Models of impulsive culling of mosquitoes to interrupt transmission of West Nile Virus to birds

A mathematical model describing the transmission of West Nile virus (WNV) between vector mosquitoes and birds, incorporating a control strategy of culling mosquitoes and defined by impulsive differential equations is presented and its properties investigated. First, we consider a strategy of periodic impulsive culling of the mosquitoes. Theoretical results indicate that if the threshold R 0 is greater than unity the disease uniformly persists, but, if not, the disease does not necessarily become extinct. The explicit conditions determining the backward or forward bifurcation were obtained. The culling rate has a major effect on the occurrence of backward bifurcation. Analysis shows that the disease is most sensitive to mosquito-bird contacts, mosquito-culling rate and intervals between culls. The dependence of the outcomes of the culling strategy on mosquito biting rate is discussed. When the complete elimination of disease is impossible, mosquito culls are implemented once the infected birds reach a predefined but adjustable threshold value. Numerical analysis shows that the period of mosquito culling finally stabilizes at a fixed value. In addition, variations of mean prevalence of \{WNV\} in birds and the culling period are simulated

Glycogen synthase kinase-3β inhibition induces nuclear factor-κB-mediated apoptosis in pediatric acute lymphocyte leukemia cells

<p>Abstract</p> <p>Background</p> <p>Molecular therapies that target genetic abnormalities in leukemic cells and their affected signaling pathways have been emerging in pediatric acute lymphoblastic leukemia (ALL). Glycogen synthase kinase-3β (GSK-3β) has recently been found to positively regulate the activity of nuclear factor-κB (NF-κB). Here, we investigated the relationship between GSK-3β inhibition and NF-κB in apoptosis of pediatric primary leukemia cells obtained from 39 newly diagnosed ALL children in China.</p> <p>Methods</p> <p>Bone marrow mononuclear cells (BMMC) were isolated by density gradient centrifugation from the heparinized aspirates of children with ALL. We used immunofluorescence staining to detect nuclear GSK-3β in these cells. After treatment with chemically distinct GSK-3β inhibitors in vitro, NF-κB transcriptional activity was identified by means of western blotting and electrophoretic mobility shift assay (EMSA). NF-κB-mediated apoptosis was detected by Annexin V-PE/7-AAD double-staining flow cytometry. The expression level of the <it>survivin </it>gene was detected by reverse-transcriptase polymerase chain reaction (RT-PCR).</p> <p>Results</p> <p>GSK-3β significantly accumulates in the nuclei of ALL cells than in the nuclei of control cells. Cell death induced by GSK-3β inhibition in ALL cells was mediated by a downregulation of NF-κB p65 transcriptional activity. GSK-3β inhibition significantly decreased the expression of the NF-κB target gene <it>survivin</it>.</p> <p>Conclusions</p> <p>These results indicate that inhibition of GSK-3β downregulates the NF-κB activation pathway, leading to suppression of the expression of an NF-κB-regulated gene and promotion of apoptosis in ALL cells in vitro. Furthermore, our findings suggest that GSK-3β or NF-κB is a potential therapeutic target in the treatment of pediatric ALL.</p

E17110 promotes reverse cholesterol transport with liver X receptor β agonist activity in vitro

AbstractLiver X receptor (LXR) plays an important role in reverse cholesterol transport (RCT), and activation of LXR could reduce atherosclerosis. In the present study we used a cell-based screening method to identify new potential LXRβ agonists. A novel benzofuran-2-carboxylate derivative was identified with LXRβ agonist activity: E17110 showed a significant activation effect on LXRβ with an EC50 value of 0.72μmol/L. E17110 also increased the expression of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) in RAW264.7 macrophages. Moreover, E17110 significantly reduced cellular lipid accumulation and promoted cholesterol efflux in RAW264.7 macrophages. Interestingly, we found that the key amino acids in the LXRβ ligand-binding domain had distinct interactions with E17110 as compared to TO901317. These results suggest that E17110 was identified as a novel compound with LXRβ agonist activity in vitro via screening, and could be developed as a potential anti-atherosclerotic lead compound

The functions and regulatory pathways of S100A8/A9 and its receptors in cancers

Inflammation primarily influences the initiation, progression, and deterioration of many human diseases, and immune cells are the principal forces that modulate the balance of inflammation by generating cytokines and chemokines to maintain physiological homeostasis or accelerate disease development. S100A8/A9, a heterodimer protein mainly generated by neutrophils, triggers many signal transduction pathways to mediate microtubule constitution and pathogen defense, as well as intricate procedures of cancer growth, metastasis, drug resistance, and prognosis. Its paired receptors, such as receptor for advanced glycation ends (RAGEs) and toll-like receptor 4 (TLR4), also have roles and effects within tumor cells, mainly involved with mitogen-activated protein kinases (MAPKs), NF-κB, phosphoinositide 3-kinase (PI3K)/Akt, mammalian target of rapamycin (mTOR) and protein kinase C (PKC) activation. In the clinical setting, S100A8/A9 and its receptors can be used complementarily as efficient biomarkers for cancer diagnosis and treatment. This review comprehensively summarizes the biological functions of S100A8/A9 and its various receptors in tumor cells, in order to provide new insights and strategies targeting S100A8/A9 to promote novel diagnostic and therapeutic methods in cancers

Typological characteristics of interlanguage: Across L2 modalities and proficiency levels

In recent years, quantitative methods have been increasingly used in interlanguage studies, but these studies have mostly focused on the micro level with an emphasis on certain syntactic structures, rather than the macro where interlanguage is perceived as a whole. There remains a paucity of quantitative studies on interlanguage from the typological perspective. With the majority of the studies focused on the written interlanguage, there is also a lack of sufficient research on its spoken modality. Based on a syntactically annotated corpus and using the quantitative linguistic metric of dependency direction, we have investigated the typological changes in the Chinese interlanguage in both written and spoken modalities. The findings are as follows: (1) the typological features of interlanguage vary across modalities at both macro and micro levels; (2) dependency direction is proved to be an inappropriate indicator to measure the general typological characteristics of interlanguage development due to its failure to reflect the changes in the spoken modality; (3) both macro and micro perspectives taken into consideration, typological errors in the interlanguage is more likely to occur in the spoken modality than in the written one, in which learners may be restricted by greater time pressure and cognitive load in utterance. These factors may affect the distribution of dependency direction in the oral modality, and may be the reason why it is not appropriate to use dependency direction as a measure of changes in mediated language typological features in the oral modality. It is expected that our study will bring insight into second language research with more objective and holistic evidence

Transcriptomic analysis reveals transcription factors involved in vascular bundle development and tissue maturation in ginger rhizomes (Zingiber officinale Roscoe)

Ginger (Zingiber officinale Roscoe) is an important vegetable with medicinal value. Rhizome development determines ginger yield and quality. However, little information is available about the molecular features underlying rhizome expansion and maturation. In this study, we investigated anatomy characteristics, lignin accumulation and transcriptome profiles during rhizome development. In young rhizomes, the vascular bundle (VB) was generated with only vessels in it, whereas in matured rhizomes, three to five layers of fibre bundle in the xylem were formed, resulting in VB enlargement. It indicates VB development favouring rhizome swelling. With rhizome matured, the lignin content was remarkably elevated, thus facilitating tissue lignification. To explore the regulators for rhizome development, nine libraries including ginger young rhizomes (GYR), growing rhizomes (GGR), and matured rhizomes (GMR) were established for RNA-Seq, a total of 1264 transcription factors (TFs) were identified. Among them, 35, 116, and 14 differentially expressed TFs were obtained between GYR and GGR, GYR and GMR, and GGR and GMR, respectively. These TFs were further divided into three categories. Among them, three ZobHLHs (homologs of Arabidopsis LHW and AtbHLH096) as well as one DIVARICATA homolog in ginger might play crucial roles in controlling VB development. Four ZoWRKYs and two ZoNACs might be potential regulators associated with rhizome maturation. Three ZoAP2/ERFs and one ZoARF might participate in rhizome development via hormone signalling. This result provides a molecular basis for rhizome expansion and maturation in ginger

Point Primitives Based Virtual Surgery System

In order to achieve a high degree of visual realism in surgery simulation, we present a virtual surgery system framework, which is based on point primitives for the virtual surgery scene rendering and the biomechanical calculation of the soft tissue. To embody the superiority of this framework, two virtual surgery systems based on point primitives we developed are exhibited in this paper. Six critical functional modules were selected as representative of basic and advanced virtual surgery skill. These modules were: 1) point-based texture mapping; 2) deformation simulation; 3) cutting simulation; 4) tearing simulation; 5) dynamic texture mapping; and 6) 3-D display. These modules were elaborated by including working principle, execution process, and the performance of the algorithm. The experimental results have shown that point primitives-based virtual surgery systems obtained higher performance in terms of computational efficiency and rendering effect than traditional meshes-based virtual surgery system

Gut microbiome: A potential indicator for predicting treatment outcomes in major depressive disorder

The therapeutic outcomes in major depressive disorder (MDD), one of the most common and heterogeneous mental illnesses, are affected by factors that remain unclear and often yield unsatisfactory results. Herein, we characterized the composition and metabolic function of the gut microbiota of patients with MDD during antidepressant treatment, based on 16S rRNA sequencing and metabolomics. The microbial signatures at baseline differed significantly between responder and non-responder groups. The gut microbiota of the non-responder group was mainly characterized by increased relative abundances of the phylum Actinobacteria, families Christensenellaceae and Eggerthellaceae, and genera Adlercreutzia and Christensenellaceae R7 group compared to that of the responder group. Additionally, the gut microbiota composition of the responder and non-responder groups differed significantly before and after treatment, especially at the genus level. Moreover, 20 differential metabolites between the responder and non-responder groups were identified that were mainly involved in lipid metabolism (cholestane steroids and steroid esters). Eggerthellaceae and Adlercreutzia displayed strong co-occurrence relationships with certain metabolites, suggesting alternations in the gut microbiome, and associated metabolites may be potential mediators of successful antidepressant treatment. Overall, our study demonstrates that alterations in gut microbiota composition and metabolic function might be relevant to the response to antidepressants, thereby providing insight into mechanisms responsible for their efficacy