Improving Fungal Cultivability for Natural Products Discovery

The pool of fungal secondary metabolites can be extended by activating silent gene clusters of cultured strains or by using sensitive biological assays that detect metabolites missed by analytical methods. Alternatively, or in parallel with the first approach, one can increase the diversity of existing culture collections to improve the access to new natural products. This review focuses on the latter approach of screening previously uncultured fungi for chemodiversity. Both strategies have been practiced since the early days of fungal biodiscovery, yet relatively little has been done to overcome the challenge of cultivability of as-yet-uncultivated fungi. Whereas earlier cultivability studies using media formulations and biological assays to scrutinize fungal growth and associated factors were actively conducted, the application of modern omics methods remains limited to test how to culture the fungal dark matter and recalcitrant groups of described fungi. This review discusses the development of techniques to increase the cultivability of filamentous fungi that include culture media formulations and the utilization of known chemical growth factors, in situ culturing and current synthetic biology approaches that build upon knowledge from sequenced genomes. We list more than 100 growth factors, i.e., molecules, biological or physical factors that have been demonstrated to induce spore germination as well as tens of inducers of mycelial growth. We review culturing conditions that can be successfully manipulated for growth of fungi and visit recent information from omics methods to discuss the metabolic basis of cultivability. Earlier work has demonstrated the power of co-culturing fungi with their host, other microorganisms or their exudates to increase their cultivability. Co-culturing of two or more organisms is also a strategy used today for increasing cultivability. However, fungi possess an increased risk for cross-contaminations between isolates in existing in situ or microfluidics culturing devices. Technological improvements for culturing fungi are discussed in the review. We emphasize that improving the cultivability of fungi remains a relevant strategy in drug discovery and underline the importance of ecological and taxonomic knowledge in culture-dependent drug discovery. Combining traditional and omics techniques such as single cell or metagenome sequencing opens up a new era in the study of growth factors of hundreds of thousands of fungal species with high drug discovery potential

Fungi in the Marine Environment: Open Questions and Unsolved Problems

Terrestrial fungi play critical roles in nutrient cycling and food webs and can shape macroorganism communities as parasites and mutualists. Although estimates for the number of fungal species on the planet range from 1.5 to over 5 million, likely fewer than 10% of fungi have been identified so far.Terrestrial fungi play critical roles in nutrient cycling and food webs and can shape macroorganism communities as parasites and mutualists. Although estimates for the number of fungal species on the planet range from 1.5 to over 5 million, likely fewer than 10% of fungi have been identified so far. To date, a relatively small percentage of described species are associated with marine environments, with &sim;1,100 species retrieved exclusively from the marine environment. Nevertheless, fungi have been found in nearly every marine habitat explored, from the surface of the ocean to kilometers below ocean sediments. Fungi are hypothesized to contribute to phytoplankton population cycles and the biological carbon pump and are active in the chemistry of marine sediments. Many fungi have been identified as commensals or pathogens of marine animals (e.g., corals and sponges), plants, and algae. Despite their varied roles, remarkably little is known about the diversity of this major branch of eukaryotic life in marine ecosystems or their ecological functions. This perspective emerges from a Marine Fungi Workshop held in May 2018 at the Marine Biological Laboratory in Woods Hole, MA. We present the state of knowledge as well as the multitude of open questions regarding the diversity and function of fungi in the marine biosphere and geochemical cycles.</p

Testing Quantum Electrodynamics in the Lowest Singlet State of Neutral Beryllium-9

We report spectroscopic results on the 2s2p1P1 state in neutral atomic beryllium-9. The absolute frequency for the center of gravity is determined to be 42 565.4501(13)  cm−1, a factor of 130 more precise than the previous experimental measurement. The result is in agreement with and a factor of 8 more precise than the current best theoretical estimate of 42 565.441(11)  cm−1, which was calculated including the effects of quantum electrodynamics. Because of the large natural linewidth of the transition, the hyperfine constants were not able to be extracted to high precision

BIBFRAME beginnings at UT Austin

Slides from a panel discussion presented at the 2016 Texas Conference on Digital Libraries Special Forum: Exploring Linked Data for Libraries, which took place May 24, 2016.Staff from UT Libraries, the Harry Ransom Center, and the Tarlton Law Library have been collaborating in discussion group activities during the last year to develop knowledge and skills in anticipation of life after MARC, investigating the brave new world of linked data in libraries with a focus on the Library of Congress Bibliographic Framework (BIBFRAME) initiative. Our group efforts to better understand BIBFRAME and linked data for libraries include in-depth discussions of current literature, webcasts, and presentations; strategic application of Zepheira’s Practical Practitioner training; and hands-on experimentation transforming local metadata in various formats for various resource types to BIBFRAME. Our analysis of the resulting transformations has helped us gain insight on mapping complexities, data loss, false transformations, potential new metadata displays, and the limitations of the tools involved. The experimentation process overall has afforded us the opportunity to ask targeted questions about what is needed to move towards linked data and to gain a better view of the frontier of Technical Services staff skillsets. In this panel presentation, we’ll share details about our approaches to maximizing the group learning experience, and lessons learned from grappling with new concepts, data models, terminology, and tools. Representatives from our experimentation teams will report on the initial experience of transforming MARC and non-MARC data sets to BIBFRAME, and what we see as emerging questions and next steps.UT Librarie

White Light-Informed Optical Properties Improve Ultrasound-Guided Fluorescence Tomography of Photoactive Protoporphyrin IX

Subsurface fluorescence imaging is desirable for medical applications, including protoporphyrin-IX (PpIX)-based skin tumor diagnosis, surgical guidance, and dosimetry in photodynamic therapy. While tissue optical properties and heterogeneities make true subsurface fluorescence mapping an ill-posed problem, ultrasound-guided fluorescence-tomography (USFT) provides regional fluorescence mapping. Here USFT is implemented with spectroscopic decoupling of fluorescence signals (auto-fluorescence, PpIX, photoproducts), and white light spectroscopy-determined bulk optical properties. Segmented US images provide a priori spatial information for fluorescence reconstruction using region-based, diffuse FT. The method was tested in simulations, tissue homogeneous and inclusion phantoms, and an injected-inclusion animal model. Reconstructed fluorescence yield was linear with PpIX concentration, including the lowest concentration used, 0.025  μg/ml . White light spectroscopy informed optical properties, which improved fluorescence reconstruction accuracy compared to the use of fixed, literature-based optical properties, reduced reconstruction error and reconstructed fluorescence standard deviation by factors of 8.9 and 2.0, respectively. Recovered contrast-to-background error was 25% and 74% for inclusion phantoms without and with a 2-mm skin-like layer, respectively. Preliminary mouse-model imaging demonstrated system feasibility for subsurface fluorescence measurement in vivo. These data suggest that this implementation of USFT is capable of regional PpIX mapping in human skin tumors during photodynamic therapy, to be used in dosimetric evaluations

An EMG Gesture Recognition System with Flexible High-Density Sensors and Brain-Inspired High-Dimensional Classifier

EMG-based gesture recognition shows promise for human-machine interaction. Systems are often afflicted by signal and electrode variability which degrades performance over time. We present an end-to-end system combating this variability using a large-area, high-density sensor array and a robust classification algorithm. EMG electrodes are fabricated on a flexible substrate and interfaced to a custom wireless device for 64-channel signal acquisition and streaming. We use brain-inspired high-dimensional (HD) computing for processing EMG features in one-shot learning. The HD algorithm is tolerant to noise and electrode misplacement and can quickly learn from few gestures without gradient descent or back-propagation. We achieve an average classification accuracy of 96.64% for five gestures, with only 7% degradation when training and testing across different days. Our system maintains this accuracy when trained with only three trials of gestures; it also demonstrates comparable accuracy with the state-of-the-art when trained with one trial