagen in cartilage during OA. The present study focused on the role of VD in aggrecan turnover of human articular chondrocytes treated with tumor necrosis factor α (TNF-α) and the possible mechanism. Treatment with different doses of VD and different periods of intervention with TNF-α and TGF-β1 receptor (TGFβR1) inhibitor SB525334 were investigated. The viability of human chondrocytes and extracellular secretion of TGF-β1 were measured. The expression of intracellular TGFβR1 and VD receptor was examined. Transcriptional and translational levels of aggrecan and the related metabolic factors were analyzed. The results showed that TNF-α markedly reduced the viability, TGFβR1 expressions and aggrecan levels of human chondrocytes, and increased disintegrin and metalloproteinase with thrombospondin motifs. The alterations were partially inhibited by VD treatment. Furthermore, the effects of VD were blocked by the TGFβR1 inhibitor SB525334 in TNF-α-treated cells. VD may prevent proteoglycan loss due to TNF-α via TGF-β1 signaling in human chondrocytes. [ABSTRACT FROM AUTHOR]

Aims: This study was aimed to report the characteristics and treatment of ventricular tachycardia (VT) following surgical treatment of pulmonary stenosis with intact ventricular septum.Methods and Results: Five patients underwent radiofrequency catheter ablation for sustained monomorphic left bundle branch block (LBBB) type VT who previously underwent surgical treatment of pulmonary stenosis. Except stimulation, voltage and activation mapping was performed using three-dimensional (3D) electro-anatomic mapping and ablation was applied accordingly. Four VTs were induced during EP study. Two VTs were focal and the earliest activity was targeted in the right ventricular apex (RVA). The other two VTs were reentrant and the critical isthmus located in the mid-lateral wall and anterior wall of right ventricle, respectively. Ablation abolished all inducible VTs in four patients. In the patient whose VT was non-inducible, radiofrequency (RF) energy was delivered to the RVA where pacing mapping matched the clinical VT. One focal VT recurred 60 months after the initial RF ablation. Repeat mapping and ablation was performed and no VT recurred over a 24-month period.Conclusions: The mechanism of VT following surgical treatment of pulmonary stenosis can be either focal or reentrant. Ablation of this subgroup of VT is feasible. [ABSTRACT FROM AUTHOR]

Background: Ventricular conduction blocks (VCBs) are associated with poor outcomes in patients with known cardiac diseases. However, the prognostic implications of VCB patterns in dilated cardiomyopathy (DCM) patients need to be evaluated. The purpose of this study was to determine all-cause mortality in patients with DCM and VCB.Methods: This cohort study included 1119 DCM patients with a median follow-up of 34.3 (19.5-60.8) months, patients were then divided into left bundle branch block (LBBB), right bundle branch block (RBBB), intraventricular conduction delays (IVCD) and narrow QRS groups. The all-cause mortality was assessed using Kaplan-Meier survival curves and Cox regression.Results: Of those 1119 patients, the all-cause mortality rates were highest in patients with IVCD (47.8, n = 32), intermediate in those with RBBB (32.9, n = 27) and LBBB (27.1 %, n = 60), and lowest in those with narrow QRS (19.9 %, n = 149). The all-cause mortality risk was significantly different between the VCB and narrow QRS group (log-rank χ2 = 51.564, P < 0.001). The presence of RBBB, IVCD, PASP ≥ 40 mmHg, left atrium diameter and NYHA functional class were independent predictors of all-cause mortality in DCM patients.Conclusions: Our findings indicate that RBBB and IVCD at admission,but not LBBB, were independent predictors of all-cause mortality in patients with DCM. [ABSTRACT FROM AUTHOR]

Background: The mechanism(s) for acute changes in electrophysiological properties of the atria during rapid pacing induced atrial fibrillation (AF) is not completely understood. We sought to evaluate the contribution of the intrinsic cardiac autonomic nervous system in acute atrial electrical remodeling and AF induced by 6-hour rapid atrial pacing.Methods and Results: Continuous rapid pacing (1200 bpm, 2x threshold [TH]) was performed at the left atrial appendage. Group 1 (n=7) underwent 6-hour pacing immediately followed by ganglionated plexi (GP) ablation; group 2 (n=7) underwent GP ablation immediately followed by 6-hour pacing; and group 3 (n=4) underwent administration of autonomic blockers, atropine (1 mg/kg), and propranolol (0.6 mg/kg) immediately followed by 6-hour pacing. The effective refractory period (ERP) and window of vulnerability (WOV, in milliseconds), ie, the difference between the longest and the shortest coupling interval of the premature stimulus that induced AF, were measured at 2xTH and 10xTH at the left atrium, right atrium, and pulmonary veins every hour before and after GP ablation or autonomic blockade. In group 1, ERP was markedly shortened in the first 2 hours and then stabilized both at 2xTH and 10xTH; however, WOV was progressively widened throughout the 6-hour period. After GP ablation, ERP was significantly longer than before ablation and AF could not be induced (WOV=0) at either 2xTH or 10xTH. In groups 2 and 3, rapid atrial pacing failed to shorten the ERP. AF could not be induced in 6 of 7 dogs in group 2 and all 4 dogs in group 3 during the 6-hour pacing period.Conclusions: The intrinsic cardiac autonomic nervous system plays a crucial role in the acute stages of atrial electrical remodeling induced by rapid atrial pacing. [ABSTRACT FROM AUTHOR]

Abstract: The model TREEDEV is developed based on the TREEDYN and TREEGROW models. In TREEDEV model the characteristics and available data of Masson pine (Pinus massoniana) forest in Dinghushan Biosphere Reserve are taken into account as a demonstration. The model was validated by plantation forest and natural forest data. Calculation of tree growth is based on carbon and nitrogen balance, which depends on the photoproduction of its needles, respiration, nitrogen content of all organisms and that in soil, and other losses due to respiration, litterfall and renewal of stem, branch, needle and root. The model includes four aspects: (1) Exogenous driving force solar radiation, which is a function of latitude, specific meteorological conditions and seasonal time. (2) Canopy photoproduction, in this submodel the influence of temperature, solar radiation, seasonal time and nitrogen content of the soil are taken into account. (3) Biomass compartment into needles, fine roots, coarse roots, branches and stems, enabling us to calculate the appropriate respiration demands for the maintenance of the living biomass fractions, fine roots and needles renewal more accurately. (4) The cycle of carbon and nitrogen in soil, which is related to the decomposition and humification of soil organic matter and litter, nitrogen mineralization from litter, and nitrogen leaching. The dynamics of nitrogen include nitrogen uptake demand of the tree, the loss of nitrogen, and nitrogen relocation before litter shedding and the nitrogen supply from soil. Combined with field condition, scenarios involving litter removal and protective fencing were taken into account. Sensitivity analysis was performed in which 43 model independent variables were varied and analyzed in respect to their influence on 22 dependent variables describing forest state. Simulation results showed that litter removal has an influence on the growth of vegetation, which changes the environment, and retards the renewal of litter and reduces the uptake and fixation of available nitrogen, especially to needle and fine root. The forest with low intensity disturbance can be restored if it is fenced within an appropriate time (30 years in this paper), but this retards the maturation time of stands and depreciates the economic value of the wood. In this paper carbon and nitrogen cycles are analyzed in view of physiological processes with the goal of improving forest management planning. [Copyright &y& Elsevier]

Aims: The study aims to describe the long-term outcome of radiofrequency catheter ablation for ventricular tachycardia (VT) in a large cohort arrhythmogenic right ventricular cardiomyopathy (ARVC) patients., Methods and Results: Radiofrequency catheter ablation was performed in 284 ARVC patients due to VT between July 2000 and January 2019. An endocardial approach was used initially, with epicardial ablation procedures reserved for those patients who failed an endocardial ablation. Activation, entrainment, pace and substrate mapping strategies were used with regional ablation applied. A total of 393 ablation procedures were performed including endocardial approach only (n = 377) and endo and epicardial combined (n = 16). Right ventricular basal free wall was accounted as the primary substrate of VT in 258 (65.6%) patients. There were 81 patients underwent redo ablation procedure (second time = 81; ≥3 times = 28). New targets were observed in 68.8% of redo procedures. There were 171 VT recurrences and 19 deaths occurred during the follow-up. Ventricular tachycardia-free survival rate of the first, second, and last ablation procedure was 56.7%, 73.2%, and 78.1%, respectively. Multivariate analysis showed ≥3 induced VTs in the procedure was correlated with rehospitalized VT recurrence [hazard ratio (HR) 1.467, 95% confidence interval (CI) 1.052-2.046; P = 0.024]. For all-cause mortality, rehospitalized VT and ≥3 induced VTs were the independent risk factors (HR 2.954, 95% CI 1.8068.038; P = 0.034; HR 3.189, 95% CI 1.073-9.482; P = 0.037)., Conclusion: Endocardial ablation is effective to ARVC VT though it may require repeated procedures. Induced multiple VTs was correlated with worse outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Mosquito densoviruses (DNVs) are candidate agents for paratransgenic control of malaria and other vector-borne diseases. Unlike other mosquito DNVs, the Anopheles gambiae DNV (AgDNV) is non-pathogenic to larval mosquitoes. However, the cost of infection upon adults and the molecular mechanisms underpinning infection in the mosquito host are unknown. Using life table analysis, we show that AgDNV infection has minimal effects on An. gambiae survival (no significant effect in 2 replicates and a slight 2 day survival decrease in the third replicate). Using microarrays, we show that AgDNV has very minimal effect on the adult mosquito transcriptome, with only 4-15 genes differentially regulated depending on the statistical criteria imposed. The minimal impact upon global transcription provides some mechanistic understanding of lack of virus pathogenicity, suggesting a long co-evolutionary history that has shifted towards avirulence. From an applied standpoint, lack of strong induced fitness costs makes AgDNV an attractive agent for paratransgenic malaria control.