Furazan and furoxan sulfonamides are strong α-carbonic anhydrase inhibitors and potential antiglaucoma agents

A series of furazan and furoxan sulfonamides were prepared and studied for their ability to inhibit human carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, hCA II, hCA IX, and hCA XII. The simple methyl substituted products 3–5 were potent inhibitors. Differing structural modifications of these leads had differing effects on potency and selectivity. In particular, products in which the sulfonamide group is separated from the hetero ring by a phenylene bridge retained high potency only on the hCA XII isoform. The sulfonamides 3–5 exerted intraocular pressure (IOP) lowering effects in vivo in hypertensive rabbits more efficiently than dorzolamide. Some other products (39–42), although less effective in vitro hCA II/XII inhibitors, also effectively lowered IOP in two different animal models of glaucoma.     

An Optimized Proteomics Approach Reveals Novel Alternative Proteins in Mouse Liver Development

Alternative ORFs (AltORFs) are unannotated sequences in genome that encode novel peptides or proteins named alternative proteins (AltProts). Although ribosome profiling and bioinformatics predict a large number of AltProts, mass spectrometry as the only direct way of identification is hampered by the short lengths and relative low abundance of AltProts. There is an urgent need for improvement of mass spectrometry methodologies for AltProt identification. Here, we report an approach based on size-exclusion chromatography for simultaneous enrichment and fractionation of AltProts from complex proteome. This method greatly simplifies the variance of AltProts discovery by enriching small proteins smaller than 40 kDa. In a systematic comparison between 10 methods, the approach we reported enabled the discovery of more AltProts with overall higher intensities, with less cost of time and effort compared to other workflows. We applied this approach to identify 89 novel AltProts from mouse liver, 39 of which were differentially expressed between embryonic and adult mice. During embryonic development, the upregulated AltProts were mainly involved in biological pathways on RNA splicing and processing, whereas the AltProts involved in metabolisms were more active in adult livers. Our study not only provides an effective approach for identifying AltProts but also novel AltProts that are potentially important in developmental biology.     

20世纪90年代以来中国生态空间演化的时空格局和梯度效应

改革开放以来中国经济和城市化的快速发展促使生产和生活空间挤占大量生态空间，系统认识和评估我国生态空间演化的宏观格局和过程对于生态文明建设具有重要的理论和现实意义。为揭示全国生态空间变化的时空过程，在对生态空间内涵进行界定的基础上，结合全国尺度时序土地利用数据构建生态空间分类体系，并评估1990-2015年中国生态空间演化特征。结果表明：1990-2015年中国生态用地面积持续减少，主要向半生态用地转变，发生在重要的粮食生产区域及周边；半生态用地面积波动明显，前期主要表现为不断扩张，后期大量转换为弱生态用地，发生在主要城市群地区；弱生态用地持续扩张，与城镇化进程不断加速相关。中国生态空间演变过程表现出一定的区域差异和梯度效应，不同区域生态空间变化发生的拐点时间有所不同，呈现"自东向西、由南到北"的3级梯度特征，区域生态空间状况与经济发展战略及生态空间管控具有较强的相关性。本研究对于国家生态空间管控近远期战略方案制订具有一定启示，建议处于不同梯度的各地区应基于区域生态空间演化所处阶段和不同驱动机制，确定分区域生态空间安全红线目标和生态空间管控方案。     

Effect of Different Carbon and Nitrogen Sources on Clostridium argentinense Toxigenicity in Coculture withPseudomonas mendocina

The effect of different carbon and nitrogen sources on the production of toxin by Clostridium argentinense was examined. The toxin production by C. argentinense in coculture with Pseudomonas mendocina increased in all the cases in relation to that produced by monocultures independent of the nature of the source. Using dextrin as carbon source C. argentinense produced the highest levels of toxin both in monocultures (300 LD₅₀/mL) and in cocultures with P. mendocina (5000 LD₅₀/mL). Experiments run in a microfermenter showed that the slow growth of cocultures associated with the assimilation of dextrin and the pH and Eh profiles favoured the production of toxin. Of the nitrogen sources assayed, corn steep liquor sustained the highest levels of toxin in both monocultures and cocultures with 3 and 2.8 fold increases with respect to that obtained using proteose peptone. The toxin production by C. argentinense cultures and C. argentinense–P. mendocina cocultures was highly dependent on the nature of the carbon and nitrogen sources used in the culture media. Growth of C. argentinense on substrates slowly assimilated stimulated the production of toxin.     

Corals shed bacteria as a potential mechanism of resilience to organic matter enrichment

Understanding the mechanisms of resilience of coral reefs to anthropogenic stressors is a critical step toward mitigating their current global decline. Coral–bacteria associations are fundamental to reef health and disease, but direct observations of these interactions remain largely unexplored. Here, we use novel technology, high-speed laser scanning confocal microscopy on live coral (Pocillopora damicornis), to test the hypothesis that corals exert control over the abundance of their associated bacterial communities by releasing (‘shedding'') bacteria from their surface, and that this mechanism can counteract bacterial growth stimulated by organic inputs. We also test the hypothesis that the coral pathogen Vibrio coralliilyticus can evade such a defense mechanism. This first report of direct observation with high-speed confocal microscopy of living coral and its associated bacterial community revealed a layer (3.3–146.8 μm thick) on the coral surface where bacteria were concentrated. The results of two independent experiments showed that the bacterial abundance in this layer was not sensitive to enrichment (5 mg l⁻¹ peptone), and that coral fragments exposed to enrichment released significantly more bacteria from their surfaces than control corals (P<0.01; 35.9±1.4 × 10⁵ cells cm⁻² coral versus 1.3±0.5 × 10⁵ cells cm⁻² coral). Our results provide direct support to the hypothesis that shedding bacteria may be an important mechanism by which coral-associated bacterial abundances are regulated under organic matter stress. Additionally, the novel ability to watch this ecological behavior in real-time at the microscale opens an unexplored avenue for mechanistic studies of coral–microbe interactions.     

Floral organogenesis of Chloranthus sessilifolius, with special emphasis on the morphological nature of the androecium of Chloranthus (Chloranthaceae)

 Floral organogenesis of Chloranthus sessilifolius K. F. Wu is described. The inflorescence primordium is dome-like in the beginning and then elongates, and bract primordia initiate almost decussately. Each floral primordium, arising from the axil of a bract, soon becomes a scale-like structure, with three primordia of androecial lobes originating from its abaxial part, and the gynoecial primordium in adaxial position. As the androecial lobes become more distinct, four thecae are already in differentiation, and the gynoecial primordium appears as a shallow disc. The androecial lobes do not extend their length until the thecae approach maturity and the stigma is differentiated. The androecial lobes are united at all the stages of development, and the entire androecium falls off as a unit at the end of anthesis. Based on these results, combined with published evidence from neobotany, palaeobotany and phylogenetic studies, the morphological nature of the androecium of Chloranthus is further discussed. Our studies support the viewpoint that the androecial structure of Chloranthus may have arisen by splitting of a single stamen with 2 marginal thecae. Received May 2, 2001 Accepted December 18, 2001     

Phylogeny of the Altingiaceae based on cpDNA matK, PY-IGS and nrDNA ITS sequences

 Phylogenetic relationships of the three genera of the family Altingiaceae, i.e., Altingia, Liquidambar and Semiliquidambar, based on matK sequences and the intergenic spacer between the psaA and ycf3 genes (PY-IGS) of cpDNA, and on the internal transcribed spacer (ITS) of nrDNA were studied. Phylogenetic trees based on the three data sets (matK, PY-IGS and ITS) were generated using Hamamelis japonica and Mytilaria laosensis (Hamamelidaceae), Cercidiphyllum japonicum (Cercidiphyllaceae), and Daphniphyllum calycinum (Daphniphyllaceae) as outgroups. The partition-homogeneity tests indicated that the three data sets and the combined data are homogeneous. A combined analysis also generated a strongly supported phylogeny. The phylogenetic trees show that the North American and western Asian species, L. styraciflua and L. orientalis, respectively, form a monophyletic group which is sister to the clade including all Asian species in the family. The genus Liquidambar is paraphyletic with Altingia and Semiliquidambar nested within. Phylogenetic analyses of the molecular data indicate that taxonomic reexamination of the generic delimitation in the Altingiaceae is needed. Received December 20, 2000 Accepted June 25, 2001