皂荚半乳甘露聚糖胶分级醇沉及表征

使用不同浓度乙醇和异丙醇分别对皂荚半乳甘露聚糖胶水溶液进行分级沉降,沉淀物用凝胶渗透色谱(GPC)和高效液相色谱(HPLC)等进行表征.结果表明,异丙醇可在较小浓度下更快沉降皂荚多糖胶,当异丙醇溶液浓度为28.6％ (V/V)时,沉淀物中半乳甘露聚糖浓度达到12.50％(w/w);随着醇浓度上升,沉降组分半乳甘露聚糖得率呈增加趋势,且在后期增加幅度最大,多糖最高得率可达80％,纯化后皂荚多糖胶(GSG)表现出较高的甘露糖/半乳糖(M/G)之比值,在异丙醇沉降中表现更加明显(低浓度的异丙醇达到最高的M/G =4.1);低浓度醇沉主要得到大分子组分,随乙醇浓度增加组分分子量明显降低,多糖胶更加均匀,而在异丙醇沉降后期均一性有所下降.     

AEBP1 upregulation confers acquired resistance to BRAF (V600E) inhibition in melanoma

An activating BRAF (V600E) kinase mutation occurs in approximately half of melanomas. Recent clinical studies have demonstrated that vemurafenib (PLX4032) and dabrafenib, potent and selective inhibitors of mutant v-raf murine sarcoma viral oncogene homolog B1 (BRAF), exhibit remarkable activities in patients with V600 BRAF mutant melanomas. However, acquired drug resistance invariably develops after the initial treatment. Identification of acquired resistance mechanisms may inform the development of new therapies that elicit long-term responses of melanomas to BRAF inhibitors. Here we report that increased expression of AEBP1 (adipocyte enhancer-binding protein 1) confers acquired resistance to BRAF inhibition in melanoma. AEBP1 is shown to be highly upregulated in PLX4032-resistant melanoma cells because of the hyperactivation of the PI3K/Akt-cAMP response element-binding protein (CREB) signaling pathway. This upregulates AEBP1 expression and thus leads to the activation of NF-κB via accelerating IκBa degradation. In addition, inhibition of the PI3K/Akt-CREB-AEBP1-NF-κB pathway greatly reverses the PLX4032-resistant phenotype of melanoma cells. Furthermore, increased expression of AEBP1 is validated in post-treatment tumors in patients with acquired resistance to BRAF inhibitor. Therefore, these results reveal a novel PI3K/Akt-CREB-AEBP1-NF-κB pathway whose activation contributes to acquired resistance to BRAF inhibition, and suggest that this pathway, particularly AEBP1, may represent a novel therapeutic target for treating BRAF inhibitor-resistant melanoma.     

Light-controlled inhibition of malignant glioma by opsin gene transfer

Glioblastomas are aggressive cancers with low survival rates and poor prognosis because of their highly proliferative and invasive capacity. In the current study, we describe a new optogenetic strategy that selectively inhibits glioma cells through light-controlled membrane depolarization and cell death. Transfer of the engineered opsin ChETA (engineered Channelrhodopsin-2 variant) gene into primary human glioma cells or cell lines, but not normal astrocytes, unexpectedly decreased cell proliferation and increased mitochondria-dependent apoptosis, upon light stimulation. These optogenetic effects were mediated by membrane depolarization-induced reductions in cyclin expression and mitochondrial transmembrane potential. Importantly, the ChETA gene transfer and light illumination in mice significantly inhibited subcutaneous and intracranial glioma growth and increased the survival of the animals bearing the glioma. These results uncover an unexpected effect of opsin ion channels on glioma cells and offer the opportunity for the first time to treat glioma using a light-controllable optogenetic approach.     

Global Changes in the Mammary Epigenome Are Induced by Hormonal Cues and Coordinated by Ezh2

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Highlights? The mammary epigenome is highly sensitive to steroid hormones at specific developmental stages ? Ezh2 links hormonal cues to changes in chromatin structure and gene expression ? Progesterone is a key in vivo regulator of Ezh2 ? Hormone-induced chromatin changes likely play a role in the initiation of breast cancer     

Observer-based tracking control of abnormal oscillations in demyelination symptom

Fast axonal conduction of action potentials in mammals relies on myelin insulation. Demyelination can cause slowed, blocked, desynchronized, or paradoxically excessive spiking that underlies the symptoms observed in demyelination diseases. Feedback control via functional electrical stimulation (FES) seems to be a promising treatment modality in such diseases. However, there are challenges to implementing such method for neurons: high nonlinearity, biological tissue constrains and unobservable ion channel states. To address this problem, we propose an estimating and tracking control strategy for systems based on Kalman filter, in order to enhance the action potential propagation reliability of demyelinated neuron via FES. Unscented Kalman filter (UKF) is employed to estimate the unobservable states and parameters in the demyelination neuron model from membrane potential dynamics. Our method could promote the design of new closed-loop electrical stimulation systems for patients suffering from different nerve system dysfunctions.     

Genome‐wide analysis of Nilaparvata lugens nymphal responses to high‐density and low‐quality rice hosts

The brown planthopper (BPH) Nilaparvata lugens is an economically important pest on rice plants. In this study, the higher population density and yellow‐ripe stage of rice plants were used to construct adverse survival conditions (ASC) against BPH nymphs. Simultaneously, the low population density and tillering stage of rice plants were used to establish a suitable survival condition (SSC) as a control. Solexa/Illumina sequencing was used to identify genes of BPH nymphs responding to ASC. Significantly longer duration development of BPH nymphs and significantly lower brachypterous ratio of BPH adults were observed by ASC compared with SSC. A total of 2 544 differentially expressed genes (DEGs) were obtained and analyzed by BLASTx, Gene Ontology and KEGG Orthology. Gene ontology analysis revealed that the DEGs were mainly involved in categories of cell, cell part, cellular process, binding, catalytic, organelle and metabolic processes. 1 138 DEGs having enzyme commission numbers were assigned to different metabolic pathways. The largest clusters were neurodegenerative diseases (137, 12.0%), followed by carbohydrate metabolism (113, 9.9%), amino acid metabolism (94, 8.3%), nucleotide metabolism (76, 6.7%), energy metabolism (64, 5.6%), translation (60, 5.3%), lipid metabolism (58, 5.1%), and folding, sorting and degradation (52, 4.6%). Expressing profile of 11 DEGs during eight nymphal developmental stages of BPH were analyzed by quantitative real‐time polymerase chain reaction. The 11 genes exhibited differential expression between ASC and SSC during at least one developmental stage. The DEGs identified in this study provide molecular proof of how BPH reconfigures its gene expression profile to adapt to overcrowding and low‐quality hosts.     

Association of human leukocyte antigen E polymorphism with human cytomegalovirus reactivation in Chinese burn patients

The seroprevalence of human cytomegalovirus （HCMV） in adults increased steadily from 55% in developed countries to over 90% in developing countries like China [1]. As all her- pesviruses, HCMV establishes lifelong latency after primary infection. In immunocompetent individuals, host immune responses prevent the development of overt HCMV diseases. However, in immunoeompromised people who suffer from burn injuries, HCMV reactivation has been shown to lead to significant diseases with considerable morbidity and mortal- ity [2-4]. Recently, increasing evidence has suggested that HCMV reactivation might have been considerably underesti- mated in burn patients [5,6]. Review of the available litera- ture identifies 〉50% of HCMV antibody-positive burn patients may reactivate this virus [5,6]. Although the exact mechanisms of HCMV reactivation are still not clearly under- stood, the immune system and host genetics are thought to be the non-behavioral factors determining the acquisition of a reactivation.