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Lucy Foulston
Natural products are a rich source of bioactive compounds that have been used successfully in the areas of human health from infectious disease to cancer; however, traditional fermentation-based screening has provided diminishing returns over the last 20-30 years. Solutions to the unmet need of resistant bacterial infection are critically required. Technological advances in high-throughput genomic sequencing, coupled with ever-decreasing cost, are now presenting a unique opportunity for the reinvigoration of natural product discovery...
February 15, 2019: Current Opinion in Microbiology
Binbin Tu, Lisa Diestel, Zhao-Lin Shi, W R L Nisansala Bandara, Yi Chen, Weimin Lin, Yue-Biao Zhang, Shane G Telfer, Qiaowei Li
Positioning a diverse set of building blocks in a well-defined array allows for cooperativity amongst them and the systematic programming of functional properties. Extending this concept to porous metal-organic frameworks (MOFs) is challenging since installing multiple components in a well-ordered framework requires careful design of the lattice topology, judicious selection of building blocks, and precise control of the crystallization parameters. In this work, we report how we have met these challenges to prepare the first quinary MOF structure, FDM-8, by bottom-up self-assembly...
February 18, 2019: Angewandte Chemie
Dengke Pan, Ting Liu, Tiantian Lei, Huibin Zhu, Yi Wang, Shaoping Deng
Pig-to-human organ transplantation provides an alternative for critical shortage of human organs worldwide. Genetically modified pigs are promising donors for xenotransplantation as they show many anatomical and physiological similarities to humans. However, immunological rejection including hyperacute rejection (HAR), acute humoral xenograft rejection (AHXR), immune cell-mediated rejection, and other barriers associated with xenotransplantation must be overcome with various strategies for the genetic modification of pigs...
January 2019: Xenotransplantation
David W Green, Jolanta A Watson, Han-Sung Jung, Gregory S Watson
Living organisms are the ultimate survivalists, having evolved phenotypes with unprecedented adaptability, ingenuity, resourcefulness, and versatility compared to human technology. To harness these properties, functional descriptions and design principles from all sources of biodiversity information must be collated - including the hundreds of thousands of possible survival features manifest in natural history museum collections, which represent 12% of total global biodiversity. This requires a consortium of expert biologists from a range of disciplines to convert the observations, data, and hypotheses into the language of engineering...
February 2019: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
Oliver Nagel, Manuel Frey, Matthias Gerhardt, Carsten Beta
Cell-driven microtransport is one of the most prominent applications in the emerging field of biohybrid systems. While bacterial cells have been successfully employed to drive the swimming motion of micrometer-sized cargo particles, the transport capacities of motile adherent cells remain largely unexplored. Here, it is demonstrated that motile amoeboid cells can act as efficient and versatile trucks to transport microcargo. When incubated together with microparticles, cells of the social amoeba Dictyostelium discoideum readily pick up and move the cargo particles...
February 6, 2019: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Abi Beane, Ambepitiyawaduge Pubudu De Silva, Priyantha Lakmini Athapattu, Saroj Jayasinghe, Anuja Unnathie Abayadeera, Mandika Wijerathne, Ishara Udayanga, Shriyananda Rathnayake, Arjen M Dondorp, Rashan Haniffa
Lack of investment in low-income and middle-income countries (LMICs) in systems capturing continuous information regarding care of the acutely unwell patient is hindering global efforts to address inequalities, both at facility and national level. Furthermore, this of lack of data is disempowering frontline staff and those seeking to support them, from progressing setting-relevant research and quality improvement. In contrast to high-income country (HIC) settings, where electronic surveillance has boosted the capability of governments, clinicians and researchers to engage in service-wide healthcare evaluation, healthcare information in resource-limited settings remains almost exclusively paper based...
2019: BMJ Global Health
Zuxiao Zhang, Leah M Stateman, David A Nagib
A Cu-catalyzed strategy has been developed that harnesses a radical relay mechanism to intercept a distal C-centered radical for C-C bond formation. This approach enables selective δ C-H (hetero)arylation of sulfonamides via intramolecular hydrogen atom transfer (HAT) by an N-centered radical. The radical relay is both initiated and terminated by a Cu catalyst, which enables incorporation of arenes and heteroarenes by cross-coupling with boronic acids. The broad scope and utility of this catalytic method for δ C-H arylation is shown, along with mechanistic probes for selectivity of the HAT mechanism...
January 28, 2019: Chemical Science
Concetta Burgarella, Adeline Barnaud, Ndjido Ardo Kane, Frédérique Jankowski, Nora Scarcelli, Claire Billot, Yves Vigouroux, Cécile Berthouly-Salazar
Global environmental changes strongly impact wild and domesticated species biology and their associated ecosystem services. For crops, global warming has led to significant changes in terms of phenology and/or yield. To respond to the agricultural challenges of this century, there is a strong need for harnessing the genetic variability of crops and adapting them to new conditions. Gene flow, from either the same species or a different species, may be an immediate primary source to widen genetic diversity and adaptions to various environments...
2019: Frontiers in Plant Science
Rosemery Membreno, Brendon E Cook, Brian M Zeglis
While radioimmunotherapy (RIT) is a promising approach for the treatment of cancer, the long pharmacokinetic half-life of radiolabeled antibodies can result in high radiation doses to healthy tissues. Perhaps not surprisingly, several different strategies have been developed to circumvent this troubling limitation. One of the most promising of these approaches is pretargeted radioimmunotherapy (PRIT). PRIT is predicated on decoupling the radionuclide from the immunoglobulin, injecting them separately, and then allowing them to combine in vivo at the target tissue...
January 29, 2019: Journal of Visualized Experiments: JoVE
Xiucui Ma, Kartik Mani, Haiyan Liu, Attila Kovacs, John T Murphy, Layla Foroughi, Brent A French, Carla J Weinheimer, Aldi Kraja, Ivor J Benjamin, Joseph A Hill, Ali Javaheri, Abhinav Diwan
Background Mutations in αB-crystallin result in proteotoxic cardiomyopathy with desmin mislocalization to protein aggregates. Intermittent fasting ( IF ) is a novel approach to activate transcription factor EB (TFEB), a master regulator of the autophagy-lysosomal pathway, in the myocardium. We tested whether TFEB activation can be harnessed to treat advanced proteotoxic cardiomyopathy. Methods and Results Mice overexpressing the R120G mutant of αB-crystallin in cardiomyocytes ( Myh6-Cry ABR 120G) were subjected to IF or ad-lib feeding, or transduced with adeno-associated virus- TFEB or adeno-associated virus-green fluorescent protein after development of advanced proteotoxic cardiomyopathy...
February 19, 2019: Journal of the American Heart Association
Hathaichanok Phuengkham, Long Ren, Il Woo Shin, Yong Taik Lim
Cancer immunotherapies that harness the body's immune system to combat tumors have received extensive attention and become mainstream strategies for treating cancer. Despite promising results, some problems remain, such as the limited patient response rate and the emergence of severe immune-related adverse effects. For most patients, the therapeutic efficacy of cancer immunotherapy is mainly limited by the immunosuppressive tumor microenvironment (TME). To overcome such obstacles in the TME, the immunomodulation of immunosuppressive factors and therapeutic immune cells (e...
February 18, 2019: Advanced Materials
David A Russo, Julie A Z Zedler, Poul Erik Jensen
In recent years, efforts to exploit sunlight, a free and abundant energy source, have sped up dramatically. Oxygenic photosynthetic organisms, such as higher plants, algae and cyanobacteria, can very efficiently convert solar energy into chemical energy using water as an electron donor. Therefore, by providing organic building blocks for life, photosynthesis is undoubtedly one of the most important processes on Earth. The aim of light-driven catalysis is to harness solar energy, in the form of reducing power, to drive enzymatic reactions requiring electrons for their catalytic cycle...
February 18, 2019: Journal of Experimental Botany
Thomas Reid, Ian G Droppo, Subba Rao Chaganti, Christopher G Weisener
The success and sustainability of aquatic ecosystems are driven by the complex, cooperative metabolism of microbes. Ecological engineering strategies often strive to harness this syntrophic synergy of microbial metabolism for the reclamation of contaminated environments worldwide. Currently, there is a significant knowledge gap in our understanding of how the natural microbial ecology overcomes thermodynamic limitations in recovering contaminated environments. Here, we used in-situ metatranscriptomics and associated metataxonomic analyses on sediments collected from naturalized freshwater man-made reservoirs within the Athabasca Oil Sands region of Alberta, Canada...
February 8, 2019: Science of the Total Environment
Steven A Connor, Jonathan Elegheert, Yicheng Xie, Ann Marie Craig
Synapse development depends on a dynamic balance between synapse promoters and suppressors. MDGAs, immunoglobulin superfamily proteins, negatively regulate synapse development through blocking neuroligin-neurexin interactions. Recent analyses of MDGA-neuroligin complexes revealed the structural basis of this activity and indicate that MDGAs interact with all neuroligins with differential affinities. Surprisingly, analyses of mouse mutants revealed a functional divergence, with targeted mutation of Mdga1 and Mdga2 elevating inhibitory and excitatory synapses, respectively, on hippocampal pyramidal neurons...
February 13, 2019: Current Opinion in Neurobiology
Harshada Sowani, Mohan Kulkarni, Smita Zinjarde
The genus Gordonia includes variedly pigmented aerobic, non-motile, non-sporulating Gram positive (sometimes variable) coccoid forms and rods. Different isolates display distinguishing physiological traits and biochemical properties that are significant in remediation applications. Strains inherently prevalent in soils, seawater, sediments and wastewaters can degrade hydrocarbons. Immobilized cells and microbial consortia containing Gordonia species have been used for in situ applications. Hydrocarbon uptake in this Actinomycete is mediated by attachment to large droplets or by pseudosolubilization of substrates...
February 13, 2019: Biotechnology Advances
Vojtěch Brlík, Jaroslav Koleček, Malcolm Burgess, Steffen Hahn, Diana Humple, Miloš Krist, Janne Ouwehand, Emily L Weiser, Peter Adamík, José A Alves, Debora Arlt, Sanja Barišić, Detlef Becker, Eduardo J Belda, Václav Beran, Christiaan Both, Susana P Bravo, Martins Briedis, Bohumír Chutný, Davor Ćiković, Nathan W Cooper, Joana S Costa, Víctor R Cueto, Tamara Emmenegger, Kevin Fraser, Olivier Gilg, Marina Guerrero, Michael T Hallworth, Chris Hewson, Frédéric Jiguet, James A Johnson, Tosha Kelly, Dmitry Kishkinev, Michel Leconte, Terje Lislevand, Simeon Lisovski, Cosme López, Kent P McFarland, Peter P Marra, Steven M Matsuoka, Piotr Matyjasiak, Christoph M Meier, Benjamin Metzger, Juan S Monrós, Roland Neumann, Amy Newman, Ryan Norris, Tomas Pärt, Václav Pavel, Noah Perlut, Markus Piha, Jeroen Reneerkens, Christopher C Rimmer, Amélie Roberto-Charron, Chiara Scandolara, Natalia Sokolova, Makiko Takenaka, Dirk Tolkmitt, Herman van Oosten, Arndt H J Wellbrock, Hazel Wheeler, Jan van der Winden, Klaudia Witte, Brad Woodworth, Petr Procházka
Currently, the deployment of tracking devices is one of the most frequently used approaches to study movement ecology of birds. Recent miniaturisation of light-level geolocators enabled studying small bird species whose migratory patterns were widely unknown. However, geolocators may reduce vital rates in tagged birds and may bias obtained movement data. There is a need for a thorough assessment of the potential tag effects on small birds, as previous meta-analyses did not evaluate unpublished data and impact of multiple life-history traits, focused mainly on large species and the number of published studies tagging small birds has increased substantially...
February 16, 2019: Journal of Animal Ecology
Vinod S Ipar, Anisha Dsouza, Padma V Devarajan
Curcumin is a promising therapeutic agent that exhibits manifold therapeutic activities. However, it is challenging to study curcumin as it exhibits poor aqueous solubility and low permeability and it is a substrate for P-glycoprotein (P-gp). It is readily metabolized in the body, but many active metabolites of curcumin have been identified that could also be exploited for therapy. Strategies for the oral bioenhancement of curcumin to leverage the potential of curcumin as a therapeutic molecule are discussed here in light of these challenges...
February 15, 2019: European Journal of Drug Metabolism and Pharmacokinetics
Salim Kadhim, Mark F Bird, David G Lambert
Classical opioids (μ: mu, MOP; δ: delta, DOP and κ: kappa, KOP) variably affect immune function; they are immune depressants and there is good clinical evidence in the periphery. In addition, there is evidence for a central role in the control of a number of neuropathologies, e.g., neuropathic pain. Nociceptin/Orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ peptide receptor, NOP; peripheral and central activation can modulate immune function. In the periphery, NOP activation generally depresses immune function, but unlike classical opioids this is in part driven by NOP located on circulating immune cells...
February 16, 2019: Handbook of Experimental Pharmacology
Christopher Opie, Hidetoshi Noda, Masakatsu Shibasaki, Naoya Kumagai
The B3NO2 six-membered heterocycle (1,3-dioxa-5-aza-2,4,6-triborinane: DATB), comprising of three different non-carbon second-row elements, was recently demonstrated to be a powerful catalyst for dehydrative condensation of carboxylic acids and amines. The tedious synthesis of DATB, however, significantly diminished its utility as a catalyst, and thus the inherent chemical properties of the ring system remained virtually unexplored. Herein we disclose a general and facile synthetic strategy that harnesses a pyrimidine-containing scaffold for the reliable installation of boron atoms, giving rise to a series of Pym-DATBs from inexpensive materials in a modular fashion...
February 15, 2019: Chemistry: a European Journal
Kota Katayama, Sahil Gulati, Joseph T Ortega, Nathan S Alexander, Wenyu Sun, Marina M Shenouda, Krzysztof Palczewski, Beata Jastrzebska
The variable composition of the chromophore-binding pocket in visual receptors is essential for vision. The visual phototransduction starts with the cis-trans isomerization of the retinal chromophore upon absorption of photons. Despite sharing the common 11-cis-retinal chromophore, rod and cone photoreceptors possess distinct photochemical properties. Thus, a detailed molecular characterization of the chromophore-binding pocket of these receptors is critical to understanding the differences in the photochemistry of vision between rods and cones...
February 15, 2019: Journal of Biological Chemistry
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