Balancing crosstalk between 20-hydroxyecdysone-induced autophagy and caspase activity in the fat body during Drosophila larval-prepupal transition

In the fruitfly, Drosophila melanogaster, autophagy and caspase activity function in parallel in the salivary gland during metamorphosis and in a common regulatory hierarchy during oogenesis. Both autophagy and caspase activity progressively increase in the remodeling fat body, and they are induced by a pulse of the molting hormone (20-hydroxyecdysone, 20E) during the larval-prepupal transition. Inhibition of autophagy and/or caspase activity in the remodeling fat body results in 25–40% pupal lethality, depending on the genotypes. Interestingly, a balancing crosstalk occurs between autophagy and caspase activity in this tissue: the inhibition of autophagy induces caspase activity and the inhibition of caspases induces autophagy. The Drosophila remodeling fat body provides an in vivo model for understanding the molecular mechanism of the balancing crosstalk between autophagy and caspase activity, which oppose with each other and are induced by the common stimulus 20E, and blockage of either path reinforces the other path.     

Mitogenomes provide new insights into the evolutionary history of Prodiamesinae (Diptera: Chironomidae)

Evolutionary analysis of Prodiamesinae has long been impeded by lack of information, and its phylogenetic relationship with Orthocladiinae remains questionable. Here, ten complete mitochondrial genomes (mitogenomes) of Orthocladiinae sensu lato were newly sequenced, including three Prodiamesinae species and seven Orthocladiinae species. Coupled with published mitogenomes, a total of 12 mitogenomes of Orthocladiinae sensu lato were selected for a comparative mitogenomic analysis and phylogenetic reconstruction. Mitogenomes of Orthocladiinae sensu lato are conserved in structure, and all genes arrange the same gene order as the ancestral insect mitogenome. Nucleotide composition is highly biased, and the control region displayed the highest A + T content. All protein-coding genes are under purifying selection, and the ATP8 evolves at the fastest rate. In addition, the mitogenomes of Orthocladiinae sensu lato are highly conserved, and they are practically useful for phylogenetic inference, suggesting a re-classification of Orthocladiinae by sinking Prodiamesinae as a subgroup of Orthocladiinae.     

光诱导角膜交联及检测技术的研究进展

由于圆锥角膜疾病导致越来越多的人患有近视,常见的矫正方法有佩戴近视眼镜、隐形眼镜等.随着科技的进步,利用光对近视等眼科疾病进行屈光矫正已经成为当前临床中常用的方法.使用光诱导角膜胶原蛋白发生交联,从而达到治疗圆锥角膜疾病、提高患者视力水平的目的,这是一种新型的光治疗眼睛疾病的方法.同时这种方法由于无侵入性、对操作者能力依赖性小等优势成为新的研究热点.本文阐述光诱导角膜交联的基本原理,并介绍其发展历程,分析现有的各种交联方法和角膜检测技术的原理,并对现有交联方法和检测方法的优缺点进行讨论.最后,本文对光诱导角膜交联和检测技术的最新进展进行系统的论述,并对未来的发展趋势进行展望.     

Genome Sequence of the Aerobic Bacterium Bacillus sp. Strain FJAT-13831

Bacillus sp. strain FJAT-13831 was isolated from the no. 1 pit soil of Emperor Qin''s Terracotta Warriors in Xi''an City, People''s Republic of China. The isolate showed a close relationship to the Bacillus cereus group. The draft genome sequence of Bacillus sp. FJAT-13831 was 4,425,198 bp in size and consisted of 5,567 genes (protein-coding sequences [CDS]) with an average length of 782 bp and a G+C value of 36.36%.     

Synthesis,Biological Evaluation,and Docking Study of Ring-Opening Amide Analogs of Matrine as Antitumor Agents

In this article, we designed and synthesized two series of matrine analogs with ring-opening in the lactam portion of the molecule. Our in vitro cytotoxicity study showed that analog N-(3-bromophenyl)-4-[(1R,3aS,10aR,10bS)-decahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl]butanamide ( B11 ) with a meta-bromide on the phenyl ring displayed the best antiproliferative activity. Moreover, B11 induced cell cycle arrest in G1 phase and cell apoptosis in a dose-dependent manner in A549 cells. Molecular modeling revealed that B11 achieved a higher docking score compared to its precursor tert-butyl (1R,3aS,10aR,10bS)-1-[4-(3-bromoanilino)-4-oxobutyl]octahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridine-2(3H)-carboxylate ( A11 , an analog of B11 with a Boc group) and parent compound matrine, possibly because B11 formed a hydrogen bond with SER91 and a halogen bond with GLN320 on the binding site of annexin A2. Overall, we discovered the potential anticancer lead compound B11 , which can be used for further study both in vitro and in vivo.     

Activation of AMPK by Bitter Melon Triterpenoids Involves CaMKKβ

We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo. Here we interrogated the mechanism by which these novel compounds activate AMPK, a leading anti-diabetic drug target. BMTs did not activate AMPK directly in an allosteric manner as AMP or the Abbott compound (A-769662) does, nor did they activate AMPK by inhibiting cellular respiration like many commonly used anti-diabetic medications. BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20–35%. Incubation with the CaMKKβ inhibitor, STO-609, completely attenuated this effect suggesting a key role for CaMKKβ in this activation. Incubation of L6 myotubes with the calcium chelator EGTA-AM did not alter this activation suggesting that the BMT-dependent activation was Ca²⁺-independent. We therefore propose that CaMKKβ is a key upstream kinase for BMT-induced activation of AMPK.     

Inducible nuclear expression of NF-kappa B in primary B cells stimulated through the surface Ig receptor

Constitutive expression of NF-kappa B has been associated with developmental maturity in B cells on the basis of studies using continuously growing cell lines and plasmacytomas; however, little is known about the behavior of NF-kappa B in primary, mature B cells. In the present work, the regulation of NF-kappa B expression was studied by analyzing subcellular fractions of adult murine splenic B cells with the electrophoretic mobility shift assay using a kappa B-containing oligonucleotide. Although nuclear extracts from resting B cells contained kappa B-binding activity, additional kappa B-binding activity was present in cytosolic fractions in a form that became apparent after treatment with detergent. Competition analysis indicated that the DNA binding activity detected by electrophoretic gel mobility shift assay was specific for the kappa B motif, and UV photo-cross-linking showed the molecular size of kappa B-binding protein to be similar to that of the DNA binding subunit of NF-kappa B. Nuclear expression of kappa B-binding activity was markedly induced by treatment of B cells with phorbol ester or with LPS. Most notably, kappa B-binding activity was induced after surface IgR cross-linking, and the mechanism of this induction involved PKC. Further, anti-Ig-induced activity was superinduced in the presence of cycloheximide. These results indicate that nuclear NF-kappa B is rapidly induced as a result of B cell stimulation, and further suggest that NF-kappa B may play a specific role in mature B cells after ligand binding to surface Ig distinct from its postulated developmental role as a stage-specific factor involved in kappa-enhancer function.     

Genome‐wide detection of CNVs associated with beak deformity in chickens using high‐density 600K SNP arrays

Beak deformity (crossed beaks) is found in several indigenous chicken breeds including Beijing‐You studied here. Birds with deformed beaks have reduced feed intake and poor production performance. Recently, copy number variation (CNV) has been examined in many species and is recognized as a source of genetic variation, especially for disease phenotypes. In this study, to unravel the genetic mechanisms underlying beak deformity, we performed genome‐wide CNV detection using Affymetrix chicken high‐density 600K data on 48 deformed‐beak and 48 normal birds using penncnv . As a result, two and eight CNV regions (CNVRs) covering 0.32 and 2.45 Mb respectively on autosomes were identified in deformed‐beak and normal birds respectively. Further RT‐qPCR studies validated nine of the 10 CNVRs. The ratios of six CNVRs were significantly different between deformed‐beak and normal birds (P < 0.01). Within these six regions, three and 21 known genes were identified in deformed‐beak and normal birds respectively. Bioinformatics analysis showed that these genes were enriched in six GO terms and one KEGG pathway. Five candidate genes in the CNVRs were further validated using RT‐qPCR. The expression of LRIG2 (leucine rich repeats and immunoglobulin like domains 2) was lower in birds with deformed beaks (P < 0.01). Therefore, the LRIG2 gene could be considered a key factor in view of its known functions and its potential roles in beak deformity. Overall, our results will be helpful for future investigations of the genomic structural variations underlying beak deformity in chickens.