Natural Products from the Lithistida: A Review of the Literature since 2000

Lithistid sponges are known to produce a diverse array of compounds ranging from polyketides, cyclic and linear peptides, alkaloids, pigments, lipids, and sterols. A majority of these structurally complex compounds have very potent and interesting biological activities. It has been a decade since a thorough review has been published that summarizes the literature on the natural products reported from this amazing sponge order. This review provides an update on the current taxonomic classification of the Lithistida, describes structures and biological activities of 131 new natural products, and discusses highlights from the total syntheses of 16 compounds from marine sponges of the Order Lithistida providing a compilation of the literature since the last review published in 2002

A prospective compound screening contest identified broader inhibitors for Sirtuin 1

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using in silico methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified

Prediction of Phenotype-Associated Genes via a Cellular Network Approach: A Candida albicans Infection Case Study

Candida albicans is the most prevalent opportunistic fungal pathogen in humans causing superficial and serious systemic infections. The infection process can be divided into three stages: adhesion, invasion, and host cell damage. To enhance our understanding of these C. albicans infection stages, this study aimed to predict phenotype-associated genes involved during these three infection stages and their roles in C. albicans–host interactions. In light of the principles that proteins that lie closer to one another in a protein interaction network are more likely to have similar functions, and that genes regulated by the same transcription factors tend to have similar functions, a cellular network approach was proposed to predict the phenotype-associated genes in this study. A total of 4, 12, and 3 genes were predicted as adhesion-, invasion-, and damage-associated genes during C. albicans infection, respectively. These predicted genes highlight the facts that cell surface components are critical for cell adhesion, and that morphogenesis is crucial for cell invasion. In addition, they provide targets for further investigations into the mechanisms of the three C. albicans infection stages. These results give insights into the responses elicited in C. albicans during interaction with the host, possibly instrumental in identifying novel therapies to treat C. albicans infection

Principles of genetic circuit design

Cells navigate environments, communicate and build complex patterns by initiating gene expression in response to specific signals. Engineers seek to harness this capability to program cells to perform tasks or create chemicals and materials that match the complexity seen in nature. This Review describes new tools that aid the construction of genetic circuits. Circuit dynamics can be influenced by the choice of regulators and changed with expression 'tuning knobs'. We collate the failure modes encountered when assembling circuits, quantify their impact on performance and review mitigation efforts. Finally, we discuss the constraints that arise from circuits having to operate within a living cell. Collectively, better tools, well-characterized parts and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials.National Institute of General Medical Sciences (U.S.) (Grant P50 GM098792)National Institute of General Medical Sciences (U.S.) (Grant R01 GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (EEC0540879)Life Technologies, Inc. (A114510)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant 4500000552

Regulation of antibiotic production in Actinobacteria: new perspectives from the post-genomic era

The antimicrobial activity of many of their natural products has brought prominence to the Streptomycetaceae, a family of Gram-positive bacteria that inhabit both soil and aquatic sediments. In the natural environment, antimicrobial compounds are likely to limit the growth of competitors, thereby offering a selective advantage to the producer, in particular when nutrients become limited and the developmental programme leading to spores commences. The study of the control of this secondary metabolism continues to offer insights into its integration with a complex lifecycle that takes multiple cues from the environment and primary metabolism. Such information can then be harnessed to devise laboratory screening conditions to discover compounds with new or improved clinical value. Here we provide an update of the review we published in NPR in 2011. Besides providing the essential background, we focus on recent developments in our understanding of the underlying regulatory networks, ecological triggers of natural product biosynthesis, contributions from comparative genomics and approaches to awaken the biosynthesis of otherwise silent or cryptic natural products. In addition, we highlight recent discoveries on the control of antibiotic production in other Actinobacteria, which have gained considerable attention since the start of the genomics revolution. New technologies that have the potential to produce a step change in our understanding of the regulation of secondary metabolism are also described

<原著>後方からの直腸粘膜切除と回腸貫通術式 : 新しい大腸全摘再建法

We reported a new method of restorative proctocolectomy using posterior approach and pull through reconstruction. This method obviated transanal manipulation, a major factor causing damage to the internal sphincter, thus preventing fecal incontinence due to sphincter dysfunction. Also, temporary ileostomy was not necessary becaasue the spout of an S-pouch was pulled down below the anal verge and its distal free end acted as a diverting stoma while the more proximal, healing zone (future anastomotic line) was kept from fecal contamination. This method was applied to a 32-year-old woman with familial polyposis coli and a 50 year old woman with ulcerative colitis. Their bowel movements steadily decreased to three times and five times a day, respectively. There was no fecal leakage or perianal excoriation. The advantages as well as disadvantages of this method compared with the conventional techniques were discussed.後方からの直腸到達法と貫通術式による新しい大腸全摘再建法を報告した. 本法は内肛門括約筋損傷の主因である経肛門操作を必要とせず, 括約筋障害による便失禁を予防できる. またS型貯留嚢の下方遊離断端が肛門外に引き出されて人工肛門の役割を果たし, 口側の回腸肛門癒合帯(将来の吻合線)の便汚染を防ぐために, 一時的回腸瘻造設も不必要である. 本法を32歳の家族性結腸腺腫症の女性と50歳の潰瘍性大腸炎の女性に施行した. 術後便回数は着実に減少し各々1日3回と5回となった. また肛門からの便漏れや皮膚びらんも認めなかった. 本法の利点や欠点を他の方法と比較検討した