Highly Selective Hydrogenation and Hydrogenolysis Using a Copper-doped Porous Metal Oxide Catalyst

A copper-doped porous metal oxide catalyst in combination with hydrogen shows selective and quantitative hydrogenolysis of benzyl ketones and aldehydes, and hydrogenation of alkenes. The approach provides an alternative to noble-metal catalysed reductions and stoichiometric Wolff-Kishner and Clemmensen methods

Safer Chemicals Design Diagrams

The NRF2-ARE antioxidant pathway is an important biological sensing and regulating system that responds to chemical insults. At minute level, it protects a living species to go through hard environmental conditions. However, when the external disruption exceeds the inherent resilience, cellular damage can occur, eventually leading to cytotoxicity. Therefore, studying the likelihood of a chemical activating the NRF2-ARE pathway is interesting to discovering therapeutic agents and designing safer chemicals. In this research, we engaged a combination of computational chemistry, statistical learning and mechanistic toxicology to estimate the likelihood of a chemical to perturb this critical toxicological pathway and derive a scheme to guide chemical design with safer potency

Granulin Secreted by the Food-Borne Liver Fluke Opisthorchis viverrini Promotes Angiogenesis in Human Endothelial Cells

The liver fluke Opisthorchis viverrini is a food-borne, zoonotic pathogen endemic to Thailand and adjacent countries in Southeast Asia. The adult developmental stage of the O. viverrini parasite excretes and secretes numerous proteins within the biliary tract including the gall bladder. Lesions caused by the feeding activities of the liver fluke represent wounds that undergo protracted cycles of healing and re-injury during chronic infection, which can last for decades. Components of the excretory/secretory (ES) complement released by the worms capably drive proliferation of bile duct epithelial cells and are implicated in establishing the oncogenic milieu that leads to bile duct cancer, cholangiocarcinoma. An ES protein, the secreted granulin-like growth factor termed Ov-GRN-1, accelerates wound resolution in mice and in vitro. To investigate angiogenesis (blood vessel development) that may contribute to wound healing promoted by liver fluke granulin and, by implication, to carcinogenesis during chronic opisthorchiasis, we employed an in vitro tubule formation assay (TFA) where human umbilical vein endothelial cells were grown on gelled basement matrix. Ten and 40 nM Ov-GRN-1 significantly stimulated angiogenesis as monitored by cellular proliferation and by TFA in real time. This demonstration of potent angiogenic property of Ov-GRN-1 bolsters earlier reports on the therapeutic potential for chronic non-healing wounds of diabetics, tobacco users, and the elderly and, in addition, showcases another of the hallmark of cancer characteristic of this carcinogenic liver fluke

Granulin Secreted by the Food-Borne Liver Fluke

The liver fluke Opisthorchis viverrini is a food-borne, zoonotic pathogen endemic to Thailand and adjacent countries in Southeast Asia. The adult developmental stage of the O. viverrini parasite excretes and secretes numerous proteins within the biliary tract including the gall bladder. Lesions caused by the feeding activities of the liver fluke represent wounds that undergo protracted cycles of healing and re-injury during chronic infection, which can last for decades. Components of the excretory/secretory (ES) complement released by the worms capably drive proliferation of bile duct epithelial cells and are implicated in establishing the oncogenic milieu that leads to bile duct cancer, cholangiocarcinoma. An ES protein, the secreted granulin-like growth factor termed Ov-GRN-1, accelerates wound resolution in mice and in vitro. To investigate angiogenesis (blood vessel development) that may contribute to wound healing promoted by liver fluke granulin and, by implication, to carcinogenesis during chronic opisthorchiasis, we employed an in vitro tubule formation assay (TFA) where human umbilical vein endothelial cells were grown on gelled basement matrix. Ten and 40 nM Ov-GRN-1 significantly stimulated angiogenesis as monitored by cellular proliferation and by TFA in real time. This demonstration of potent angiogenic property of Ov-GRN-1 bolsters earlier reports on the therapeutic potential for chronic non-healing wounds of diabetics, tobacco users, and the elderly and, in addition, showcases another of the hallmark of cancer characteristic of this carcinogenic liver fluke

Overcoming the Challenges to the Implementation of Green Chemistry

The Harvard-Yale-ACS GCI Green Chemistry Project is investigating the overall question of the circumstances under which firms can enact innovations that have both economic and environmental benefits, through a focused examination of the implementation of green chemistry. The research project has taken up three fundamental, interrelated questions: What factors act as barriers to the implementation of green chemistry? What actions can be taken by the government, academia, NGO’s and industry that will help alleviate these factors? What are the policy implications of these barriers and potential actions, for all of the involved stakeholders? During its initial phases, through interviews with a dozen green chemistry leaders from industry and academia, and through a multi-stakeholder workshop, the project has focused on the first two questions, and is working towards the third. Overall, we determined that there are six major classes of barriers to the implementation of green chemistry: economic, regulatory, technical, organizational, cultural and definition and metrics. From the workshop participants, six major action themes emerged to address these. They are: create incentives for the development and implementation of innovations; consider policies to shift focus to hazard reduction; facilitate linkages, networks and collaborations; act as a facilitator for multi-stakeholder initiatives; promote actions that make environmental and health impacts a larger part of the decision calculus; and support research, knowledge creation, and educational efforts to support green chemistry across a range of disciplines and problem areas

Synthesis of Semiochemicals via Olefin Metathesis

Semiochemicals are substances or mixtures that carry messages and are used for communication between individuals of the same or different species. Semiochemicals that are used in pest control are called biopesticides. Conventional pesticides, which are generally synthetically derived and unnatural, inactivate or kill the pests, whereas biopesticides are naturally occurring compounds that attract insects to a trap or interfere with their reproduction. There are several advantages to biopesticides. Compared with conventional pesticides, biochemical-based pesticides are often less toxic and therefore have a significantly lower impact on human health and the environment. Moreover, biopesticides are pest-selective and as such do not negatively impact other organisms such as insects, mammals, or birds. Other advantages of biopesticides include high potency, meaning that smaller amounts of biopesticide are required, less resistance by target organisms, and the ability to biodegrade more quickly than conventional pesticides. Although biochemical-based pesticides are very promising materials, their production is often cumbersome, and their application is often limited. To date, most biopesticides have been synthesized by multistep, classical organic reactions that are not economical and have high environmental impact. However, in recent decades many efforts have been made to implement cost-effective and safer chemical procedures for the widespread application of biochemical-based pesticides. The purpose of this Perspective is to draw the attention of the green chemistry community to the applicability of olefin metathesis reactions in environmentally benign and cost-effective biopesticide synthesis. We review seminal work on the total synthesis of biopesticides using olefin metathesis as a key reaction step, and in doing so, we hope to inspire new ideas for forthcoming olefin-metathesis-based biopesticide development

Soft Templating and Disorder in an Applied 1D Cobalt Coordination Polymer Electrocatalyst

Disordered materials with resilient and soft-templated functional units bear the potential to fill the pipeline of robust catalysts for renewable energy storage. However, for novel materials lacking long-range order, the ability to discern local structure with atomic resolution still pushes the boundaries of current analytical and modeling approaches. We introduce a two-pillar strategy to monitor the formation and unravel the structure of the first disordered onedimensional cobalt coordination polymer catalyst, Co-dppeO2. This target material excels through proven high performance in commercial alkaline electrolyzers and organic transformations. We demonstrate that the key architecture behind this activity is the unconventional embedding of hydrated {H2O-Co2(OH)2-OH2} edge-site motifs, nested into a flexible organic matrix of highly oxidized and bridging hydrophobic dppeO2 ligands. Our combination of in situ spectroscopy and computational modeling of X-ray scattering and absorption spectra, backed with complementary experimental techniques, holds the key to understanding the atomic-range structure of important disordered materials

Septins of platyhelminths: identification, phylogeny, expression and localization among developmental stages of Schistosoma mansoni

Septins are a family of eukaryotic GTP binding proteins conserved from yeasts to humans. Originally identified in mutants of budding yeast, septins participate in diverse cellular functions including cytokinesis, organization of actin networks, cell polarity, vesicle trafficking and many others. Septins assemble into heteroligomers to form filaments and rings. Here, four septins of Schistosoma mansoni are described, which appear to be conserved within the phylum Platyhelminthes. These orthologues were related to the SEPT5, SEPT10 and SEPT7 septins of humans, and hence we have termed the schistosome septins SmSEPT5, SmSEPT10, SmSEPT7.1 and SmSEPT7.2. Septin transcripts were detected throughout the developmental cycle of the schistosome and a similar expression profile was observed for septins in the stages examined, consistent with concerted production of these proteins to form heterocomplexes. Immunolocalization analyses undertaken with antibodies specific for SmSEPT5 and SmSEPT10 revealed a broad tissue distribution of septins in the schistosomulum and colocalization of septin and actin in the longitudinal and circular muscles of the sporocyst. Ciliated epidermal plates of the miracidium were rich in septins. Expression levels for these septins were elevated in germ cells in the miracidium and sporocyst. Intriguingly, septins colocalize with the protonephridial system of the cercaria, which extends laterally along the length of this larval stage. Together, the findings revealed that schistosomes expressed several septins which likely form filaments within the cells, as in other eukaryotes. Identification and localization demonstrating a broad distribution of septins across organs and tissues of schistosome contributes towards the understanding of septins in schistosomes and other flatworms.NIH Shared Instrumentation (S10RR025565)CNPqInstituto Nacional de Ciência e Tecnologia de Biotecnologia Estrutural e Química Medicinal em Doenças Infecciosas (INBEQMeDI)CAPES (BEX: 9193/11-1

Genetic Manipulation of Schistosoma haematobium, the Neglected Schistosome

More people are infected with Schistosoma haematobium than other major human schistosomes yet it has been less studied because of difficulty in maintaining the life cycle in the laboratory. S. haematobium might be considered the ‘neglected schistosome’ since minimal information on the genome and proteome of S. haematobium is available, in marked contrast to the other major schistosomes. In this report we describe tools and protocols to investigate the genome and genetics of this neglected schistosome. We cultured developmental stages of S. haematobium, and investigated the utility of introducing gene probes into the parasites to silence two model genes. One of these, firefly luciferase, was a reporter gene whereas the second was a schistosome gene encoding a surface protein, termed Sh-tsp-2. We observed that both genes could be silenced – a phenomenon known as experimental RNA interference (RNAi). These findings indicated that the genome of S. haematobium will be amenable to genetic manipulation investigations designed to determine the function and importance of genes of this schistosome and to investigate for novel anti-parasite treatments