Two New Antibiotic Pyridones Produced by a Marine Fungus, Trichoderma sp. Strain MF106

Two unusual pyridones, trichodin A (1) and trichodin B (2), together with the known compound, pyridoxatin (3), were extracted from mycelia and culture broth of the marine fungus, Trichoderma sp. strain MF106 isolated from the Greenland Seas. The structures of the new compounds were characterized as an intramolecular cyclization of a pyridine basic backbone with a phenyl group. The structure and relative configuration of the new compounds were established by spectroscopic means. The new compound 1 and the known compound 3 showed antibiotic activities against the clinically relevant microorganism, Staphylococcus epidermidis, with IC50 values of 24 μM and 4 μM, respectively

Immunohistochemical Ki67 after short-term hormone therapy identifies low-risk breast cancers as reliably as genomic markers.

BACKGROUND: The purpose of this study was to test whether immunohistochemical (IHC) Ki67 levels after short-term preoperative hormone therapy (post-Ki67) predict similar numbers of patients with favorable prognoses as genomic markers. RESULTS: Thirty paired cases (60 samples) were enrolled in this study. Post-Ki67 levels were significantly lower than pre-treatment Ki67 levels (P < 0.001). Post-Ki67 predicted more low-risk cases (83.3%, 25/30) than pre-genomic surrogate signature(GSS) (66.7%: 20/30), but the difference in predictive power was not significant (P = 0.233). Proliferation (MKI67, STK15, Survivin, CCNB1, and MYBL2) and estrogen (ER, PGR, BCL2, and SCUBE2) related signatures were significantly downregulated after therapy (P < 0.001 and 0.041, respectively). MATERIALS AND METHODS: Core needle biopsy specimens of primary breast cancer were collected at Okayama University Hospital from hormone receptor-positive and human epidermal growth factor 2-negative patients that subsequently received two weeks of neoadjuvant hormone therapy. Paired post-treatment specimens from surgical samples were also collected. IHC Ki67 levels and GSS were compared between pre- and post-hormone treatment samples. Changes of gene expression pattern in short-term hormone therapy were also assessed. CONCLUSIONS: IHC based post-Ki67 levels may have distinct predictive power compared with the naive IHC Ki67. Future studies with larger cohorts and longer follow-up periods may be needed to validate our results

Calcarides A–E, Antibacterial Macrocyclic and Linear Polyesters from a Calcarisporium Strain

Bioactive compounds were detected in crude extracts of the fungus, Calcarisporium sp. KF525, which was isolated from German Wadden Sea water samples. Purification of the metabolites from the extracts yielded the five known polyesters, 15G256α, α-2, β, β-2 and π (1–5), and five new derivatives thereof, named calcarides A–E (6–10). The chemical structures of the isolated compounds were elucidated on the basis of one- and two-dimensional NMR spectroscopy supported by UV and HRESIMS data. The compounds exhibited inhibitory activities against Staphylococcus epidermidis, Xanthomonas campestris and Propionibacterium acnes. As the antibacterial activities were highly specific with regard to compound and test strain, a tight structure-activity relationship is assumed

Midwestern US Farmers Perceive Crop Advisers as Conduits of Information on Agricultural Conservation Practices

Nonpoint source pollution from agricultural land uses continues to pose one of the most significant threats to water quality in the US, with measurable impacts across local, regional, and national scales. The impact and the influence of targeted conservation efforts are directly related to the degree to which farmers are familiar with and trust the entities providing the information and/or outreach. Recent research suggests that farmers consistently rank independent and retail-affiliated crop advisers as among the most trusted and influential sources for agronomic information, but little is understood about whether farmers are willing to receive advice from crop advisers on the use of practices that conserve soil and water, and, if so, whether crop advisers will be perceived as influential. We present survey data from farmers (n = 1461) in Michigan’s Saginaw Bay (Lake Huron) watershed to explore these questions. Results suggest that farmers view crop advisers as trustworthy sources of information about conservation, and influential on management practices that have large conservation implications. We discuss these results, along with perceived barriers and opportunities to crop advisers partnering with traditional conservation agencies to enhance the impact of voluntary conservation programs

Spirocyclic Drimanes from the Marine Fungus Stachybotrys sp. Strain MF347

A novel spirocyclic drimane coupled by two drimane fragment building blocks 2 and a new drimane 1 were identified in mycelia and culture broth of Stachybotrys sp. MF347. Their structures were established by spectroscopic means. This is the first example of spirocyclic drimane coupled by a spirodihydrobenzofuranlactam unit and a spirodihydroisobenzofuran unit; and the connecting position being N-C instead of an N and N connecting unit. Strain MF347 produced also the known spirocyclic drimanes stachybocin A (12) and stachybocin B (11) featured by two sesquiterpene-spirobenzofuran structural units connected by a lysine residue; the known spirocyclic drimanes chartarlactam O (5); chartarlactam K (6); F1839A (7); stachybotrylactam (8); stachybotramide (9); and 2α-acetoxystachybotrylactam acetate (10); as well as ilicicolin B (13), a known sesquiterpene. The relative configuration of two known spirobenzofuranlactams (3 and 4) was determined. All compounds were subjected to biological activity tests. The spirocyclic drimane 2, 11, and 12, as well as the sesquiterpene 13, exhibited antibacterial activity against the clinically relevant methicillin-resistant Staphylococcus aureus (MRSA)

Large-Scale Biotechnological Production of the Antileukemic Marine Natural Product Sorbicillactone A

In the search for novel bioactive compounds from sponge-derived microorganisms, we have recently identified two structurally and biosynthetically unprecedented fungal metabolites, the novel-type alkaloids sorbicillactone A and sorbicillactone B. Sorbicillactone A is active against leukemia cells without showing notable cytotoxicity. Therefore, we have developed an efficient process for its biotechnological production and isolation on a large scale supplying sufficient material for the ongoing preclinical investigations and structure-activity relationship (SAR) studies

Cancer survivorship research: the challenge of recruiting adult long term cancer survivors from a cooperative clinical trials group

With the growing number of adult cancer survivors, there is increasing need for information that links potential late and long term effects with specific treatment regimens. Few adult cancer patients are treated on clinical trials; however, patients previously enrolled in these trials are an important source of information about treatment-related late effects. Focusing on colorectal cancer survivors, we used the database from five phase III randomized clinical trials from the National Surgical Adjuvant Breast &amp; Bowel Project (NSABP) to recruit and enroll long term survivors in a study of late health outcomes and quality of life. We describe the challenges to recruitment of patients more than 5 –20 years after treatment. Sixty-five NSABP treatment sites were invited to enroll patients in the study. Sixty participated with the potential to recruit 2,408 patients. We received registration forms on only 976 patients (41%) of whom 744 (76%) expressed interest in participating and 708 completed interviews (95% of those expressing interest; 29% of total potential sample). There were multiple barriers to recruitment (difficulty locating patients, lack of institutional commitment, lack of patient interest). Patients treated on clinical trials are an important potential source for examining the late effects of cancer treatments. Retrospective recruitment has substantial limitations. In the future, mechanisms should be established for prospective long-term follow-up to identify and understand the frequency and type of late effects associated with cancer treatments. As cancer patients are living longer, it will be important to learn from participants in clinical trials whether or not specific treatment regimens are associated with any serious late effects

Prevention of breast cancer by recapitulation of pregnancy hormone levels

At the present time, the only approved method of breast cancer prevention is use of the selective estrogen receptor modulator (SERM) tamoxifen. Many breast cancers are driven to grow by estrogen, and tamoxifen exploits this by blocking estrogen action at the estrogen receptor. A counter-intuitive and controversial approach to breast cancer prevention is administration of estrogen and progestin at an early age to achieve pregnancy levels. This approach is supported by the fact that breast cancer incidence is halved by early (≤ 20 years of age) full-term pregnancy. Moreover, it has been demonstrated in rodent models that mimicking the hormonal milieu can effectively prevent carcinogen-induced mammary cancer. In this issue of Breast Cancer Research Rajkumar and colleagues use the rodent model to further define the timing and type of hormonal therapy that is effective in preventing mammary carcinogenesis. Clearly, application of this approach in humans may be difficult, but the potential benefit is intriguing

Marine yeast isolation and industrial application

Over the last century, terrestrial yeasts have been widely used in various industries, such as baking, brewing, wine, bioethanol and pharmaceutical protein production. However, only little attention has been given to marine yeasts. Recent research showed that marine yeasts have several unique and promising features over the terrestrial yeasts, for example higher osmosis tolerance, higher special chemical productivity and production of industrial enzymes. These indicate that marine yeasts have great potential to be applied in various industries. This review gathers the most recent techniques used for marine yeast isolation as well as the latest applications of marine yeast in bioethanol, pharmaceutical and enzyme production fields. Keyword

High-level expression of Aspergillus niger β-galactosidase in Ashbya gossypii

Ashbya gossypii has been recently considered as a host for the expression of recombinant proteins. The production levels achieved thus far were similar to those obtained with Saccharomyces cerevisiae for the same proteins. Here, the β-galactosidase from Aspergillus niger was successfully expressed and secreted by A. gossypii from 2-micron plasmids carrying the native signal sequence at higher levels than those secreted by S. cerevisiae laboratorial strains. Four different constitutive promoters were used to regulate the expression of β-galactosidase: A. gossypii AgTEF and AgGPD promoters, and S. cerevisiae ScADH1 and ScPGK1 promoters. The native AgTEF promoter drove the highest expression levels of recombinant β-galactosidase in A. gossypii, leading to 2- and 8-fold higher extracellular activity than the AgGPD promoter and the heterologous promoters, respectively. In similar production conditions, the levels of active β-galactosidase secreted by A. gossypii were up to 37 times higher than those secreted by recombinant S. cerevisiae and approximately 2.5 times higher than those previously reported for the β-galactosidase-high producing S. cerevisiae NCYC869-A3/pVK1.1. The substitution of glucose by glycerol in the production medium led to a 1.5-fold increase in the secretion of active β-galactosidase by A. gossypii. Recombinant β-galactosidase secreted by A. gossypii was extensively glycosylated, as are the native A. niger β-galactosidase and recombinant β-galactosidase produced by yeast. These results highlight the potential of A. gossypii as a recombinant protein producer and open new perspectives to further optimize recombinant protein secretion in this fungus.Project AshByofactory (grant PTDC/EBB-EBI/101985/2008 - FCOMP-01-0124-FEDER-009701), MIT-Portugal Program (PhD grant SFRH/BD/39112/2007 to Tatiana Q. Aguiar) and grant SFRH/BDP/63831/2009 to Carla Oliveir